Smooth transition for CPG-based body shape control of a snake-like robot

International Nuclear Information System (INIS)

Nor, Norzalilah Mohamad; Ma, Shugen

2014-01-01

This paper presents a locomotion control based on central pattern generator (CPG) of a snake-like robot. The main point addressed in this paper is a method that produces a smooth transition of the body shape of a snake-like robot. Body shape transition is important for snake-like robot locomotion to adapt to different space widths and also for obstacle avoidance. By manipulating the phase difference of the CPG outputs instantly, it will results in a sharp point or discontinuity which lead to an unstable movement of the snake-like robot. To tackle the problem, we propose a way of controlling the body shape: by incorporating activation function in the phase oscillator CPG model. The simplicity of the method promises an easy implementation and simple control. Simulation results and torque analysis confirm the effectiveness of the proposed control method and thus, can be used as a locomotion control in various potential applications of a snake-like robot. (paper)

CpG islands undermethylation in human genomic regions under selective pressure.

Directory of Open Access Journals (Sweden)

Sergio Cocozza

Full Text Available DNA methylation at CpG islands (CGIs is one of the most intensively studied epigenetic mechanisms. It is fundamental for cellular differentiation and control of transcriptional potential. DNA methylation is involved also in several processes that are central to evolutionary biology, including phenotypic plasticity and evolvability. In this study, we explored the relationship between CpG islands methylation and signatures of selective pressure in Homo Sapiens, using a computational biology approach. By analyzing methylation data of 25 cell lines from the Encyclopedia of DNA Elements (ENCODE Consortium, we compared the DNA methylation of CpG islands in genomic regions under selective pressure with the methylation of CpG islands in the remaining part of the genome. To define genomic regions under selective pressure, we used three different methods, each oriented to provide distinct information about selective events. Independently of the method and of the cell type used, we found evidences of undermethylation of CGIs in human genomic regions under selective pressure. Additionally, by analyzing SNP frequency in CpG islands, we demonstrated that CpG islands in regions under selective pressure show lower genetic variation. Our findings suggest that the CpG islands in regions under selective pressure seem to be somehow more "protected" from methylation when compared with other regions of the genome.

AtMBD6, a methyl CpG binding domain protein, maintains gene ...

Indian Academy of Sciences (India)

DNA methylation, mediated by double-stranded RNA, is a conserved epigenetic phenomenon that protects a genome fromtransposons, silences unwanted genes and has a paramount function in plant or animal development. Methyl CpG bindingdomain proteins are members of a class of proteins that bind tomethylated ...

AtMBD6, a methyl CpG binding domain protein, maintains gene ...

Indian Academy of Sciences (India)

2017-01-13

Jan 13, 2017 ... 13 methyl CpG binding domain (MBD) proteins, but the molecular/biological functions of most of these ... AtMBD5, AtMBD6 and AtMBD7 are more similar to those .... prey were able to grow on -AHLW (-Ade, -His, -Leu, -Trp).

Clustering aspects in nuclear structure functions

International Nuclear Information System (INIS)

Hirai, M.; Saito, K.; Watanabe, T.; Kumano, S.

2011-01-01

For understanding an anomalous nuclear effect experimentally observed for the beryllium-9 nucleus at the Thomas Jefferson National Accelerator Facility, clustering aspects are studied in structure functions of deep inelastic lepton-nucleus scattering by using momentum distributions calculated in antisymmetrized (or fermionic) molecular dynamics (AMD) and also in a simple shell model for comparison. According to AMD, the 9 Be nucleus consists of two α-like clusters with a surrounding neutron. The clustering produces high-momentum components in nuclear wave functions, which affects nuclear modifications of the structure functions. We investigated whether clustering features could appear in the structure function F 2 of 9 Be along with studies for other light nuclei. We found that nuclear modifications of F 2 are similar in both AMD and shell models within our simple convolution description although there are slight differences in 9 Be. It indicates that the anomalous 9 Be result should be explained by a different mechanism from the nuclear binding and Fermi motion. If nuclear-modification slopes d(F 2 A /F 2 D )/dx are shown by the maximum local densities, the 9 Be anomaly can be explained by the AMD picture, namely by the clustering structure, whereas it certainly cannot be described in the simple shell model. This fact suggests that the large nuclear modification in 9 Be should be explained by large densities in the clusters. For example, internal nucleon structure could be modified in the high-density clusters. The clustering aspect of nuclear structure functions is an unexplored topic which is interesting for future investigations.

CpG + CpNpG Analysis of Protein-Coding Sequences from Tomato

DEFF Research Database (Denmark)

Hobolth, Asger; Nielsen, Rasmus; Wang, Ying

2006-01-01

We develop codon-based models for simultaneously inferring the mutational effects of CpG and CpNpG methylation in coding regions. In a data set of 369 tomato genes, we show that there is very little effect of CpNpG methylation but a strong effect of CpG methylation affecting almost all genes. We...... further show that the CpNpG and CpG effects are largely uncorrelated. Our results suggest different roles of CpG and CpNpG methylation, with CpNpG methylation possibly playing a specialized role in defense against transposons and RNA viruses....

Distribution of CpG Motifs in Upstream Gene Domains in a Reef Coral and Sea Anemone: Implications for Epigenetics in Cnidarians.

Science.gov (United States)

Marsh, Adam G; Hoadley, Kenneth D; Warner, Mark E

2016-01-01

Coral reefs are under assault from stressors including global warming, ocean acidification, and urbanization. Knowing how these factors impact the future fate of reefs requires delineating stress responses across ecological, organismal and cellular scales. Recent advances in coral reef biology have integrated molecular processes with ecological fitness and have identified putative suites of temperature acclimation genes in a Scleractinian coral Acropora hyacinthus. We wondered what unique characteristics of these genes determined their coordinate expression in response to temperature acclimation, and whether or not other corals and cnidarians would likewise possess these features. Here, we focus on cytosine methylation as an epigenetic DNA modification that is responsive to environmental stressors. We identify common conserved patterns of cytosine-guanosine dinucleotide (CpG) motif frequencies in upstream promoter domains of different functional gene groups in two cnidarian genomes: a coral (Acropora digitifera) and an anemone (Nematostella vectensis). Our analyses show that CpG motif frequencies are prominent in the promoter domains of functional genes associated with environmental adaptation, particularly those identified in A. hyacinthus. Densities of CpG sites in upstream promoter domains near the transcriptional start site (TSS) are 1.38x higher than genomic background levels upstream of -2000 bp from the TSS. The increase in CpG usage suggests selection to allow for DNA methylation events to occur more frequently within 1 kb of the TSS. In addition, observed shifts in CpG densities among functional groups of genes suggests a potential role for epigenetic DNA methylation within promoter domains to impact functional gene expression responses in A. digitifera and N. vectensis. Identifying promoter epigenetic sequence motifs among genes within specific functional groups establishes an approach to describe integrated cellular responses to environmental stress in

Distribution of CpG Motifs in Upstream Gene Domains in a Reef Coral and Sea Anemone: Implications for Epigenetics in Cnidarians.

Directory of Open Access Journals (Sweden)

Adam G Marsh

Full Text Available Coral reefs are under assault from stressors including global warming, ocean acidification, and urbanization. Knowing how these factors impact the future fate of reefs requires delineating stress responses across ecological, organismal and cellular scales. Recent advances in coral reef biology have integrated molecular processes with ecological fitness and have identified putative suites of temperature acclimation genes in a Scleractinian coral Acropora hyacinthus. We wondered what unique characteristics of these genes determined their coordinate expression in response to temperature acclimation, and whether or not other corals and cnidarians would likewise possess these features. Here, we focus on cytosine methylation as an epigenetic DNA modification that is responsive to environmental stressors. We identify common conserved patterns of cytosine-guanosine dinucleotide (CpG motif frequencies in upstream promoter domains of different functional gene groups in two cnidarian genomes: a coral (Acropora digitifera and an anemone (Nematostella vectensis. Our analyses show that CpG motif frequencies are prominent in the promoter domains of functional genes associated with environmental adaptation, particularly those identified in A. hyacinthus. Densities of CpG sites in upstream promoter domains near the transcriptional start site (TSS are 1.38x higher than genomic background levels upstream of -2000 bp from the TSS. The increase in CpG usage suggests selection to allow for DNA methylation events to occur more frequently within 1 kb of the TSS. In addition, observed shifts in CpG densities among functional groups of genes suggests a potential role for epigenetic DNA methylation within promoter domains to impact functional gene expression responses in A. digitifera and N. vectensis. Identifying promoter epigenetic sequence motifs among genes within specific functional groups establishes an approach to describe integrated cellular responses to

The impact of intragenic CpG content on gene expression.

Science.gov (United States)

Bauer, Asli Petra; Leikam, Doris; Krinner, Simone; Notka, Frank; Ludwig, Christine; Längst, Gernot; Wagner, Ralf

2010-07-01

The development of vaccine components or recombinant therapeutics critically depends on sustained expression of the corresponding transgene. This study aimed to determine the contribution of intragenic CpG content to expression efficiency in transiently and stably transfected mammalian cells. Based upon a humanized version of green fluorescent protein (GFP) containing 60 CpGs within its coding sequence, a CpG-depleted variant of the GFP reporter was established by carefully modulating the codon usage. Interestingly, GFP reporter activity and detectable protein amounts in stably transfected CHO and 293 cells were significantly decreased upon CpG depletion and independent from promoter usage (CMV, EF1 alpha). The reduction in protein expression associated with CpG depletion was likewise observed for other unrelated reporter genes and was clearly reflected by a decline in mRNA copy numbers rather than translational efficiency. Moreover, decreased mRNA levels were neither due to nuclear export restrictions nor alternative splicing or mRNA instability. Rather, the intragenic CpG content influenced de novo transcriptional activity thus implying a common transcription-based mechanism of gene regulation via CpGs. Increased high CpG transcription correlated with changed nucleosomal positions in vitro albeit histone density at the two genes did not change in vivo as monitored by ChIP.

Integrated analysis of gene expression, CpG island methylation, and gene copy number in breast cancer cells by deep sequencing.

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Zhifu Sun

Full Text Available We used deep sequencing technology to profile the transcriptome, gene copy number, and CpG island methylation status simultaneously in eight commonly used breast cell lines to develop a model for how these genomic features are integrated in estrogen receptor positive (ER+ and negative breast cancer. Total mRNA sequence, gene copy number, and genomic CpG island methylation were carried out using the Illumina Genome Analyzer. Sequences were mapped to the human genome to obtain digitized gene expression data, DNA copy number in reference to the non-tumor cell line (MCF10A, and methylation status of 21,570 CpG islands to identify differentially expressed genes that were correlated with methylation or copy number changes. These were evaluated in a dataset from 129 primary breast tumors. Gene expression in cell lines was dominated by ER-associated genes. ER+ and ER- cell lines formed two distinct, stable clusters, and 1,873 genes were differentially expressed in the two groups. Part of chromosome 8 was deleted in all ER- cells and part of chromosome 17 amplified in all ER+ cells. These loci encoded 30 genes that were overexpressed in ER+ cells; 9 of these genes were overexpressed in ER+ tumors. We identified 149 differentially expressed genes that exhibited differential methylation of one or more CpG islands within 5 kb of the 5' end of the gene and for which mRNA abundance was inversely correlated with CpG island methylation status. In primary tumors we identified 84 genes that appear to be robust components of the methylation signature that we identified in ER+ cell lines. Our analyses reveal a global pattern of differential CpG island methylation that contributes to the transcriptome landscape of ER+ and ER- breast cancer cells and tumors. The role of gene amplification/deletion appears to more modest, although several potentially significant genes appear to be regulated by copy number aberrations.

The CpG island methylator phenotype: What's in a name?

NARCIS (Netherlands)

L.A.E. Hughes (Laura A.); V. Melotte (Veerle); J.D. Schrijver (Joachim De); M.P.M. de Maat (Moniek); V.T.H.B.M. Smit (Vincent); J.V.M.G. Bovée (Judith); P.J. French (Pim); P.A. van den Brandt (Piet); L. Schouten (Leo); T. Meyer (Thorsten); W. van Criekinge (Wim); N. Ahuja (Nita); J.G. Herman (James); M.P. Weijenberg (Matty); M. van Engeland (Manon)

2013-01-01

textabstractAlthough the CpG island methylator phenotype (CIMP) was first identified and has been most extensively studied in colorectal cancer, the term "CIMP" has been repeatedly used over the past decade to describe CpG island promoter methylation in other tumor types, including bladder, breast,

CpG oligodeoxynucleotides are potent enhancers of radio- and chemoresponses of murine tumors

International Nuclear Information System (INIS)

Mason, Kathryn A.; Neal, Robert; Hunter, Nancy; Ariga, Hisanori; Ang, Kian; Milas, Luka

2006-01-01

Background and purpose: Synthetic oligodeoxynucleotides (ODNs) containing unmethylated cytosine-guanine (CpG) motifs bind to Toll-like receptor 9 (TLR9) and stimulate both innate and adaptive immune reactions and possess anti-tumor activity. We recently reported that CpG ODN 1826 strongly enhances radioresponse of both immunogenic [Milas L, Mason K, Ariga H, et al. CpG oligodeoxynucleotide enhances tumor response to radiation. Cancer Res 2004;64:5074-7] and non-immunogenic [Mason KA, Ariga H, Neal R, et al. Targeting toll-like receptor-9 with CpG oligodeoxynucleotides enhances tumor response to fractionated radiotherapy. Clin Cancer Res 2005;11:361-9] murine tumors. Using two immunogenic murine tumors, a fibrosarcoma (FSa) and a mammary carcinoma (MCa-K), the present study explored whether CpG ODN 1826 also improves the response of murine tumors to the chemotherapeutic agent docetaxel (DOC). Materials and methods: CpG ODN 1826 (100 μg) was given sc three times: when leg tumors were 6 mm, when they grew to 8 mm and again 1 week later. DOC (33 mg/kg iv) and local tumor radiation (10 Gy) were given when tumors were 8 mm. Effects of the treatments were assayed by tumor growth delay, defined as days for tumors to grow from 8 to 12 mm in diameter. Results: Treatment with CpG ODN 1826 resulted in strongly enhanced response of FSa tumors to radiation and MCa-K tumors to the chemotherapeutic agent DOC. Enhancement of tumor treatment response was demonstrated by a strong prolongation in the primary tumor treatment endpoint, tumor growth delay. Coincidentally, this treatment also resulted in a higher rate of tumor cure than that observed after tumor radiotherapy or chemotherapy alone. When all three agents were combined the effect was comparable to that of the combination of CpG ODN 1826 with radiation in the case of FSa or of the combination of CpG ODN 1826 with DOC in the case of MCa-K. Conclusion: Overall results show that CpG ODN 1826 can markedly improve tumor response

Depletion of CpG Dinucleotides in Papillomaviruses and Polyomaviruses: A Role for Divergent Evolutionary Pressures.

Science.gov (United States)

Upadhyay, Mohita; Vivekanandan, Perumal

2015-01-01

Papillomaviruses and polyomaviruses are small ds-DNA viruses infecting a wide-range of vertebrate hosts. Evidence supporting co-evolution of the virus with the host does not fully explain the evolutionary path of papillomaviruses and polyomaviruses. Studies analyzing CpG dinucleotide frequencies in virus genomes have provided interesting insights on virus evolution. CpG dinucleotide depletion has not been extensively studied among papillomaviruses and polyomaviruses. We sought to analyze the relative abundance of dinucleotides and the relative roles of evolutionary pressures in papillomaviruses and polyomaviruses. We studied 127 full-length sequences from papillomaviruses and 56 full-length sequences from polyomaviruses. We analyzed the relative abundance of dinucleotides, effective codon number (ENC), differences in synonymous codon usage. We examined the association, if any, between the extent of CpG dinucleotide depletion and the evolutionary lineage of the infected host. We also investigated the contribution of mutational pressure and translational selection to the evolution of papillomaviruses and polyomaviruses. All papillomaviruses and polyomaviruses are CpG depleted. Interestingly, the evolutionary lineage of the infected host determines the extent of CpG depletion among papillomaviruses and polyomaviruses. CpG dinucleotide depletion was more pronounced among papillomaviruses and polyomaviruses infecting human and other mammals as compared to those infecting birds. Our findings demonstrate that CpG depletion among papillomaviruses is linked to mutational pressure; while CpG depletion among polyomaviruses is linked to translational selection. We also present evidence that suggests methylation of CpG dinucleotides may explain, at least in part, the depletion of CpG dinucleotides among papillomaviruses but not polyomaviruses. The extent of CpG depletion among papillomaviruses and polyomaviruses is linked to the evolutionary lineage of the infected host. Our

Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample.

Directory of Open Access Journals (Sweden)

Katsuhiko Nosho

Full Text Available The CpG island methylator phenotype (CIMP is a distinct phenotype associated with microsatellite instability (MSI and BRAF mutation in colon cancer. Recent investigations have selected 5 promoters (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 as surrogate markers for CIMP-high. However, no study has comprehensively evaluated an expanded set of methylation markers (including these 5 markers using a large number of tumors, or deciphered the complex clinical and molecular associations with CIMP-high determined by the validated marker panel. METHOLODOLOGY/PRINCIPAL FINDINGS: DNA methylation at 16 CpG islands [the above 5 plus CDKN2A (p16, CHFR, CRABP1, HIC1, IGFBP3, MGMT, MINT1, MINT31, MLH1, p14 (CDKN2A/ARF and WRN] was quantified in 904 colorectal cancers by real-time PCR (MethyLight. In unsupervised hierarchical clustering analysis, the 5 markers (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1, CDKN2A, CRABP1, MINT31, MLH1, p14 and WRN were generally clustered with each other and with MSI and BRAF mutation. KRAS mutation was not clustered with any methylation marker, suggesting its association with a random methylation pattern in CIMP-low tumors. Utilizing the validated CIMP marker panel (including the 5 markers, multivariate logistic regression demonstrated that CIMP-high was independently associated with older age, proximal location, poor differentiation, MSI-high, BRAF mutation, and inversely with LINE-1 hypomethylation and beta-catenin (CTNNB1 activation. Mucinous feature, signet ring cells, and p53-negativity were associated with CIMP-high in only univariate analysis. In stratified analyses, the relations of CIMP-high with poor differentiation, KRAS mutation and LINE-1 hypomethylation significantly differed according to MSI status.Our study provides valuable data for standardization of the use of CIMP-high-specific methylation markers. CIMP-high is independently associated with clinical and key molecular features in colorectal cancer. Our data also

CpG dinucleotide frequencies reveal the role of host methylation capabilities in parvovirus evolution.

Science.gov (United States)

Upadhyay, Mohita; Samal, Jasmine; Kandpal, Manish; Vasaikar, Suhas; Biswas, Banhi; Gomes, James; Vivekanandan, Perumal

2013-12-01

Parvoviruses are rapidly evolving viruses that infect a wide range of hosts, including vertebrates and invertebrates. Extensive methylation of the parvovirus genome has been recently demonstrated. A global pattern of methylation of CpG dinucleotides is seen in vertebrate genomes, compared to "fractional" methylation patterns in invertebrate genomes. It remains unknown if the loss of CpG dinucleotides occurs in all viruses of a given DNA virus family that infect host species spanning across vertebrates and invertebrates. We investigated the link between the extent of CpG dinucleotide depletion among autonomous parvoviruses and the evolutionary lineage of the infected host. We demonstrate major differences in the relative abundance of CpG dinucleotides among autonomous parvoviruses which share similar genome organization and common ancestry, depending on the infected host species. Parvoviruses infecting vertebrate hosts had significantly lower relative abundance of CpG dinucleotides than parvoviruses infecting invertebrate hosts. The strong correlation of CpG dinucleotide depletion with the gain in TpG/CpA dinucleotides and the loss of TpA dinucleotides among parvoviruses suggests a major role for CpG methylation in the evolution of parvoviruses. Our data present evidence that links the relative abundance of CpG dinucleotides in parvoviruses to the methylation capabilities of the infected host. In sum, our findings support a novel perspective of host-driven evolution among autonomous parvoviruses.

Glucocorticoid receptor gene expression and promoter CpG modifications throughout the human brain.

Science.gov (United States)

Cao-Lei, Lei; Suwansirikul, Songkiet; Jutavijittum, Prapan; Mériaux, Sophie B; Turner, Jonathan D; Muller, Claude P

2013-11-01

Glucocorticoids and the glucocorticoid (GR) and mineralocorticoid (MR) receptors have been implicated in many processes, particularly in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. Epigenetically programmed GR alternative promoter usage underlies transcriptional control of GR levels, generation of GR 3' splice variants, and the overall GC response in the brain. No detailed analysis of GR first exons or GR transcript variants throughout the human brain has been reported. Therefore we investigated post mortem tissues from 28 brain regions of 5 individuals. GR first exons were expressed throughout the healthy human brain with no region-specific usage patterns. First exon levels were highly inter-correlated suggesting that they are co-regulated. GR 3' splice variants (GRα and GR-P) were equally distributed in all regions, and GRβ expression was always low. GR/MR ratios showed significant differences between the 28 tissues with the highest ratio in the pituitary gland. Modification levels of individual CpG dinucleotides, including 5-mC and 5-hmC, in promoters 1D, 1E, 1F, and 1H were low, and diffusely clustered; despite significant heterogeneity between the donors. In agreement with this clustering, sum modification levels rather than individual CpG modifications correlated with GR expression. Two-way ANOVA showed that this sum modification was both promoter and brain region specific, but that there was however no promoter*tissue interaction. The heterogeneity between donors may however hide such an interaction. In both promoters 1F and 1H modification levels correlated with GRα expression suggesting that 5-mC and 5-hmC play an important role in fine tuning GR expression levels throughout the brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reproducibility of methylated CpG typing with the Illumina MiSeq

DEFF Research Database (Denmark)

Kampmann, Marie-Louise; Meyer, Olivia Strunge; Greby Schmidt, Suzanne

2017-01-01

DNA methylation patterns may be used for identification of body fluids and for age estimation of human individuals. We evaluated some of the challenges and pitfalls of studying methylated CpG sites. We compared the methylated CpG analysis of two different methods 1) massively parallel sequencing...

CpG methylation differences between neurons and glia are highly conserved from mouse to human.

Science.gov (United States)

Kessler, Noah J; Van Baak, Timothy E; Baker, Maria S; Laritsky, Eleonora; Coarfa, Cristian; Waterland, Robert A

2016-01-15

Understanding epigenetic differences that distinguish neurons and glia is of fundamental importance to the nascent field of neuroepigenetics. A recent study used genome-wide bisulfite sequencing to survey differences in DNA methylation between these two cell types, in both humans and mice. That study minimized the importance of cell type-specific differences in CpG methylation, claiming these are restricted to localized genomic regions, and instead emphasized that widespread and highly conserved differences in non-CpG methylation distinguish neurons and glia. We reanalyzed the data from that study and came to markedly different conclusions. In particular, we found widespread cell type-specific differences in CpG methylation, with a genome-wide tendency for neuronal CpG-hypermethylation punctuated by regions of glia-specific hypermethylation. Alarmingly, our analysis indicated that the majority of genes identified by the primary study as exhibiting cell type-specific CpG methylation differences were misclassified. To verify the accuracy of our analysis, we isolated neuronal and glial DNA from mouse cortex and performed quantitative bisulfite pyrosequencing at nine loci. The pyrosequencing results corroborated our analysis, without exception. Most interestingly, we found that gene-associated neuron vs. glia CpG methylation differences are highly conserved across human and mouse, and are very likely to be functional. In addition to underscoring the importance of independent verification to confirm the conclusions of genome-wide epigenetic analyses, our data indicate that CpG methylation plays a major role in neuroepigenetics, and that the mouse is likely an excellent model in which to study the role of DNA methylation in human neurodevelopment and disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

CpG Island Methylator Phenotype in Primary Gastric Carcinoma

OpenAIRE

TOJO Masayuki:筆頭著者; KONISHI Kazuo; YANO Yuichiro; KATAGIRI Atsushi; NOZAWA Hisako; KUBOTA Yutaro; MURAMOTO Takashi; KONDA Kenichi; SHINMURA Kensuke; TAKIMOTO Masafumi; IMAWARI Michio; YOSHIDA Hitoshi

2013-01-01

Gastric cancers (GC) with methylation of multiple CpG islands have a CpG island methylator phenotype (CIMP) and they can have different biological features. The aim of this study was to investigate the DNA methylation status of GCs and its association with their clinicopathological features. We evaluated the methylation status of four genes (MINT1, MINT2, MINT25 and MINT31) in 105 primary GCs using bisulfite-pyrosequencing analysis. We classified tumors as CIMP-high (CIMP-H), CIMP-low (CIMP-L...

CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers, infectious diseases, and allergies.

Science.gov (United States)

Hanagata, Nobutaka

2017-01-01

Unmethylated cytosine-guanine dinucleotide-containing oligodeoxynucleotides (CpG ODNs), which are synthetic agonists of Toll-like receptor 9 (TLR9), activate humoral and cellular immunity and are being developed as vaccine adjuvants to prevent or treat cancers, infectious diseases, and allergies. Free CpG ODNs have been used in many clinical trials implemented to verify their effects. However, recent research has reported that self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes demonstrate higher adjuvant effects than free CpG ODNs, owing to their improved uptake efficiency into cells expressing TLR9. Moreover, protein/peptide-CpG ODN conjugates and nanomaterial-CpG ODN complexes are able to deliver CpG ODNs and antigens (or allergens) to the same types of cells, which enables a higher degree of prophylaxis or therapeutic effect. In this review, the author describes recent trends in the research and development of CpG ODN nanomedicines containing self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes, focusing mainly on the results of preclinical and clinical studies.

Compositional searching of CpG islands in the human genome

Science.gov (United States)

Luque-Escamilla, Pedro Luis; Martínez-Aroza, José; Oliver, José L.; Gómez-Lopera, Juan Francisco; Román-Roldán, Ramón

2005-06-01

We report on an entropic edge detector based on the local calculation of the Jensen-Shannon divergence with application to the search for CpG islands. CpG islands are pieces of the genome related to gene expression and cell differentiation, and thus to cancer formation. Searching for these CpG islands is a major task in genetics and bioinformatics. Some algorithms have been proposed in the literature, based on moving statistics in a sliding window, but its size may greatly influence the results. The local use of Jensen-Shannon divergence is a completely different strategy: the nucleotide composition inside the islands is different from that in their environment, so a statistical distance—the Jensen-Shannon divergence—between the composition of two adjacent windows may be used as a measure of their dissimilarity. Sliding this double window over the entire sequence allows us to segment it compositionally. The fusion of those segments into greater ones that satisfy certain identification criteria must be achieved in order to obtain the definitive results. We find that the local use of Jensen-Shannon divergence is very suitable in processing DNA sequences for searching for compositionally different structures such as CpG islands, as compared to other algorithms in literature.

Methylation of the estrogen receptor CpG island distinguishes spontaneous and plutonium-induced tumors from nitrosamine-induced lung tumors

Energy Technology Data Exchange (ETDEWEB)

Belinsky, S.A.; Baylin, S.B.; Issa, J.J. [Johns Hopkins Univ., Baltimore, MD (United States)

1995-12-01

CpG islands located in the promoter region of genes constitute one mechanism for regulating transcription. These islands are normally free of methylation, regardless of the expression state of the gene. Hypermethylation of CpG islands, the addition of a methyl group to the internal cytosine within CpG dinucleotides, can cause silencing of a gene. Hypermethylation has been detected as an early event at specific chromosome loci during the development of colon cancer and represents one mechanism used by neoplatic cells to inactivate tumor suppressor genes. Recent studies have demonstrated this mechanism in inactivation of the VHL tumor suppressor gene in 19% of sporadic renal tumors and the p16 {sup INK4a} tumor suppressor gene in 30% of non-small cell lung cancers. A recent report indicates that the estrogen receptor gene could also be inactivated through methylation. In addition, estrogen receptor CpG island methylation arises as a direct function of age in normal colonic mucosa and is present in virtually all colonic tumors. In cultured colon cancer cells, methylation-associated loss of expression of the estrogen receptor gene results in deregulated growth, suggesting a role for the estrogen receptor in colon cancer development. These results provide further evidence that gene silencing through methylation could be a predominant epigenetic mechanism underlying the development of many different types of cancer. The purpose of the current investigation was to determine whether estrogen receptor CpG island methylation is involved in the development of lung cancer. The frequency for methylation of the estrogen receptor CpG island in rodent lung tumors is summarized.

Reinforcement learning for a biped robot based on a CPG-actor-critic method.

Science.gov (United States)

Nakamura, Yutaka; Mori, Takeshi; Sato, Masa-aki; Ishii, Shin

2007-08-01

Animals' rhythmic movements, such as locomotion, are considered to be controlled by neural circuits called central pattern generators (CPGs), which generate oscillatory signals. Motivated by this biological mechanism, studies have been conducted on the rhythmic movements controlled by CPG. As an autonomous learning framework for a CPG controller, we propose in this article a reinforcement learning method we call the "CPG-actor-critic" method. This method introduces a new architecture to the actor, and its training is roughly based on a stochastic policy gradient algorithm presented recently. We apply this method to an automatic acquisition problem of control for a biped robot. Computer simulations show that training of the CPG can be successfully performed by our method, thus allowing the biped robot to not only walk stably but also adapt to environmental changes.

Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42-C1/Alhydrogel with and without CPG 7909 in malaria naïve adults.

Directory of Open Access Journals (Sweden)

Ruth D Ellis

2010-01-01

Full Text Available Merozoite surface protein 1(42 (MSP1(42 is a leading blood stage malaria vaccine candidate. In order to induce immune responses that cover the major antigenic polymorphisms, FVO and 3D7 recombinant proteins of MSP1(42 were mixed (MSP1(42-C1. To improve the level of antibody response, MSP1(42-C1 was formulated with Alhydrogel plus the novel adjuvant CPG 7909.A Phase 1 clinical trial was conducted in healthy malaria-naïve adults at the Center for Immunization Research in Washington, D.C., to evaluate the safety and immunogenicity of MSP1(42-C1/Alhydrogel +/- CPG 7909. Sixty volunteers were enrolled in dose escalating cohorts and randomized to receive three vaccinations of either 40 or 160 microg protein adsorbed to Alhydrogel +/- 560 microg CPG 7909 at 0, 1 and 2 months.Vaccinations were well tolerated, with only one related adverse event graded as severe (Grade 3 injection site erythema and all other vaccine related adverse events graded as either mild or moderate. Local adverse events were more frequent and severe in the groups receiving CPG. The addition of CPG enhanced anti-MSP1(42 antibody responses following vaccination by up to 49-fold two weeks after second immunization and 8-fold two weeks after the third immunization when compared to MSP1(42-C1/Alhydrogel alone (p<0.0001. After the third immunization, functionality of the antibody was tested by an in vitro growth inhibition assay. Inhibition was a function of antibody titer, with an average of 3% (range -2 to 10% in the non CPG groups versus 14% (3 to 32% in the CPG groups.The favorable safety profile and high antibody responses induced with MSP1(42-C1/Alhydrogel + CPG 7909 are encouraging. MSP1(42-C1/Alhydrogel is being combined with other blood stage antigens and will be taken forward in a formulation adjuvanted with CPG 7909.ClinicalTrials.gov Identifier: NCT00320658.

Mass functions for eight galactic clusters in the solar neighborhood

International Nuclear Information System (INIS)

Francic, S.P.

1989-01-01

Mass functions for eight galactic clusters in the solar neighborhood have been obtained. The mass functions have been determined from proper motion membership probabilities and unlike similar investigations, corrected for outlying cluster stars. The membership probabilities have been determined from the joint proper motion and surface density distributions for the field and clusters stars. They have also been corrected for any magnitude dependences. Comparison of the mass functions with the Salpeter IMF shows that the older clusters tend to be deficient in the number of low mass stars, while the younger clusters tend to have more. Analysis of the relaxation times shows that the deficiency of faint stars in the older clusters is likely due to their evaporation from the cluster. The combined mass function for six of the cluster results in a power law with a power law index of -1.97 ± 0.17 for 1.1 < M/Mass of sun < 2.5. This agrees with a recent determination of the field star IMF where the power law index is -2.00 ± 0.18 for 0.8 < M/Mass of sun < 18. If the older clusters are not considered, then comparison of the combined mass function with the individual cluster mass functions shows that the universality hypothesis cannot be denied

In vivo control of CpG and non-CpG DNA methylation by DNA methyltransferases.

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Julia Arand

2012-06-01

Full Text Available The enzymatic control of the setting and maintenance of symmetric and non-symmetric DNA methylation patterns in a particular genome context is not well understood. Here, we describe a comprehensive analysis of DNA methylation patterns generated by high resolution sequencing of hairpin-bisulfite amplicons of selected single copy genes and repetitive elements (LINE1, B1, IAP-LTR-retrotransposons, and major satellites. The analysis unambiguously identifies a substantial amount of regional incomplete methylation maintenance, i.e. hemimethylated CpG positions, with variant degrees among cell types. Moreover, non-CpG cytosine methylation is confined to ESCs and exclusively catalysed by Dnmt3a and Dnmt3b. This sequence position-, cell type-, and region-dependent non-CpG methylation is strongly linked to neighboring CpG methylation and requires the presence of Dnmt3L. The generation of a comprehensive data set of 146,000 CpG dyads was used to apply and develop parameter estimated hidden Markov models (HMM to calculate the relative contribution of DNA methyltransferases (Dnmts for de novo and maintenance DNA methylation. The comparative modelling included wild-type ESCs and mutant ESCs deficient for Dnmt1, Dnmt3a, Dnmt3b, or Dnmt3a/3b, respectively. The HMM analysis identifies a considerable de novo methylation activity for Dnmt1 at certain repetitive elements and single copy sequences. Dnmt3a and Dnmt3b contribute de novo function. However, both enzymes are also essential to maintain symmetrical CpG methylation at distinct repetitive and single copy sequences in ESCs.

The Use of Chlorhexidine/n-Propyl Gallate (CPG) as an Ambient-Temperature Urine Preservative

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Nillen, Jeannie L.; Smith, Scott M.

2003-01-01

A safe, effective ambient temperature urine preservative, chlorhexidine/n-propyl gallate (CPG), has been formulated for use during spacefli ght that reduces the effects of oxidation and bacterial contamination on sample integrity while maintaining urine pH. The ability of this preservative to maintain stability of nine key analytes was evaluated for a period of one year. CPG effectively maintained stability of a mmonia, total nitrogen, 3-methylhistidine, chloride, sodium, potassiu m, and urea; however, creatinine and osmolality were not preserved by CPG. These data indicate that CPG offers prolonged room-temperature storage for multiple urine analytes, reducing the requirements for f rozen urine storage on future spaceflights. Iii medical applications on Earth, this technology can allow urine samples to be collected in remote settings and eliminate the need to ship frozen samples.

CpG island methylation phenotype (CIMP) in oral cancer: associated with a marked inflammatory response and less aggressive tumour biology.

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Shaw, Richard J; Hall, Gillian L; Lowe, Derek; Bowers, Naomi L; Liloglou, Triantafillos; Field, John K; Woolgar, Julia A; Risk, Janet M

2007-10-01

Studies in several tumour sites highlight the significance of the CpG island methylation phenotype (CIMP), with distinct features of histology, biological aggression and outcome. We utilise pyrosequencing techniques of quantitative methylation analysis to investigate the presence of CIMP in oral squamous cell carcinoma (OSCC) for the first time, and evaluate its correlation with allelic imbalance, pathology and clinical behaviour. Tumour tissue, control tissue and PBLs were obtained from 74 patients with oral squamous cell carcinoma. Pyrosequencing was used to analyse methylation patterns in 75-200 bp regions of the CpG rich gene promoters of 10 genes with a broad range of cellular functions. Allelic imbalance was investigated using a multiplexed panel of 11 microsatellite markers. Corresponding variables, histopathological staging and grading were correlated with these genetic and epigenetic aberrations. A cluster of tumours with a greater degree of promoter methylation than would be predicted by chance alone (P=0.001) were designated CIMP+ve. This group had less aggressive tumour biology in terms of tumour thickness (p=0.015) and nodal metastasis (P=0.012), this being apparently independent of tumour diameter. Further, it seems that these CIMP+ve tumours excited a greater host inflammatory response (P=0.019). The exact mechanisms underlying CIMP remain obscure but the association with a greater inflammatory host response supports existing theories relating these features in other tumour sites. As CIMP has significant associations with other well documented prognostic indicators, it may prove beneficial to include methylation analyses in molecular risk modelling of tumours.

CpG island methylator phenotype-low (CIMP-low) colorectal cancer shows not only few methylated CIMP-high-specific CpG islands, but also low-level methylation at individual loci.

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Kawasaki, Takako; Ohnishi, Mutsuko; Nosho, Katsuhiko; Suemoto, Yuko; Kirkner, Gregory J; Meyerhardt, Jeffrey A; Fuchs, Charles S; Ogino, Shuji

2008-03-01

The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct phenotype in colorectal cancer. However, the concept of CIMP-low with less extensive CpG island methylation is still evolving. Our aim is to examine whether density of methylation in individual CpG islands was different between CIMP-low and CIMP-high tumors. Utilizing MethyLight technology and 889 population-based colorectal cancers, we quantified DNA methylation (methylation index, percentage of methylated reference) at 14 CpG islands, including 8 CIMP-high-specific loci (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1). Methylation positivity in each locus was defined as methylation index>4. Low-level methylation (methylation index>0, CIMP-high-specific locus was significantly more common in 340 CIMP-low tumors (1/8-5/8 methylation-positive loci) than 133 CIMP-high tumors (> or =6/8 methylation-positive loci) and 416 CIMP-0 tumors (0/8 methylation-positive loci) (PCIMP-high, low-level methylation, was not persistently more prevalent in CIMP-low tumors. In conclusion, compared to CIMP-high and CIMP-0 tumors, CIMP-low colorectal cancers show not only few methylated CIMP-high-specific CpG islands, but also more frequent low-level methylation at individual loci. Our data may provide supporting evidence for a difference in pathogenesis of DNA methylation between CIMP-low and CIMP-high tumors.

Parvovirus b19 DNA CpG dinucleotide methylation and epigenetic regulation of viral expression.

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Francesca Bonvicini

Full Text Available CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression. For DNA viruses whose genome has the ability to integrate in the host genome or to maintain as a latent episome, a correlation has been found between the extent of DNA methylation and viral quiescence. No information is available for Parvovirus B19, a human pathogenic virus, which is capable of both lytic and persistent infections. Within Parvovirus B19 genome, the inverted terminal regions display all the characteristic signatures of a genomic CpG island; therefore we hypothesised a role of CpG dinucleotide methylation in the regulation of viral genome expression.The analysis of CpG dinucleotide methylation of Parvovirus B19 DNA was carried out by an aptly designed quantitative real-time PCR assay on bisulfite-modified DNA. The effects of CpG methylation on the regulation of viral genome expression were first investigated by transfection of either unmethylated or in vitro methylated viral DNA in a model cell line, showing that methylation of viral DNA was correlated to lower expression levels of the viral genome. Then, in the course of in vitro infections in different cellular environments, it was observed that absence of viral expression and genome replication were both correlated to increasing levels of CpG methylation of viral DNA. Finally, the presence of CpG methylation was documented in viral DNA present in bioptic samples, indicating the occurrence and a possible role of this epigenetic modification in the course of natural infections.The presence of an epigenetic level of regulation of viral genome expression, possibly correlated to the silencing of the viral genome and contributing to the maintenance of the virus in tissues, can be relevant to the balance and outcome of the different types of infection associated to Parvovirus B19.

Parvovirus B19 DNA CpG Dinucleotide Methylation and Epigenetic Regulation of Viral Expression

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Bonvicini, Francesca; Manaresi, Elisabetta; Di Furio, Francesca; De Falco, Luisa; Gallinella, Giorgio

2012-01-01

CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression. For DNA viruses whose genome has the ability to integrate in the host genome or to maintain as a latent episome, a correlation has been found between the extent of DNA methylation and viral quiescence. No information is available for Parvovirus B19, a human pathogenic virus, which is capable of both lytic and persistent infections. Within Parvovirus B19 genome, the inverted terminal regions display all the characteristic signatures of a genomic CpG island; therefore we hypothesised a role of CpG dinucleotide methylation in the regulation of viral genome expression. The analysis of CpG dinucleotide methylation of Parvovirus B19 DNA was carried out by an aptly designed quantitative real-time PCR assay on bisulfite-modified DNA. The effects of CpG methylation on the regulation of viral genome expression were first investigated by transfection of either unmethylated or in vitro methylated viral DNA in a model cell line, showing that methylation of viral DNA was correlated to lower expression levels of the viral genome. Then, in the course of in vitro infections in different cellular environments, it was observed that absence of viral expression and genome replication were both correlated to increasing levels of CpG methylation of viral DNA. Finally, the presence of CpG methylation was documented in viral DNA present in bioptic samples, indicating the occurrence and a possible role of this epigenetic modification in the course of natural infections. The presence of an epigenetic level of regulation of viral genome expression, possibly correlated to the silencing of the viral genome and contributing to the maintenance of the virus in tissues, can be relevant to the balance and outcome of the different types of infection associated to Parvovirus B19. PMID:22413013

Physiological, anatomical and genetic identification of CPG neurons in the developing mammalian spinal cord

DEFF Research Database (Denmark)

Kiehn, Ole; Butt, Simon J.B.

2003-01-01

. These latter experiments have defined EphA4 as a molecular marker for mammalian excitatory hindlimb CPG neurons. We also review genetic approaches that can be applied to the mouse spinal cord. These include methods for identifying sub-populations of neurons by genetically encoded reporters, techniques to trace...... network connectivity with cell-specific genetically encoded tracers, and ways to selectively ablate or eliminate neuron populations from the CPG. We propose that by applying a multidisciplinary approach it will be possible to understand the network structure of the mammalian locomotor CPG...

Tumor vaccine composed of C-class CpG oligodeoxynucleotides and irradiated tumor cells induces long-term antitumor immunity

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Cerkovnik Petra

2010-09-01

Full Text Available Abstract Background An ideal tumor vaccine should activate both effector and memory immune response against tumor-specific antigens. Beside the CD8+ T cells that play a central role in the generation of a protective immune response and of long-term memory, dendritic cells (DCs are important for the induction, coordination and regulation of the adaptive immune response. The DCs can conduct all of the elements of the immune orchestra and are therefore a fundamental target and tool for vaccination. The present study was aimed at assessing the ability of tumor vaccine composed of C-class CpG ODNs and irradiated melanoma tumor cells B16F1 followed by two additional injections of CpG ODNs to induce the generation of a functional long-term memory response in experimental tumor model in mice (i.p. B16F1. Results It has been shown that the functional memory response in vaccinated mice persists for at least 60 days after the last vaccination. Repeated vaccination also improves the survival of experimental animals compared to single vaccination, whereas the proportion of animals totally protected from the development of aggressive i.p. B16F1 tumors after vaccination repeated three times varies between 88.9%-100.0%. Additionally, the long-term immune memory and tumor protection is maintained over a prolonged period of time of at least 8 months. Finally, it has been demonstrated that following the vaccination the tumor-specific memory cells predominantly reside in bone marrow and peritoneal tissue and are in a more active state than their splenic counterparts. Conclusions In this study we demonstrated that tumor vaccine composed of C-class CpG ODNs and irradiated tumor cells followed by two additional injections of CpG ODNs induces a long-term immunity against aggressive B16F1 tumors.

A nonparametric Bayesian approach for clustering bisulfate-based DNA methylation profiles.

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Zhang, Lin; Meng, Jia; Liu, Hui; Huang, Yufei

2012-01-01

DNA methylation occurs in the context of a CpG dinucleotide. It is an important epigenetic modification, which can be inherited through cell division. The two major types of methylation include hypomethylation and hypermethylation. Unique methylation patterns have been shown to exist in diseases including various types of cancer. DNA methylation analysis promises to become a powerful tool in cancer diagnosis, treatment and prognostication. Large-scale methylation arrays are now available for studying methylation genome-wide. The Illumina methylation platform simultaneously measures cytosine methylation at more than 1500 CpG sites associated with over 800 cancer-related genes. Cluster analysis is often used to identify DNA methylation subgroups for prognosis and diagnosis. However, due to the unique non-Gaussian characteristics, traditional clustering methods may not be appropriate for DNA and methylation data, and the determination of optimal cluster number is still problematic. A Dirichlet process beta mixture model (DPBMM) is proposed that models the DNA methylation expressions as an infinite number of beta mixture distribution. The model allows automatic learning of the relevant parameters such as the cluster mixing proportion, the parameters of beta distribution for each cluster, and especially the number of potential clusters. Since the model is high dimensional and analytically intractable, we proposed a Gibbs sampling "no-gaps" solution for computing the posterior distributions, hence the estimates of the parameters. The proposed algorithm was tested on simulated data as well as methylation data from 55 Glioblastoma multiform (GBM) brain tissue samples. To reduce the computational burden due to the high data dimensionality, a dimension reduction method is adopted. The two GBM clusters yielded by DPBMM are based on data of different number of loci (P-value < 0.1), while hierarchical clustering cannot yield statistically significant clusters.

Improved Density Functional Tight Binding Potentials for Metalloid Aluminum Clusters

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2016-06-01

unlimited IMPROVED DENSITY-FUNCTIONAL TIGHT BINDING POTENTIALS FOR METALLOID ALUMINUM CLUSTERS by Joon H. Kim June 2016 Thesis Advisor...DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE IMPROVED DENSITY-FUNCTIONAL TIGHT BINDING POTENTIALS FOR METALLOID ALUMINUM CLUSTERS 5. FUNDING...repulsive potentials for use in density-functional tight binding (DFTB) simulations of low-valence aluminum metalloid clusters . These systems are under

Effect of the assignment of ancestral CpG state on the estimation of nucleotide substitution rates in mammals

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Keightley Peter D

2008-09-01

Full Text Available Abstract Background Molecular evolutionary studies in mammals often estimate nucleotide substitution rates within and outside CpG dinucleotides separately. Frequently, in alignments of two sequences, the division of sites into CpG and non-CpG classes is based simply on the presence or absence of a CpG dinucleotide in either sequence, a procedure that we refer to as CpG/non-CpG assignment. Although it likely that this procedure is biased, it is generally assumed that the bias is negligible if species are very closely related. Results Using simulations of DNA sequence evolution we show that assignment of the ancestral CpG state based on the simple presence/absence of the CpG dinucleotide can seriously bias estimates of the substitution rate, because many true non-CpG changes are misassigned as CpG. Paradoxically, this bias is most severe between closely related species, because a minimum of two substitutions are required to misassign a true ancestral CpG site as non-CpG whereas only a single substitution is required to misassign a true ancestral non-CpG site as CpG in a two branch tree. We also show that CpG misassignment bias differentially affects fourfold degenerate and noncoding sites due to differences in base composition such that fourfold degenerate sites can appear to be evolving more slowly than noncoding sites. We demonstrate that the effects predicted by our simulations occur in a real evolutionary setting by comparing substitution rates estimated from human-chimp coding and intronic sequence using CpG/non-CpG assignment with estimates derived from a method that is largely free from bias. Conclusion Our study demonstrates that a common method of assigning sites into CpG and non CpG classes in pairwise alignments is seriously biased and recommends against the adoption of ad hoc methods of ancestral state assignment.

Endogenous sunk costs and the geographic differences in the market structures of CPG Categories

NARCIS (Netherlands)

Bronnenberg, B.J.; Dhar, S.; Dube, J.P.

2011-01-01

We describe the industrial market structure of CPG categories. The analysis uses a unique database spanning 31 consumer package goods (CPG) categories, 39 months, and the 50 largest US metropolitan markets. We organize our description of market structure around the notion that firms can improve

A CpG oligonucleotide can protect mice from a low aerosol challenge dose of Burkholderia mallei.

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Waag, David M; McCluskie, Michael J; Zhang, Ningli; Krieg, Arthur M

2006-03-01

Treatment with an oligodeoxynucleotide (ODN) containing CPG motifs (CpG ODN 7909) was found to protect BALB/c mice from lung infection or death after aerosol challenge with Burkholderia mallei. Protection was associated with enhanced levels of gamma interferon (IFN-gamma)-inducible protein 10, interleukin-12 (IL-12), IFN-gamma, and IL-6. Preexposure therapy with CpG ODNs may protect victims of a biological attack from glanders.

Polycomb-like proteins link the PRC2 complex to CpG islands

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Li, Haojie; Liefke, Robert; Jiang, Junyi; Kurland, Jesse Vigoda; Tian, Wei; Deng, Pujuan; Zhang, Weidi; He, Qian; Patel, Dinshaw J.; Bulyk, Martha L.; Shi, Yang; Wang, Zhanxin

2017-09-06

The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression1,2 and has essential roles in various biological processes including the maintenance of cell identity and proper differentiation. Polycomb-like (PCL) proteins, such as PHF1, MTF2 and PHF19, are PRC2-associated factors that form sub-complexes with PRC2 core components3, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci4,5,6,7,8,9,10,11,12,13. Mammalian PRC2-binding sites are enriched in CG content, which correlates with CpG islands that display a low level of DNA methylation14. However, the mechanism of PRC2 recruitment to CpG islands is not fully understood. Here we solve the crystal structures of the N-terminal domains of PHF1 and MTF2 with bound CpG-containing DNAs in the presence of H3K36me3-containing histone peptides. We show that the extended homologous regions of both proteins fold into a winged-helix structure, which specifically binds to the unmethylated CpG motif but in a completely different manner from the canonical winged-helix DNA recognition motif. We also show that the PCL extended homologous domains are required for efficient recruitment of PRC2 to CpG island-containing promoters in mouse embryonic stem cells. Our research provides the first, to our knowledge, direct evidence to demonstrate that PCL proteins are crucial for PRC2 recruitment to CpG islands, and further clarifies the roles of these proteins in transcriptional regulation in vivo.

The effect of TLR9 agonist CpG oligodeoxynucleotides on the intestinal immune response of cobia (Rachycentron canadum).

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Byadgi, Omkar; Puteri, Dinda; Lee, Jai-Wei; Chang, Tsung-Chou; Lee, Yan-Horn; Chu, Chun-Yen; Cheng, Ta-Chih

2014-01-01

Cytosine-guanine oligodeoxynucleotide (CpG ODN) motifs of bacterial DNA are recognized through toll-like receptor 9 (TLR9) and are potent activators of innate immunity. However, the interaction between TLR9 and CpG ODN in aquatic species has not been well characterized. Hence, cobia TLR9 isoform B (RCTLR9B) was cloned and its expression and induction in intestine were investigated. RCTLR9B cDNA consists of 3113bp encoding 1009 amino acids containing three regions, leucine rich repeats, transmembrane domain, and toll/interleukin-1 receptor (TIR) domain. Intraperitoneal injection of CpG ODN 2395 upregulated RCTLR9 A and B and MyD88 and also induced the expressions of Mx, chemokine CC, and interleukin IL-1 β . Cobia intraperitoneally injected with CpG ODN 1668 and 2395 had increased survival rates after challenge with Photobacterium damselae subsp. piscicida. In addition, formulation of CpG ODN with formalin-killed bacteria (FKB) and aluminum hydroxide gel significantly increased expressions of RCTLR9 A (50 folds) and B (30 folds) isoforms at 10 dpi (CpG ODN 1668) and MyD88 (21 folds) at 6 dpv (CpG ODN 2395). Subsequently, IL-1 β increased at 6 dpv in 1668 group. No histopathological damage and inflammatory responses were observed in the injected cobia. Altogether, these results facilitate CpG ODNs as an adjuvant to increase bacterial disease resistance and efficacy of vaccines in cobia.

The Effect of TLR9 Agonist CpG Oligodeoxynucleotides on the Intestinal Immune Response of Cobia (Rachycentron canadum

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Omkar Byadgi

2014-01-01

Full Text Available Cytosine-guanine oligodeoxynucleotide (CpG ODN motifs of bacterial DNA are recognized through toll-like receptor 9 (TLR9 and are potent activators of innate immunity. However, the interaction between TLR9 and CpG ODN in aquatic species has not been well characterized. Hence, cobia TLR9 isoform B (RCTLR9B was cloned and its expression and induction in intestine were investigated. RCTLR9B cDNA consists of 3113bp encoding 1009 amino acids containing three regions, leucine rich repeats, transmembrane domain, and toll/interleukin-1 receptor (TIR domain. Intraperitoneal injection of CpG ODN 2395 upregulated RCTLR9 A and B and MyD88 and also induced the expressions of Mx, chemokine CC, and interleukin IL-1β. Cobia intraperitoneally injected with CpG ODN 1668 and 2395 had increased survival rates after challenge with Photobacterium damselae subsp. piscicida. In addition, formulation of CpG ODN with formalin-killed bacteria (FKB and aluminum hydroxide gel significantly increased expressions of RCTLR9 A (50 folds and B (30 folds isoforms at 10 dpi (CpG ODN 1668 and MyD88 (21 folds at 6 dpv (CpG ODN 2395. Subsequently, IL-1β increased at 6 dpv in 1668 group. No histopathological damage and inflammatory responses were observed in the injected cobia. Altogether, these results facilitate CpG ODNs as an adjuvant to increase bacterial disease resistance and efficacy of vaccines in cobia.

Protective immunity against Megalocytivirus infection in rock bream (Oplegnathus fasciatus) following CpG ODN administration.

Science.gov (United States)

Jung, Myung-Hwa; Lee, Jehee; Ortega-Villaizan, M; Perez, Luis; Jung, Sung-Ju

2017-06-27

Rock bream iridovirus (RBIV) disease in rock bream (Oplegnathus fasciatus) remains an unsolved problem in Korea aquaculture farms. CpG ODNs are known as immunostimulant, can improve the innate immune system of fish providing resistance to diseases. In this study, we evaluated the potential of CpG ODNs to induce anti-viral status protecting rock bream from different RBIV infection conditions. We found that, when administered into rock bream, CpG ODN 1668 induces better antiviral immune responses compared to other 5 CpG ODNs (2216, 1826, 2133, 2395 and 1720). All CpG ODN 1668 administered fish (1/5µg) at 2days before infection (1.1×10 7 ) held at 26°C died even though mortality was delayed from 8days (1µg) and 4days (5µg). Similarly, CpG ODN 1668 administered (5µg) at 2days before infection (1.2×10 6 ) held at 23/20°C had 100% mortality; the mortality was delayed from 9days (23°C) and 11days (20°C). Moreover, when CpG ODN 1668 administered (1/5/10µg) at 2/4/7days before infection or virus concentration was decreased to 1.1×10 4 and held at 20°C had mortality rates of 20/60/30% (2days), 30/40/60% (4days) and 60/60/20% (7days), respectively, for the respective administration dose, through 100 dpi. To investigate the development of a protective immune response, survivors were re-infected with RBIV (1.1×10 7 ) at 100 and 400 dpi, respectively. While 100% of the previously unexposed fish died, 100% of the previously infected fish survived. The high survival rate of fish following re-challenge with RBIV indicates that protective immunity was established in the surviving rock bream. Our results showed the possibility of developing preventive measures against RBIV using CpG ODN 1668 by reducing RBIV replication speed (i.e. water temperature of 20°C and infection dose of 1.1×10 4 ). Copyright © 2017 Elsevier Ltd. All rights reserved.

Protection of CpG ODN 1826 against radiation pulmonary fibrosis in rats

International Nuclear Information System (INIS)

Li Xuan; Qiao Tiankui; Zhuang Xibing; Zhang Jihong

2014-01-01

Objective: To explore the protectional function of CpG ODN 1826 against radiation pulmonary fibrosis in rats. Methods: The rat left lung was exposed to 20 Gy of 6 MV X-rays for establishing a radiation pulmonary fibrosis model. SD rats were randomly divided into control group, irradiated group and intervention group, with 30 rats in each group. CpG ODN 1826 was intraperitoneally injected into rats at 0, 1, 2, 5 and 7 d post-irradiation. The rats were terminated at 5, 15, 30 and 90 d post-irradiation, and the lung indexes were recorded. Paraffin sections of the radiated lung were conducted with HE staining and Masson staining, the pulmonary fibrosis scores were recorded. The serum concentrations of TGF-β1 and hydroxyproline (Hyp) were measured. Results: The radiation pulmonary fibrosis rat model was successfully established. The lung indexes of the control group were lower than those of the irradiated and intervention groups at 5 d post-irradiation (t = 3.046, 2.252, P < 0.05). The lung indexes of the intervention group were lower than those of the irradiated group (t = 4.120, 5.226, 5.719, P < 0.05). Pulmonary fibrosis scores of intervention group were lower than those of irradiated group (t = 3.212, 4.959, P < 0.05). The serum concentrations of TGF-β1 of irradiated group were higher than those of the intervention group (t = 4.138, 5.924, 4.138, 5.924, P < 0.05). The Hyp in the lung of irradiated group was higher than that of intervention group (t = 7.527, 8.416, P < 0.05). Conclusions: CpG ODN1826 will not worse the radiation pulmonary fibrosis, on the contrary, it could reduce the serum concentrations of TGF-β1 and the lung content of Hyp in radiation pulmonary fibrosis, and protects rat against radiation pulmonary fibrosis. (authors)

Photometric studies of globular clusters in the Andromeda Nebula. Luminosity function for old globular clusters

International Nuclear Information System (INIS)

Sharov, A.S.; Lyutyj, V.M.

1989-01-01

The luminosity function for old globular clusters in M 31 is presented. The objects were selected according to their structural and photometric properties. At the usually accepted normal (Gaussian) distribution, the luminosity function is characterized by the following parameters: the mean magnitude, corrected for the extinction inside M 31, V-bar 0 =16 m ,38±0 m .08, and the absolute magnitude M-bar v =-8 m .29 assuming )m-M) v =23 m .67, standard deviation σ M v =1 m .16±0 m .08 and total object number N=300±17. Old globular clusters in M 31 are in the average about one magnitude more luminous then those in our Galaxy (M v ≅ -7 m .3). Intrinsic luminosity dispersions of globular clusters are nearly the same in both galaxies. Available data on globular clusters in the Local Group galaxies against the universality of globular luminosity function with identical parameters M v and σ M v

Clustering of near clusters versus cluster compactness

International Nuclear Information System (INIS)

Yu Gao; Yipeng Jing

1989-01-01

The clustering properties of near Zwicky clusters are studied by using the two-point angular correlation function. The angular correlation functions for compact and medium compact clusters, for open clusters, and for all near Zwicky clusters are estimated. The results show much stronger clustering for compact and medium compact clusters than for open clusters, and that open clusters have nearly the same clustering strength as galaxies. A detailed study of the compactness-dependence of correlation function strength is worth investigating. (author)

Protection of Balb/c mice against infection with FMDV by immunostimulation with CpG oligonucleotides

DEFF Research Database (Denmark)

Kamstrup, Søren; Frimann, Tine; Barfoed, Annette Malene

2006-01-01

disease virus (FMDV). Susceptibility of Balb/c mice to infection with isolates from the different serotypes of FMDV was investigated, and, at the same time, the capacity of CpG ODN to modulate the infection was evaluated. Treatment with CpG significantly reduced viremia, disease and death in five of six...... serotypes, when compared to no treatment or treatment with a control ODN. The effect was observed when ODN was administered simultaneously with, or up to 12 h after, infection with FMDV, and lasted for 14 days post treatment. The potential application of CpG ODN for control of FMDV during an outbreak...

Lithuanian medical tourism cluster: conditions and background for functioning

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Korol A. N.

2017-10-01

Full Text Available as the global economy develops, more and more attention is paid to the creation of tourist clusters, which are extremely important for the economy and national competitiveness. This article analyzes the cluster of medical tourism in Lithuania, and explores the conditions for its successful functioning. The creation of the medical tourism cluster is highly influenced by a number of factors: the regulation of tourist and medical services, the level of entrepreneurial activity, human resources, the experience of partnership. In addition, the article analyzes the structure of the medical tourism cluster, determines the prerequisites for the functioning of the Lithuanian medical tourism cluster, including a wide range of services, European standards for the provision of medical services, high qualification of specialists, etc. When writing the article, the methods of systematic and logical analysis of scientific literature were used.

CpG oligodeoxyribonucleotides protect mice from Burkholderia pseudomallei but not Francisella tularensis Schu S4 aerosols.

Science.gov (United States)

Rozak, David A; Gelhaus, Herbert C; Smith, Mark; Zadeh, Mojgan; Huzella, Louis; Waag, David; Adamovicz, Jeffrey J

2010-02-05

Studies have shown that CpG oligodeoxyribonucleotides (ODN) protect mice from various bacterial pathogens, including Burkholderia pseudomallei and Francisella tularensis live vaccine strain (LVS), when administered before parenteral challenge. Given the potential to develop CpG ODN as a pre-treatment for multiple bacterial biological warfare agents, we examined survival, histopathology, and cytokine data from CpG ODN-treated C57BL/6 mice to determine whether previously-reported protection extended to aerosolized B. pseudomallei 1026b and highly virulent F. tularensis Schu S4 infections. We found that, although CpG ODN protected mice from aerosolized B. pseudomallei challenges, the immunostimulant failed to benefit the animals exposed to F. tularensis Schu S4 aerosols. Our results, which contrast with earlier F. tularensis LVS studies, highlight potential differences in Francisella species pathogenesis and underscore the need to evaluate immunotherapies against human pathogenic species.

Cranked cluster wave function for molecular states

International Nuclear Information System (INIS)

Horiuchi, Hisashi; Yabana, Kazuhiro; Wada, Takahiro.

1986-01-01

Construction of the cranked cluster wave function is discussed by focussing on three problems; the self-consistency between the potential and the density distribution, the properties of the rotational angular frequency which is strongly influenced by the inter-cluster Pauli principle and by the parity projection, and the spin alignment along the rotation axis with the resulting structure-change of the molecular state. (author)

Characterization of Immune Responses to an Inactivated Avian Influenza Virus Vaccine Adjuvanted with Nanoparticles Containing CpG ODN.

Science.gov (United States)

Singh, Shirene M; Alkie, Tamiru N; Abdelaziz, Khaled Taha; Hodgins, Douglas C; Novy, Anastasia; Nagy, Éva; Sharif, Shayan

2016-06-01

Avian influenza virus (AIV), a mucosal pathogen, gains entry into host chickens through respiratory and gastrointestinal routes. Most commercial AIV vaccines for poultry consist of inactivated, whole virus with adjuvant, delivered by parenteral administration. Recent advances in vaccine development have led to the application of nanoparticle emulsion delivery systems, such as poly (d,l-lactic-co-glycolic acid) (PLGA) nanoparticles to enhance antigen-specific immune responses. In chickens, the Toll-like receptor 21 ligand, CpG oligodeoxynucleotides (ODNs), have been demonstrated to be immunostimulatory. The objective of this study was to compare the adjuvant potential of CpG ODN 2007 encapsulated in PLGA nanoparticles with nonencapsulated CpG ODN 2007 when combined with a formalin-inactivated H9N2 virus, through intramuscular and aerosol delivery routes. Chickens were vaccinated at days 7 and 21 posthatch for the intramuscular route and at days 7, 21, and 35 for the aerosol route. Antibody-mediated responses were evaluated weekly in sera and lacrimal secretions in specific pathogen-free chickens. The results indicate that nonencapsulated CpG ODN 2007 in inactivated AIV vaccines administered by the intramuscular route generated higher antibody responses compared to the encapsulated CpG ODN 2007 formulation by the same route. Additionally, encapsulated CpG ODN 2007 in AIV vaccines administered by the aerosol route elicited higher mucosal responses compared to nonencapsulated CpG ODN 2007. Future studies may be aimed at evaluating protective immune responses induced with PLGA encapsulation of AIV and adjuvants.

Inelastic electron scattering as an indicator of clustering in wave functions

International Nuclear Information System (INIS)

1998-01-01

While the shell model is the most fundamental of nuclear structure models, states in light nuclei also have been described successfully in terms of clusters. Indeed, Wildemuth and Tang have shown a correspondence between the cluster and shell models, the clusters arising naturally as correlations out of the shell model Hamiltonian. For light nuclei, the cluster model reduces the many-body problem to a few-body one, with interactions occurring between the clusters. These interactions involve particle exchanges, since the nucleons may still be considered somewhat freely moving, with their motion not strictly confined to the clusters themselves. Such is the relation of the cluster model to the shell model. For a realistic shell model then, one may expect some evidence of clustering in the wave functions for those systems in which the cluster model is valid. The results obtained using the multi-ℎωshell model wave functions are closer in agreement with experiment than the results obtained using the 0ℎωwave functions. Yet in all cases, that level of agreement is not good, with the calculations underpredicting the measured values by at least a factor of two. This indicates that the shell model wave functions do not exhibit clustering behavior, which is expected to manifest itself at small momentum transfer. The exception is the transition to the 7 - /2 state in 7 Li, for which the value obtained from the γ-decay width is in agreement with the value obtained from the MK3W and (0 + 2 + 4)ℎωshell model calculations

Evolution of the cluster X-ray luminosity function

DEFF Research Database (Denmark)

Mullis, C.R.; Vikhlinin, A.; Henry, J.P.

2004-01-01

We report measurements of the cluster X-ray luminosity function out to z = 0.8 based on the final sample of 201 galaxy systems from the 160 Square Degree ROSAT Cluster Survey. There is little evidence for any measurable change in cluster abundance out to z similar to 0.6 at luminosities of less...... than a few times 10(44) h(50)(-2) ergs s(-1) (0.5 - 2.0 keV). However, for 0.6 cluster deficit using integrated number counts...... independently confirm the presence of evolution. Whereas the bulk of the cluster population does not evolve, the most luminous and presumably most massive structures evolve appreciably between z = 0.8 and the present. Interpreted in the context of hierarchical structure formation, we are probing sufficiently...

Glutamatergic mechanisms for speed control and network operation in the rodent locomotor CPG

DEFF Research Database (Denmark)

Talpalar, Adolfo E.; Kiehn, Ole

2010-01-01

in mammals have produced conflicting results regarding the necessity and role of the different ionotropic glutamate receptors (GluRs) in the CPG function. Here, we use electrophysiological and pharmacological techniques in the in vitro neonatal mouse lumbar spinal cord to investigate the role of a broad...... mechanisms acting at various network levels. AMPA and kainate receptors are necessary for generating the highest locomotor frequencies. For coordination, NMDARs are more important than non-NMDARs for conveying the rhythmic signal from the network to the motor neurons during long-lasting and steady locomotor...

Unique DNA methylome profiles in CpG island methylator phenotype colon cancers

Science.gov (United States)

Xu, Yaomin; Hu, Bo; Choi, Ae-Jin; Gopalan, Banu; Lee, Byron H.; Kalady, Matthew F.; Church, James M.; Ting, Angela H.

2012-01-01

A subset of colorectal cancers was postulated to have the CpG island methylator phenotype (CIMP), a higher propensity for CpG island DNA methylation. The validity of CIMP, its molecular basis, and its prognostic value remain highly controversial. Using MBD-isolated genome sequencing, we mapped and compared genome-wide DNA methylation profiles of normal, non-CIMP, and CIMP colon specimens. Multidimensional scaling analysis revealed that each specimen could be clearly classified as normal, non-CIMP, and CIMP, thus signifying that these three groups have distinctly different global methylation patterns. We discovered 3780 sites in various genomic contexts that were hypermethylated in both non-CIMP and CIMP colon cancers when compared with normal colon. An additional 2026 sites were found to be hypermethylated in CIMP tumors only; and importantly, 80% of these sites were located in CpG islands. These data demonstrate on a genome-wide level that the additional hypermethylation seen in CIMP tumors occurs almost exclusively at CpG islands and support definitively that these tumors were appropriately named. When these sites were examined more closely, we found that 25% were adjacent to sites that were also hypermethylated in non-CIMP tumors. Thus, CIMP is also characterized by more extensive methylation of sites that are already prone to be hypermethylated in colon cancer. These observations indicate that CIMP tumors have specific defects in controlling both DNA methylation seeding and spreading and serve as an important first step in delineating molecular mechanisms that control these processes. PMID:21990380

Inelastic electron scattering as an indicator of clustering in wave functions

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-09-01

While the shell model is the most fundamental of nuclear structure models, states in light nuclei also have been described successfully in terms of clusters. Indeed, Wildemuth and Tang have shown a correspondence between the cluster and shell models, the clusters arising naturally as correlations out of the shell model Hamiltonian. For light nuclei, the cluster model reduces the many-body problem to a few-body one, with interactions occurring between the clusters. These interactions involve particle exchanges, since the nucleons may still be considered somewhat freely moving, with their motion not strictly confined to the clusters themselves. Such is the relation of the cluster model to the shell model. For a realistic shell model then, one may expect some evidence of clustering in the wave functions for those systems in which the cluster model is valid. The results obtained using the multi-{Dirac_h}{omega}shell model wave functions are closer in agreement with experiment than the results obtained using the 0{Dirac_h}{omega}wave functions. Yet in all cases, that level of agreement is not good, with the calculations underpredicting the measured values by at least a factor of two. This indicates that the shell model wave functions do not exhibit clustering behavior, which is expected to manifest itself at small momentum transfer. The exception is the transition to the 7{sup -}/2 state in {sup 7}Li, for which the value obtained from the {gamma}-decay width is in agreement with the value obtained from the MK3W and (0 + 2 + 4){Dirac_h}{omega}shell model calculations 17 refs., 1 tab., 2 figs.

CpG island methylator phenotype (CIMP) in cancer: causes and implications.

Science.gov (United States)

Teodoridis, Jens M; Hardie, Catriona; Brown, Robert

2008-09-18

Strong evidence exists for a subgroup of tumours, from a variety of tissue types, exhibiting concordant tumour specific DNA methylation: the "CpG island methylator phenotype" (CIMP). Occurrence of CIMP is associated with a range of genetic and environmental factors, although the molecular causes are not well-understood. Both increased expression and aberrant targeting of DNA methyltransferases (DNMTs) could contribute to the occurrence of CIMP. One under-explored area is the possibility that DNA damage may induce or select for CIMP during carcinogenesis or treatment of tumours with chemotherapy. DNA damaging agents can induce DNA damage at guanine rich regions throughout the genome, including CpG islands. This DNA damage can result in stalled DNA synthesis, which will lead to localised increased DNMT1 concentration and therefore potentially increased DNA methylation at these sites. Chemotherapy can select for cells which have increased tolerance to DNA damage due to increased lesion bypass, in some cases by mechanisms which involve inactivation of genes by CpG island methylation. CIMP has been associated with worse patient prognosis, probably due to increased epigenetic plasticity. Therefore, further clinical testing of the diagnostic and prognostic value of the current CIMP markers, as well as increasing our understanding of the molecular causes underlying CIMP are required.

Evolution of the cluster x-ray luminosity function slope

International Nuclear Information System (INIS)

Henry, J.P.; Soltan, A.; Briel, U.; Gunn, J.E.

1982-01-01

We report the results of an X-ray survey of 58 clusters of galaxies at moderate and high redshifts. Using a luminosity-limited subsample of 25 objects, we find that to a redshift of 0.5 the slope (i.e., power-law index) of the luminosity function of distant clusters is independent of redshift and consistent with that of nearby clusters. The time scale for change in the slope must be greater than 9 billion years. We cannot measure the normalization of the luminosity function because our sample is not complete. We discuss the implications of our data for theoretical models. In particular, Perrenod's models with high Ω are excluded by the present data

eMethylsorb: electrochemical quantification of DNA methylation at CpG resolution using DNA-gold affinity interactions.

Science.gov (United States)

Sina, Abu Ali Ibn; Howell, Sidney; Carrascosa, Laura G; Rauf, Sakandar; Shiddiky, Muhammad J A; Trau, Matt

2014-11-07

We report a simple electrochemical method referred to as "eMethylsorb" for the detection of DNA methylation. The method relies on the base dependent affinity interaction of DNA with gold. The methylation status of DNA is quantified by monitoring the electrochemical current as a function of the relative adsorption level of bisulphite treated DNA samples onto a bare gold electrode. This method can successfully distinguish methylated and unmethylated epigenotypes at single CpG resolution.

Dualism of gene GC content and CpG pattern in regard to expression in the human genome: magnitude versus breadth.

Science.gov (United States)

Vinogradov, Alexander E

2005-12-01

In this article, I show that, in the human genome, the GC content in genes (but not the CpG island in the promoter) is related to the maximum level of gene expression among tissues, whereas the promoter CpG island and gene CpG level are more strongly related to the breadth of expression among tissues. The relevance of gene GC content to expression cannot be a consequence (i.e. a byproduct) of transcription because it does not correlate with expression in the germline. The variation of GC content and CpG level can determine the characteristics of gene expression in a synergistic interplay with transcription-factor-binding sites (mediated by chromatin condensation).

CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury

Science.gov (United States)

Vartanian, Keri B; Mitchell, Hugh D; Stevens, Susan L; Conrad, Valerie K; McDermott, Jason E; Stenzel-Poore, Mary P

2015-01-01

Cytosine-phosphate-guanine (CpG) preconditioning reprograms the genomic response to stroke to protect the brain against ischemic injury. The mechanisms underlying genomic reprogramming are incompletely understood. MicroRNAs (miRNAs) regulate gene expression; however, their role in modulating gene responses produced by CpG preconditioning is unknown. We evaluated brain miRNA expression in response to CpG preconditioning before and after stroke using microarray. Importantly, we have data from previous gene microarrays under the same conditions, which allowed integration of miRNA and gene expression data to specifically identify regulated miRNA gene targets. CpG preconditioning did not significantly alter miRNA expression before stroke, indicating that miRNA regulation is not critical for the initiation of preconditioning-induced neuroprotection. However, after stroke, differentially regulated miRNAs between CpG- and saline-treated animals associated with the upregulation of several neuroprotective genes, implicating these miRNAs in genomic reprogramming that increases neuroprotection. Statistical analysis revealed that the miRNA targets were enriched in the gene population regulated in the setting of stroke, implying that miRNAs likely orchestrate this gene expression. These data suggest that miRNAs regulate endogenous responses to stroke and that manipulation of these miRNAs may have the potential to acutely activate novel neuroprotective processes that reduce damage. PMID:25388675

Estimation of cluster stability using the theory of electron density functional

International Nuclear Information System (INIS)

Borisov, Yu.A.

1985-01-01

Prospects of using simple versions of the electron density functional for studying the energy characteristics of cluster compounds Was discussed. These types of cluster compounds were considered: clusters of Cs, Be, B, Sr, Cd, Sc, In, V, Tl, I elements as intermediate form between molecule and solid body, metalloorganic Mo, W, Tc, Re, Rn clusters and elementoorganic compounds of nido-cluster type. The problem concerning changes in the binding energy of homoatomic clusters depending on their size and three-dimensional structure was analysed

Consolidated Recovered Materials Advisory Notice (RMAN) for the Comprehensive Procurement Guideline (CPG)

Data.gov (United States)

U.S. Environmental Protection Agency — EPA's Comprehensive Procurement Guideline (CPG) designates recycled content products that government agencies should buy. EPA publishes purchasing guidance and...

Photoluminescence quenching of chemically functionalized porous silicon by a ruthenium cluster

Energy Technology Data Exchange (ETDEWEB)

Boukherroub, R.; Wayner, D.D.M. [Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Ontario (Canada); Lockwood, D.J. [Institute for Microstructural Sciences, National Research Council of Canada, Ottawa, Ontario (Canada); Zargarian, D. [Chemistry Department, University of Montreal, C.P. 6128, succursale, Centre-ville, Montreal QC (Canada)

2003-05-01

This paper describes photoluminescence (PL) quenching of hydrogen-terminated and chemically derivatized porous silicon (PSi) nanostructures by a green ruthenium cluster (I). Chemisorption of freshly prepared PSi surfaces in a hexane solution of the Ru cluster for several days at room temperature led to a complete quenching of the PSi PL. The only visible PL was due to the original PL of the cluster. When the PSi surface functionalized with undecylenic acid was immersed in the same hexane solution of (I), the PSi PL was completely quenched and accompanied with a shift to a lower energy of the cluster PL. This shift was assigned to the formation of an ester linkage resulting from the nucleophilic attack of the PO anion of the cluster on the terminal acid functional group. (Abstract Copyright [2003], Wiley Periodicals, Inc.)

Photoluminescence quenching of chemically functionalized porous silicon by a ruthenium cluster

Science.gov (United States)

Boukherroub, R.; Wayner, D. D. M.; Lockwood, D. J.; Zargarian, D.

2003-05-01

This paper describes photoluminescence (PL) quenching of hydrogen-terminated and chemically derivatized porous silicon (PSi) nanostructures by a green ruthenium cluster (I). Chemisorption of freshly prepared PSi surfaces in a hexane solution of the Ru cluster for several days at room temperature led to a complete quenching of the PSi PL. The only visible PL was due to the original PL of the cluster. When the PSi surface functionalized with undecylenic acid was immersed in the same hexane solution of (I), the PSi PL was completely quenched and accompanied with a shift to a lower energy of the cluster PL. This shift was assigned to the formation of an ester linkage resulting from the nucleophilic attack of the PO anion of the cluster on the terminal acid functional group.

A Clustering-Based Automatic Transfer Function Design for Volume Visualization

Directory of Open Access Journals (Sweden)

Tianjin Zhang

2016-01-01

Full Text Available The two-dimensional transfer functions (TFs designed based on intensity-gradient magnitude (IGM histogram are effective tools for the visualization and exploration of 3D volume data. However, traditional design methods usually depend on multiple times of trial-and-error. We propose a novel method for the automatic generation of transfer functions by performing the affinity propagation (AP clustering algorithm on the IGM histogram. Compared with previous clustering algorithms that were employed in volume visualization, the AP clustering algorithm has much faster convergence speed and can achieve more accurate clustering results. In order to obtain meaningful clustering results, we introduce two similarity measurements: IGM similarity and spatial similarity. These two similarity measurements can effectively bring the voxels of the same tissue together and differentiate the voxels of different tissues so that the generated TFs can assign different optical properties to different tissues. Before performing the clustering algorithm on the IGM histogram, we propose to remove noisy voxels based on the spatial information of voxels. Our method does not require users to input the number of clusters, and the classification and visualization process is automatic and efficient. Experiments on various datasets demonstrate the effectiveness of the proposed method.

Nucleosomes correlate with in vivo progression pattern of de novo methylation of p16 CpG islands in human gastric carcinogenesis.

Directory of Open Access Journals (Sweden)

Zhe-Ming Lu

Full Text Available BACKGROUND: The exact relationship between nucleosome positioning and methylation of CpG islands in human pathogenesis is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the nucleosome position within the p16 CpG island and established a seeding methylation-specific PCR (sMSP assay based on bisulfite modification to enrich the p16 alleles containing methylated-CpG at the methylation "seeding" sites within its intron-1 in gastric carcinogenesis. The sMSP-positive rate in primary gastric carcinoma (GC samples (36/40 was significantly higher than that observed in gastritis (19/45 or normal samples (7/13 (P<0.01. Extensive clone sequencing of these sMSP products showed that the density of methylated-CpGs in p16 CpG islands increased gradually along with the severity of pathological changes in gastric tissues. In gastritis lesions the methylation was frequently observed in the region corresponding to the exon-1 coding-nucleosome and the 5'UTR-nucleosome; the methylation was further extended to the region corresponding to the promoter-nucleosome in GC samples. Only few methylated-CpG sites were randomly detected within p16 CpG islands in normal tissues. The significantly inversed relationship between the p16 exon-1 methylation and its transcription was observed in GC samples. An exact p16 promoter-specific 83 bp-MSP assay confirms the result of sMSP (33/55 vs. 1/6, P<0.01. In addition, p16 methylation in chronic gastritis lesions significantly correlated with H. pylori infection; however, such correlation was not observed in GC specimens. CONCLUSIONS/SIGNIFICANCE: It was determined that de novo methylation was initiated in the coding region of p16 exon-1 in gastritis, then progressed to its 5'UTR, and ultimately to the proximal promoter in GCs. Nucleosomes may function as the basic extension/progression unit of de novo methylation of p16 CpG islands in vivo.

Mathematical model for research and analyze relations and functions between enterprises, members of cluster

Science.gov (United States)

Angelov, Kiril; Kaynakchieva, Vesela

2017-12-01

The aim of the current study is to research and analyze Mathematical model for research and analyze of relations and functions between enterprises, members of cluster, and its approbation in given cluster. Subject of the study are theoretical mechanisms for the definition of mathematical models for research and analyze of relations and functions between enterprises, members of cluster. Object of the study are production enterprises, members of cluster. Results of this study show that described theoretical mathematical model is applicable for research and analyze of functions and relations between enterprises, members of cluster from different industrial sectors. This circumstance creates alternatives for election of cluster, where is experimented this model for interaction improvement between enterprises, members of cluster.

A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN–based vaginal microbicide

Science.gov (United States)

Shen, Hong; Iwasaki, Akiko

2006-01-01

Topical microbicides represent a promising new approach to preventing HIV and other sexually transmitted infections. TLR agonists are ideal candidates for microbicides, as they trigger a multitude of antiviral genes effective against a broad range of viruses. Although vaginal application of CpG oligodeoxynucleotides (ODNs) and poly I:C has been shown to protect mice from genital herpes infection, the mechanism by which these agents provide protection remains unclear. Here, we show that plasmacytoid DCs (pDCs) are required for CpG ODN–mediated protection against lethal vaginal challenge with herpes simplex virus type 2 (HSV-2). Moreover, we demonstrate that cells of both the hematopoietic and stromal compartments must respond to CpG ODN via TLR9 and to type I IFNs through IFN-αβ receptor (IFN-αβR) for protection. Thus, crosstalk between pDCs and vaginal stromal cells provides for optimal microbicide efficacy. Our results imply that temporally and spatially controlled targeting of CpG ODN to pDCs and epithelial cells can potentially maximize their effectiveness as microbicides while minimizing the associated inflammatory responses. PMID:16878177

Fine mapping of the EDA gene: A translocation breakpoint is associated with a CpG island that is transcribed

Energy Technology Data Exchange (ETDEWEB)

Srivastava, A.K.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States); Montonen, O. [Univ. of Helsinki (Finland)] [and others

1996-01-01

In order to identify the gene for human X-linked anhidrotic ectodermal dysplasia (EDA), a translocation breakpoint in a female with t(X;1)(q13.1;p36.3) and EDA (patient AK) was finely mapped. The EDA region contains five groups of rare-cutter restriction sites that define CpG islands. The two more centromeric of these islands are associated with transcripts of 3.5 kb and 1.8 kb. The third CpG island maps within <1 kb of the translocation breakpoint in patient AK, as indicated by a genomic rearrangement, and {approximately}100 kb centromeric from another previously mapped translocation breakpoint (patient AnLy). Northern analysis with a probe from this CpG island detected an {approximately}6-kb mRNA in several fetal tissues tested. An extended YAC contig of 1,200 kb with an average of fivefold coverage was constructed. The two most telomeric CpG islands map 350 kb telomeric of the two translocations. Taken together, the results suggest that the CpG island just proximal of the AK translocation breakpoint lies at the 5{prime} end of a candidate gene for EDA. 26 refs., 4 figs., 1 tab.

De novo CpG methylation on an artificial chromosome-like vector maintained for a long-term in mammalian cells.

Science.gov (United States)

Nishioka, Keisuke; Kishida, Tsunao; Masui, Shinji; Mazda, Osam

2016-04-01

To examine whether an autonomously replicating, artificial chromosome-like vector containing a long genomic DNA sequence (namely, Epigenosome-Nanog) undergoes de novo CpG methylation after maintenance in cultured cells for more than a half year. Epigenosome-Nanog efficiently replicated in iPS cells after transfection. In HeLa and C2C12 cells Epigenosome-Nanog was stably maintained for more than eight months. The CpG methylation occurred de novo at the Nanog gene promoter region on the epigenosome in C2C12 cells but the degrees of methylation were much lower than those at the same CpG sites on the chromosomes. Among the four CpG sites at the region, the upstream two CpGs underwent methylation in a correlated manner while methylation at the downstream two CpGs was also correlated to each other, and these correlations were commonly shared between the epigenosome and the chromosome. CpG methylation thus was not solely dependent on the nucleotide sequence at the DNA locus. The epigenosome may become a useful tool to study the mechanisms of epigenetic regulation of a genetic region of interest in mammalian cells.

Long-range autocorrelations of CpG islands in the human genome.

Directory of Open Access Journals (Sweden)

Benjamin Koester

Full Text Available In this paper, we use a statistical estimator developed in astrophysics to study the distribution and organization of features of the human genome. Using the human reference sequence we quantify the global distribution of CpG islands (CGI in each chromosome and demonstrate that the organization of the CGI across a chromosome is non-random, exhibits surprisingly long range correlations (10 Mb and varies significantly among chromosomes. These correlations of CGI summarize functional properties of the genome that are not captured when considering variation in any particular separate (and local feature. The demonstration of the proposed methods to quantify the organization of CGI in the human genome forms the basis of future studies. The most illuminating of these will assess the potential impact on phenotypic variation of inter-individual variation in the organization of the functional features of the genome within and among chromosomes, and among individuals for particular chromosomes.

Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria.

Directory of Open Access Journals (Sweden)

Gregory E D Mullen

2008-08-01

Full Text Available Apical Membrane Antigen 1 (AMA1, a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909.A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 15, 80 microg of AMA1-C1/Alhydrogel (n = 30, or 80 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 30.Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG were detected by enzyme-linked immunosorbent assay (ELISA, and the immune sera of volunteers that received 20 microg or 80 microg of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 microg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition.The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing.ClinicalTrials.gov NCT00344539.

CpG plus radiotherapy: a review of preclinical works leading to clinical trial

Energy Technology Data Exchange (ETDEWEB)

Mason, Kathy A.; Hunter, Nancy R., E-mail: kmason@mdanderson.org [Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

2012-08-14

Studies performed three decades ago in our laboratory supported the hypothesis that radiation efficacy may be augmented by bacterial extracts that stimulate non-specific systemic antitumor immune responses. Application to the clinic was halted by unacceptable side effects and toxicities resulting from exposure to whole bacterial pathogens. Later scientific advances demonstrated that DNA isolated from bacteria was immunostimulatory and could be reproduced with synthetic oligodeoxynucleotides (ODNs), thus fueling the transition from bugs to drugs. Unmethylated CpG motifs within bacterial DNA induce activation of Toll-like receptor 9 and subsequently activate antigen-specific cellular immune responses. CpG ODNs have demonstrated favorable toxicity profiles in phase I clinical trials. We showed that this potent immunoadjuvant can be used in combination with radiation therapy to enhance local and systemic responses of several murine tumors. Studies demonstrated that enhanced tumor response is mediated in part by the host immune system. Antitumor efficacy was diminished in immunocompromised mice. Animals cured by combination of radiation and CpG ODN were resistant to subsequent tumor rechallenge. This body of work contributes to our understanding of the dynamic interplay between tumor irradiation and the host immune system and may facilitate translation to clinical trials.

CpG plus radiotherapy: a review of preclinical works leading to clinical trial

International Nuclear Information System (INIS)

Mason, Kathy A.; Hunter, Nancy R.

2012-01-01

Studies performed three decades ago in our laboratory supported the hypothesis that radiation efficacy may be augmented by bacterial extracts that stimulate non-specific systemic antitumor immune responses. Application to the clinic was halted by unacceptable side effects and toxicities resulting from exposure to whole bacterial pathogens. Later scientific advances demonstrated that DNA isolated from bacteria was immunostimulatory and could be reproduced with synthetic oligodeoxynucleotides (ODNs), thus fueling the transition from bugs to drugs. Unmethylated CpG motifs within bacterial DNA induce activation of Toll-like receptor 9 and subsequently activate antigen-specific cellular immune responses. CpG ODNs have demonstrated favorable toxicity profiles in phase I clinical trials. We showed that this potent immunoadjuvant can be used in combination with radiation therapy to enhance local and systemic responses of several murine tumors. Studies demonstrated that enhanced tumor response is mediated in part by the host immune system. Antitumor efficacy was diminished in immunocompromised mice. Animals cured by combination of radiation and CpG ODN were resistant to subsequent tumor rechallenge. This body of work contributes to our understanding of the dynamic interplay between tumor irradiation and the host immune system and may facilitate translation to clinical trials.

Functional clustering of time series gene expression data by Granger causality

Science.gov (United States)

2012-01-01

Background A common approach for time series gene expression data analysis includes the clustering of genes with similar expression patterns throughout time. Clustered gene expression profiles point to the joint contribution of groups of genes to a particular cellular process. However, since genes belong to intricate networks, other features, besides comparable expression patterns, should provide additional information for the identification of functionally similar genes. Results In this study we perform gene clustering through the identification of Granger causality between and within sets of time series gene expression data. Granger causality is based on the idea that the cause of an event cannot come after its consequence. Conclusions This kind of analysis can be used as a complementary approach for functional clustering, wherein genes would be clustered not solely based on their expression similarity but on their topological proximity built according to the intensity of Granger causality among them. PMID:23107425

Novel Functions of MicroRNA-17-92 Cluster in the Endocrine System.

Science.gov (United States)

Wan, Shan; Chen, Xiang; He, Yuedong; Yu, Xijie

2018-01-01

MiR-17-92 cluster is coded by MIR17HG in chromosome 13, which is highly conserved in vertebrates. Published literatures have proved that miR-17-92 cluster critically regulates tumorigenesis and metastasis. Recent researches showed that the miR-17-92 cluster also plays novel functions in the endocrine system. To summarize recent findings on the physiological and pathological roles of miR-17-92 cluster in bone, lipid and glucose metabolisms. MiR-17-92 cluster plays significant regulatory roles in bone development and metabolism through regulating the differentiation and function of osteoblasts and osteoclasts. In addition, miR-17- 92 cluster is nearly involved in every aspect of lipid metabolism. Last but not the least, the miR-17-92 cluster is closely bound up with pancreatic beta cell function, development of type 1 diabetes and insulin resistance. However, whether miR-17-92 cluster is involved in the communication among bone, fat and glucose metabolisms remains unknown. Growing evidence indicates that miR-17-92 cluster plays significant roles in bone, lipid and glucose metabolisms through a variety of signaling pathways. Fully understanding its modulating mechanisms may necessarily facilitate to comprehend the clinical and molecule features of some metabolic disorders such as osteoporosis, arthrosclerosis and diabetes mellitus. It may provide new drug targets to prevent and cure these disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oglionucleotides

National Research Council Canada - National Science Library

Klinman, Dennise

2001-01-01

.... Additional studies examining the ability of these CpG ODN to act as adjuvants when co-administered with vaccines being developed to prevent infection by biowarfare pathogens are also being pursued...

Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oglionucleotides

National Research Council Canada - National Science Library

Klinman, Dennise

2001-01-01

This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory 'CpG motifs' to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents...

Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oligonucleotides

National Research Council Canada - National Science Library

Klinman, Dennis

2003-01-01

This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory "CpG motifs' to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents...

Rapid Induction of Protective Immunity Against Biothreat Agens Using CPG-Based Oglionucleotides

National Research Council Canada - National Science Library

Klinman, Dennis

1999-01-01

This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory 'CpG' motifs to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents...

Cluster-cluster clustering

International Nuclear Information System (INIS)

Barnes, J.; Dekel, A.; Efstathiou, G.; Frenk, C.S.; Yale Univ., New Haven, CT; California Univ., Santa Barbara; Cambridge Univ., England; Sussex Univ., Brighton, England)

1985-01-01

The cluster correlation function xi sub c(r) is compared with the particle correlation function, xi(r) in cosmological N-body simulations with a wide range of initial conditions. The experiments include scale-free initial conditions, pancake models with a coherence length in the initial density field, and hybrid models. Three N-body techniques and two cluster-finding algorithms are used. In scale-free models with white noise initial conditions, xi sub c and xi are essentially identical. In scale-free models with more power on large scales, it is found that the amplitude of xi sub c increases with cluster richness; in this case the clusters give a biased estimate of the particle correlations. In the pancake and hybrid models (with n = 0 or 1), xi sub c is steeper than xi, but the cluster correlation length exceeds that of the points by less than a factor of 2, independent of cluster richness. Thus the high amplitude of xi sub c found in studies of rich clusters of galaxies is inconsistent with white noise and pancake models and may indicate a primordial fluctuation spectrum with substantial power on large scales. 30 references

CpG promoter methylation of the ALKBH3 alkylation repair gene in breast cancer.

Science.gov (United States)

Stefansson, Olafur Andri; Hermanowicz, Stefan; van der Horst, Jasper; Hilmarsdottir, Holmfridur; Staszczak, Zuzanna; Jonasson, Jon Gunnlaugur; Tryggvadottir, Laufey; Gudjonsson, Thorkell; Sigurdsson, Stefan

2017-07-05

DNA repair of alkylation damage is defective in various cancers. This occurs through somatically acquired inactivation of the MGMT gene in various cancer types, including breast cancers. In addition to MGMT, the two E. coli AlkB homologs ALKBH2 and ALKBH3 have also been linked to direct reversal of alkylation damage. However, it is currently unknown whether ALKBH2 or ALKBH3 are found inactivated in cancer. Methylome datasets (GSE52865, GSE20713, GSE69914), available through Omnibus, were used to determine whether ALKBH2 or ALKBH3 are found inactivated by CpG promoter methylation. TCGA dataset enabled us to then assess the impact of CpG promoter methylation on mRNA expression for both ALKBH2 and ALKBH3. DNA methylation analysis for the ALKBH3 promoter region was carried out by pyrosequencing (PyroMark Q24) in 265 primary breast tumours and 30 proximal normal breast tissue samples along with 8 breast-derived cell lines. ALKBH3 mRNA and protein expression were analysed in cell lines using RT-PCR and Western blotting, respectively. DNA alkylation damage assay was carried out in cell lines based on immunofluorescence and confocal imaging. Data on clinical parameters and survival outcomes in patients were obtained and assessed in relation to ALKBH3 promoter methylation. The ALKBH3 gene, but not ALKBH2, undergoes CpG promoter methylation and transcriptional silencing in breast cancer. We developed a quantitative alkylation DNA damage assay based on immunofluorescence and confocal imaging revealing higher levels of alkylation damage in association with epigenetic inactivation of the ALKBH3 gene (P = 0.029). In our cohort of 265 primary breast cancer, we found 72 cases showing aberrantly high CpG promoter methylation over the ALKBH3 promoter (27%; 72 out of 265). We further show that increasingly higher degree of ALKBH3 promoter methylation is associated with reduced breast-cancer specific survival times in patients. In this analysis, ALKBH3 promoter methylation at >20

CpG oligodeoxynucleotides containing GACGTT motifs enhance the immune responses elicited by a goose parvovirus vaccine in ducks.

Science.gov (United States)

Lee, Jai-Wei; Lin, Yu-Ming; Yen, Ting-Ying; Yang, Wen-Jen; Chu, Chun-Yen

2010-11-23

Recombinant parvovirus VP2 (rVP2) was formulated with different types of adjuvant, including aluminum adjuvant and CpG oligodeoxynucleotides (ODNs), and the immunological responses after vaccination in ducks were examined. In comparison with the control group, production of rVP2-specific antibodies, expression of cytokines in peripheral blood mononuclear cells (PBMC) stimulated by rVP2, and percentage of CD4(+)/CD8(+) cells in PBMC were significantly increased in ducks immunized with rVP2 formulated with CpG ODNs containing 3 copies of GACGTT motif. CpG ODNs with GACGTT motifs might be used to improve the efficacy of vaccines for ducks. Copyright © 2010 Elsevier Ltd. All rights reserved.

Intratracheal synthetic CpG oligodeoxynucleotide causes acute lung injury with systemic inflammatory response

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Hasegawa Naoki

2009-09-01

Full Text Available Abstract Bacterial genome is characterized by frequent unmethylated cytosine-phosphate-guanine (CpG motifs. Deleterious effects can occur when synthetic oligodeoxynucleotides (ODN with unmethylated CpG dinucleotides (CpG-ODN are administered in a systemic fashion. We aimed to evaluate the effect of intratracheal CpG-ODN on lung inflammation and systemic inflammatory response. C57BL/6J mice received intratracheal administration of CpG-ODN (0.01, 0.1, 1.0, 10, or 100 μM or control ODN without CpG motif. Bronchoalveolar lavage (BAL fluid was obtained 3 or 6 h or 1, 2, 7, or 14 days after the instillation and subjected to a differential cell count and cytokine measurement. Lung permeability was evaluated as the BAL fluid-to-plasma ratio of the concentration of human serum albumin that was injected 1 h before euthanasia. Nuclear factor (NF-κB DNA binding activity was also evaluated in lung homogenates. Intratracheal administration of 10 μM or higher concentration of CpG-ODN induced significant inflammatory cell accumulation into the airspace. The peak accumulation of neutrophils and lymphocytes occurred 1 and 2 days after the CpG-ODN administration, respectively. Lung permeability was increased 1 day after the 10 μM CpG-ODN challenge. CpG-ODN also induced nuclear translocation of NF-κB and upregulation of various inflammatory cytokines in BAL fluid and plasma. Histopathology of the lungs and liver revealed acute lung injury and liver damage with necrosis, respectively. Control ODN without CpG motif did not induce any inflammatory change. Since intratracheal CpG-ODN induced acute lung injury as well as systemic inflammatory response, therapeutic strategies to neutralize bacterial DNA that is released after administration of bactericidal agents should be considered.

CpG methylation controls reactivation of HIV from latency

Czech Academy of Sciences Publication Activity Database

Blažková, Jana; Trejbalová, Kateřina; Gondois-Rey, F.; Halfon, P.; Philibert, P.; Guiguen, A.; Verdin, E.; Olive, D.; Van Lint, C.; Hejnar, Jiří; Hirsch, I.

2009-01-01

Roč. 5, č. 8 (2009), e1000554-e1000554 E-ISSN 1553-7374 R&D Projects: GA ČR GA204/05/0939; GA ČR GP204/08/P616 Institutional research plan: CEZ:AV0Z50520514 Keywords : HIV-1 * proviral latency * CpG methylation * histone modifications * HAART * epigenetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.978, year: 2009

The rates of G:C[yields]T:A and G:C[yields]C:G transversions at CpG dinucleotides in the human factor IX gene

Energy Technology Data Exchange (ETDEWEB)

Ketterling, R.P.; Vielhaber, E.; Sommer, S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

1994-05-01

The authors have identified eight independent transversions at CpG in 290 consecutive families with hemophilia B. These eight transversions account for 16.3% of all independent transversions in the sample, yet the expected frequency of CpG transversions at random in the factor IX gene is only 2.6% (P<0.1). The aggregate data suggest that the two types of CpG transversions (G:C[yields]T:A and G:C[yields]C:G) possess similar mutation rates (24.8 [times] 10[sup [minus]10] and 20.6 [times] 10[sup [minus]10], respectively), which are about fivefold greater than the comparable rates for transversions at non-CpG dinucleotides. The enhancement of transversions at CpG suggest that the model by which mutations occur at CpG may need to be reevaluated. The relationship, if any, between deamination of 5-methyl cytosine and enhancement of transversions at CpG remains to be defined. 28 refs., 2 tabs.

CpG methylation controls reactivation of HIV from latency.

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Jana Blazkova

2009-08-01

Full Text Available DNA methylation of retroviral promoters and enhancers localized in the provirus 5' long terminal repeat (LTR is considered to be a mechanism of transcriptional suppression that allows retroviruses to evade host immune responses and antiretroviral drugs. However, the role of DNA methylation in the control of HIV-1 latency has never been unambiguously demonstrated, in contrast to the apparent importance of transcriptional interference and chromatin structure, and has never been studied in HIV-1-infected patients. Here, we show in an in vitro model of reactivable latency and in a latent reservoir of HIV-1-infected patients that CpG methylation of the HIV-1 5' LTR is an additional epigenetic restriction mechanism, which controls resistance of latent HIV-1 to reactivation signals and thus determines the stability of the HIV-1 latency. CpG methylation acts as a late event during establishment of HIV-1 latency and is not required for the initial provirus silencing. Indeed, the latent reservoir of some aviremic patients contained high proportions of the non-methylated 5' LTR. The latency controlled solely by transcriptional interference and by chromatin-dependent mechanisms in the absence of significant promoter DNA methylation tends to be leaky and easily reactivable. In the latent reservoir of HIV-1-infected individuals without detectable plasma viremia, we found HIV-1 promoters and enhancers to be hypermethylated and resistant to reactivation, as opposed to the hypomethylated 5' LTR in viremic patients. However, even dense methylation of the HIV-1 5'LTR did not confer complete resistance to reactivation of latent HIV-1 with some histone deacetylase inhibitors, protein kinase C agonists, TNF-alpha, and their combinations with 5-aza-2deoxycytidine: the densely methylated HIV-1 promoter was most efficiently reactivated in virtual absence of T cell activation by suberoylanilide hydroxamic acid. Tight but incomplete control of HIV-1 latency by CpG

Deletions of a differentially methylated CpG island at SNRPN define a putative imprinting control region

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Sutcliffe, J.S.,; Nakao, M.; Beaudet, A.L. [Baylor College of Medicine, Houston, TX (United States)] [and others

1994-09-01

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are associated with paternal and maternal deficiencies, respectively, of gene expression within human chromosome 15q11-q13, and are caused by deletion, uniparental disomy, or other mutations. Four transcripts designated PAR-5, PAR-7, PAR-1 and PAR-4 were isolated and localized to a region within 300 kb telomeric to the gene encoding small nuclear ribonucleoprotein-associated polypeptide N (SNRPN). Analysis of the transcripts in cultured fibroblasts and lymphoblasts from deletion patients demonstrated that SNRPN, PAR-5 and PAR-1 are expressed exclusively from the paternal chromosome, defining an imprinted domain that spans at least 200 kb. All three imprinted transcripts were absent in cells from three PWS patients (one pair of sibs and one sporadic case) with small deletions that involve a differentially methylated CpG island containing a previously undescribed 5{prime} untranslated exon ({alpha}) of SNRPN. Methylation of the CpG island is specific for the maternal chromosome consistent with paternal expression of the imprinted domain. One deletion, which is benign when maternally transmitted, extends upstream <30 kb from the CpG island, and is associated with altered methylation centromeric to SNRPN, and loss of transcription telomeric to SNRPN, implying the presence of an imprinting control region around the CpG island containing exon {alpha}.

The Mass Function of Young Star Clusters in the "Antennae" Galaxies.

Science.gov (United States)

Zhang; Fall

1999-12-20

We determine the mass function of young star clusters in the merging galaxies known as the "Antennae" (NGC 4038/9) from deep images taken with the Wide Field Planetary Camera 2 on the refurbished Hubble Space Telescope. This is accomplished by means of reddening-free parameters and a comparison with stellar population synthesis tracks to estimate the intrinsic luminosity and age, and hence the mass, of each cluster. We find that the mass function of the young star clusters (with ages less, similar160 Myr) is well represented by a power law of the form psi&parl0;M&parr0;~M-2 over the range 104 less, similarM less, similar106 M middle dot in circle. This result may have important implications for our understanding of the origin of globular clusters during the early phases of galactic evolution.

Diffusion Geometry Unravels the Emergence of Functional Clusters in Collective Phenomena

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De Domenico, Manlio

2017-04-01

Collective phenomena emerge from the interaction of natural or artificial units with a complex organization. The interplay between structural patterns and dynamics might induce functional clusters that, in general, are different from topological ones. In biological systems, like the human brain, the overall functionality is often favored by the interplay between connectivity and synchronization dynamics, with functional clusters that do not coincide with anatomical modules in most cases. In social, sociotechnical, and engineering systems, the quest for consensus favors the emergence of clusters. Despite the unquestionable evidence for mesoscale organization of many complex systems and the heterogeneity of their interconnectivity, a way to predict and identify the emergence of functional modules in collective phenomena continues to elude us. Here, we propose an approach based on random walk dynamics to define the diffusion distance between any pair of units in a networked system. Such a metric allows us to exploit the underlying diffusion geometry to provide a unifying framework for the intimate relationship between metastable synchronization, consensus, and random search dynamics in complex networks, pinpointing the functional mesoscale organization of synthetic and biological systems.

Phosphoinositide 3-kinaseγ controls the intracellular localization of CpG to limit DNA-PKcs-dependent IL-10 production in macrophages.

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Kaoru Hazeki

Full Text Available Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG stimulate innate immune responses. Phosphoinositide 3-kinase (PI3K has been implicated in CpG-induced immune activation; however, its precise role has not yet been clarified. CpG-induced production of IL-10 was dramatically increased in macrophages deficient in PI3Kγ (p110γ(-/-. By contrast, LPS-induced production of IL-10 was unchanged in the cells. CpG-induced, but not LPS-induced, IL-10 production was almost completely abolished in SCID mice having mutations in DNA-dependent protein kinase catalytic subunit (DNA-PKcs. Furthermore, wortmannin, an inhibitor of DNA-PKcs, completely inhibited CpG-induced IL-10 production, both in wild type and p110γ(-/- cells. Microscopic analyses revealed that CpG preferentially localized with DNA-PKcs in p110γ(-/- cells than in wild type cells. In addition, CpG was preferentially co-localized with the acidic lysosomal marker, LysoTracker, in p110γ(-/- cells, and with an early endosome marker, EEA1, in wild type cells. Over-expression of p110γ in Cos7 cells resulted in decreased acidification of CpG containing endosome. A similar effect was reproduced using kinase-dead mutants, but not with a ras-binding site mutant, of p110γ. Thus, it is likely that p110γ, in a manner independent of its kinase activity, inhibits the acidification of CpG-containing endosomes. It is considered that increased acidification of CpG-containing endosomes in p110γ(-/- cells enforces endosomal escape of CpG, which results in increased association of CpG with DNA-PKcs to up-regulate IL-10 production in macrophages.

CpG Methylation Analysis—Current Status of Clinical Assays and Potential Applications in Molecular Diagnostics

Science.gov (United States)

Sepulveda, Antonia R.; Jones, Dan; Ogino, Shuji; Samowitz, Wade; Gulley, Margaret L.; Edwards, Robin; Levenson, Victor; Pratt, Victoria M.; Yang, Bin; Nafa, Khedoudja; Yan, Liying; Vitazka, Patrick

2009-01-01

Methylation of CpG islands in gene promoter regions is a major molecular mechanism of gene silencing and underlies both cancer development and progression. In molecular oncology, testing for the CpG methylation of tissue DNA has emerged as a clinically useful tool for tumor detection, outcome prediction, and treatment selection, as well as for assessing the efficacy of treatment with the use of demethylating agents and monitoring for tumor recurrence. In addition, because CpG methylation occurs early in pre-neoplastic tissues, methylation tests may be useful as markers of cancer risk in patients with either infectious or inflammatory conditions. The Methylation Working Group of the Clinical Practice Committee of the Association of Molecular Pathology has reviewed the current state of clinical testing in this area. We report here our summary of both the advantages and disadvantages of various methods, as well as the needs for standardization and reporting. We then conclude by summarizing the most promising areas for future clinical testing in cancer molecular diagnostics. PMID:19541921

Antisymmetrized four-body wave function and coexistence of single particle and cluster structures

International Nuclear Information System (INIS)

Sasakawa, T.

1979-01-01

It is shown that each Yakubovski component of the totally antisymmetric four-body wave function satisfies the same equation as the unantisymmetric wave function. In the antisymmetric total wave function, the wave functions belonging to the same kind of partition are totally antisymmetric among themselves. This leads to the coexistence of cluster models, including the single particle model as a special case of the cluster model, as a sum

Functional Interference Clusters in Cancer Patients With Bone Metastases: A Secondary Analysis of RTOG 9714

International Nuclear Information System (INIS)

Chow, Edward; James, Jennifer; Barsevick, Andrea; Hartsell, William; Ratcliffe, Sarah; Scarantino, Charles; Ivker, Robert; Roach, Mack; Suh, John; Petersen, Ivy; Konski, Andre; Demas, William; Bruner, Deborah

2010-01-01

Purpose: To explore the relationships (clusters) among the functional interference items in the Brief Pain Inventory (BPI) in patients with bone metastases. Methods: Patients enrolled in the Radiation Therapy Oncology Group (RTOG) 9714 bone metastases study were eligible. Patients were assessed at baseline and 4, 8, and 12 weeks after randomization for the palliative radiotherapy with the BPI, which consists of seven functional items: general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life. Principal component analysis with varimax rotation was used to determine the clusters between the functional items at baseline and the follow-up. Cronbach's alpha was used to determine the consistency and reliability of each cluster at baseline and follow-up. Results: There were 448 male and 461 female patients, with a median age of 67 years. There were two functional interference clusters at baseline, which accounted for 71% of the total variance. The first cluster (physical interference) included normal work and walking ability, which accounted for 58% of the total variance. The second cluster (psychosocial interference) included relations with others and sleep, which accounted for 13% of the total variance. The Cronbach's alpha statistics were 0.83 and 0.80, respectively. The functional clusters changed at week 12 in responders but persisted through week 12 in nonresponders. Conclusion: Palliative radiotherapy is effective in reducing bone pain. Functional interference component clusters exist in patients treated for bone metastases. These clusters changed over time in this study, possibly attributable to treatment. Further research is needed to examine these effects.

Inactivation of Adenomatous Polyposis Coli Reduces Bile Acid/Farnesoid X Receptor Expression through Fxr gene CpG Methylation in Mouse Colon Tumors and Human Colon Cancer Cells.

Science.gov (United States)

Selmin, Ornella I; Fang, Changming; Lyon, Adam M; Doetschman, Tom C; Thompson, Patricia A; Martinez, Jesse D; Smith, Jeffrey W; Lance, Peter M; Romagnolo, Donato F

2016-02-01

The farnesoid X receptor (FXR) regulates bile acid (BA) metabolism and possesses tumor suppressor functions. FXR expression is reduced in colorectal tumors of subjects carrying inactivated adenomatous polyposis coli (APC). Identifying the mechanisms responsible for this reduction may offer new molecular targets for colon cancer prevention. We investigated how APC inactivation influences the regulation of FXR expression in colonic mucosal cells. We hypothesized that APC inactivation would epigenetically repress nuclear receptor subfamily 1, group H, member 4 (FXR gene name) expression through increased CpG methylation. Normal proximal colonic mucosa and normal-appearing adjacent colonic mucosa and colon tumors were collected from wild-type C57BL/6J and Apc-deficient (Apc(Min) (/+)) male mice, respectively. The expression of Fxr, ileal bile acid-binding protein (Ibabp), small heterodimer partner (Shp), and cyclooxygenase-2 (Cox-2) were determined by real-time polymerase chain reaction. In both normal and adjacent colonic mucosa and colon tumors, we measured CpG methylation of Fxr in bisulfonated genomic DNA. In vitro, we measured the impact of APC inactivation and deoxycholic acid (DCA) treatment on FXR expression in human colon cancer HCT-116 cells transfected with silencing RNA for APC and HT-29 cells carrying inactivated APC. In Apc(Min) (/+) mice, constitutive CpG methylation of the Fxrα3/4 promoter was linked to reduced (60-90%) baseline Fxr, Ibabp, and Shp and increased Cox-2 expression in apparently normal adjacent mucosa and colon tumors. Apc knockdown in HCT-116 cells increased cellular myelocytomatosis (c-MYC) and lowered (∼50%) FXR expression, which was further reduced (∼80%) by DCA. In human HCT-116 but not HT-29 colon cancer cells, DCA induced FXR expression and lowered CpG methylation of FXR. We conclude that the loss of APC function favors the silencing of FXR expression through CpG hypermethylation in mouse colonic mucosa and human colon cells

Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles.

Science.gov (United States)

Aiba, Toshiki; Saito, Toshiyuki; Hayashi, Akiko; Sato, Shinji; Yunokawa, Harunobu; Maruyama, Toru; Fujibuchi, Wataru; Kurita, Hisaka; Tohyama, Chiharu; Ohsako, Seiichiroh

2017-03-09

It has been pointed out that environmental factors or chemicals can cause diseases that are developmental in origin. To detect abnormal epigenetic alterations in DNA methylation, convenient and cost-effective methods are required for such research, in which multiple samples are processed simultaneously. We here present methylated site display (MSD), a unique technique for the preparation of DNA libraries. By combining it with amplified fragment length polymorphism (AFLP) analysis, we developed a new method, MSD-AFLP. Methylated site display libraries consist of only DNAs derived from DNA fragments that are CpG methylated at the 5' end in the original genomic DNA sample. To test the effectiveness of this method, CpG methylation levels in liver, kidney, and hippocampal tissues of mice were compared to examine if MSD-AFLP can detect subtle differences in the levels of tissue-specific differentially methylated CpGs. As a result, many CpG sites suspected to be tissue-specific differentially methylated were detected. Nucleotide sequences adjacent to these methyl-CpG sites were identified and we determined the methylation level by methylation-sensitive restriction endonuclease (MSRE)-PCR analysis to confirm the accuracy of AFLP analysis. The differences of the methylation level among tissues were almost identical among these methods. By MSD-AFLP analysis, we detected many CpGs showing less than 5% statistically significant tissue-specific difference and less than 10% degree of variability. Additionally, MSD-AFLP analysis could be used to identify CpG methylation sites in other organisms including humans. MSD-AFLP analysis can potentially be used to measure slight changes in CpG methylation level. Regarding the remarkable precision, sensitivity, and throughput of MSD-AFLP analysis studies, this method will be advantageous in a variety of epigenetics-based research.

Spectroscopic constraints on the form of the stellar cluster mass function

Science.gov (United States)

Bastian, N.; Konstantopoulos, I. S.; Trancho, G.; Weisz, D. R.; Larsen, S. S.; Fouesneau, M.; Kaschinski, C. B.; Gieles, M.

2012-05-01

This contribution addresses the question of whether the initial cluster mass function (ICMF) has a fundamental limit (or truncation) at high masses. The shape of the ICMF at high masses can be studied using the most massive young (advantages are that more clusters can be used and that the ICMF leaves a distinct pattern on the global relation between the cluster luminosity and median age within a population. If a truncation is present, a generic prediction (nearly independent of the cluster disruption law adopted) is that the median age of bright clusters should be younger than that of fainter clusters. In the case of an non-truncated ICMF, the median age should be independent of cluster luminosity. Here, we present optical spectroscopy of twelve young stellar clusters in the face-on spiral galaxy NGC 2997. The spectra are used to estimate the age of each cluster, and the brightness of the clusters is taken from the literature. The observations are compared with the model expectations of Larsen (2009, A&A, 494, 539) for various ICMF forms and both mass dependent and mass independent cluster disruption. While there exists some degeneracy between the truncation mass and the amount of mass independent disruption, the observations favour a truncated ICMF. For low or modest amounts of mass independent disruption, a truncation mass of 5-6 × 105 M⊙ is estimated, consistent with previous determinations. Additionally, we investigate possible truncations in the ICMF in the spiral galaxy M 83, the interacting Antennae galaxies, and the collection of spiral and dwarf galaxies present in Larsen (2009, A&A, 494, 539) based on photometric catalogues taken from the literature, and find that all catalogues are consistent with having a truncation in the cluster mass functions. However for the case of the Antennae, we find a truncation mass of a few × 106M⊙ , suggesting a dependence on the environment, as has been previously suggested.

Determining coding CpG islands by identifying regions significant for pattern statistics on Markov chains.

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Singer, Meromit; Engström, Alexander; Schönhuth, Alexander; Pachter, Lior

2011-09-23

Recent experimental and computational work confirms that CpGs can be unmethylated inside coding exons, thereby showing that codons may be subjected to both genomic and epigenomic constraint. It is therefore of interest to identify coding CpG islands (CCGIs) that are regions inside exons enriched for CpGs. The difficulty in identifying such islands is that coding exons exhibit sequence biases determined by codon usage and constraints that must be taken into account. We present a method for finding CCGIs that showcases a novel approach we have developed for identifying regions of interest that are significant (with respect to a Markov chain) for the counts of any pattern. Our method begins with the exact computation of tail probabilities for the number of CpGs in all regions contained in coding exons, and then applies a greedy algorithm for selecting islands from among the regions. We show that the greedy algorithm provably optimizes a biologically motivated criterion for selecting islands while controlling the false discovery rate. We applied this approach to the human genome (hg18) and annotated CpG islands in coding exons. The statistical criterion we apply to evaluating islands reduces the number of false positives in existing annotations, while our approach to defining islands reveals significant numbers of undiscovered CCGIs in coding exons. Many of these appear to be examples of functional epigenetic specialization in coding exons.

Comparison of two schemes for automatic keyword extraction from MEDLINE for functional gene clustering.

Science.gov (United States)

Liu, Ying; Ciliax, Brian J; Borges, Karin; Dasigi, Venu; Ram, Ashwin; Navathe, Shamkant B; Dingledine, Ray

2004-01-01

One of the key challenges of microarray studies is to derive biological insights from the unprecedented quatities of data on gene-expression patterns. Clustering genes by functional keyword association can provide direct information about the nature of the functional links among genes within the derived clusters. However, the quality of the keyword lists extracted from biomedical literature for each gene significantly affects the clustering results. We extracted keywords from MEDLINE that describes the most prominent functions of the genes, and used the resulting weights of the keywords as feature vectors for gene clustering. By analyzing the resulting cluster quality, we compared two keyword weighting schemes: normalized z-score and term frequency-inverse document frequency (TFIDF). The best combination of background comparison set, stop list and stemming algorithm was selected based on precision and recall metrics. In a test set of four known gene groups, a hierarchical algorithm correctly assigned 25 of 26 genes to the appropriate clusters based on keywords extracted by the TDFIDF weighting scheme, but only 23 og 26 with the z-score method. To evaluate the effectiveness of the weighting schemes for keyword extraction for gene clusters from microarray profiles, 44 yeast genes that are differentially expressed during the cell cycle were used as a second test set. Using established measures of cluster quality, the results produced from TFIDF-weighted keywords had higher purity, lower entropy, and higher mutual information than those produced from normalized z-score weighted keywords. The optimized algorithms should be useful for sorting genes from microarray lists into functionally discrete clusters.

Restoration of CpG Methylation in The Egf Promoter Region during Rat Liver Regeneration

Science.gov (United States)

Deming, Li; Ziwei, Li; Xueqiang, Guo; Cunshuan, Xu

2015-01-01

Epidermal growth factor (EGF) is an important factor for healing after tissue damage in diverse experimental models. It plays an important role in liver regeneration (LR). The objective of this experiment is to investigate the methylation variation of 10 CpG sites in the Egf promoter region and their relevance to Egf expression during rat liver regenera- tion. As a follow up of our previous study, rat liver tissue was collected after rat 2/3 partial hepatectomy (PH) during the re-organization phase (from days 14 to days 28). Liver DNA was extracted and modified by sodium bisulfate. The methylation status of 10 CpG sites in Egf promoter region was determined using bisulfite sequencing polymerase chain reaction (PCR), as BSP method. The results showed that 3 (sites 3, 4 and 9) out of 10 CpG sites have strikingly methylation changes during the re-organization phase compared to the regeneration phase (from 2 hours to 168 hours, P=0.002, 0.048 and 0.018, respectively). Our results showed that methylation modification of CpGs in the Egf promoter region could be restored to the status before PH operation and changes of methylation didn’t affect Egf mRNA expression during the re-organization phase. PMID:26464832

The luminosity function for globular clusters, 4: M3

International Nuclear Information System (INIS)

Simoda, Mahiro; Fukuoka, Takashi

1976-01-01

The subgiant-turnoff portion (V = 17.2 - 20.0 mag) of the luminosity function for the globular cluster M3 has been determined from photometry of the stars within the annuli 3'-8' and 6'-8' for V = 17.2 - 19.0 mag and 19.0 - 20.0 mag, respectively, by using plates taken with the Kitt Peak 2.1-m reflector. Our result shows that the luminosity function for M3 has a similar steep rise in the subgiant portion as other clusters so far studied (M5, M13, and M92), in direct conflict with the result by SANDAGE (1954, 1957). A probable cause of this discrepancy is given. Comparison with theoretical luminosity functions by SIMODA and IBEN (1970) suggests that theory and observation are not inconsistent if the initial helium abundance of M3 stars is taken to be about 20 percent. It is suggested that M13 has a larger helium abundance than M3 and M92 from the intercomparison of their luminosity functions and color-magnitude diagrams. (auth.)

The galaxy cluster mid-infrared luminosity function at 1.3 < z < 3.2

Energy Technology Data Exchange (ETDEWEB)

Wylezalek, Dominika; Vernet, Joël; De Breuck, Carlos [European Southern Observatory, Karl-Schwarzschildstr.2, D-85748 Garching bei München (Germany); Stern, Daniel [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States); Brodwin, Mark [Department of Physics and Astronomy, University of Missouri, 5110 Rockhill Road, Kansas City, MO 64110 (United States); Galametz, Audrey [INAF-Osservatorio di Roma, Via Frascati 33, I-00040, Monteporzio (Italy); Gonzalez, Anthony H. [Department of Astronomy, University of Florida, Gainesville, FL 32611 (United States); Jarvis, Matt [Astrophysics, Department of Physics, Keble Road, Oxford OX1 3RH (United Kingdom); Hatch, Nina [School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom); Seymour, Nick [CASS, P.O. Box 76, Epping, NSW, 1710 (Australia); Stanford, Spencer A. [Physics Department, University of California, Davis, CA 95616 (United States)

2014-05-01

We present 4.5 μm luminosity functions for galaxies identified in 178 candidate galaxy clusters at 1.3 < z < 3.2. The clusters were identified as Spitzer/Infrared Array Camera (IRAC) color-selected overdensities in the Clusters Around Radio-Loud AGN project, which imaged 420 powerful radio-loud active galactic nuclei (RLAGNs) at z > 1.3. The luminosity functions are derived for different redshift and richness bins, and the IRAC imaging reaches depths of m* + 2, allowing us to measure the faint end slopes of the luminosity functions. We find that α = –1 describes the luminosity function very well in all redshift bins and does not evolve significantly. This provides evidence that the rate at which the low mass galaxy population grows through star formation gets quenched and is replenished by in-falling field galaxies does not have a major net effect on the shape of the luminosity function. Our measurements for m* are consistent with passive evolution models and high formation redshifts (z{sub f} ∼ 3). We find a slight trend toward fainter m* for the richest clusters, implying that the most massive clusters in our sample could contain older stellar populations, yet another example of cosmic downsizing. Modeling shows that a contribution of a star-forming population of up to 40% cannot be ruled out. This value, found from our targeted survey, is significantly lower than the values found for slightly lower redshift, z ∼ 1, clusters found in wide-field surveys. The results are consistent with cosmic downsizing, as the clusters studied here were all found in the vicinity of RLAGNs—which have proven to be preferentially located in massive dark matter halos in the richest environments at high redshift—and they may therefore be older and more evolved systems than the general protocluster population.

The galaxy cluster mid-infrared luminosity function at 1.3 < z < 3.2

International Nuclear Information System (INIS)

Wylezalek, Dominika; Vernet, Joël; De Breuck, Carlos; Stern, Daniel; Brodwin, Mark; Galametz, Audrey; Gonzalez, Anthony H.; Jarvis, Matt; Hatch, Nina; Seymour, Nick; Stanford, Spencer A.

2014-01-01

We present 4.5 μm luminosity functions for galaxies identified in 178 candidate galaxy clusters at 1.3 < z < 3.2. The clusters were identified as Spitzer/Infrared Array Camera (IRAC) color-selected overdensities in the Clusters Around Radio-Loud AGN project, which imaged 420 powerful radio-loud active galactic nuclei (RLAGNs) at z > 1.3. The luminosity functions are derived for different redshift and richness bins, and the IRAC imaging reaches depths of m* + 2, allowing us to measure the faint end slopes of the luminosity functions. We find that α = –1 describes the luminosity function very well in all redshift bins and does not evolve significantly. This provides evidence that the rate at which the low mass galaxy population grows through star formation gets quenched and is replenished by in-falling field galaxies does not have a major net effect on the shape of the luminosity function. Our measurements for m* are consistent with passive evolution models and high formation redshifts (z f ∼ 3). We find a slight trend toward fainter m* for the richest clusters, implying that the most massive clusters in our sample could contain older stellar populations, yet another example of cosmic downsizing. Modeling shows that a contribution of a star-forming population of up to 40% cannot be ruled out. This value, found from our targeted survey, is significantly lower than the values found for slightly lower redshift, z ∼ 1, clusters found in wide-field surveys. The results are consistent with cosmic downsizing, as the clusters studied here were all found in the vicinity of RLAGNs—which have proven to be preferentially located in massive dark matter halos in the richest environments at high redshift—and they may therefore be older and more evolved systems than the general protocluster population.

A-dependence of structure functions and multiquark clusters in nuclei

International Nuclear Information System (INIS)

Kondratyuk, L.; Shmatikov, M.

1984-01-01

Assuming existence of 12q-clusters (bags) in nuclei the structure functions of deep inelastic scattering of leptons on nuclei are discussed. Universal momentum distribution of quarks in a multiquark cluster is used with high-momentum component falling exponentially PHIsub(q)sup(2)(k) approximately esup(-k/ksub(0)) with k 0 approximately equal to 50-60 MeV/c. The admixture of 12q-cluster W required for the description of SLAG data increases from 10% for 4 He to 30% for Au. The A-dependence of W agrees well with the A-dependence of cumulative particle spectra

Effects of CPG ODN on biological behavior of PANC-1 and expression of TLR9 in pancreatic cancer.

Science.gov (United States)

Wu, Han-Qing; Wang, Bo; Zhu, Shi-Kai; Tian, Yuan; Zhang, Jing-Hui; Wu, He-Shui

2011-02-28

To determine the expression of toll-like receptor 9 (TLR9) in pancreatic tumor and the effects of cytosine phosphate-guanosine oligodeoxynucleotides 2216 (CPG ODN2216) on biological behavior of pancreatic carcinoma cell line PANC-1 and explore their clinical significance. The immunohistochemistry and Western blot were used to determine the expression of TLR9 protein in pancreatic cancer tissues, and immunofluorescence staining was performed to detect the TLR9 protein expression in pancreatic carcinoma cell line PANC-1. To assess the effects of CPG ODN2216 on the invasive property of Panc-1 cells, in vitro cell adhesion, wound-healing scrape, and invasion and cell colony formation were evaluated. TLR9 was highly expressed in pancreatic cancer tissues and PANC-1 cells. The percentage of positive cells expressing TLR9 protein in human pancreatic tissues, paracancerous tissues and normal tissues were 73.3%, 33.3% and 20.0%, respectively, and the protein expression level of TLR9 was gradually descending (P PANC-1 cells in CPG ODN 2216 treatment group were significantly lower than in the control group (P PANC-1 cells in treatment group was significantly decreased and CPG ODN2216 had an inhibitive effect in the growth of Panc-1 cells in a dose and time-dependent manner (P Panc-1 cells.

FPGA implementation of a configurable neuromorphic CPG-based locomotion controller.

Science.gov (United States)

Barron-Zambrano, Jose Hugo; Torres-Huitzil, Cesar

2013-09-01

Neuromorphic engineering is a discipline devoted to the design and development of computational hardware that mimics the characteristics and capabilities of neuro-biological systems. In recent years, neuromorphic hardware systems have been implemented using a hybrid approach incorporating digital hardware so as to provide flexibility and scalability at the cost of power efficiency and some biological realism. This paper proposes an FPGA-based neuromorphic-like embedded system on a chip to generate locomotion patterns of periodic rhythmic movements inspired by Central Pattern Generators (CPGs). The proposed implementation follows a top-down approach where modularity and hierarchy are two desirable features. The locomotion controller is based on CPG models to produce rhythmic locomotion patterns or gaits for legged robots such as quadrupeds and hexapods. The architecture is configurable and scalable for robots with either different morphologies or different degrees of freedom (DOFs). Experiments performed on a real robot are presented and discussed. The obtained results demonstrate that the CPG-based controller provides the necessary flexibility to generate different rhythmic patterns at run-time suitable for adaptable locomotion. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improvement of the Immunogenicity of Porcine Circovirus Type 2 DNA Vaccine by Recombinant ORF2 Gene and CpG Motifs.

Science.gov (United States)

Li, Jun; Shi, Jian-Li; Wu, Xiao-Yan; Fu, Fang; Yu, Jiang; Yuan, Xiao-Yuan; Peng, Zhe; Cong, Xiao-Yan; Xu, Shao-Jian; Sun, Wen-Bo; Cheng, Kai-Hui; Du, Yi-Jun; Wu, Jia-Qiang; Wang, Jin-Bao; Huang, Bao-Hua

2015-06-01

Nowadays, adjuvant is still important for boosting immunity and improving resistance in animals. In order to boost the immunity of porcine circovirus type 2 (PCV2) DNA vaccine, CpG motifs were inserted. In this study, the dose-effect was studied, and the immunity of PCV2 DNA vaccines by recombinant open reading frame 2 (ORF2) gene and CpG motifs was evaluated. Three-week-old Changbai piglets were inoculated intramuscularly with 200 μg, 400 μg, and 800 μg DNA vaccines containing 14 and 18 CpG motifs, respectively. Average gain and rectum temperature were recorded everyday during the experiments. Blood was collected from the piglets after vaccination to detect the changes of specific antibodies, interleukin-2, and immune cells every week. Tissues were collected for histopathology and polymerase chain reaction. The results indicated that compared to those of the control piglets, all concentrations of two DNA vaccines could induce PCV2-specific antibodies. A cellular immunity test showed that PCV2-specific lymphocytes proliferated the number of TH, TC, and CD3+ positive T-cells raised in the blood of DNA vaccine immune groups. There was no distinct pathological damage and viremia occurring in pigs that were inoculated with DNA vaccines, but there was some minor pathological damage in the control group. The results demonstrated that CpG motifs as an adjuvant could boost the humoral and cellular immunity of pigs to PCV2, especially in terms of cellular immunity. Comparing two DNA vaccines that were constructed, the one containing 18 CpG motifs was more effective. This is the first report that CpG motifs as an adjuvant insert to the PCV2 DNA vaccine could boost immunity.

A spectral scheme for Kohn-Sham density functional theory of clusters

Science.gov (United States)

Banerjee, Amartya S.; Elliott, Ryan S.; James, Richard D.

2015-04-01

Starting from the observation that one of the most successful methods for solving the Kohn-Sham equations for periodic systems - the plane-wave method - is a spectral method based on eigenfunction expansion, we formulate a spectral method designed towards solving the Kohn-Sham equations for clusters. This allows for efficient calculation of the electronic structure of clusters (and molecules) with high accuracy and systematic convergence properties without the need for any artificial periodicity. The basis functions in this method form a complete orthonormal set and are expressible in terms of spherical harmonics and spherical Bessel functions. Computation of the occupied eigenstates of the discretized Kohn-Sham Hamiltonian is carried out using a combination of preconditioned block eigensolvers and Chebyshev polynomial filter accelerated subspace iterations. Several algorithmic and computational aspects of the method, including computation of the electrostatics terms and parallelization are discussed. We have implemented these methods and algorithms into an efficient and reliable package called ClusterES (Cluster Electronic Structure). A variety of benchmark calculations employing local and non-local pseudopotentials are carried out using our package and the results are compared to the literature. Convergence properties of the basis set are discussed through numerical examples. Computations involving large systems that contain thousands of electrons are demonstrated to highlight the efficacy of our methodology. The use of our method to study clusters with arbitrary point group symmetries is briefly discussed.

Topological defect clustering and plastic deformation mechanisms in functionalized graphene

Science.gov (United States)

Nunes, Ricardo; Araujo, Joice; Chacham, Helio

2011-03-01

We present ab initio results suggesting that strain plays a central role in the clustering of topological defects in strained and functionalized graphene models. We apply strain onto the topological-defect graphene networks from our previous work, and obtain topological-defect clustering patterns which are in excellent agreement with recent observations in samples of reduced graphene oxide. In our models, the graphene layer, containing an initial concentration of isolated topological defects, is covered by hydrogen or hydroxyl groups. Our results also suggest a rich variety of plastic deformation mechanism in functionalized graphene systems. We acknowledge support from the Brazilian agencies: CNPq, Fapemig, and INCT-Materiais de Carbono.

Density functional study of the bonding in small silicon clusters

International Nuclear Information System (INIS)

Fournier, R.; Sinnott, S.B.; DePristo, A.E.

1992-01-01

We report the ground electronic state, equilibrium geometry, vibrational frequencies, and binding energy for various isomers of Si n (n = 2--8) obtained with the linear combination of atomic orbitals-density functional method. We used both a local density approximation approach and one with gradient corrections. Our local density approximation results concerning the relative stability of electronic states and isomers are in agreement with Hartree--Fock and Moller--Plesset (MP2) calculations [K. Raghavachari and C. M. Rohlfing, J. Chem. Phys. 89, 2219 (1988)]. The binding energies calculated with the gradient corrected functional are in good agreement with experiment (Si 2 and Si 3 ) and with the best theoretical estimates. Our analysis of the bonding reveals two limiting modes of bonding and classes of silicon clusters. One class of clusters is characterized by relatively large s atomic populations and a large number of weak bonds, while the other class of clusters is characterized by relatively small s atomic populations and a small number of strong bonds

Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood.

Science.gov (United States)

Huang, R C; Garratt, E S; Pan, H; Wu, Y; Davis, E A; Barton, S J; Burdge, G C; Godfrey, K M; Holbrook, J D; Lillycrop, K A

2015-01-01

Childhood obesity is a major public health issue. Here we investigated whether differential DNA methylation was associated with childhood obesity. We studied DNA methylation profiles in whole blood from 78 obese children (mean BMI Z-score: 2.6) and 71 age- and sex-matched controls (mean BMI Z-score: 0.1). DNA samples from obese and control groups were pooled and analyzed using the Infinium HumanMethylation450 BeadChip array. Comparison of the methylation profiles between obese and control subjects revealed 129 differentially methylated CpG (DMCpG) loci associated with 80 unique genes that had a greater than 10% difference in methylation (P-value obesity were validated using sodium bisulfite pyrosequencing across loci within the FYN, PIWIL4, and TAOK3 genes in individual subjects. Three CpG loci within FYN were hypermethylated in obese individuals (all P obesity was associated with lower methylation of CpG loci within PIWIL4 (P = 0.003) and TAOK3 (P = 0.001). After building logistic regression models, we determined that a 1% increase in methylation in TAOK3, multiplicatively decreased the odds of being obese by 0.91 (95% CI: 0.86 - 0.97), and an increase of 1% methylation in FYN CpG3, multiplicatively increased the odds of being obese by 1.03 (95% CI: 0.99 - 1.07). In conclusion, these findings provide evidence that childhood obesity is associated with specific DNA methylation changes in whole blood, which may have utility as biomarkers of obesity risk.

The Magellanic Bridge Cluster NGC 796: Deep Optical AO Imaging Reveals the Stellar Content and Initial Mass Function of a Massive Open Cluster

Science.gov (United States)

Kalari, Venu M.; Carraro, Giovanni; Evans, Christopher J.; Rubio, Monica

2018-04-01

NGC 796 is a massive young cluster located 59 kpc from us in the diffuse intergalactic medium of the 1/5–1/10 Z⊙ Magellanic Bridge, allowing us to probe variations in star formation and stellar evolution processes as a function of metallicity in a resolved fashion, and providing a link between resolved studies of nearby solar-metallicity and unresolved distant metal-poor clusters located in high-redshift galaxies. In this paper, we present adaptive optics griHα imaging of NGC 796 (at 0.″5, which is ∼0.14 pc at the cluster distance) along with optical spectroscopy of two bright members to quantify the cluster properties. Our aim is to explore whether star formation and stellar evolution vary as a function of metallicity by comparing the properties of NGC 796 to higher-metallicity clusters. We find an age of {20}-5+12 Myr from isochronal fitting of the cluster main sequence in the color–magnitude diagram. Based on the cluster luminosity function, we derive a top-heavy stellar initial mass function (IMF) with a slope α = 1.99 ± 0.2, hinting at a metallicity and/or environmental dependence of the IMF, which may lead to a top-heavy IMF in the early universe. Study of the Hα emission-line stars reveals that classical Be stars constitute a higher fraction of the total B-type stars when compared with similar clusters at greater metallicity, providing some support to the chemically homogeneous theory of stellar evolution. Overall, NGC 796 has a total estimated mass of 990 ± 200 M⊙, and a core radius of 1.4 ± 0.3 pc, which classifies it as a massive young open cluster, unique in the diffuse interstellar medium of the Magellanic Bridge.

Functional Characterization and Drug Response of Freshly Established Patient-Derived Tumor Models with CpG Island Methylator Phenotype.

Directory of Open Access Journals (Sweden)

Claudia Maletzki

Full Text Available Patient-individual tumor models constitute a powerful platform for basic and translational analyses both in vitro and in vivo. However, due to the labor-intensive and highly time-consuming process, only few well-characterized patient-derived cell lines and/or corresponding xenografts exist. In this study, we describe successful generation and functional analysis of novel tumor models from patients with sporadic primary colorectal carcinomas (CRC showing CpG island methylator phenotype (CIMP. Initial DNA fingerprint analysis confirmed identity with the patient in all four cases. These freshly established cells showed characteristic features associated with the CIMP-phenotype (HROC40: APCwt, TP53 mut, KRAS mut; 3/8 marker methylated; HROC43: APC mut, TP53 mut, KRAS mut; 4/8 marker methylated; HROC60: APCwt, TP53 mut, KRASwt; 4/8 marker methylated; HROC183: APC mut, TP53 mut, KRAS mut; 6/8 marker methylated. Cell lines were of epithelial origin (EpCAM+ with distinct morphology and growth kinetics. Response to chemotherapeutics was quite individual between cells, with stage I-derived cell line HROC60 being most susceptible towards standard clinically approved chemotherapeutics (e.g. 5-FU, Irinotecan. Of note, most cell lines were sensitive towards "non-classical" CRC standard drugs (sensitivity: Gemcitabin > Rapamycin > Nilotinib. This comprehensive analysis of tumor biology, genetic alterations and assessment of chemosensitivity towards a broad range of (chemo- therapeutics helps bringing forward the concept of personalized tumor therapy.

WebGimm: An integrated web-based platform for cluster analysis, functional analysis, and interactive visualization of results.

Science.gov (United States)

Joshi, Vineet K; Freudenberg, Johannes M; Hu, Zhen; Medvedovic, Mario

2011-01-17

Cluster analysis methods have been extensively researched, but the adoption of new methods is often hindered by technical barriers in their implementation and use. WebGimm is a free cluster analysis web-service, and an open source general purpose clustering web-server infrastructure designed to facilitate easy deployment of integrated cluster analysis servers based on clustering and functional annotation algorithms implemented in R. Integrated functional analyses and interactive browsing of both, clustering structure and functional annotations provides a complete analytical environment for cluster analysis and interpretation of results. The Java Web Start client-based interface is modeled after the familiar cluster/treeview packages making its use intuitive to a wide array of biomedical researchers. For biomedical researchers, WebGimm provides an avenue to access state of the art clustering procedures. For Bioinformatics methods developers, WebGimm offers a convenient avenue to deploy their newly developed clustering methods. WebGimm server, software and manuals can be freely accessed at http://ClusterAnalysis.org/.

Deletion and aberrant CpG island methylation of Caspase 8 gene in medulloblastoma.

Science.gov (United States)

Gonzalez-Gomez, Pilar; Bello, M Josefa; Inda, M Mar; Alonso, M Eva; Arjona, Dolores; Amiñoso, Cinthia; Lopez-Marin, Isabel; de Campos, Jose M; Sarasa, Jose L; Castresana, Javier S; Rey, Juan A

2004-09-01

Aberrant methylation of promoter CpG islands in human genes is an alternative genetic inactivation mechanism that contributes to the development of human tumors. Nevertheless, few studies have analyzed methylation in medulloblastomas. We determined the frequency of aberrant CpG island methylation for Caspase 8 (CASP8) in a group of 24 medulloblastomas arising in 8 adult and 16 pediatric patients. Complete methylation of CASP8 was found in 15 tumors (62%) and one case displayed hemimethylation. Three samples amplified neither of the two primer sets for methylated or unmethylated alleles, suggesting that genomic deletion occurred in the 5' flanking region of CASP8. Our findings suggest that methylation commonly contributes to CASP8 silencing in medulloblastomas and that homozygous deletion or severe sequence changes involving the promoter region may be another mechanism leading to CASP8 inactivation in this neoplasm.

A spectral scheme for Kohn–Sham density functional theory of clusters

Energy Technology Data Exchange (ETDEWEB)

Banerjee, Amartya S., E-mail: baner041@umn.edu; Elliott, Ryan S., E-mail: relliott@umn.edu; James, Richard D., E-mail: james@umn.edu

2015-04-15

Starting from the observation that one of the most successful methods for solving the Kohn–Sham equations for periodic systems – the plane-wave method – is a spectral method based on eigenfunction expansion, we formulate a spectral method designed towards solving the Kohn–Sham equations for clusters. This allows for efficient calculation of the electronic structure of clusters (and molecules) with high accuracy and systematic convergence properties without the need for any artificial periodicity. The basis functions in this method form a complete orthonormal set and are expressible in terms of spherical harmonics and spherical Bessel functions. Computation of the occupied eigenstates of the discretized Kohn–Sham Hamiltonian is carried out using a combination of preconditioned block eigensolvers and Chebyshev polynomial filter accelerated subspace iterations. Several algorithmic and computational aspects of the method, including computation of the electrostatics terms and parallelization are discussed. We have implemented these methods and algorithms into an efficient and reliable package called ClusterES (Cluster Electronic Structure). A variety of benchmark calculations employing local and non-local pseudopotentials are carried out using our package and the results are compared to the literature. Convergence properties of the basis set are discussed through numerical examples. Computations involving large systems that contain thousands of electrons are demonstrated to highlight the efficacy of our methodology. The use of our method to study clusters with arbitrary point group symmetries is briefly discussed.

A spectral scheme for Kohn–Sham density functional theory of clusters

International Nuclear Information System (INIS)

Banerjee, Amartya S.; Elliott, Ryan S.; James, Richard D.

2015-01-01

Starting from the observation that one of the most successful methods for solving the Kohn–Sham equations for periodic systems – the plane-wave method – is a spectral method based on eigenfunction expansion, we formulate a spectral method designed towards solving the Kohn–Sham equations for clusters. This allows for efficient calculation of the electronic structure of clusters (and molecules) with high accuracy and systematic convergence properties without the need for any artificial periodicity. The basis functions in this method form a complete orthonormal set and are expressible in terms of spherical harmonics and spherical Bessel functions. Computation of the occupied eigenstates of the discretized Kohn–Sham Hamiltonian is carried out using a combination of preconditioned block eigensolvers and Chebyshev polynomial filter accelerated subspace iterations. Several algorithmic and computational aspects of the method, including computation of the electrostatics terms and parallelization are discussed. We have implemented these methods and algorithms into an efficient and reliable package called ClusterES (Cluster Electronic Structure). A variety of benchmark calculations employing local and non-local pseudopotentials are carried out using our package and the results are compared to the literature. Convergence properties of the basis set are discussed through numerical examples. Computations involving large systems that contain thousands of electrons are demonstrated to highlight the efficacy of our methodology. The use of our method to study clusters with arbitrary point group symmetries is briefly discussed

Theoretical stellar luminosity functions and globular cluster ages and compositions

International Nuclear Information System (INIS)

Ratcliff, S.J.

1985-01-01

The ages and chemical compositions of the stars in globular clusters are of great interest, particularly because age estimates from the well-known exercise of fitting observed color-magnitude diagrams to theoretical predictions tend to yield ages in excess of the Hubble time (an estimate to the age of the Universe) in standard cosmological models, for currently proposed high values of Hubble's constant (VandenBerg 1983). Relatively little use has been made of stellar luminosity functions of the globular clusters, for which reliable observations are now becoming available, to constrain the ages or compositions. The comparison of observed luminosity functions to theoretical ones allows one to take advantage of information not usually used, and has the advantage of being relatively insensitive to our lack of knowledge of the detailed structure of stellar envelopes and atmospheres. A computer program was developed to apply standard stellar evolutionary theory, using the most recently available input physics (opacities, nuclear reaction rates), to the calculation of the evolution of low-mass Population II stars. An algorithm for computing luminosity functions from the evolutionary tracks was applied to sets of tracks covering a broad range of chemical compositions and ages, such as may be expected for globular clusters

Density functional study of structural and electronic properties of bimetallic silver-gold clusters: Comparison with pure gold and silver clusters

Science.gov (United States)

Bonacic-Koutecky, Vlasta; Burda, Jaroslav; Mitric, Roland; Ge, Maofa; Zampella, Giuseppe; Fantucci, Piercarlo

2002-08-01

Bimetallic silver-gold clusters offer an excellent opportunity to study changes in metallic versus "ionic" properties involving charge transfer as a function of the size and the composition, particularly when compared to pure silver and gold clusters. We have determined structures, ionization potentials, and vertical detachment energies for neutral and charged bimetallic AgmAun 3[less-than-or-equal](m+n)[less-than-or-equal]5 clusters. Calculated VDE values compare well with available experimental data. In the stable structures of these clusters Au atoms assume positions which favor the charge transfer from Ag atoms. Heteronuclear bonding is usually preferred to homonuclear bonding in clusters with equal numbers of hetero atoms. In fact, stable structures of neutral Ag2Au2, Ag3Au3, and Ag4Au4 clusters are characterized by the maximum number of hetero bonds and peripheral positions of Au atoms. Bimetallic tetramer as well as hexamer are planar and have common structural properties with corresponding one-component systems, while Ag4Au4 and Ag8 have 3D forms in contrast to Au8 which assumes planar structure. At the density functional level of theory we have shown that this is due to participation of d electrons in bonding of pure Aun clusters while s electrons dominate bonding in pure Agm as well as in bimetallic clusters. In fact, Aun clusters remain planar for larger sizes than Agm and AgnAun clusters. Segregation between two components in bimetallic systems is not favorable, as shown in the example of Ag5Au5 cluster. We have found that the structures of bimetallic clusters with 20 atoms Ag10Au10 and Ag12Au8 are characterized by negatively charged Au subunits embedded in Ag environment. In the latter case, the shape of Au8 is related to a pentagonal bipyramid capped by one atom and contains three exposed negatively charged Au atoms. They might be suitable for activating reactions relevant to catalysis. According to our findings the charge transfer in bimetallic

The food, GI tract functionality and human health cluster

NARCIS (Netherlands)

Mattila-Sandholm, T.; Blaut, M.; Daly, C.; Vuyst, de L.; Dore, J.; Gibson, G.; Goossens, H.; Knorr, D.; Lucas, J.; Lahteenmaki, L.; Mercenier, A.M.E.; Saarela, M.; Shanahan, F.; Vos, de W.M.

2002-01-01

The Food, GI-tract Functionality and Human Health (PROEUHEALTH) Cluster brings together eight complementary, multicentre interdisciplinary research projects. All have the common aim of improving the health and quality of life of European comsumers. The collaboration involves 64 different research

Dengue-1 envelope protein domain III along with PELC and CpG oligodeoxynucleotides synergistically enhances immune responses.

Directory of Open Access Journals (Sweden)

Chen-Yi Chiang

Full Text Available The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy. Adjuvants can help to overcome some of these inherent defects with subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system, termed PELC, in potentiating the protective capacity of dengue-1 envelope protein domain III. Unlike aluminum phosphate, dengue-1 envelope protein domain III formulated with PELC plus CpG oligodeoxynucleotides induced neutralizing antibodies against dengue-1 virus and increased the splenocyte secretion of IFN-γ after in vitro re-stimulation. The induced antibodies contained both the IgG1 and IgG2a subclasses. A rapid anamnestic neutralizing antibody response against a live dengue virus challenge was elicited at week 26 after the first immunization. These results demonstrate that PELC plus CpG oligodeoxynucleotides broaden the dengue-1 envelope protein domain III-specific immune responses. PELC plus CpG oligodeoxynucleotides is a promising adjuvant for recombinant protein based vaccination against dengue virus.

Methylation status of individual CpG sites within Alu elements in the human genome and Alu hypomethylation in gastric carcinomas

International Nuclear Information System (INIS)

Xiang, Shengyan; Liu, Zhaojun; Zhang, Baozhen; Zhou, Jing; Zhu, Bu-Dong; Ji, Jiafu; Deng, Dajun

2010-01-01

Alu methylation is correlated with the overall level of DNA methylation and recombination activity of the genome. However, the maintenance and methylation status of each CpG site within Alu elements (Alu) and its methylation status have not well characterized. This information is useful for understanding natural status of Alu in the genome and helpful for developing an optimal assay to quantify Alu hypomethylation. Bisulfite clone sequencing was carried out in 14 human gastric samples initially. A Cac8I COBRA-DHPLC assay was developed to detect methylated-Alu proportion in cell lines and 48 paired gastric carcinomas and 55 gastritis samples. DHPLC data were statistically interpreted using SPSS version 16.0. From the results of 427 Alu bisulfite clone sequences, we found that only 27.2% of CpG sites within Alu elements were preserved (4.6 of 17 analyzed CpGs, A ~ Q) and that 86.6% of remaining-CpGs were methylated. Deamination was the main reason for low preservation of methylation targets. A high correlation coefficient of methylation was observed between Alu clones and CpG site J (0.963), A (0.950), H (0.946), D (0.945). Comethylation of the sites H and J were used as an indicator of the proportion of methylated-Alu in a Cac8I COBRA-DHPLC assay. Validation studies showed that hypermethylation or hypomethylation of Alu elements in human cell lines could be detected sensitively by the assay after treatment with 5-aza-dC and M.SssI, respectively. The proportion of methylated-Alu copies in gastric carcinomas (3.01%) was significantly lower than that in the corresponding normal samples (3.19%) and gastritis biopsies (3.23%). Most Alu CpG sites are deaminated in the genome. 27% of Alu CpG sites represented in our amplification products. 87% of the remaining CpG sites are methylated. Alu hypomethylation in primary gastric carcinomas could be detected with the Cac8I COBRA-DHPLC assay quantitatively

DELETION AND 5'CPG ISLAND METHYLATION OF p15 GENE IN BRAIN GLIOMA

Institute of Scientific and Technical Information of China (English)

无

2000-01-01

Objective: To investigate the abnormality of p15 gene in brain glioma and the correlation of it with occurrence or malignant progression of brain glioma. Methods: Deletion and 5'CPG island methylation of p15 gene were detected by the methods of PCR and PCR-based methylation in 56 cases of brain glioma. Results: Out of 43 cases of high grade glioma, 14 cases were found to have homozygous deletion of p15E1, while none of the 13 cases of low grade glioma was found to have deletion of p15E1 (P<0.05). Methylation of 5'CPG Island of p15 gene was found only in four cases of glioma. Conclusion: Abnormality of p15 gene may involved in the occurrence and malignant progression of brain glioma. Homozygous deletion of gene is the major mechanism of inactivation for p15 gene in brain glioma.

DMPD: Signal transduction pathways mediated by the interaction of CpG DNA withToll-like receptor 9. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 14751759 Signal transduction pathways mediated by the interaction of CpG DNA withTo...;16(1):17-22. (.png) (.svg) (.html) (.csml) Show Signal transduction pathways mediated by the interaction of... CpG DNA withToll-like receptor 9. PubmedID 14751759 Title Signal transduction pathways media

Statistical indicators of collective behavior and functional clusters in gene networks of yeast

Science.gov (United States)

Živković, J.; Tadić, B.; Wick, N.; Thurner, S.

2006-03-01

We analyze gene expression time-series data of yeast (S. cerevisiae) measured along two full cell-cycles. We quantify these data by using q-exponentials, gene expression ranking and a temporal mean-variance analysis. We construct gene interaction networks based on correlation coefficients and study the formation of the corresponding giant components and minimum spanning trees. By coloring genes according to their cell function we find functional clusters in the correlation networks and functional branches in the associated trees. Our results suggest that a percolation point of functional clusters can be identified on these gene expression correlation networks.

Constraints on Ωm and σ8 from the potential-based cluster temperature function

Science.gov (United States)

Angrick, Christian; Pace, Francesco; Bartelmann, Matthias; Roncarelli, Mauro

2015-12-01

The abundance of galaxy clusters is in principle a powerful tool to constrain cosmological parameters, especially Ωm and σ8, due to the exponential dependence in the high-mass regime. While the best observables are the X-ray temperature and luminosity, the abundance of galaxy clusters, however, is conventionally predicted as a function of mass. Hence, the intrinsic scatter and the uncertainties in the scaling relations between mass and either temperature or luminosity lower the reliability of galaxy clusters to constrain cosmological parameters. In this article, we further refine the X-ray temperature function for galaxy clusters by Angrick et al., which is based on the statistics of perturbations in the cosmic gravitational potential and proposed to replace the classical mass-based temperature function, by including a refined analytic merger model and compare the theoretical prediction to results from a cosmological hydrodynamical simulation. Although we find already a good agreement if we compare with a cluster temperature function based on the mass-weighted temperature, including a redshift-dependent scaling between mass-based and spectroscopic temperature yields even better agreement between theoretical model and numerical results. As a proof of concept, incorporating this additional scaling in our model, we constrain the cosmological parameters Ωm and σ8 from an X-ray sample of galaxy clusters and tentatively find agreement with the recent cosmic microwave background based results from the Planck mission at 1σ-level.

Density functional theory and surface reactivity study of bimetallic AgnYm (n+m = 10) clusters

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Hussain, Riaz; Hussain, Abdullah Ijaz; Chatha, Shahzad Ali Shahid; Hussain, Riaz; Hanif, Usman; Ayub, Khurshid

2018-06-01

Density functional theory calculations have been performed on pure silver (Agn), yttrium (Ym) and bimetallic silver yttrium clusters AgnYm (n + m = 2-10) for reactivity descriptors in order to realize sites for nucleophilic and electrophilic attack. The reactivity descriptors of the clusters, studied as a function of cluster size and shape, reveal the presence of different type of reactive sites in a cluster. The size and shape of the pure silver, yttrium and bimetallic silver yttrium cluster (n = 2-10) strongly influences the number and position of active sites for an electrophilic and/or nucleophilic attack. The trends of reactivities through reactivity descriptors are confirmed through comparison with experimental data for CO binding with silver clusters. Moreover, the adsorption of CO on bimetallic silver yttrium clusters is also evaluated. The trends of binding energies support the reactivity descriptors values. Doping of pure cluster with the other element also influence the hardness, softness and chemical reactivity of the clusters. The softness increases as we increase the number of silver atoms in the cluster, whereas the hardness decreases. The chemical reactivity increases with silver doping whereas it decreases by increasing yttrium concentration. Silver atoms are nucleophilic in small clusters but changed to electrophilic in large clusters.

Characterization of human gastric carcinoma-related methylation of 9 miR CpG islands and repression of their expressions in vitro and in vivo

International Nuclear Information System (INIS)

Du, Yantao; Liu, Zhaojun; Gu, Liankun; Zhou, Jing; Zhu, Bu-dong; Ji, Jiafu; Deng, Dajun

2012-01-01

Many miR genes are located within or around CpG islands. It is unclear whether methylation of these CpG islands represses miR transcription regularly. The aims of this study are to characterize gastric carcinoma (GC)-related methylation of miR CpG islands and its relationship with miRNA expression. Methylation status of 9 representative miR CpG islands in a panel of cell lines and human gastric samples (including 13 normal biopsies, 38 gastritis biopsies, 112 pairs of GCs and their surgical margin samples) was analyzed by bisulfite-DHPLC and sequencing. Mature miRNA levels were determined with quantitative RT-PCR. Relationships between miR methylation, transcription, GC development, and clinicopathological characteristics were statistically analyzed. Methylation frequency of 5 miR CpG islands (miR-9-1, miR-9-3, miR-137, miR-34b, and miR-210) gradually increased while the proportion of methylated miR-200b gradually decreased during gastric carcinogenesis (Ps < 0.01). More miR-9-1 methylation was detected in 62%-64% of the GC samples and 4% of the normal or gastritis samples (18/28 versus 2/48; Odds ratio, 41.4; P < 0.01). miR-210 methylation showed high correlation with H. pylori infection. miR-375, miR-203, and miR-193b methylation might be host adaptation to the development of GCs. Methylation of these miR CpG islands was consistently shown to significantly decrease the corresponding miRNA levels presented in human cell lines. The inverse relationship was also observed for miR-9-1, miR-9-3, miR-137, and miR-200b in gastric samples. Among 112 GC patients, miR-9-1 methylation was an independent favourable predictor of overall survival of GC patients in both univariate and multivariate analysis (P < 0.02). In conclusion, alteration of methylation status of 6 of 9 tested miR CpG islands was characterized in gastric carcinogenesis. miR-210 methylation correlated with H. pylori infection. miR-9-1 methylation may be a GC-specific event. Methylation of miR CpG islands may

Defective functional connectivity between posterior hypothalamus and regions of the diencephalic-mesencephalic junction in chronic cluster headache.

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Ferraro, Stefania; Nigri, Anna; Bruzzone, Maria Grazia; Brivio, Luca; Proietti Cecchini, Alberto; Verri, Mattia; Chiapparini, Luisa; Leone, Massimo

2018-01-01

Objective We tested the hypothesis of a defective functional connectivity between the posterior hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache based on: a) clinical and neuro-endocrinological findings in cluster headache patients; b) neuroimaging findings during cluster headache attacks; c) neuroimaging findings in drug-refractory chronic cluster headache patients improved after successful deep brain stimulation. Methods Resting state functional magnetic resonance imaging, associated with a seed-based approach, was employed to investigate the functional connectivity of the posterior hypothalamus in chronic cluster headache patients (n = 17) compared to age and sex-matched healthy subjects (n = 16). Random-effect analyses were performed to study differences between patients and controls in ipsilateral and contralateral-to-the-pain posterior hypothalamus functional connectivity. Results Cluster headache patients showed an increased functional connectivity between the ipsilateral posterior hypothalamus and a number of diencephalic-mesencephalic structures, comprising ventral tegmental area, dorsal nuclei of raphe, and bilateral substantia nigra, sub-thalamic nucleus, and red nucleus ( p cluster headache patients mainly involves structures that are part of (i.e. ventral tegmental area, substantia nigra) or modulate (dorsal nuclei of raphe, sub-thalamic nucleus) the midbrain dopaminergic systems. The midbrain dopaminergic systems could play a role in cluster headache pathophysiology and in particular in the chronicization process. Future studies are needed to better clarify if this finding is specific to cluster headache or if it represents an unspecific response to chronic pain.

Modulated modularity clustering as an exploratory tool for functional genomic inference.

Directory of Open Access Journals (Sweden)

Eric A Stone

2009-05-01

Full Text Available In recent years, the advent of high-throughput assays, coupled with their diminishing cost, has facilitated a systems approach to biology. As a consequence, massive amounts of data are currently being generated, requiring efficient methodology aimed at the reduction of scale. Whole-genome transcriptional profiling is a standard component of systems-level analyses, and to reduce scale and improve inference clustering genes is common. Since clustering is often the first step toward generating hypotheses, cluster quality is critical. Conversely, because the validation of cluster-driven hypotheses is indirect, it is critical that quality clusters not be obtained by subjective means. In this paper, we present a new objective-based clustering method and demonstrate that it yields high-quality results. Our method, modulated modularity clustering (MMC, seeks community structure in graphical data. MMC modulates the connection strengths of edges in a weighted graph to maximize an objective function (called modularity that quantifies community structure. The result of this maximization is a clustering through which tightly-connected groups of vertices emerge. Our application is to systems genetics, and we quantitatively compare MMC both to the hierarchical clustering method most commonly employed and to three popular spectral clustering approaches. We further validate MMC through analyses of human and Drosophila melanogaster expression data, demonstrating that the clusters we obtain are biologically meaningful. We show MMC to be effective and suitable to applications of large scale. In light of these features, we advocate MMC as a standard tool for exploration and hypothesis generation.

Effect of functionalization of boron nitride flakes by main group metal clusters on their optoelectronic properties

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Chakraborty, Debdutta; Chattaraj, Pratim Kumar

2017-10-01

The possibility of functionalizing boron nitride flakes (BNFs) with some selected main group metal clusters, viz. OLi4, NLi5, CLi6, BLI7 and Al12Be, has been analyzed with the aid of density functional theory (DFT) based computations. Thermochemical as well as energetic considerations suggest that all the metal clusters interact with the BNF moiety in a favorable fashion. As a result of functionalization, the static (first) hyperpolarizability (β ) values of the metal cluster supported BNF moieties increase quite significantly as compared to that in the case of pristine BNF. Time dependent DFT analysis reveals that the metal clusters can lower the transition energies associated with the dominant electronic transitions quite significantly thereby enabling the metal cluster supported BNF moieties to exhibit significant non-linear optical activity. Moreover, the studied systems demonstrate broad band absorption capability spanning the UV-visible as well as infra-red domains. Energy decomposition analysis reveals that the electrostatic interactions principally stabilize the metal cluster supported BNF moieties.

Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

International Nuclear Information System (INIS)

Wang, Tingting; Chen, Man; Liu, Lian; Cheng, Huaiyan; Yan, You-E; Feng, Ying-Hong; Wang, Hui

2011-01-01

Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a single site CpG methylation at nt -377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. -- Highlights: ► Nicotine-induced StAR inhibition in two human adrenal cell models. ► Nicotine-induced single CpG site methylation in StAR promoter. ► Persistent StAR inhibition and single CpG methylation after nicotine termination. ► Single CpG methylation located at Pax6 binding motif regulates St

Proinflammatory Stimulation of Toll-Like Receptor 9 with High Dose CpG ODN 1826 Impairs Endothelial Regeneration and Promotes Atherosclerosis in Mice.

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Alexander O Krogmann

Full Text Available Toll-like receptors (TLR of the innate immune system have been closely linked with the development of atherosclerotic lesions. TLR9 is activated by unmethylated CpG motifs within ssDNA, but also by CpG motifs in nucleic acids released during vascular apoptosis and necrosis. The role of TLR9 in vascular disease remains controversial and we sought to investigate the effects of a proinflammatory TLR9 stimulation in mice.TLR9-stimulation with high dose CpG ODN at concentrations between 6.25 nM to 30 nM induced a significant proinflammatory cytokine response in mice. This was associated with impaired reendothelialization upon acute denudation of the carotid and increased numbers of circulating endothelial microparticles, as a marker for amplified endothelial damage. Chronic TLR9 agonism in apolipoprotein E-deficient (ApoE-/- mice fed a cholesterol-rich diet increased aortic production of reactive oxygen species, the number of circulating endothelial microparticles, circulating sca-1/flk-1 positive cells, and most importantly augmented atherosclerotic plaque formation when compared to vehicle treated animals. Importantly, high concentrations of CpG ODN are required for these proatherogenic effects.Systemic stimulation of TLR9 with high dose CpG ODN impaired reendothelialization upon acute vascular injury and increased atherosclerotic plaque development in ApoE-/- mice. Further studies are necessary to fully decipher the contradictory finding of TLR9 agonism in vascular biology.

Pan-cancer stratification of solid human epithelial tumors and cancer cell lines reveals commonalities and tissue-specific features of the CpG island methylator phenotype.

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Sánchez-Vega, Francisco; Gotea, Valer; Margolin, Gennady; Elnitski, Laura

2015-01-01

The term CpG island methylator phenotype (CIMP) has been used to describe widespread DNA hypermethylation at CpG-rich genomic regions affecting clinically distinct subsets of cancer patients. Even though there have been numerous studies of CIMP in individual cancer types, a uniform analysis across tissues is still lacking. We analyze genome-wide patterns of CpG island hypermethylation in 5,253 solid epithelial tumors from 15 cancer types from TCGA and 23 cancer cell lines from ENCODE. We identify differentially methylated loci that define CIMP+ and CIMP- samples, and we use unsupervised clustering to provide a robust molecular stratification of tumor methylomes for 12 cancer types and all cancer cell lines. With a minimal set of 89 discriminative loci, we demonstrate accurate pan-cancer separation of the 12 CIMP+/- subpopulations, based on their average levels of methylation. Tumor samples in different CIMP subclasses show distinctive correlations with gene expression profiles and recurrence of somatic mutations, copy number variations, and epigenetic silencing. Enrichment analyses indicate shared canonical pathways and upstream regulators for CIMP-targeted regions across cancer types. Furthermore, genomic alterations showing consistent associations with CIMP+/- status include genes involved in DNA repair, chromatin remodeling genes, and several histone methyltransferases. Associations of CIMP status with specific clinical features, including overall survival in several cancer types, highlight the importance of the CIMP+/- designation for individual tumor evaluation and personalized medicine. We present a comprehensive computational study of CIMP that reveals pan-cancer commonalities and tissue-specific differences underlying concurrent hypermethylation of CpG islands across tumors. Our stratification of solid tumors and cancer cell lines based on CIMP status is data-driven and agnostic to tumor type by design, which protects against known biases that have hindered

A Comparison between Standard and Functional Clustering Methodologies: Application to Agricultural Fields for Yield Pattern Assessment

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Simone Pascucci

2018-04-01

Full Text Available The recognition of spatial patterns within agricultural fields, presenting similar yield potential areas, stable through time, is very important for optimizing agricultural practices. This study proposes the evaluation of different clustering methodologies applied to multispectral satellite time series for retrieving temporally stable (constant patterns in agricultural fields, related to within-field yield spatial distribution. The ability of different clustering procedures for the recognition and mapping of constant patterns in fields of cereal crops was assessed. Crop vigor patterns, considered to be related to soils characteristics, and possibly indicative of yield potential, were derived by applying the different clustering algorithms to time series of Landsat images acquired on 94 agricultural fields near Rome (Italy. Two different approaches were applied and validated using Landsat 7 and 8 archived imagery. The first approach automatically extracts and calculates for each field of interest (FOI the Normalized Difference Vegetation Index (NDVI, then exploits the standard K-means clustering algorithm to derive constant patterns at the field level. The second approach applies novel clustering procedures directly to spectral reflectance time series, in particular: (1 standard K-means; (2 functional K-means; (3 multivariate functional principal components clustering analysis; (4 hierarchical clustering. The different approaches were validated through cluster accuracy estimates on a reference set of FOIs for which yield maps were available for some years. Results show that multivariate functional principal components clustering, with an a priori determination of the optimal number of classes for each FOI, provides a better accuracy than those of standard clustering algorithms. The proposed novel functional clustering methodologies are effective and efficient for constant pattern retrieval and can be used for a sustainable management of

CpG ODN 1668 induce innate and adaptive immune responses in rock bream (Oplegnathus fasciatus) against rock bream iridovirus (RBIV) infection.

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Jung, Myung-Hwa; Jung, Sung-Ju

2017-10-01

Rock bream iridovirus (RBIV) causes severe mass mortalities in rock bream in Korea. CpG ODN 1668 showed promise as immunoprotective agents against RBIV infection in rock bream. In this study, we assessed innate/adaptive-related gene expression patterns in RBIV-infected rock bream with and without CpG ODN 1668 administration to determine important immune defense related factors that may affect fish survival. In the CpG ODN 1668+virus-injected group, virus copies were more than 7.4- to 790591-fold lower than in the virus-injected group at 4 d (8.79 × 10 4 and 6.58 × 10 5 /μl, respectively), 7 d (5.30 × 10 2 and 2.29 × 10 7 /μl, respectively) and 10 dpi (7.79 × 10 1 and 6.16 × 10 7 /μl, respectively). Furthermore, in the CpG ODN 1668+virus-injected group, significantly higher levels of MyD88 (6 h, 1 d, 4 d and 7 dpi), IL1β (1 d, 2 d and 7 dpi) and perforin/granzyme (1 dpi) expression were observed, whereas these genes were not significantly expressed in the virus-injected group at that time points. Mx, ISG15 and PKR were significantly highly expressed at 4 d and 7 dpi and reduced when low viral loads at 10 dpi in the CpG ODN 1668+virus-injected group. Conversely, in the virus-injected group, Mx, ISG15 and PKR expression were significantly higher than the control group until 10 dpi. However, MHC class I, CD8, Fas, Fas ligand and caspases (3, 8 and 9) expression levels showed no statistically significant differences between virus- and CpG ODN 1668+virus-injected group. In summary, CpG ODN 1668 administration in fish induces innate immune response or cell death pathway, which could be a major contributing factor to effective fish control over viral transcription on 4 d to 10 dpi. Expression of MyD88, IL1β, perforin and granzyme-related immune gene response is critical factor for inhibition of RBIV replication. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regulatory domain or CpG site variation in SLC12A5, encoding the chloride transporter KCC2, in human autism and schizophrenia

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Nancy D Merner

2015-10-01

Full Text Available Many encoded gene products responsible for neurodevelopmental disorders (NDs like autism spectrum disorders (ASD, schizophrenia (SCZ, intellectual disability (ID, and idiopathic generalized epilepsy (IGE converge on networks controlling synaptic function. An increase in KCC2 (SLC12A5 Cl- transporter activity drives the developmental GABA excitatory-inhibitory sequence, but the role of KCC2 in human NDs is essentially unknown. Here, we report two rare, non-synonymous (NS, functionally-impairing variants in the KCC2 C-terminal regulatory domain (CTRD in human ASD (R952H and R1049C and SCZ (R952H previously linked with IGE and familial febrile seizures, and another novel NS KCC2 variant in ASD (R1048W with highly-predicted pathogenicity. Exome data from 2517 simplex families in the ASD Simon Simplex Collection revealed significantly more KCC2 CTRD variants in ASD cases than controls, and interestingly, these were more often synonymous and predicted to disrupt or introduce a CpG site. Furthermore, full gene analysis showed ASD cases are more likely to contain rare KCC2 variants affecting CpG sites than controls. These data suggest genetically-encoded dysregulation of KCC2-dependent GABA signaling may contribute to multiple human NDs.

Isomers of Cu6 cluster: a density function theory study

International Nuclear Information System (INIS)

Jia Yanhui; Wang Shanshan; Li Gongping

2008-01-01

The possible structure of Cu 6 cluster has been given with the GaussView that is a graphical user interface software. The structure optimization was performed on the B3LYP functional and SDD basic set of the quantum computational software of Gaussian03. And eight isomers of Cu 6 cluster were calculated. The binding energy and the structure of eight isomers have been investigated in detail. The result showed that the value of the binding energy was in reasonable agreement with available experimental data, as well as with other theoretical results, and the most stable structure was the triangle of plane. Three new isomers of the Cu 6 cluster have been got in our work, which would be the valuable data for the further theoretical and experimental study. (authors)

Prognostication of patients with clear cell renal cell carcinomas based on quantification of DNA methylation levels of CpG island methylator phenotype marker genes.

Science.gov (United States)

Tian, Ying; Arai, Eri; Gotoh, Masahiro; Komiyama, Motokiyo; Fujimoto, Hiroyuki; Kanai, Yae

2014-10-20

The CpG island methylator phenotype (CIMP) of clear cell renal cell carcinomas (ccRCCs) is characterized by accumulation of DNA methylation at CpG islands and poorer patient outcome. The aim of this study was to establish criteria for prognostication of patients with ccRCCs using the ccRCC-specific CIMP marker genes. DNA methylation levels at 299 CpG sites in the 14 CIMP marker genes were evaluated quantitatively in tissue specimens of 88 CIMP-negative and 14 CIMP-positive ccRCCs in a learning cohort using the MassARRAY system. An additional 100 ccRCCs were also analyzed as a validation cohort. Receiver operating characteristic curve analysis showed that area under the curve values for the 23 CpG units including the 32 CpG sites in the 7 CIMP-marker genes, i.e. FAM150A, ZNF540, ZNF671, ZNF154, PRAC, TRH and SLC13A5, for discrimination of CIMP-positive from CIMP-negative ccRCCs were larger than 0.95. Criteria combining the 23 CpG units discriminated CIMP-positive from CIMP-negative ccRCCs with 100% sensitivity and specificity in the learning cohort. Cancer-free and overall survival rates of patients with CIMP-positive ccRCCs diagnosed using the criteria combining the 23 CpG units in a validation cohort were significantly lower than those of patients with CIMP-negative ccRCCs (P = 1.41 × 10-5 and 2.43 × 10-13, respectively). Patients with CIMP-positive ccRCCs in the validation cohort had a higher likelihood of disease-related death (hazard ratio, 75.8; 95% confidence interval, 7.81 to 735; P = 1.89 × 10-4) than those with CIMP-negative ccRCCs. The established criteria are able to reproducibly diagnose CIMP-positive ccRCCs and may be useful for personalized medicine for patients with ccRCCs.

Structure and Stability of GeAun, n = 1-10 clusters: A Density Functional Study

International Nuclear Information System (INIS)

Priyanka,; Dharamvir, Keya; Sharma, Hitesh

2011-01-01

The structures of Germanium doped gold clusters GeAu n (n = 1-10) have been investigated using ab initio calculations based on density functional theory (DFT). We have obtained ground state geometries of GeAu n clusters and have it compared with Silicon doped gold clusters and pure gold clusters. The ground state geometries of the GeAu n clusters show patterns similar to silicon doped gold clusters except for n = 5, 6 and 9. The introduction of germanium atom increases the binding energy of gold clusters. The binding energy per atom of germanium doped cluster is smaller than the corresponding silicon doped gold cluster. The HUMO-LOMO gap for Au n Ge clusters have been found to vary between 0.46 eV-2.09 eV. The mullikan charge analysis indicates that charge of order of 0.1e always transfers from germanium atom to gold atom.

78 FR 28904 - CPG Carlyle Private Equity Fund, LLC, et al.; Notice of Application

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2013-05-16

... as Delaware limited liability companies. The Feeder Fund operates as a feeder fund in a master-feeder..., and mezzanine). 2. The Adviser, a Delaware limited liability company and wholly- owned subsidiary of... SECURITIES AND EXCHANGE COMMISSION [Investment Company Act Release No. 30512; 812-14089] CPG...

Low-mass stars in globular clusters. III. The mass function of 47 Tucanae.

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de Marchi, G.; Paresce, F.

1995-12-01

We have used the WFPC2 on board HST to investigate the stellar population in a field located 4'6 E of the center of the globular cluster 47 Tuc (NGC 104), close to the half-mass radius, through wide band imaging at 606 and 812nm. A total of ~3000 stars are accurately classified by two-color photometry to form a color-magnitude diagram extending down to a limiting magnitude m_814_=~m_I_=~24. A rich cluster main sequence is detected spanning the range from m_814_=~18 through m_814_=~23, where it spreads considerably due to the increasing photometric uncertainty and galaxy contamination. A secondary sequence of objects is also detected, parallel to the main sequence, as expected for a population of binary stars. The measured binary fraction in the range 195%. The main sequence luminosity function obtained from the observed CMD increases with decreasing luminosity following a power-law trend with index α=~0.15 in the range 5crowding. On the basis of the available mass-luminosity relation for this metallicity, the resultant mass function shows a power-law increase in numbers for decreasing masses in the range 0.8-0.3Msun_ with a slope α=~1.5, but then flattens out in the 0.3-0.15Msun_ range. The comparison of the mass function of 47 Tuc with that of NGC 6397 (Paper I) and of M 15 (Paper II), previously investigated with the same instrumentation, suggests that the stellar population near the half-mass radius of these clusters should not be very sensitive to either internal or externally-driven dynamical processes. The difference between their mass functions could then be attributed to metallicity, reflecting an intrinsic difference in their initial mass functions, unless mass-segregation is stronger in 47 Tuc than in the other two clusters. This latter circumstance could be due, for instance, to the large number of binaries discovered in 47 Tuc. In all cases, however, the mass function is found to flatten below 0.3Msun_ and the flattening is most likely an intrinsic

Differential Retention of Gene Functions in a Secondary Metabolite Cluster.

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Reynolds, Hannah T; Slot, Jason C; Divon, Hege H; Lysøe, Erik; Proctor, Robert H; Brown, Daren W

2017-08-01

In fungi, distribution of secondary metabolite (SM) gene clusters is often associated with host- or environment-specific benefits provided by SMs. In the plant pathogen Alternaria brassicicola (Dothideomycetes), the DEP cluster confers an ability to synthesize the SM depudecin, a histone deacetylase inhibitor that contributes weakly to virulence. The DEP cluster includes genes encoding enzymes, a transporter, and a transcription regulator. We investigated the distribution and evolution of the DEP cluster in 585 fungal genomes and found a wide but sporadic distribution among Dothideomycetes, Sordariomycetes, and Eurotiomycetes. We confirmed DEP gene expression and depudecin production in one fungus, Fusarium langsethiae. Phylogenetic analyses suggested 6-10 horizontal gene transfers (HGTs) of the cluster, including a transfer that led to the presence of closely related cluster homologs in Alternaria and Fusarium. The analyses also indicated that HGTs were frequently followed by loss/pseudogenization of one or more DEP genes. Independent cluster inactivation was inferred in at least four fungal classes. Analyses of transitions among functional, pseudogenized, and absent states of DEP genes among Fusarium species suggest enzyme-encoding genes are lost at higher rates than the transporter (DEP3) and regulatory (DEP6) genes. The phenotype of an experimentally-induced DEP3 mutant of Fusarium did not support the hypothesis that selective retention of DEP3 and DEP6 protects fungi from exogenous depudecin. Together, the results suggest that HGT and gene loss have contributed significantly to DEP cluster distribution, and that some DEP genes provide a greater fitness benefit possibly due to a differential tendency to form network connections. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution 2017. This work is written by US Government employees and is in the public domain in the US.

The externally corrected coupled cluster approach with four- and five-body clusters from the CASSCF wave function.

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Xu, Enhua; Li, Shuhua

2015-03-07

An externally corrected CCSDt (coupled cluster with singles, doubles, and active triples) approach employing four- and five-body clusters from the complete active space self-consistent field (CASSCF) wave function (denoted as ecCCSDt-CASSCF) is presented. The quadruple and quintuple excitation amplitudes within the active space are extracted from the CASSCF wave function and then fed into the CCSDt-like equations, which can be solved in an iterative way as the standard CCSDt equations. With a size-extensive CASSCF reference function, the ecCCSDt-CASSCF method is size-extensive. When the CASSCF wave function is readily available, the computational cost of the ecCCSDt-CASSCF method scales as the popular CCSD method (if the number of active orbitals is small compared to the total number of orbitals). The ecCCSDt-CASSCF approach has been applied to investigate the potential energy surface for the simultaneous dissociation of two O-H bonds in H2O, the equilibrium distances and spectroscopic constants of 4 diatomic molecules (F2(+), O2(+), Be2, and NiC), and the reaction barriers for the automerization reaction of cyclobutadiene and the Cl + O3 → ClO + O2 reaction. In most cases, the ecCCSDt-CASSCF approach can provide better results than the CASPT2 (second order perturbation theory with a CASSCF reference function) and CCSDT methods.

Information processing architecture of functionally defined clusters in the macaque cortex.

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Shen, Kelly; Bezgin, Gleb; Hutchison, R Matthew; Gati, Joseph S; Menon, Ravi S; Everling, Stefan; McIntosh, Anthony R

2012-11-28

Computational and empirical neuroimaging studies have suggested that the anatomical connections between brain regions primarily constrain their functional interactions. Given that the large-scale organization of functional networks is determined by the temporal relationships between brain regions, the structural limitations may extend to the global characteristics of functional networks. Here, we explored the extent to which the functional network community structure is determined by the underlying anatomical architecture. We directly compared macaque (Macaca fascicularis) functional connectivity (FC) assessed using spontaneous blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) to directed anatomical connectivity derived from macaque axonal tract tracing studies. Consistent with previous reports, FC increased with increasing strength of anatomical connection, and FC was also present between regions that had no direct anatomical connection. We observed moderate similarity between the FC of each region and its anatomical connectivity. Notably, anatomical connectivity patterns, as described by structural motifs, were different within and across functional modules: partitioning of the functional network was supported by dense bidirectional anatomical connections within clusters and unidirectional connections between clusters. Together, our data directly demonstrate that the FC patterns observed in resting-state BOLD-fMRI are dictated by the underlying neuroanatomical architecture. Importantly, we show how this architecture contributes to the global organizational principles of both functional specialization and integration.

Density functional studies: First principles and semiempirical calculations of clusters and surfaces

International Nuclear Information System (INIS)

Sinnott, S.B.

1993-01-01

In the research presented here, various theoretical electronic structure techniques are utilized to analyze widely different systems from silicon clusters to transition metal solids and surfaces. For the silicon clusters, first principles density functional methods are used to investigate Si N for N = 2-8. The goal is to understand the different types of bonding that can occur in such small clusters where the coordination of the atoms differs substantially from that of the stable bulk tetrahedral bonding. Such uncoordinated structures can provide a good test of more approximate theories that can be used eventually to model silicon surfaces, of obvious technological importance. For the transition metal systems, non-self-consistent electronic structure methods are used to provide an understanding of the driving force for surface relaxations. An in-depth analysis of the results is presented and the physical basis of surface relaxation within the theory is discussed. In addition, the limitations inherent in calculations of metal surface relaxation are addressed. Finally, in an effort to increase understanding of approximate methods, a novel non-self-consistent density functional electronic structure method is developed that is ∼1000 times faster computationally than more sophisticated methods. This new method is tested for a variety of systems including diatomics, mixed clusters, surfaces and bulk lattices. The strengths and weaknesses of the new theory are discussed in detail, leading to greater understanding of non-self-consistent density functional theories as a whole

The Luminosity Functions of Old and Intermediate-Age Globular Clusters in NGC 3610

OpenAIRE

Whitmore, B. C.; Schweizer, F.; Kundu, A.; Miller, B. W.

2002-01-01

The WFPC2 Camera on board HST has been used to obtain high-resolution images of NGC 3610, a dynamically young elliptical galaxy. These observations supersede shorter, undithered HST observations where an intermediate-age population of globular clusters was first discovered. The new observations show the bimodal color distribution of globular clusters more clearly, with peaks at (V-I)o = 0.95 and 1.17. The luminosity function (LF) of the blue, metal-poor population of clusters in NGC 3610 turn...

Symmetrized partial-wave method for density-functional cluster calculations

International Nuclear Information System (INIS)

Averill, F.W.; Painter, G.S.

1994-01-01

The computational advantage and accuracy of the Harris method is linked to the simplicity and adequacy of the reference-density model. In an earlier paper, we investigated one way the Harris functional could be extended to systems outside the limits of weakly interacting atoms by making the charge density of the interacting atoms self-consistent within the constraints of overlapping spherical atomic densities. In the present study, a method is presented for augmenting the interacting atom charge densities with symmetrized partial-wave expansions on each atomic site. The added variational freedom of the partial waves leads to a scheme capable of giving exact results within a given exchange-correlation approximation while maintaining many of the desirable convergence and stability properties of the original Harris method. Incorporation of the symmetry of the cluster in the partial-wave construction further reduces the level of computational effort. This partial-wave cluster method is illustrated by its application to the dimer C 2 , the hypothetical atomic cluster Fe 6 Al 8 , and the benzene molecule

Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

Energy Technology Data Exchange (ETDEWEB)

Wang, Tingting [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Chen, Man; Liu, Lian [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Cheng, Huaiyan [Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Yan, You-E [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Feng, Ying-Hong, E-mail: yhfeng@usuhs.edu [Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

2011-12-15

Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a single site CpG methylation at nt -377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. -- Highlights: Black-Right-Pointing-Pointer Nicotine-induced StAR inhibition in two human adrenal cell models. Black-Right-Pointing-Pointer Nicotine-induced single CpG site methylation in StAR promoter. Black-Right-Pointing-Pointer Persistent StAR inhibition and single CpG methylation after nicotine termination

Comparative anatomy of the human APRT gene and enzyme: nucleotide sequence divergence and conservation of a nonrandom CpG dinucleotide arrangement

International Nuclear Information System (INIS)

Broderick, T.P.; Schaff, D.A.; Bertino, A.M.; Dush, M.K.; Tischfield, J.A.; Stambrook, P.J.

1987-01-01

The functional human adenine phosphoribosyltransferase (APRT) gene is <2.6 kilobases in length and contains five exons. The amino acid sequences of APRTs have been highly conserved throughout evolution. The human enzyme is 82%, 90%, and 40% identical to the mouse, hamster, and Escherichia coli enzymes, respectively. The promoter region of the human APRT gene, like that of several other housekeeping genes, lacks TATA and CCAAT boxes but contains five GC boxes that are potential binding sites for the Sp1 transcription factor. The distal three, however, are dispensable for gene expression. Comparison between human and mouse APRT gene nucleotide sequences reveals a high degree of homology within protein coding regions but an absence of significant homology in 5' flanking, 3' untranslated, and intron sequences, except for similarly positioned GC boxes in the promoter region and a 26-base-pair region in intron 3. This 26-base-pair sequence is 92% identical with a similarly positioned sequence in the mouse gene and is also found in intron 3 of the hamster gene, suggesting that its retention may be a consequence of stringent selection. The positions of all introns have been precisely retained in the human and both rodent genes. Retention of an elevated CpG dinucleotide content, despite loss of sequence homology, suggests that there may be selection for CpG dinucleotides in these regions and that their maintenance may be important for APRT gene function

Anchoring selenido-carbonyl ruthenium clusters to functionalized silica xerogels

International Nuclear Information System (INIS)

Cauzzi, Daniele; Graiff, Claudia; Pattacini, Roberto; Predieri, Giovanni; Tiripicchio, Antonio

2003-01-01

Silica Xerogels containing carbonyl Ru 3 Se 2 nido clusters were prepared in three different ways. The simple dispersion of [Ru 3 (μ 3 -Se) 2 (CO) 7 (PPh 3 ) 2 ] via sol gel process produces an inhomogeneous material; by contrast, homogeneous xerogels were obtained by reaction of [Ru 3 (μ 3 -Se) 2 (CO) 8 (PPh 3 )] with functionalized xerogels containing grafted diphenylphosphine moieties and by reaction of [Ru 3 (CO) 12 ] with a xerogel containing grafted phosphine-selenide groups. The reaction between [Ru 3 (CO) 12 ] and dodecyl diphenylphosphine selenide led to the formation of four selenido carbonyl clusters, which are soluble in hydrocarbon solvents and can be deposited as thin films from their solution by slow evaporation. (author)

Functional Principal Component Analysis and Randomized Sparse Clustering Algorithm for Medical Image Analysis

Science.gov (United States)

Lin, Nan; Jiang, Junhai; Guo, Shicheng; Xiong, Momiao

2015-01-01

Due to the advancement in sensor technology, the growing large medical image data have the ability to visualize the anatomical changes in biological tissues. As a consequence, the medical images have the potential to enhance the diagnosis of disease, the prediction of clinical outcomes and the characterization of disease progression. But in the meantime, the growing data dimensions pose great methodological and computational challenges for the representation and selection of features in image cluster analysis. To address these challenges, we first extend the functional principal component analysis (FPCA) from one dimension to two dimensions to fully capture the space variation of image the signals. The image signals contain a large number of redundant features which provide no additional information for clustering analysis. The widely used methods for removing the irrelevant features are sparse clustering algorithms using a lasso-type penalty to select the features. However, the accuracy of clustering using a lasso-type penalty depends on the selection of the penalty parameters and the threshold value. In practice, they are difficult to determine. Recently, randomized algorithms have received a great deal of attentions in big data analysis. This paper presents a randomized algorithm for accurate feature selection in image clustering analysis. The proposed method is applied to both the liver and kidney cancer histology image data from the TCGA database. The results demonstrate that the randomized feature selection method coupled with functional principal component analysis substantially outperforms the current sparse clustering algorithms in image cluster analysis. PMID:26196383

Accurate density-functional calculations on large systems: Fullerenes and magnetic clusters

International Nuclear Information System (INIS)

Dunlap, B.I.

1996-01-01

Efforts to accurately compute all-electron density-functional energies for large molecules and clusters using Gaussian basis sets will be reviewed. The foundation of this effort, variational fitting, will be described and followed by three applications of the method. The first application concerns fullerenes. When first discovered, C 60 is quite unstable relative to the higher fullerenes. In addition, to raising questions about the relative abundance of the various fullerenes, this work conflicted with the then state-of-the art density-funcitonal calculations on crystalline graphite. Now high accuracy molecular and band structure calculations are in fairly good agreement. Second, we have used these methods to design transition metal clusters having the highest magnetic moment by maximizing the symmetry-required degeneracy of the one-electron orbitals. Most recently, we have developed accurate, variational generalized-gradient approximation (GGA) forces for use in geometry optimization of clusters and in molecular-dynamics simulations of friction. The GGA optimized geometries of a number of large clusters will be given

B-CLL cells acquire APC- and CTL-like phenotypic characteristics after stimulation with CpG ODN and IL-21

Science.gov (United States)

Hagn, Magdalena; Blackwell, Sue E.; Beyer, Thamara; Ebel, Verena; Fabricius, Dorit; Lindner, Stefanie; Stilgenbauer, Stefan; Simmet, Thomas; Tam, Constantine; Neeson, Paul; Trapani, Joseph A.; Schrezenmeier, Hubert; Weiner, George J.

2014-01-01

CpG oligodeoxynucleotides (CpG) and IL-21 are two promising agents for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). Recently, we reported that the combination of CpG and IL-21 (CpG/IL-21) can induce granzyme B (GrB)-dependent apoptosis in B-CLL cells. Here, we demonstrate that treatment of B-CLL cells with CpG and IL-21 results in the development of antigen-presenting cell (APC)-like cells with cytotoxic features. These properties eventually give rise to B-CLL cell apoptosis, independently of their cytogenetic phenotype, whereas normal B-cell survival is not negatively affected by CpG/IL-21. APC- and CTL-typical molecules found to be up-regulated in CpG/IL-21-stimulated B-CLL cells include GrB, perforin, T-bet, monokine-induced by IFN-γ and IFN-γ-inducible protein 10 (IP-10), as well as molecules important for cell adhesion, antigen cross-presentation and costimulation. Also induced are molecules involved in GrB induction, trafficking and processing, whereas the GrB inhibitor Serpin B9 [formerly proteinase inhibitor-9 (PI-9)] is down-modulated by CpG/IL-21. In conclusion, CpG/IL-21-stimulated B-CLL cells acquire features that are reminiscent of killer dendritic cells, and which result in enhanced immunogenicity, cytotoxicity and apoptosis. Our results provide novel insights into the aberrant immune state of B-CLL cells and may establish a basis for the development of an innovative cellular vaccination approach in B-CLL. PMID:24497611

Determination of spectral, structural and energetic properties of small lithium clusters, within the density functional theory formalism

International Nuclear Information System (INIS)

Gardet, G.

1995-01-01

A systematic study of small lithium clusters (with size less than 19), within the Density Functional Theory (DFT) formalism is presented. We examine structural properties of the so called local level of approximation. For clusters with size smaller than 8, the conformations are well known from ab initio calculations and are found here at much lower computational cost, with only small differences. For bigger clusters, two growth pattern have been used, based upon the increase of the number of pentagonal subunits in the clusters by absorption of one or two Li atoms. Several new stable structures are proposed. Then DFT gradient-corrected functionals have been used for relative stability determination of these clusters. Ionisation potentials and binding energies are also investigated in regard to clusters size and geometry. Calculations of excited states of lithium clusters (with size less than 9) have been performed within two different approaches. Using a set of Kohn-Sham orbitals to construct wave functions, oscillator strengths calculation of the electric dipole transitions is performed. Transition energies, oscillator strengths and optical absorption presented here are generally in reasonable agreement with the experimental data and the Configuration Interaction calculations. (author)

Diametrical clustering for identifying anti-correlated gene clusters.

Science.gov (United States)

Dhillon, Inderjit S; Marcotte, Edward M; Roshan, Usman

2003-09-01

Clustering genes based upon their expression patterns allows us to predict gene function. Most existing clustering algorithms cluster genes together when their expression patterns show high positive correlation. However, it has been observed that genes whose expression patterns are strongly anti-correlated can also be functionally similar. Biologically, this is not unintuitive-genes responding to the same stimuli, regardless of the nature of the response, are more likely to operate in the same pathways. We present a new diametrical clustering algorithm that explicitly identifies anti-correlated clusters of genes. Our algorithm proceeds by iteratively (i). re-partitioning the genes and (ii). computing the dominant singular vector of each gene cluster; each singular vector serving as the prototype of a 'diametric' cluster. We empirically show the effectiveness of the algorithm in identifying diametrical or anti-correlated clusters. Testing the algorithm on yeast cell cycle data, fibroblast gene expression data, and DNA microarray data from yeast mutants reveals that opposed cellular pathways can be discovered with this method. We present systems whose mRNA expression patterns, and likely their functions, oppose the yeast ribosome and proteosome, along with evidence for the inverse transcriptional regulation of a number of cellular systems.

Defining functioning levels in patients with schizophrenia: A combination of a novel clustering method and brain SPECT analysis.

Science.gov (United States)

Catherine, Faget-Agius; Aurélie, Vincenti; Eric, Guedj; Pierre, Michel; Raphaëlle, Richieri; Marine, Alessandrini; Pascal, Auquier; Christophe, Lançon; Laurent, Boyer

2017-12-30

This study aims to define functioning levels of patients with schizophrenia by using a method of interpretable clustering based on a specific functioning scale, the Functional Remission Of General Schizophrenia (FROGS) scale, and to test their validity regarding clinical and neuroimaging characterization. In this observational study, patients with schizophrenia have been classified using a hierarchical top-down method called clustering using unsupervised binary trees (CUBT). Socio-demographic, clinical, and neuroimaging SPECT perfusion data were compared between the different clusters to ensure their clinical relevance. A total of 242 patients were analyzed. A four-group functioning level structure has been identified: 54 are classified as "minimal", 81 as "low", 64 as "moderate", and 43 as "high". The clustering shows satisfactory statistical properties, including reproducibility and discriminancy. The 4 clusters consistently differentiate patients. "High" functioning level patients reported significantly the lowest scores on the PANSS and the CDSS, and the highest scores on the GAF, the MARS and S-QoL 18. Functioning levels were significantly associated with cerebral perfusion of two relevant areas: the left inferior parietal cortex and the anterior cingulate. Our study provides relevant functioning levels in schizophrenia, and may enhance the use of functioning scale. Copyright © 2017 Elsevier B.V. All rights reserved.

MPT-51/CpG DNA vaccine protects mice against Mycobacterium tuberculosis.

Science.gov (United States)

Silva, Bruna Daniella de Souza; da Silva, Ediane Batista; do Nascimento, Ivan Pereira; Dos Reis, Michelle Cristina Guerreiro; Kipnis, André; Junqueira-Kipnis, Ana Paula

2009-07-16

Tuberculosis (TB) is a severe infectious disease that kills approximately two million people worldwide every year. Because BCG protection is variable and does not protects adults, there is a great need for a new vaccine against TB that does not represent a risk for immunocompromised patients and that is also capable of protecting adult individuals. MPT-51 is a protein found in the genome of mycobacteria and binds to the fibronectin of the extracellular matrix, which may have a role in host tissue attachment and virulence. In order to test the usefulness of MPT-51 as a subunit vaccine, BALB/c were vaccinated and challenged with Mycobacterium tuberculosis. The infection of BALB/c with M. tuberculosis increased the number of IFN-gamma(+) T lymphocytes specific to MPT-51 in the spleen and lungs. Inoculation with rMPT-51/FIA and with rMPT-51/CpG DNA in non-infected BALB/c increased the amounts of IFN-gamma(+) T lymphocytes. Inoculation with rMPT-51/FIA also induced a humoral response specific to MPT-51. CFU counts of lung tissues done 60 days after infection showed a reduction of about 2 log in the bacteria load in the group of animals inoculated with rMPT-51/CpG DNA. These results make MPT-51 a valuable component to be further evaluated in the development of other subunit vaccines.

The evolution of the global stellar mass function of star clusters: an analytic description

NARCIS (Netherlands)

Lamers, H.J.G.L.M.; Baumgardt, H.; Gieles, M.

2013-01-01

The evolution of the global stellar mass function of star clusters is studied based on a large set of N-body simulations of clusters with a range of initial masses, initial concentrations, in circular or elliptical orbits in different tidal environments. Models with and without initial mass

Dyadic Green's function of a cluster of spheres.

Science.gov (United States)

Moneda, Angela P; Chrissoulidis, Dimitrios P

2007-11-01

The electric dyadic Green's function (dGf) of a cluster of spheres is obtained by application of the superposition principle, dyadic algebra, and the indirect mode-matching method. The analysis results in a set of linear equations for the unknown, vector, wave amplitudes of the dGf; that set is solved by truncation and matrix inversion. The theory is exact in the sense that no simplifying assumptions are made in the analytical steps leading to the dGf, and it is general in the sense that any number, position, size and electrical properties can be considered for the spheres that cluster together. The point source can be anywhere, even within one of the spheres. Energy conservation, reciprocity, and other tests prove that this solution is correct. Numerical results are presented for an electric Hertz dipole radiating in the presence of an array of rexolite spheres, which manifests lensing and beam-forming capabilities.

Identification of alterations associated with age in the clustering structure of functional brain networks.

Science.gov (United States)

Guzman, Grover E C; Sato, Joao R; Vidal, Maciel C; Fujita, Andre

2018-01-01

Initial studies using resting-state functional magnetic resonance imaging on the trajectories of the brain network from childhood to adulthood found evidence of functional integration and segregation over time. The comprehension of how healthy individuals' functional integration and segregation occur is crucial to enhance our understanding of possible deviations that may lead to brain disorders. Recent approaches have focused on the framework wherein the functional brain network is organized into spatially distributed modules that have been associated with specific cognitive functions. Here, we tested the hypothesis that the clustering structure of brain networks evolves during development. To address this hypothesis, we defined a measure of how well a brain region is clustered (network fitness index), and developed a method to evaluate its association with age. Then, we applied this method to a functional magnetic resonance imaging data set composed of 397 males under 31 years of age collected as part of the Autism Brain Imaging Data Exchange Consortium. As results, we identified two brain regions for which the clustering change over time, namely, the left middle temporal gyrus and the left putamen. Since the network fitness index is associated with both integration and segregation, our finding suggests that the identified brain region plays a role in the development of brain systems.

A theoretical study of lithium-doped gallium clusters by density functional theory

Energy Technology Data Exchange (ETDEWEB)

Sentuerk, Suekrue; Ekincioglu, Yavuz [Dumlupinar Univ., Kutahya (Turkey). Dept. of Physics

2012-05-15

The geometrical structures, stabilities, and electronic properties of Ga{sub n}Li (n = 1-13) clusters were investigated within the density functional theory (DFT). The impurity lithium atom enhances the stability of Ga{sub n}Li (n = 1-13) clusters, especially Ga{sub n}Li (n = 9-13) compared to Ga{sub n} (n = 9-14), that is at either apex position or side position. The dissociation energy, second-order energy differences, and the energy gaps between highest occupied and lowest unoccupied molecular orbital (HOMO-LUMO) indicate that the Ga{sub 7}Li, Ga{sub 9}Li, and Ga{sub 11}Li clusters are more stable within the studied cluster range. Moreover, the variation of the average bond length of Ga - Li is due to the surface effect, and the binding strength increases resulting from the increase of charge amount. (orig.)

A cross-study analysis of prenatal exposures to environmental contaminants and the epigenome: support for stress-responsive transcription factor occupancy as a mediator of gene-specific CpG methylation patterning

Science.gov (United States)

Martin, Elizabeth M.; Fry, Rebecca C.

2016-01-01

Abstract A biological mechanism by which exposure to environmental contaminants results in gene-specific CpG methylation patterning is currently unknown. We hypothesize that gene-specific CpG methylation is related to environmentally perturbed transcription factor occupancy. To test this hypothesis, a database of 396 genes with altered CpG methylation either in cord blood leukocytes or placental tissue was compiled from 14 studies representing assessments of six environmental contaminants. Subsequently, an in silico approach was used to identify transcription factor binding sites enriched among the genes with altered CpG methylation in relationship to the suite of environmental contaminants. For each study, the sequences of the promoter regions (representing −1000 to +500 bp from the transcription start site) of all genes with altered CpG methylation were analyzed for enrichment of transcription factor binding sites. Binding sites for a total of 56 unique transcription factors were identified to be enriched within the promoter regions of the genes. Binding sites for the Kidney-Enriched Krupple-like Factor 15, a known responder to endogenous stress, were enriched ( P  contaminants. These data support the transcription factor occupancy theory as a potential mechanism underlying environmentally-induced gene-specific CpG methylation. PMID:27066266

Filling- and interaction-driven Mott transition. Quantum cluster calculations within self-energy-functional theory

International Nuclear Information System (INIS)

Balzer, Matthias

2008-01-01

The central goal of this thesis is the examination of strongly correlated electron systems on the basis of the two-dimensional Hubbard model. We analyze how the properties of the Mott insulator change upon doping and with interaction strength. The numerical evaluation is done using quantum cluster approximations, which allow for a thermodynamically consistent description of the ground state properties. The framework of self-energy-functional theory offers great flexibility for the construction of cluster approximations. A detailed analysis sheds light on the quality and the convergence properties of different cluster approximations within the self-energy-functional theory. We use the one-dimensional Hubbard model for these examinations and compare our results with the exact solution. In two dimensions the ground state of the particle-hole symmetric model at half-filling is an antiferromagnetic insulator, independent of the interaction strength. The inclusion of short-range spatial correlations by our cluster approach leads to a considerable improvement of the antiferromagnetic order parameter as compared to dynamical mean-field theory. In the paramagnetic phase we furthermore observe a metal-insulator transition as a function of the interaction strength, which qualitatively differs from the pure mean-field scenario. Starting from the antiferromagnetic Mott insulator a filling-controlled metal-insulator transition in a paramagnetic metallic phase can be observed. Depending on the cluster approximation used an antiferromagnetic metallic phase may occur at first. In addition to long-range antiferromagnetic order, we also considered superconductivity in our calculations. The superconducting order parameter as a function of doping is in good agreement with other numerical methods, as well as with experimental results. (orig.)

Functional Clustering of the Human Inferior Parietal Lobule by Whole-Brain Connectivity Mapping of Resting-State Functional Magnetic Resonance Imaging Signals

Science.gov (United States)

Li, Chiang-Shan R.

2014-01-01

Abstract The human inferior parietal lobule (IPL) comprised the lateral bank of the intraparietal sulcus, angular gyrus, and supramarginal gyrus, defined on the basis of anatomical landmarks and cytoarchitectural organization of neurons. However, it is not clear as to whether the three areas represent functional subregions within the IPL. For instance, imaging studies frequently identified clusters of activities that cut across areal boundaries. Here, we used resting-state functional magnetic resonance imaging (fMRI) data to examine how individual voxels within the IPL are best clustered according to their connectivity to the whole brain. The results identified a best estimate of seven clusters that are hierarchically arranged as the anterior, middle, and posterior subregions. The anterior, middle, and posterior IPL are each significantly connected to the somatomotor areas, superior/middle/inferior frontal gyri, and regions of the default mode network. This functional segregation is supported by recent cytoarchitechtonics and tractography studies. IPL showed hemispheric differences in connectivity that accord with a predominantly left parietal role in tool use and language processing and a right parietal role in spatial attention and mathematical cognition. The functional clusters may also provide a more parsimonious and perhaps even accurate account of regional activations of the IPL during a variety of cognitive challenges, as reported in earlier fMRI studies. PMID:24308753

Gene Silencing Triggers Polycomb Repressive Complex 2 Recruitment to CpG Islands Genome Wide

DEFF Research Database (Denmark)

Riising, Eva Madi; Vacher-Comet, Itys; Leblanc, Benjamin Olivier

2014-01-01

-wide ectopic PRC2 recruitment to endogenous PcG target genes found in other tissues. PRC2 binding analysis shows that it is restricted to nucleosome-free CpG islands (CGIs) of untranscribed genes. Our results show that it is the transcriptional state that governs PRC2 binding, and we propose that it binds...

Density functional calculations on 13-atom Pd12M (M = Sc—Ni) bimetallic clusters

International Nuclear Information System (INIS)

Tang Chun-Mei; Chen Sheng-Wei; Zhu Wei-Hua; Tao Cheng-Jun; Zhang Ai-Mei; Gong Jiang-Feng; Zou Hua; Liu Ming-Yi; Zhu Feng

2012-01-01

The geometric structures, electronic and magnetic properties of the 3d transition metal doped clusters Pd 12 M (M = Sc—Ni) are studied using the semi-core pseudopots density functional theory. The groundstate geometric structure of the Pd 12 M cluster is probably of pseudoicosahedron. The I h -Pd 12 M cluster has the most thermodynamic stability in five different symmetric isomers. The energy gap shows that Pd 12 M cluster is partly metallic. Both the absolutely predominant metal bond and very weak covalent bond might exist in the Pd 12 M cluster. The magnetic moment of Pd 12 M varies from 0 to 5 μ B , implying that it has a potential application in new nanomaterials with tunable magnetic properties

Machine learning etudes in astrophysics: selection functions for mock cluster catalogs

Energy Technology Data Exchange (ETDEWEB)

Hajian, Amir; Alvarez, Marcelo A.; Bond, J. Richard, E-mail: ahajian@cita.utoronto.ca, E-mail: malvarez@cita.utoronto.ca, E-mail: bond@cita.utoronto.ca [Canadian Institute for Theoretical Astrophysics, University of Toronto, Toronto, ON M5S 3H8 (Canada)

2015-01-01

Making mock simulated catalogs is an important component of astrophysical data analysis. Selection criteria for observed astronomical objects are often too complicated to be derived from first principles. However the existence of an observed group of objects is a well-suited problem for machine learning classification. In this paper we use one-class classifiers to learn the properties of an observed catalog of clusters of galaxies from ROSAT and to pick clusters from mock simulations that resemble the observed ROSAT catalog. We show how this method can be used to study the cross-correlations of thermal Sunya'ev-Zeldovich signals with number density maps of X-ray selected cluster catalogs. The method reduces the bias due to hand-tuning the selection function and is readily scalable to large catalogs with a high-dimensional space of astrophysical features.

Machine learning etudes in astrophysics: selection functions for mock cluster catalogs

International Nuclear Information System (INIS)

Hajian, Amir; Alvarez, Marcelo A.; Bond, J. Richard

2015-01-01

Making mock simulated catalogs is an important component of astrophysical data analysis. Selection criteria for observed astronomical objects are often too complicated to be derived from first principles. However the existence of an observed group of objects is a well-suited problem for machine learning classification. In this paper we use one-class classifiers to learn the properties of an observed catalog of clusters of galaxies from ROSAT and to pick clusters from mock simulations that resemble the observed ROSAT catalog. We show how this method can be used to study the cross-correlations of thermal Sunya'ev-Zeldovich signals with number density maps of X-ray selected cluster catalogs. The method reduces the bias due to hand-tuning the selection function and is readily scalable to large catalogs with a high-dimensional space of astrophysical features

Human Vav1 expression in hematopoietic and cancer cell lines is regulated by c-Myb and by CpG methylation.

Directory of Open Access Journals (Sweden)

Lena Ilan

Full Text Available Vav1 is a signal transducer protein that functions as a guanine nucleotide exchange factor for the Rho/Rac GTPases in the hematopoietic system where it is exclusively expressed. Recently, Vav1 was shown to be involved in several human malignancies including neuroblastoma, lung cancer, and pancreatic ductal adenocarcinoma (PDA. Although some factors that affect vav1 expression are known, neither the physiological nor pathological regulation of vav1 expression is completely understood. We demonstrate herein that mutations in putative transcription factor binding sites at the vav1 promoter affect its transcription in cells of different histological origin. Among these sites is a consensus site for c-Myb, a hematopoietic-specific transcription factor that is also found in Vav1-expressing lung cancer cell lines. Depletion of c-Myb using siRNA led to a dramatic reduction in vav1 expression in these cells. Consistent with this, co-transfection of c-Myb activated transcription of a vav1 promoter-luciferase reporter gene construct in lung cancer cells devoid of Vav1 expression. Together, these results indicate that c-Myb is involved in vav1 expression in lung cancer cells. We also explored the methylation status of the vav1 promoter. Bisulfite sequencing revealed that the vav1 promoter was completely unmethylated in human lymphocytes, but methylated to various degrees in tissues that do not normally express vav1. The vav1 promoter does not contain CpG islands in proximity to the transcription start site; however, we demonstrated that methylation of a CpG dinucleotide at a consensus Sp1 binding site in the vav1 promoter interferes with protein binding in vitro. Our data identify two regulatory mechanisms for vav1 expression: binding of c-Myb and CpG methylation of 5' regulatory sequences. Mutation of other putative transcription factor binding sites suggests that additional factors regulate vav1 expression as well.

Gender differences in associations between DSM-5 posttraumatic stress disorder symptom clusters and functional impairment in war veterans.

Science.gov (United States)

Meyer, Eric C; Konecky, Brian; Kimbrel, Nathan A; DeBeer, Bryann B; Marx, Brian P; Schumm, Jeremiah; Penk, Walter E; Gulliver, Suzy Bird; Morissette, Sandra B

2018-05-01

Understanding the links between posttraumatic stress disorder (PTSD) symptoms and functional impairment is essential for assisting veterans in transitioning to civilian life. Moreover, there may be differences between men and women in the relationships between PTSD symptoms and functional impairment. However, no prior studies have examined the links between functional impairment and the revised symptom clusters as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5; American Psychiatric Association, 2013) or whether the associations between PTSD symptom clusters and functional impairment differ by gender. We examined the associations between the DSM-5 PTSD symptom clusters and functional impairment in 252 trauma-exposed Iraq and Afghanistan war veterans (79 females). Regression analyses included demographic factors and exposure to both combat and military sexual trauma as covariates. In the total sample, both the intrusions cluster (β = .18, p = .045) and the negative alterations in cognition and mood cluster (β = .45, p < .001) were associated with global functional impairment. Among male veterans, global functional impairment was associated only with negative alterations in cognition and mood (β = .52, p < .001). However, by contrast, among female veterans, only marked alterations in arousal and reactivity were associated with global functional impairment (β = .35, p = .027). These findings suggest that there may be important gender differences with respect to the relationship between PTSD symptoms and functional impairment. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

High CpG island methylation ofp16 gene and loss of p16 protein ...

Indian Academy of Sciences (India)

Navya

employed to detect CpG island methylation in p16 promoter region and ... of Fallot;p16 gene;p16 protein;CpG islands;Methylation;Promoter regions ..... Our findings that p16 has a role in heart development is ... Asian Pac J Cancer Prev 15, 75-84. .... phenotype in colorectal cancer using a large population-based sample.

Benchmark CCSD(T) and DFT study of binding energies in Be7 - 12: in search of reliable DFT functional for beryllium clusters

Science.gov (United States)

Labanc, Daniel; Šulka, Martin; Pitoňák, Michal; Černušák, Ivan; Urban, Miroslav; Neogrády, Pavel

2018-05-01

We present a computational study of the stability of small homonuclear beryllium clusters Be7 - 12 in singlet electronic states. Our predictions are based on highly correlated CCSD(T) coupled cluster calculations. Basis set convergence towards the complete basis set limit as well as the role of the 1s core electron correlation are carefully examined. Our CCSD(T) data for binding energies of Be7 - 12 clusters serve as a benchmark for performance assessment of several density functional theory (DFT) methods frequently used in beryllium cluster chemistry. We observe that, from Be10 clusters on, the deviation from CCSD(T) benchmarks is stable with respect to size, and fluctuating within 0.02 eV error bar for most examined functionals. This opens up the possibility of scaling the DFT binding energies for large Be clusters using CCSD(T) benchmark values for smaller clusters. We also tried to find analogies between the performance of DFT functionals for Be clusters and for the valence-isoelectronic Mg clusters investigated recently in Truhlar's group. We conclude that it is difficult to find DFT functionals that perform reasonably well for both beryllium and magnesium clusters. Out of 12 functionals examined, only the M06-2X functional gives reasonably accurate and balanced binding energies for both Be and Mg clusters.

CytoCluster: A Cytoscape Plugin for Cluster Analysis and Visualization of Biological Networks.

Science.gov (United States)

Li, Min; Li, Dongyan; Tang, Yu; Wu, Fangxiang; Wang, Jianxin

2017-08-31

Nowadays, cluster analysis of biological networks has become one of the most important approaches to identifying functional modules as well as predicting protein complexes and network biomarkers. Furthermore, the visualization of clustering results is crucial to display the structure of biological networks. Here we present CytoCluster, a cytoscape plugin integrating six clustering algorithms, HC-PIN (Hierarchical Clustering algorithm in Protein Interaction Networks), OH-PIN (identifying Overlapping and Hierarchical modules in Protein Interaction Networks), IPCA (Identifying Protein Complex Algorithm), ClusterONE (Clustering with Overlapping Neighborhood Expansion), DCU (Detecting Complexes based on Uncertain graph model), IPC-MCE (Identifying Protein Complexes based on Maximal Complex Extension), and BinGO (the Biological networks Gene Ontology) function. Users can select different clustering algorithms according to their requirements. The main function of these six clustering algorithms is to detect protein complexes or functional modules. In addition, BinGO is used to determine which Gene Ontology (GO) categories are statistically overrepresented in a set of genes or a subgraph of a biological network. CytoCluster can be easily expanded, so that more clustering algorithms and functions can be added to this plugin. Since it was created in July 2013, CytoCluster has been downloaded more than 9700 times in the Cytoscape App store and has already been applied to the analysis of different biological networks. CytoCluster is available from http://apps.cytoscape.org/apps/cytocluster.

Interplay between experiments and calculations for organometallic clusters and caged clusters

International Nuclear Information System (INIS)

Nakajima, Atsushi

2015-01-01

Clusters consisting of 10-1000 atoms exhibit size-dependent electronic and geometric properties. In particular, composite clusters consisting of several elements and/or components provide a promising way for a bottom-up approach for designing functional advanced materials, because the functionality of the composite clusters can be optimized not only by the cluster size but also by their compositions. In the formation of composite clusters, their geometric symmetry and dimensionality are emphasized to control the physical and chemical properties, because selective and anisotropic enhancements for optical, chemical, and magnetic properties can be expected. Organometallic clusters and caged clusters are demonstrated as a representative example of designing the functionality of the composite clusters. Organometallic vanadium-benzene forms a one dimensional sandwich structure showing ferromagnetic behaviors and anomalously large HOMO-LUMO gap differences of two spin orbitals, which can be regarded as spin-filter components for cluster-based spintronic devices. Caged clusters of aluminum (Al) are well stabilized both geometrically and electronically at Al 12 X, behaving as a “superatom”

THE REST-FRAME OPTICAL LUMINOSITY FUNCTION OF CLUSTER GALAXIES AT z < 0.8 AND THE ASSEMBLY OF THE CLUSTER RED SEQUENCE

International Nuclear Information System (INIS)

Rudnick, Gregory; Von der Linden, Anja; De Lucia, Gabriella; White, Simon; Pello, Roser; Aragon-Salamanca, Alfonso; Marchesini, Danilo; Clowe, Douglas; Halliday, Claire; Jablonka, Pascale; Milvang-Jensen, Bo; Poggianti, Bianca; Saglia, Roberto; Simard, Luc; Zaritsky, Dennis

2009-01-01

We present the rest-frame optical luminosity function (LF) of red-sequence galaxies in 16 clusters at 0.4 < z < 0.8 drawn from the ESO Distant Cluster Survey (EDisCS). We compare our clusters to an analogous sample from the Sloan Digital Sky Survey (SDSS) and match the EDisCS clusters to their most likely descendants. We measure all LFs down to M ∼ M * + (2.5-3.5). At z < 0.8, the bright end of the LF is consistent with passive evolution but there is a significant buildup of the faint end of the red sequence toward lower redshift. There is a weak dependence of the LF on cluster velocity dispersion for EDisCS but no such dependence for the SDSS clusters. We find tentative evidence that red-sequence galaxies brighter than a threshold magnitude are already in place, and that this threshold evolves to fainter magnitudes toward lower redshifts. We compare the EDisCS LFs with the LF of coeval red-sequence galaxies in the field and find that the bright end of the LFs agree. However, relative to the number of bright red galaxies, the field has more faint red galaxies than clusters at 0.6 < z < 0.8 but fewer at 0.4 < z < 0.6, implying differential evolution. We compare the total light in the EDisCS cluster red sequences to the total red-sequence light in our SDSS cluster sample. Clusters at 0.4 < z < 0.8 must increase their luminosity on the red sequence (and therefore stellar mass in red galaxies) by a factor of 1-3 by z = 0. The necessary processes that add mass to the red sequence in clusters predict local clusters that are overluminous as compared to those observed in the SDSS. The predicted cluster luminosities can be reconciled with observed local cluster luminosities by combining multiple previously known effects.

Cluster evolution

International Nuclear Information System (INIS)

Schaeffer, R.

1987-01-01

The galaxy and cluster luminosity functions are constructed from a model of the mass distribution based on hierarchical clustering at an epoch where the matter distribution is non-linear. These luminosity functions are seen to reproduce the present distribution of objects as can be inferred from the observations. They can be used to deduce the redshift dependence of the cluster distribution and to extrapolate the observations towards the past. The predicted evolution of the cluster distribution is quite strong, although somewhat less rapid than predicted by the linear theory

The Seven Sisters DANCe. I. Empirical isochrones, luminosity, and mass functions of the Pleiades cluster

Science.gov (United States)

Bouy, H.; Bertin, E.; Sarro, L. M.; Barrado, D.; Moraux, E.; Bouvier, J.; Cuillandre, J.-C.; Berihuete, A.; Olivares, J.; Beletsky, Y.

2015-05-01

Context. The DANCe survey provides photometric and astrometric (position and proper motion) measurements for approximately 2 million unique sources in a region encompassing ~80 deg2 centered on the Pleiades cluster. Aims: We aim at deriving a complete census of the Pleiades and measure the mass and luminosity functions of the cluster. Methods: Using the probabilistic selection method previously described, we identified high probability members in the DANCe (i ≥ 14 mag) and Tycho-2 (V ≲ 12 mag) catalogues and studied the properties of the cluster over the corresponding luminosity range. Results: We find a total of 2109 high-probability members, of which 812 are new, making it the most extensive and complete census of the cluster to date. The luminosity and mass functions of the cluster are computed from the most massive members down to ~0.025 M⊙. The size, sensitivity, and quality of the sample result in the most precise luminosity and mass functions observed to date for a cluster. Conclusions: Our census supersedes previous studies of the Pleiades cluster populations, in terms of both sensitivity and accuracy. Based on service observations made with the William Herschel Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias.Table 1 and Appendices are available in electronic form at http://www.aanda.orgDANCe catalogs (Tables 6 and 7) and full Tables 2-5 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/577/A148

High CpG island methylation of p16 gene and loss of p16 protein

Indian Academy of Sciences (India)

Methylation-specific polymerase chain reaction (MSP) was employed to detect CpG island methylation in p16 promoter region andWestern blotting was used to detect p16 expression of all subjects. Real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) was performed to test p16 mRNA expression.

Covalent functionalization of octagraphene with magnetic octahedral B6- and non-planar C6- clusters

Science.gov (United States)

Chigo-Anota, E.; Cárdenas-Jirón, G.; Salazar Villanueva, M.; Bautista Hernández, A.; Castro, M.

2017-10-01

The interaction between the magnetic boron octahedral (B6-) and non-planar (C6-) carbon clusters with semimetal nano-sheet of octa-graphene (C64H24) in the gas phase is studied by means of DFT calculations. These results reveal that non-planar-1 (anion) carbon cluster exhibits structural stability, low chemical reactivity, magnetic (1.0 magneton bohr) and semiconductor behavior. On the other hand, there is chemisorption phenomena when the stable B6- and C6- clusters are absorbed on octa-graphene nanosheets. Such absorption generates high polarity and the low-reactivity remains as on the individual pristine cases. Electronic charge transference occurs from the clusters toward the nanosheets, producing a reduction of the work function for the complexes and also induces a magnetic behavior on the functionalized sheets. The quantum descriptors obtained for these systems reveal that they are feasible candidates for the design of molecular circuits, magnetic devices, and nano-vehicles for drug delivery.

A novel method to quantify local CpG methylation density by regional methylation elongation assay on microarray

Directory of Open Access Journals (Sweden)

Qiao Yingjuan

2008-01-01

Full Text Available Abstract Background DNA methylation based techniques are important tools in both clinical diagnostics and therapeutics. But most of these methods only analyze a few CpG sites in a target region. Indeed, difference of site-specific methylation may also lead to a change of methylation density in many cases, and it has been found that the density of methylation is more important than methylation of single CpG site for gene silencing. Results We have developed a novel approach for quantitative analysis of CpG methylation density on the basis of microarray-based hybridization and incorporation of Cy5-dCTP into the Cy3 labeled target DNA by using Taq DNA Polymerase on microarray. The quantification is achieved by measuring Cy5/Cy3 signal ratio which is proportional to methylation density. This methylation-sensitive technique, termed RMEAM (regional methylation elongation assay on microarray, provides several advantages over existing methods used for methylation analysis. It can determine an exact methylation density of the given region, and has potential of high throughput. We demonstrate a use of this method in determining the methylation density of the promoter region of the tumor-related gene MLH1, TERT and MGMT in colorectal carcinoma patients. Conclusion This technique allows for quantitative analysis of regional methylation density, which is the representative of all allelic methylation patterns in the sample. The results show that this technique has the characteristics of simplicity, rapidness, specificity and high-throughput.

Which Density Functional Should Be Used to Describe Protonated Water Clusters?

Science.gov (United States)

Shi, Ruili; Huang, Xiaoming; Su, Yan; Lu, Hai-Gang; Li, Si-Dian; Tang, Lingli; Zhao, Jijun

2017-04-27

Protonated water cluster is one of the most important hydrogen-bond network systems. Finding an appropriate DFT method to study the properties of protonated water clusters can substantially improve the economy in computational resources without sacrificing the accuracy compared to high-level methods. Using high-level MP2 and CCSD(T) methods as well as experimental results as benchmark, we systematically examined the effect of seven exchange-correlation GGA functionals (with BLYP, B3LYP, X3LYP, PBE0, PBE1W, M05-2X, and B97-D parametrizations) in describing the geometric parameters, interaction energies, dipole moments, and vibrational properties of protonated water clusters H + (H 2 O) 2-9,12 . The overall performance of all these functionals is acceptable, and each of them has its advantage in certain aspects. X3LYP is the best to describe the interaction energies, and PBE0 and M05-2X are also recommended to investigate interaction energies. PBE0 gives the best anharmonic frequencies, followed by PBE1W, B97-D and BLYP methods. PBE1W, B3LYP, B97-D, and X3LYP can yield better geometries. The capability of B97-D to distinguish the relative energies between isomers is the best among all the seven methods, followed by M05-2X and PBE0.

Clusters of Insomnia Disorder: An Exploratory Cluster Analysis of Objective Sleep Parameters Reveals Differences in Neurocognitive Functioning, Quantitative EEG, and Heart Rate Variability

Science.gov (United States)

Miller, Christopher B.; Bartlett, Delwyn J.; Mullins, Anna E.; Dodds, Kirsty L.; Gordon, Christopher J.; Kyle, Simon D.; Kim, Jong Won; D'Rozario, Angela L.; Lee, Rico S.C.; Comas, Maria; Marshall, Nathaniel S.; Yee, Brendon J.; Espie, Colin A.; Grunstein, Ronald R.

2016-01-01

Study Objectives: To empirically derive and evaluate potential clusters of Insomnia Disorder through cluster analysis from polysomnography (PSG). We hypothesized that clusters would differ on neurocognitive performance, sleep-onset measures of quantitative (q)-EEG and heart rate variability (HRV). Methods: Research volunteers with Insomnia Disorder (DSM-5) completed a neurocognitive assessment and overnight PSG measures of total sleep time (TST), wake time after sleep onset (WASO), and sleep onset latency (SOL) were used to determine clusters. Results: From 96 volunteers with Insomnia Disorder, cluster analysis derived at least two clusters from objective sleep parameters: Insomnia with normal objective sleep duration (I-NSD: n = 53) and Insomnia with short sleep duration (I-SSD: n = 43). At sleep onset, differences in HRV between I-NSD and I-SSD clusters suggest attenuated parasympathetic activity in I-SSD (P insomnia clusters derived from cluster analysis differ in sleep onset HRV. Preliminary data suggest evidence for three clusters in insomnia with differences for sustained attention and sleep-onset q-EEG. Clinical Trial Registration: Insomnia 100 sleep study: Australia New Zealand Clinical Trials Registry (ANZCTR) identification number 12612000049875. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=347742. Citation: Miller CB, Bartlett DJ, Mullins AE, Dodds KL, Gordon CJ, Kyle SD, Kim JW, D'Rozario AL, Lee RS, Comas M, Marshall NS, Yee BJ, Espie CA, Grunstein RR. Clusters of Insomnia Disorder: an exploratory cluster analysis of objective sleep parameters reveals differences in neurocognitive functioning, quantitative EEG, and heart rate variability. SLEEP 2016;39(11):1993–2004. PMID:27568796

One- and two-particle correlation functions in the dynamical quantum cluster approach

International Nuclear Information System (INIS)

Hochkeppel, Stephan

2008-01-01

This thesis is dedicated to a theoretical study of the 1-band Hubbard model in the strong coupling limit. The investigation is based on the Dynamical Cluster Approximation (DCA) which systematically restores non-local corrections to the Dynamical Mean Field approximation (DMFA). The DCA is formulated in momentum space and is characterised by a patching of the Brillouin zone where momentum conservation is only recovered between two patches. The approximation works well if k-space correlation functions show a weak momentum dependence. In order to study the temperature and doping dependence of the spin- and charge excitation spectra, we explicitly extend the Dynamical Cluster Approximation to two-particle response functions. The full irreducible two-particle vertex with three momenta and frequencies is approximated by an effective vertex dependent on the momentum and frequency of the spin and/or charge excitations. The effective vertex is calculated by using the Quantum Monte Carlo method on the finite cluster whereas the analytical continuation of dynamical quantities is performed by a stochastic version of the maximum entropy method. A comparison with high temperature auxiliary field quantum Monte Carlo data serves as a benchmark for our approach to two-particle correlation functions. Our method can reproduce basic characteristics of the spin- and charge excitation spectrum. Near and beyond optimal doping, our results provide a consistent overall picture of the interplay between charge, spin and single-particle excitations: a collective spin mode emerges at optimal doping and sufficiently low temperatures in the spin response spectrum and exhibits the energy scale of the magnetic exchange interaction J. Simultaneously, the low energy single-particle excitations are characterised by a coherent quasiparticle with bandwidth J. The origin of the quasiparticle can be quite well understood in a picture of a more or less antiferromagnetic ordered background in which holes

High CpG island methylation of p16 gene and loss of p16 protein ...

Indian Academy of Sciences (India)

SI-JU GAO

The study subjects consisted of 75 healthy controls and 63 ToF ... Additionally, our analysis suggested that CpG island methylation in p16 promoters in ToF ..... reduced p16 protein expression in lung cancer (Kondo et al. 2006). In this context ..... promoter methylation in gastric carcinogenesis: a meta-analysis. Mol. Biol. Rep.

Cluster size statistic and cluster mass statistic: two novel methods for identifying changes in functional connectivity between groups or conditions.

Science.gov (United States)

Ing, Alex; Schwarzbauer, Christian

2014-01-01

Functional connectivity has become an increasingly important area of research in recent years. At a typical spatial resolution, approximately 300 million connections link each voxel in the brain with every other. This pattern of connectivity is known as the functional connectome. Connectivity is often compared between experimental groups and conditions. Standard methods used to control the type 1 error rate are likely to be insensitive when comparisons are carried out across the whole connectome, due to the huge number of statistical tests involved. To address this problem, two new cluster based methods--the cluster size statistic (CSS) and cluster mass statistic (CMS)--are introduced to control the family wise error rate across all connectivity values. These methods operate within a statistical framework similar to the cluster based methods used in conventional task based fMRI. Both methods are data driven, permutation based and require minimal statistical assumptions. Here, the performance of each procedure is evaluated in a receiver operator characteristic (ROC) analysis, utilising a simulated dataset. The relative sensitivity of each method is also tested on real data: BOLD (blood oxygen level dependent) fMRI scans were carried out on twelve subjects under normal conditions and during the hypercapnic state (induced through the inhalation of 6% CO2 in 21% O2 and 73%N2). Both CSS and CMS detected significant changes in connectivity between normal and hypercapnic states. A family wise error correction carried out at the individual connection level exhibited no significant changes in connectivity.

Strand bias in complementary single-nucleotide polymorphisms of transcribed human sequences: evidence for functional effects of synonymous polymorphisms

Directory of Open Access Journals (Sweden)

Majewski Jacek

2006-08-01

Full Text Available Abstract Background Complementary single-nucleotide polymorphisms (SNPs may not be distributed equally between two DNA strands if the strands are functionally distinct, such as in transcribed genes. In introns, an excess of A↔G over the complementary C↔T substitutions had previously been found and attributed to transcription-coupled repair (TCR, demonstrating the valuable functional clues that can be obtained by studying such asymmetry. Here we studied asymmetry of human synonymous SNPs (sSNPs in the fourfold degenerate (FFD sites as compared to intronic SNPs (iSNPs. Results The identities of the ancestral bases and the direction of mutations were inferred from human-chimpanzee genomic alignment. After correction for background nucleotide composition, excess of A→G over the complementary T→C polymorphisms, which was observed previously and can be explained by TCR, was confirmed in FFD SNPs and iSNPs. However, when SNPs were separately examined according to whether they mapped to a CpG dinucleotide or not, an excess of C→T over G→A polymorphisms was found in non-CpG site FFD SNPs but was absent from iSNPs and CpG site FFD SNPs. Conclusion The genome-wide discrepancy of human FFD SNPs provides novel evidence for widespread selective pressure due to functional effects of sSNPs. The similar asymmetry pattern of FFD SNPs and iSNPs that map to a CpG can be explained by transcription-coupled mechanisms, including TCR and transcription-coupled mutation. Because of the hypermutability of CpG sites, more CpG site FFD SNPs are relatively younger and have confronted less selection effect than non-CpG FFD SNPs, which can explain the asymmetric discrepancy of CpG site FFD SNPs vs. non-CpG site FFD SNPs.

Equilibrium Structures and Absorption Spectra for SixOy Molecular Clusters using Density Functional Theory

Science.gov (United States)

2017-05-05

Naval Research Laboratory Washington, DC 20375-5320 NRL/MR/6390--17-9724 Equilibrium Structures and Absorption Spectra for SixOy Molecular Clusters...TELEPHONE NUMBER (include area code) b. ABSTRACT c. THIS PAGE 18. NUMBER OF PAGES 17. LIMITATION OF ABSTRACT Equilibrium Structures and Absorption...and electronic excited-state absorption spectra for eqilibrium structures of SixOy molecular clusters using density function theory (DFT) and time

Identification of Flood Reactivity Regions via the Functional Clustering of Hydrographs

Science.gov (United States)

Brunner, Manuela I.; Viviroli, Daniel; Furrer, Reinhard; Seibert, Jan; Favre, Anne-Catherine

2018-03-01

Flood hydrograph shapes contain valuable information on the flood-generation mechanisms of a catchment. To make good use of this information, we express flood hydrograph shapes as continuous functions using a functional data approach. We propose a clustering approach based on functional data for flood hydrograph shapes to identify a set of representative hydrograph shapes on a catchment scale and use these catchment-specific sets of representative hydrographs to establish regions of catchments with similar flood reactivity on a regional scale. We applied this approach to flood samples of 163 medium-size Swiss catchments. The results indicate that three representative hydrograph shapes sufficiently describe the hydrograph shape variability within a catchment and therefore can be used as a proxy for the flood behavior of a catchment. These catchment-specific sets of three hydrographs were used to group the catchments into three reactivity regions of similar flood behavior. These regions were not only characterized by similar hydrograph shapes and reactivity but also by event magnitudes and triggering event conditions. We envision these regions to be useful in regionalization studies, regional flood frequency analyses, and to allow for the construction of synthetic design hydrographs in ungauged catchments. The clustering approach based on functional data which establish these regions is very flexible and has the potential to be extended to other geographical regions or toward the use in climate impact studies.

Guided basin-hopping search of small boron clusters with density functional theory

Energy Technology Data Exchange (ETDEWEB)

Ng, Wei Chun; Yoon, Tiem Leong [School of Physics, Universiti Sains Malaysia, 11800 USM, Penang (Malaysia); Lim, Thong Leng [Faculty of Engineering and Technology, Multimedia University, Melacca Campus, 75450 Melaka (Malaysia)

2015-04-24

The search for the ground state structures of Boron clusters has been a difficult computational task due to the unique metalloid nature of Boron atom. Previous research works had overcome the problem in the search of the Boron ground-state structures by adding symmetry constraints prior to the process of locating the local minima in the potential energy surface (PES) of the Boron clusters. In this work, we shown that, with the deployment of a novel computational approach that incorporates density functional theory (DFT) into a guided global optimization search algorithm based on basin-hopping, it is possible to directly locate the local minima of small Boron clusters in the PES at the DFT level. The ground-state structures search algorithm as proposed in this work is initiated randomly and needs not a priori symmetry constraint artificially imposed throughout the search process. Small sized Boron clusters so obtained compare well to the results obtained by similar calculations in the literature. The electronic properties of each structures obtained are calculated within the DFT framework.

Guided basin-hopping search of small boron clusters with density functional theory

International Nuclear Information System (INIS)

Ng, Wei Chun; Yoon, Tiem Leong; Lim, Thong Leng

2015-01-01

The search for the ground state structures of Boron clusters has been a difficult computational task due to the unique metalloid nature of Boron atom. Previous research works had overcome the problem in the search of the Boron ground-state structures by adding symmetry constraints prior to the process of locating the local minima in the potential energy surface (PES) of the Boron clusters. In this work, we shown that, with the deployment of a novel computational approach that incorporates density functional theory (DFT) into a guided global optimization search algorithm based on basin-hopping, it is possible to directly locate the local minima of small Boron clusters in the PES at the DFT level. The ground-state structures search algorithm as proposed in this work is initiated randomly and needs not a priori symmetry constraint artificially imposed throughout the search process. Small sized Boron clusters so obtained compare well to the results obtained by similar calculations in the literature. The electronic properties of each structures obtained are calculated within the DFT framework

Evolution of the stellar mass function in multiple-population globular clusters

Science.gov (United States)

Vesperini, Enrico; Hong, Jongsuk; Webb, Jeremy J.; D'Antona, Franca; D'Ercole, Annibale

2018-05-01

We present the results of a survey of N-body simulations aimed at studying the effects of the long-term dynamical evolution on the stellar mass function (MF) of multiple stellar populations in globular clusters. Our simulations show that if first-(1G) and second-generation (2G) stars have the same initial MF (IMF), the global MFs of the two populations are affected similarly by dynamical evolution and no significant differences between the 1G and 2G MFs arise during the cluster's evolution. If the two populations have different IMFs, dynamical effects do not completely erase memory of the initial differences. Should observations find differences between the global 1G and 2G MFs, these would reveal the fingerprints of differences in their IMFs. Irrespective of whether the 1G and 2G populations have the same global IMF or not, dynamical effects can produce differences between the local (measured at various distances from the cluster centre) 1G and 2G MFs; these differences are a manifestation of the process of mass segregation in populations with different initial structural properties. In dynamically old and spatially mixed clusters, however, differences between the local 1G and 2G MFs can reveal differences between the 1G and 2G global MFs. In general, for clusters with any dynamical age, large differences between the local 1G and 2G MFs are more likely to be associated with differences in the global MF. Our study also reveals a dependence of the spatial mixing rate on the stellar mass, another dynamical consequence of the multiscale nature of multiple-population clusters.

A density functional study of structures and stability of SinCN clusters

International Nuclear Information System (INIS)

Gai Zhigang; Yang Li; Zhao Jie; Chu Shibo

2011-01-01

In this paper, density functional theory (DFT) B3LYP method with 6-311G * basis set has been used to investigate geometric configurations, vibrational frequencies and ground state energies of Si n CN (n = 2 ∼ 6) clusters. The energies and spin multiplicities of ground states and substable states have been discussed, respectively. Harmonic frequencies and infrared spectra intensity for these clusters are given in order to aid in the characterization of the stable structures. The results show that the zero point energy (ZPE), thermocapacity and entropies are nearly in proportion to increased n, whose average enhancement are 0.80 kcal/mol, 5.20 cal/mol · K and 12.72 cal/ mol · K, respectively. The stability of Si n CN (n = 2 ∼ 6) clusters with even n are greater than that with odd n. (authors)

PRIMUS: Galaxy clustering as a function of luminosity and color at 0.2 < z < 1

Energy Technology Data Exchange (ETDEWEB)

Skibba, Ramin A.; Smith, M. Stephen M.; Coil, Alison L.; Mendez, Alexander J. [Department of Physics, Center for Astrophysics and Space Sciences, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093 (United States); Moustakas, John [Department of Physics and Astronomy, Siena College, 515 Loudon Road, Loudonville, NY 12211 (United States); Aird, James [Department of Physics, Durham University, Durham DH1 3LE (United Kingdom); Blanton, Michael R. [Center for Cosmology and Particle Physics, Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States); Bray, Aaron D.; Eisenstein, Daniel J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Cool, Richard J. [MMT Observatory, 1540 E Second Street, University of Arizona, Tucson, AZ 85721 (United States); Wong, Kenneth C. [Steward Observatory, The University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Zhu, Guangtun, E-mail: rskibba@ucsd.edu [Department of Physics and Astronomy, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States)

2014-04-01

We present measurements of the luminosity and color-dependence of galaxy clustering at 0.2 < z < 1.0 in the Prism Multi-object Survey. We quantify the clustering with the redshift-space and projected two-point correlation functions, ξ(r{sub p} , π) and w{sub p} (r{sub p} ), using volume-limited samples constructed from a parent sample of over ∼130, 000 galaxies with robust redshifts in seven independent fields covering 9 deg{sup 2} of sky. We quantify how the scale-dependent clustering amplitude increases with increasing luminosity and redder color, with relatively small errors over large volumes. We find that red galaxies have stronger small-scale (0.1 Mpc h {sup –1} < r{sub p} < 1 Mpc h {sup –1}) clustering and steeper correlation functions compared to blue galaxies, as well as a strong color dependent clustering within the red sequence alone. We interpret our measured clustering trends in terms of galaxy bias and obtain values of b {sub gal} ≈ 0.9-2.5, quantifying how galaxies are biased tracers of dark matter depending on their luminosity and color. We also interpret the color dependence with mock catalogs, and find that the clustering of blue galaxies is nearly constant with color, while redder galaxies have stronger clustering in the one-halo term due to a higher satellite galaxy fraction. In addition, we measure the evolution of the clustering strength and bias, and we do not detect statistically significant departures from passive evolution. We argue that the luminosity- and color-environment (or halo mass) relations of galaxies have not significantly evolved since z ∼ 1. Finally, using jackknife subsampling methods, we find that sampling fluctuations are important and that the COSMOS field is generally an outlier, due to having more overdense structures than other fields; we find that 'cosmic variance' can be a significant source of uncertainty for high-redshift clustering measurements.

Self Organizing Maps to efficiently cluster and functionally interpret protein conformational ensembles

Directory of Open Access Journals (Sweden)

Fabio Stella

2013-09-01

Full Text Available An approach that combines Self-Organizing maps, hierarchical clustering and network components is presented, aimed at comparing protein conformational ensembles obtained from multiple Molecular Dynamic simulations. As a first result the original ensembles can be summarized by using only the representative conformations of the clusters obtained. In addition the network components analysis allows to discover and interpret the dynamic behavior of the conformations won by each neuron. The results showed the ability of this approach to efficiently derive a functional interpretation of the protein dynamics described by the original conformational ensemble, highlighting its potential as a support for protein engineering.

Analysis and comparison of very large metagenomes with fast clustering and functional annotation

Directory of Open Access Journals (Sweden)

Li Weizhong

2009-10-01

Full Text Available Abstract Background The remarkable advance of metagenomics presents significant new challenges in data analysis. Metagenomic datasets (metagenomes are large collections of sequencing reads from anonymous species within particular environments. Computational analyses for very large metagenomes are extremely time-consuming, and there are often many novel sequences in these metagenomes that are not fully utilized. The number of available metagenomes is rapidly increasing, so fast and efficient metagenome comparison methods are in great demand. Results The new metagenomic data analysis method Rapid Analysis of Multiple Metagenomes with a Clustering and Annotation Pipeline (RAMMCAP was developed using an ultra-fast sequence clustering algorithm, fast protein family annotation tools, and a novel statistical metagenome comparison method that employs a unique graphic interface. RAMMCAP processes extremely large datasets with only moderate computational effort. It identifies raw read clusters and protein clusters that may include novel gene families, and compares metagenomes using clusters or functional annotations calculated by RAMMCAP. In this study, RAMMCAP was applied to the two largest available metagenomic collections, the "Global Ocean Sampling" and the "Metagenomic Profiling of Nine Biomes". Conclusion RAMMCAP is a very fast method that can cluster and annotate one million metagenomic reads in only hundreds of CPU hours. It is available from http://tools.camera.calit2.net/camera/rammcap/.

Benchmarking density-functional-theory calculations of rotational g tensors and magnetizabilities using accurate coupled-cluster calculations.

Science.gov (United States)

Lutnaes, Ola B; Teale, Andrew M; Helgaker, Trygve; Tozer, David J; Ruud, Kenneth; Gauss, Jürgen

2009-10-14

An accurate set of benchmark rotational g tensors and magnetizabilities are calculated using coupled-cluster singles-doubles (CCSD) theory and coupled-cluster single-doubles-perturbative-triples [CCSD(T)] theory, in a variety of basis sets consisting of (rotational) London atomic orbitals. The accuracy of the results obtained is established for the rotational g tensors by careful comparison with experimental data, taking into account zero-point vibrational corrections. After an analysis of the basis sets employed, extrapolation techniques are used to provide estimates of the basis-set-limit quantities, thereby establishing an accurate benchmark data set. The utility of the data set is demonstrated by examining a wide variety of density functionals for the calculation of these properties. None of the density-functional methods are competitive with the CCSD or CCSD(T) methods. The need for a careful consideration of vibrational effects is clearly illustrated. Finally, the pure coupled-cluster results are compared with the results of density-functional calculations constrained to give the same electronic density. The importance of current dependence in exchange-correlation functionals is discussed in light of this comparison.

Comprehensive cluster analysis with Transitivity Clustering.

Science.gov (United States)

Wittkop, Tobias; Emig, Dorothea; Truss, Anke; Albrecht, Mario; Böcker, Sebastian; Baumbach, Jan

2011-03-01

Transitivity Clustering is a method for the partitioning of biological data into groups of similar objects, such as genes, for instance. It provides integrated access to various functions addressing each step of a typical cluster analysis. To facilitate this, Transitivity Clustering is accessible online and offers three user-friendly interfaces: a powerful stand-alone version, a web interface, and a collection of Cytoscape plug-ins. In this paper, we describe three major workflows: (i) protein (super)family detection with Cytoscape, (ii) protein homology detection with incomplete gold standards and (iii) clustering of gene expression data. This protocol guides the user through the most important features of Transitivity Clustering and takes ∼1 h to complete.

A density functional study of carbon monoxide adsorption on small cationic, neutral, and anionic gold clusters

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Wu, X.; Senapati, L.; Nayak, S. K.; Selloni, A.; Hajaligol, M.

2002-08-01

CO adsorption on small cationic, neutral, and anionic Aun (n=1-6) clusters has been investigated using density functional theory in the generalized gradient approximation. Among various possible CO adsorption sites, the on-top (one-fold coordinated) is found to be the most favorable one, irrespective of the charge state of the cluster. In addition, planar structures are preferred by both the bare and the CO-adsorbed clusters. The adsorption energies of CO on the cationic clusters are generally greater than those on the neutral and anionic complexes, and decrease with size. The adsorption energies on the anions, instead, increase with cluster size and reach a local maximum at Au5CO-, in agreement with recent experiment. The differences in adsorption energies for the different charge states decrease with increasing cluster size.

On the accuracy of density-functional theory exchange-correlation functionals for H bonds in small water clusters: Benchmarks approaching the complete basis set limit

Science.gov (United States)

Santra, Biswajit; Michaelides, Angelos; Scheffler, Matthias

2007-11-01

The ability of several density-functional theory (DFT) exchange-correlation functionals to describe hydrogen bonds in small water clusters (dimer to pentamer) in their global minimum energy structures is evaluated with reference to second order Møller-Plesset perturbation theory (MP2). Errors from basis set incompleteness have been minimized in both the MP2 reference data and the DFT calculations, thus enabling a consistent systematic evaluation of the true performance of the tested functionals. Among all the functionals considered, the hybrid X3LYP and PBE0 functionals offer the best performance and among the nonhybrid generalized gradient approximation functionals, mPWLYP and PBE1W perform best. The popular BLYP and B3LYP functionals consistently underbind and PBE and PW91 display rather variable performance with cluster size.

Evolution of the Black Hole Mass Function in Star Clusters from Multiple Mergers

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Christian, Pierre; Mocz, Philip; Loeb, Abraham

2018-05-01

We investigate the effects of black hole (BH) mergers in star clusters on the black hole mass function (BHMF). As BHs are not produced in pair-instability supernovae, it is suggested that there is a dearth of high-mass stellar BHs. This dearth generates a gap in the upper end of the BHMF. Meanwhile, parameter fitting of X-ray binaries suggests the existence of a gap in the mass function under 5 solar masses. We show, through evolving a coagulation equation, that BH mergers can appreciably fill the upper mass gap, and that the lower mass gap generates potentially observable features at larger mass scales. We also explore the importance of ejections in such systems and whether dynamical clusters can be formation sites of intermediate-mass BH seeds.

An Atlas of Peroxiredoxins Created Using an Active Site Profile-Based Approach to Functionally Relevant Clustering of Proteins.

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Angela F Harper

2017-02-01

Full Text Available Peroxiredoxins (Prxs or Prdxs are a large protein superfamily of antioxidant enzymes that rapidly detoxify damaging peroxides and/or affect signal transduction and, thus, have roles in proliferation, differentiation, and apoptosis. Prx superfamily members are widespread across phylogeny and multiple methods have been developed to classify them. Here we present an updated atlas of the Prx superfamily identified using a novel method called MISST (Multi-level Iterative Sequence Searching Technique. MISST is an iterative search process developed to be both agglomerative, to add sequences containing similar functional site features, and divisive, to split groups when functional site features suggest distinct functionally-relevant clusters. Superfamily members need not be identified initially-MISST begins with a minimal representative set of known structures and searches GenBank iteratively. Further, the method's novelty lies in the manner in which isofunctional groups are selected; rather than use a single or shifting threshold to identify clusters, the groups are deemed isofunctional when they pass a self-identification criterion, such that the group identifies itself and nothing else in a search of GenBank. The method was preliminarily validated on the Prxs, as the Prxs presented challenges of both agglomeration and division. For example, previous sequence analysis clustered the Prx functional families Prx1 and Prx6 into one group. Subsequent expert analysis clearly identified Prx6 as a distinct functionally relevant group. The MISST process distinguishes these two closely related, though functionally distinct, families. Through MISST search iterations, over 38,000 Prx sequences were identified, which the method divided into six isofunctional clusters, consistent with previous expert analysis. The results represent the most complete computational functional analysis of proteins comprising the Prx superfamily. The feasibility of this novel method is

Gene expression profiling of chicken cecal tonsils and ileum following oral exposure to soluble and PLGA-encapsulated CpG ODN, and lysate of Campylobacter jejuni.

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Taha-Abdelaziz, Khaled; Alkie, Tamiru Negash; Hodgins, Douglas C; Yitbarek, Alexander; Shojadoost, Bahram; Sharif, Shayan

2017-12-01

Campylobacter jejuni (C. jejuni) is a leading bacterial cause of food-borne illness in humans. Contaminated chicken meat is an important source of infection for humans. Chickens are not clinically affected by colonization, and immune responses following natural infection have limited effects on bacterial load in the gut. Induction of intestinal immune responses may possibly lead to a breakdown of the commensal relationship of chickens with Campylobacter. We have recently shown that soluble and poly D, L-lactic-co-glycolic acid (PLGA)-encapsulated CpG oligodeoxynucleotide (ODN) as well as C. jejuni lysate, are effective in reducing the intestinal burden of C. jejuni in chickens; however, the mechanisms behind this protection have yet to be determined. The present study was undertaken to investigate the mechanisms of host responses conferred by these treatments. Chickens were treated orally with soluble CpG ODN, or PLGA-encapsulated CpG ODN, or C. jejuni lysate, and expression of cytokines and antimicrobial peptides was evaluated in cecal tonsils and ileum using quantitative RT-PCR. Oral administration of soluble CpG ODN upregulated the expression of interferon (IFN)-γ, interleukin (IL)-1β, CXCLi2, transforming growth factor (TGF)-β4/1, IL-10 and IL-13, while treatment with PLGA-encapsulated CpG ODN upregulated the expression of IL-1β, CXCLi2, TGF-β4/1, IL-13, avian β-defensin (AvBD) 1, AvBD2 and cathelicidin 3 (CATHL-3). C. jejuni lysate upregulated the expression of IFN-γ, IL-1β, TGF-β4/1, IL-13, AvBD1, and CATHL-3. In conclusion, induction of cytokine and antimicrobial peptides expression in intestinal microenvironments may provide a means of reducing C. jejuni colonization in broiler chickens, a key step in reducing the incidence of campylobacteriosis in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

The Low-mass Population in the Young Cluster Stock 8: Stellar Properties and Initial Mass Function

Energy Technology Data Exchange (ETDEWEB)

Jose, Jessy; Herczeg, Gregory J.; Fang, Qiliang [Kavli Institute for Astronomy and Astrophysics, Peking University, Yi He Yuan Lu 5, Haidian Qu, Beijing 100871 (China); Samal, Manash R. [Graduate Institute of Astronomy, National Central University 300, Jhongli City, Taoyuan County 32001, Taiwan (China); Panwar, Neelam, E-mail: jessyvjose1@gmail.com [Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India)

2017-02-10

The evolution of H ii regions/supershells can trigger a new generation of stars/clusters at their peripheries, with environmental conditions that may affect the initial mass function, disk evolution, and star formation efficiency. In this paper we study the stellar content and star formation processes in the young cluster Stock 8, which itself is thought to be formed during the expansion of a supershell. We present deep optical photometry along with JHK and 3.6 and 4.5 μ m photometry from UKIDSS and Spitzer -IRAC. We use multicolor criteria to identify the candidate young stellar objects in the region. Using evolutionary models, we obtain a median log(age) of ∼6.5 (∼3.0 Myr) with an observed age spread of ∼0.25 dex for the cluster. Monte Carlo simulations of the population of Stock 8, based on estimates for the photometric uncertainty, differential reddening, binarity, and variability, indicate that these uncertainties introduce an age spread of ∼0.15 dex. The intrinsic age spread in the cluster is ∼0.2 dex. The fraction of young stellar objects surrounded by disks is ∼35%. The K -band luminosity function of Stock 8 is similar to that of the Trapezium cluster. The initial mass function (IMF) of Stock 8 has a Salpeter-like slope at >0.5 M {sub ⊙} and flattens and peaks at ∼0.4 M {sub ⊙}, below which it declines into the substellar regime. Although Stock 8 is surrounded by several massive stars, there seems to be no severe environmental effect in the form of the IMF due to the proximity of massive stars around the cluster.

The stellar and substellar mass function in central region of the old open cluster Praesepe from deep LBT observations

Directory of Open Access Journals (Sweden)

Goldman B.

2011-07-01

Full Text Available Studies of the mass function of open clusters of different ages allow us to study the efficiency with which brown dwarfs are evaporated from clusters to populate the field. Surveys in relatively old clusters (age ≳100 Myr do not suffer from problems found in young clusters, such as intra-cluster extinction and large uncertainties in brown dwarf models. In this paper, we present the results of a photometric survey to study the mass function of the old open cluster Praesepe (age of ~590 Myr and distance of ~190 pc, down to the substellar regime. We have performed optical (riz and Y-band photometric survey of Praesepe with the Large Binocular Telescope Camera, for a spatial coverage of 0.61 deg2 from ~90 MJ down to a 5σ detection limit at 40 MJ.

Approximation Of Multi-Valued Inverse Functions Using Clustering And Sugeno Fuzzy Inference

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Walden, Maria A.; Bikdash, Marwan; Homaifar, Abdollah

1998-01-01

Finding the inverse of a continuous function can be challenging and computationally expensive when the inverse function is multi-valued. Difficulties may be compounded when the function itself is difficult to evaluate. We show that we can use fuzzy-logic approximators such as Sugeno inference systems to compute the inverse on-line. To do so, a fuzzy clustering algorithm can be used in conjunction with a discriminating function to split the function data into branches for the different values of the forward function. These data sets are then fed into a recursive least-squares learning algorithm that finds the proper coefficients of the Sugeno approximators; each Sugeno approximator finds one value of the inverse function. Discussions about the accuracy of the approximation will be included.

Density-functional investigations on the neutral and charged Cun (n = 2 ∼ 12) clusters

International Nuclear Information System (INIS)

Jiang Yuanqi; Duan Haiming

2011-01-01

Combined with the semi-empirical inter-atomic potential, the geometrical and electronic properties of the ground- and low-lying states of Cu n (n = 2 ∼ 12) and Cu n ± (n = 2 ∼ 12) clusters are investigated systematically by density-functional calculations. Our results show that: the ground-state geometries prefer to linear or planar structures for the Cu n (n = 2 ∼ 6) and Cu n ± (n = 2 ∼ 5) clusters and the planar structures are all base on triangles, while for the larger clusters, the pentagonal bi-pyramids are the basic units to form the ground-state geometries, and the traditional high-symmetric structures do not dominate to the ground-states for these small copper clusters. The calculated binding energies of Cu n (n = 2 ∼ 12) clusters are in very good agreement with the experimental results, and the obtained ionization potentials (IPs) and electron affinities (EAs) are also in agreement with the observations; Several electronic properties (such as the IPs, EAs and the second-order energy differences) all exhibit oscillations, which can be due to the relatively high stabilities of the copper clusters containing even number electrons. (authors)

Frequency Modulation and Spatiotemporal Stability of the sCPG in Preterm Infants with RDS

Directory of Open Access Journals (Sweden)

Steven M. Barlow

2012-01-01

Full Text Available The nonnutritive suck (NNS is an observable and accessible motor behavior which is often used to make inference about brain development and pre-feeding skill in preterm and term infants. The purpose of this study was to model NNS burst compression pressure dynamics in the frequency and time domain among two groups of preterm infants, including those with respiratory distress syndrome (RDS, N=15 and 17 healthy controls. Digitized samples of NNS compression pressure waveforms recorded at a 1-week interval were collected 15 minutes prior to a scheduled feed. Regression analysis and ANOVA revealed that healthy preterm infants produced longer NNS bursts and the mean burst initiation cycle frequencies were higher when compared to the RDS group. Moreover, the initial 5 cycles of the NNS burst manifest a frequency modulated (FM segment which is a significant feature of the suck central pattern generator (sCPG, and differentially expressed in healthy and RDS infants. The NNS burst structure revealed significantly lower spatiotemporal index values for control versus RDS preterm infants during FM, and provides additional information on the microstructure of the sCPG which may be used to gauge the developmental status and progression of oromotor control systems among these fragile infants.

CpG in Combination with an Inhibitor of Notch Signaling Suppresses Formalin-Inactivated Respiratory Syncytial Virus-Enhanced Airway Hyperresponsiveness and Inflammation by Inhibiting Th17 Memory Responses and Promoting Tissue-Resident Memory Cells in Lungs.

Science.gov (United States)

Zhang, Lei; Li, Hongyong; Hai, Yan; Yin, Wei; Li, Wenjian; Zheng, Boyang; Du, Xiaomin; Li, Na; Zhang, Zhengzheng; Deng, Yuqing; Zeng, Ruihong; Wei, Lin

2017-05-15

Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine-enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross talk between TLR and Notch signaling pathways results in fine-tuning of TLR-triggered innate inflammatory responses. We evaluated the impact of TLR and Notch signaling on ERD in a murine model by administering CpG, an agonist of TLR9, in combination with L685,458, an inhibitor of Notch signaling during FI-RSV immunization. Activation with CpG or deficiency of MyD88-dependent TLR signaling did not alleviate airway inflammation in FI-RSV-immunized mice. Activation or inhibition of Notch signaling with Dll4, one of the Notch ligands, or L685,458 did not suppress FI-RSV-enhanced airway inflammation either. However, the CpG together with L685,458 markedly inhibited FI-RSV-enhanced airway hyperresponsiveness, weight loss, and lung inflammation. Interestingly, CpG plus L685,458 completely inhibited FI-RSV-associated Th17 and Th17-associated proinflammatory chemokine responses in lungs following RSV challenge but not Th1 or Th2, memory responses. In addition, FI-RSV plus CpG plus L685,458 promoted protective CD8 + lung tissue-resident memory (TRM) cells. These results indicate that activation of TLR signaling combined with inhibition of Notch signaling prevent FI-RSV ERD, and the mechanism appears to involve suppressing proinflammatory Th17 memory responses and promoting protective TRM in lungs. IMPORTANCE RSV is the most important cause of lower respiratory tract infections in infants. The FI-RSV-enhanced respiratory disease (ERD) is a major impediment to the development of a safe and

Relativistic form factors for clusters with nonrelativistic wave functions

International Nuclear Information System (INIS)

Mitra, A.N.; Kumari, I.

1977-01-01

Using a simple variant of an argument employed by Licht and Pagnamenta (LP) on the effect of Lorentz contraction on the elastic form factors of clusters with nonrelativistic wave functions, it is shown how their result can be generalized to inelastic form factors so as to produce (i) a symmetrical appearance of Lorentz contraction effects in the initial and final states, and (ii) asymptotic behavior in accord with dimensional scaling theories. A comparison of this result with a closely analogous parametric form obtained by Brodsky and Chertok from a propagator chain model leads, with plausible arguments, to the conclusion of an effective mass M for the cluster, with M 2 varying as the number n of the quark constituents, instead of as n 2 . A further generalization of the LP formula is obtained for an arbitrary duality-diagram vertex, again with asymptotic behavior in conformity with dimensional scaling. The practical usefulness of this approach is emphasized as a complementary tool to those of high-energy physics for phenomenological fits to data up to moderate values of q 2

Filling- and interaction-driven Mott transition. Quantum cluster calculations within self-energy-functional theory; Fuellungs- und wechselwirkungsabhaengiger Mott-Uebergang. Quanten-Cluster-Rechnungen im Rahmen der Selbstenergiefunktional-Theorie

Energy Technology Data Exchange (ETDEWEB)

Balzer, Matthias

2008-07-01

The central goal of this thesis is the examination of strongly correlated electron systems on the basis of the two-dimensional Hubbard model. We analyze how the properties of the Mott insulator change upon doping and with interaction strength. The numerical evaluation is done using quantum cluster approximations, which allow for a thermodynamically consistent description of the ground state properties. The framework of self-energy-functional theory offers great flexibility for the construction of cluster approximations. A detailed analysis sheds light on the quality and the convergence properties of different cluster approximations within the self-energy-functional theory. We use the one-dimensional Hubbard model for these examinations and compare our results with the exact solution. In two dimensions the ground state of the particle-hole symmetric model at half-filling is an antiferromagnetic insulator, independent of the interaction strength. The inclusion of short-range spatial correlations by our cluster approach leads to a considerable improvement of the antiferromagnetic order parameter as compared to dynamical mean-field theory. In the paramagnetic phase we furthermore observe a metal-insulator transition as a function of the interaction strength, which qualitatively differs from the pure mean-field scenario. Starting from the antiferromagnetic Mott insulator a filling-controlled metal-insulator transition in a paramagnetic metallic phase can be observed. Depending on the cluster approximation used an antiferromagnetic metallic phase may occur at first. In addition to long-range antiferromagnetic order, we also considered superconductivity in our calculations. The superconducting order parameter as a function of doping is in good agreement with other numerical methods, as well as with experimental results. (orig.)

Detection and discrimination of maintenance and de novo CpG methylation events using MethylBreak.

Science.gov (United States)

Hsu, William; Mercado, Augustus T; Hsiao, George; Yeh, Jui-Ming; Chen, Chung-Yung

2017-05-15

Understanding the principles governing the establishment and maintenance activities of DNA methyltransferases (DNMTs) can help in the development of predictive biomarkers associated with genetic disorders and diseases. A detection system was developed that distinguishes and quantifies methylation events using methylation-sensitive endonucleases and molecular beacon technology. MethylBreak (MB) is a 22-mer oligonucleotide with one hemimethylated and two unmethylated CpG sites, which are also recognition sites for Sau96I and SacII, and is attached to a fluorophore and a quencher. Maintenance methylation was quantified by fluorescence emission due to the digestion of SacII when the hemimethylated CpG site is methylated, which inhibits Sau96I cleavage. The signal difference between SacII digestion of both MB substrate and maintenance methylated MB corresponds to de novo methylation event. Our technology successfully discriminated and measured both methylation activities at different concentrations of MB and achieved a high correlation coefficient of R 2 =0.997. Additionally, MB was effectively applied to normal and cancer cell lines and in the analysis of enzymatic kinetics and RNA inhibition of recombinant human DNMT1. Copyright © 2017 Elsevier B.V. All rights reserved.

CPG-Based Locomotion Control of a Robotic Fish : Using Linear Oscillators and Reducing Control Parameters via PSO

NARCIS (Netherlands)

Wang, Chen; Xie, G.; Wang, L.; Cao, M.

The aim of the present study is to investigate the locomotion control of a robotic fish. To achieve this goal, we design a control architecture based on a novel central pattern generator (CPG) and implement it as a system of coupled linear oscillators. This design differs significantly from the

Diagonal Born-Oppenheimer correction for coupled-cluster wave-functions

Science.gov (United States)

Shamasundar, K. R.

2018-06-01

We examine how geometry-dependent normalisation freedom of electronic wave-functions affects extraction of a meaningful diagonal Born-Oppenheimer correction (DBOC) to the ground-state Born-Oppenheimer potential energy surface (PES). By viewing this freedom as a kind of gauge-freedom, it is shown that DBOC and the resulting associated mass-dependent adiabatic PES are gauge-invariant quantities. A sum-over-states (SOS) formula for DBOC which explicitly exhibits this invariance is derived. A biorthogonal formulation suitable for DBOC computations using standard unnormalised coupled-cluster (CC) wave-functions is presented. This is shown to lead to a biorthogonal version of SOS formula with similar properties. On this basis, different computational schemes for evaluating DBOC using approximate CC wave-functions are derived. One of this agrees with the formula used in the current literature. The connection to adiabatic-to-diabatic transformations in non-adiabatic dynamics is explored and complications arising from biorthogonal nature of CC theory are identified.

Comprehensive identification and clustering of CLV3/ESR-related (CLE) genes in plants finds groups with potentially shared function.

Science.gov (United States)

Goad, David M; Zhu, Chuanmei; Kellogg, Elizabeth A

2017-10-01

CLV3/ESR (CLE) proteins are important signaling peptides in plants. The short CLE peptide (12-13 amino acids) is cleaved from a larger pre-propeptide and functions as an extracellular ligand. The CLE family is large and has resisted attempts at classification because the CLE domain is too short for reliable phylogenetic analysis and the pre-propeptide is too variable. We used a model-based search for CLE domains from 57 plant genomes and used the entire pre-propeptide for comprehensive clustering analysis. In total, 1628 CLE genes were identified in land plants, with none recognizable from green algae. These CLEs form 12 groups within which CLE domains are largely conserved and pre-propeptides can be aligned. Most clusters contain sequences from monocots, eudicots and Amborella trichopoda, with sequences from Picea abies, Selaginella moellendorffii and Physcomitrella patens scattered in some clusters. We easily identified previously known clusters involved in vascular differentiation and nodulation. In addition, we found a number of discrete groups whose function remains poorly characterized. Available data indicate that CLE proteins within a cluster are likely to share function, whereas those from different clusters play at least partially different roles. Our analysis provides a foundation for future evolutionary and functional studies. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

The effectiveness of Cluster Organization Functions from a Member Company Perspective: The Case of Food Valley Organization

NARCIS (Netherlands)

Omta, S.W.F.; Fortuin, F.T.J.M.

2011-01-01

This paper aims to analyze the effectiveness of the different cluster organization functions (services, activities and information sources) of Food Valley Organization in the Dutch agifood innovation system, as evaluated by its member companies. It is concluded that, in accordance with cluster

Accurate CpG and non-CpG cytosine methylation analysis by high-throughput locus-specific pyrosequencing in plants.

Science.gov (United States)

How-Kit, Alexandre; Daunay, Antoine; Mazaleyrat, Nicolas; Busato, Florence; Daviaud, Christian; Teyssier, Emeline; Deleuze, Jean-François; Gallusci, Philippe; Tost, Jörg

2015-07-01

Pyrosequencing permits accurate quantification of DNA methylation of specific regions where the proportions of the C/T polymorphism induced by sodium bisulfite treatment of DNA reflects the DNA methylation level. The commercially available high-throughput locus-specific pyrosequencing instruments allow for the simultaneous analysis of 96 samples, but restrict the DNA methylation analysis to CpG dinucleotide sites, which can be limiting in many biological systems. In contrast to mammals where DNA methylation occurs nearly exclusively on CpG dinucleotides, plants genomes harbor DNA methylation also in other sequence contexts including CHG and CHH motives, which cannot be evaluated by these pyrosequencing instruments due to software limitations. Here, we present a complete pipeline for accurate CpG and non-CpG cytosine methylation analysis at single base-resolution using high-throughput locus-specific pyrosequencing. The devised approach includes the design and validation of PCR amplification on bisulfite-treated DNA and pyrosequencing assays as well as the quantification of the methylation level at every cytosine from the raw peak intensities of the Pyrograms by two newly developed Visual Basic Applications. Our method presents accurate and reproducible results as exemplified by the cytosine methylation analysis of the promoter regions of two Tomato genes (NOR and CNR) encoding transcription regulators of fruit ripening during different stages of fruit development. Our results confirmed a significant and temporally coordinated loss of DNA methylation on specific cytosines during the early stages of fruit development in both promoters as previously shown by WGBS. The manuscript describes thus the first high-throughput locus-specific DNA methylation analysis in plants using pyrosequencing.

Correction for dispersion and Coulombic interactions in molecular clusters with density functional derived methods: Application to polycyclic aromatic hydrocarbon clusters

Science.gov (United States)

Rapacioli, Mathias; Spiegelman, Fernand; Talbi, Dahbia; Mineva, Tzonka; Goursot, Annick; Heine, Thomas; Seifert, Gotthard

2009-06-01

The density functional based tight binding (DFTB) is a semiempirical method derived from the density functional theory (DFT). It inherits therefore its problems in treating van der Waals clusters. A major error comes from dispersion forces, which are poorly described by commonly used DFT functionals, but which can be accounted for by an a posteriori treatment DFT-D. This correction is used for DFTB. The self-consistent charge (SCC) DFTB is built on Mulliken charges which are known to give a poor representation of Coulombic intermolecular potential. We propose to calculate this potential using the class IV/charge model 3 definition of atomic charges. The self-consistent calculation of these charges is introduced in the SCC procedure and corresponding nuclear forces are derived. Benzene dimer is then studied as a benchmark system with this corrected DFTB (c-DFTB-D) method, but also, for comparison, with the DFT-D. Both methods give similar results and are in agreement with references calculations (CCSD(T) and symmetry adapted perturbation theory) calculations. As a first application, pyrene dimer is studied with the c-DFTB-D and DFT-D methods. For coronene clusters, only the c-DFTB-D approach is used, which finds the sandwich configurations to be more stable than the T-shaped ones.

Structural fragment clustering reveals novel structural and functional motifs in α-helical transmembrane proteins

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Vassilev Boris

2010-04-01

Full Text Available Abstract Background A large proportion of an organism's genome encodes for membrane proteins. Membrane proteins are important for many cellular processes, and several diseases can be linked to mutations in them. With the tremendous growth of sequence data, there is an increasing need to reliably identify membrane proteins from sequence, to functionally annotate them, and to correctly predict their topology. Results We introduce a technique called structural fragment clustering, which learns sequential motifs from 3D structural fragments. From over 500,000 fragments, we obtain 213 statistically significant, non-redundant, and novel motifs that are highly specific to α-helical transmembrane proteins. From these 213 motifs, 58 of them were assigned to function and checked in the scientific literature for a biological assessment. Seventy percent of the motifs are found in co-factor, ligand, and ion binding sites, 30% at protein interaction interfaces, and 12% bind specific lipids such as glycerol or cardiolipins. The vast majority of motifs (94% appear across evolutionarily unrelated families, highlighting the modularity of functional design in membrane proteins. We describe three novel motifs in detail: (1 a dimer interface motif found in voltage-gated chloride channels, (2 a proton transfer motif found in heme-copper oxidases, and (3 a convergently evolved interface helix motif found in an aspartate symporter, a serine protease, and cytochrome b. Conclusions Our findings suggest that functional modules exist in membrane proteins, and that they occur in completely different evolutionary contexts and cover different binding sites. Structural fragment clustering allows us to link sequence motifs to function through clusters of structural fragments. The sequence motifs can be applied to identify and characterize membrane proteins in novel genomes.

Choosing the Number of Clusters in K-Means Clustering

Science.gov (United States)

Steinley, Douglas; Brusco, Michael J.

2011-01-01

Steinley (2007) provided a lower bound for the sum-of-squares error criterion function used in K-means clustering. In this article, on the basis of the lower bound, the authors propose a method to distinguish between 1 cluster (i.e., a single distribution) versus more than 1 cluster. Additionally, conditional on indicating there are multiple…

Distinct functional domains within the acidic cluster of tegument protein pp28 required for trafficking and cytoplasmic envelopment of human cytomegalovirus.

Science.gov (United States)

Seo, Jun-Young; Jeon, Hyejin; Hong, Sookyung; Britt, William J

2016-10-01

Human cytomegalovirus UL99-encoded tegument protein pp28 contains a 16 aa acidic cluster that is required for pp28 trafficking to the assembly compartment (AC) and the virus assembly. However, functional signals within the acidic cluster of pp28 remain undefined. Here, we demonstrated that an acidic cluster rather than specific sorting signals was required for trafficking to the AC. Recombinant viruses with chimeric pp28 proteins expressing non-native acidic clusters exhibited delayed viral growth kinetics and decreased production of infectious virus, indicating that the native acidic cluster of pp28 was essential for wild-type virus assembly. These results suggested that the acidic cluster of pp28 has distinct functional domains required for trafficking and for efficient virus assembly. The first half (aa 44-50) of the acidic cluster was sufficient for pp28 trafficking, whereas the native acidic cluster consisting of aa 51-59 was required for the assembly of wild-type levels of infectious virus.

Cluster polylogarithms for scattering amplitudes

International Nuclear Information System (INIS)

Golden, John; Paulos, Miguel F; Spradlin, Marcus; Volovich, Anastasia

2014-01-01

Motivated by the cluster structure of two-loop scattering amplitudes in N=4 Yang-Mills theory we define cluster polylogarithm functions. We find that all such functions of weight four are made up of a single simple building block associated with the A 2 cluster algebra. Adding the requirement of locality on generalized Stasheff polytopes, we find that these A 2 building blocks arrange themselves to form a unique function associated with the A 3 cluster algebra. This A 3 function manifests all of the cluster algebraic structure of the two-loop n-particle MHV amplitudes for all n, and we use it to provide an explicit representation for the most complicated part of the n = 7 amplitude as an example. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Cluster algebras in mathematical physics’. (paper)

Phase 1 testing of detoxified LPS/group B meningococcal outer membrane protein vaccine with and without synthetic CPG 7909 adjuvant for the prevention and treatment of sepsis.

Science.gov (United States)

Cross, Alan S; Greenberg, Nancy; Billington, Melissa; Zhang, Lei; DeFilippi, Christopher; May, Ryan C; Bajwa, Kanwaldeep K

2015-11-27

Gram-negative bacteria (GNB) are a leading cause of nosocomial infection and sepsis. Increasing multi-antibiotic resistance has left clinicians with fewer therapeutic options. Antibodies to GNB lipopolysaccharide (LPS, or endotoxin) have reduced morbidity and mortality as a result of infection and are not subject to the resistance mechanisms deployed by bacteria against antibiotics. In this phase 1 study, we administered a vaccine that elicits antibodies against a highly conserved portion of LPS with and without a CpG oligodeoxynucleotide (ODN) TLR9 agonist as adjuvant. A vaccine composed of the detoxified LPS (dLPS) from E. coli O111:B4 (J5 mutant) non-covalently complexed to group B meningococcal outer membrane protein (OMP). Twenty healthy adult subjects received three doses at 0, 29 and 59 days of antigen (10 μg dLPS) with or without CPG 7909 (250 or 500 μg). Subjects were evaluated for local and systemic adverse effects and laboratory findings. Anti-J5 LPS IgG and IgM antibody levels were measured by electrochemiluminesence. Due to premature study termination, not all subjects received all three doses. All vaccine formulations were well-tolerated with no local or systemic events of greater than moderate severity. The vaccine alone group achieved a ≥ 4-fold "responder" response in IgG and IgM antibody in only one of 6 subjects. In contrast, the vaccine plus CPG 7909 groups appeared to have earlier and more sustained (to 180 days) responses, greater mean-fold increases, and a higher proportion of "responders" achieving ≥ 4-fold increases over baseline. Although the study was halted before all enrolled subjects received all three doses, the J5dLPS/OMP vaccine, with or without CpG adjuvant, was safe and well-tolerated. The inclusion of CpG increased the number of subjects with a ≥ 4-fold antibody response, evident even after the second of three planned doses. A vaccine comprising J5dLPS/OMP antigen with CpG adjuvant merits further investigation. Clinical

Density functional study of carbon monoxide adsorption on small cationic, neutral, and anionic aluminum nitride clusters

Science.gov (United States)

Guo, Ling

CO adsorption on small cationic, neutral, and anionic (AlN)n (n = 1-6) clusters has been investigated using density functional theory in the generalized gradient approximation. Among various possible CO adsorption sites, an N on-top (onefold coordinated) site is found to be the most favorable one, irrespective of the charge state of the clusters. The adsorption energies of CO on the anionic (AlN)nCO (n = 2-4) clusters are greater than those on the neutral and cationic complexes. The adsorption energies on the cationic and neutral complexes reflect the odd-even oscillations, and the adsorption energies of CO on the cationic (AlN)nCO (n = 5, 6) clusters are greater than those on the neutral and anionic complexes. The adsorption energies for the different charge states decrease with increasing cluster size.

Inhibitory effects of unmethylated CpG oligodeoxynucleotides on MHC class I-deficient and -proficient HPV16-associated tumours

Czech Academy of Sciences Publication Activity Database

Reiniš, Milan; Šímová, Jana; Bubeník, Jan

2006-01-01

Roč. 118, č. 7 (2006), s. 1836-1842 ISSN 0020-7136 R&D Projects: GA ČR(CZ) GA301/04/0492 Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV16 * immunotherapy * CpG oligodeoxynucleotides Subject RIV: EC - Immunology Impact factor: 4.693, year: 2006

Synthesis and Characterization of Rh-Co Butterfly Clusters Capped by Functionally Substituted 1-Alkynes

Institute of Scientific and Technical Information of China (English)

朱保华; 胡斌; 张伟强; 边治国; 赵全义; 殷元骐; 孙杰

2003-01-01

By the reactions of [Rh2Co2(CO)12] 1 with functionally substituted alkyne ligands HC≡CR 2 (R = FeCp2) and 3 (R = 2-OH-C6H4COOCH2), respectively in n-hexane at room temperature, two new cluster derivatives [Rh2Co2(CO)6(μ-CO)4(μ4, η2-HC≡CR)] 4 (R = FeCp2) and 5 (R = 2-OH-C6H4COOCH2) were obtained respectively. The alkyne was inserted into the Co-Co bond of cluster 1 to give two butterfly clusters. Cluster 4 has been determined by single-crystal X-ray diffraction. Crystallographic data: C22H10Co2FeO10Rh2, Mr = 813.83, orthorhombic, space group P212121, a = 11.5318(7), b = 12.6572(7), c = 17.018(1) A。, V = 2483.9(3) A。3, Z = 4, Dc = 2.176 g/cm3, F(000) = 1568, μ = 3.233 mm-1, the final R = 0.0366 and wR = 0.0899 for 5367 observed reflections with I > 2σ(I). The two clusters have also been characterized by elemental analysis, IR and 1H-NMR spectroscopy.

The potential of immunostimulatory CpG DNA for inducing immunity against genital herpes: opportunities and challenges.

Science.gov (United States)

Harandi, Ali M

2004-07-01

Herpes simplex virus type 2 (HSV-2) invades human genital tract mucosa and following local replications can be rapidly transmitted via peripheral nerve axons to the sacral ganglia where it can establish latency. Reactivation of the latent viral reservoir results in recurrent ulcers in the genital region. Innate immunity, the first line of defence during both primary and recurrent genital herpes infections, is crucial during the period of acute infection to limit early virus replication and to facilitate the development of an appropriate specific acquired immunity. Recent developments in immunology reveal that the mammalian innate immune systems use Toll-like receptor (TLR) to specifically sense evolutionary conserved molecules such as bacterial DNA in pathogens. Recently, local-vaginal delivery of CpG containing oligodeoxynucleotide (ODN), a synthetic mimic of bacterial DNA, holds substantial promise as a strong inducer of innate immunity against genital herpes infections in the animal models of the disease. These preclinical observations provide a scientific ground work for introduction of this novel intervention strategy to clinic. This review aims to highlight recent developments and future challenges in use of immunostimulatory CpG ODN for inducing immunity against genital herpes infection and disease.

CpG island methylator phenotype in adenocarcinomas from the digestive tract: Methods, conclusions, and controversies

Science.gov (United States)

Sánchez-Vega, Francisco; Gotea, Valer; Chen, Yun-Ching; Elnitski, Laura

2017-01-01

Over the last two decades, cancer-related alterations in DNA methylation that regulate transcription have been reported for a variety of tumors of the gastrointestinal tract. Due to its relevance for translational research, great emphasis has been placed on the analysis and molecular characterization of the CpG island methylator phenotype (CIMP), defined as widespread hypermethylation of CpG islands in clinically distinct subsets of cancer patients. Here, we present an overview of previous work in this field and also explore some open questions using cross-platform data for esophageal, gastric, and colorectal adenocarcinomas from The Cancer Genome Atlas. We provide a data-driven, pan-gastrointestinal stratification of individual samples based on CIMP status and we investigate correlations with oncogenic alterations, including somatic mutations and epigenetic silencing of tumor suppressor genes. Besides known events in CIMP such as BRAF V600E mutation, CDKN2A silencing or MLH1 inactivation, we discuss the potential role of emerging actors such as Wnt pathway deregulation through truncating mutations in RNF43 and epigenetic silencing of WIF1. Our results highlight the existence of molecular similarities that are superimposed over a larger backbone of tissue-specific features and can be exploited to reduce heterogeneity of response in clinical trials. PMID:28344746

Analysis of NFU-1 metallocofactor binding-site substitutions-impacts on iron-sulfur cluster coordination and protein structure and function.

Science.gov (United States)

Wesley, Nathaniel A; Wachnowsky, Christine; Fidai, Insiya; Cowan, J A

2017-11-01

Iron-sulfur (Fe/S) clusters are ancient prosthetic groups found in numerous metalloproteins and are conserved across all kingdoms of life due to their diverse, yet essential functional roles. Genetic mutations to a specific subset of mitochondrial Fe/S cluster delivery proteins are broadly categorized as disease-related under multiple mitochondrial dysfunction syndrome (MMDS), with symptoms indicative of a general failure of the metabolic system. Multiple mitochondrial dysfunction syndrome 1 (MMDS1) arises as a result of the missense mutation in NFU1, an Fe/S cluster scaffold protein, which substitutes a glycine near the Fe/S cluster-binding pocket to a cysteine (p.Gly208Cys). This substitution has been shown to promote protein dimerization such that cluster delivery to NFU1 is blocked, preventing downstream cluster trafficking. However, the possibility of this additional cysteine, located adjacent to the cluster-binding site, serving as an Fe/S cluster ligand has not yet been explored. To fully understand the consequences of this Gly208Cys replacement, complementary substitutions at the Fe/S cluster-binding pocket for native and Gly208Cys NFU1 were made, along with six other variants. Herein, we report the results of an investigation on the effect of these substitutions on both cluster coordination and NFU1 structure and function. The data suggest that the G208C substitution does not contribute to cluster binding. Rather, replacement of the glycine at position 208 changes the oligomerization state as a result of global structural alterations that result in the downstream effects manifest as MMDS1, but does not perturb the coordination chemistry of the Fe-S cluster. © 2017 Federation of European Biochemical Societies.

Structures, electronic properties and magnetisms of FeBN (N ≤ 15) clusters: density functional theory investigations

International Nuclear Information System (INIS)

Liu Huoyan; Lel Xueling; Chen Hang; Liu Zhifeng; Liu Liren; Zhu Hengjiang

2011-01-01

The equilibrium structures, electronic properties and magnetisms of FeB N (N ≤ 15) clusters have been investigated by generalized gradient approximation (GGA) of density functional theory at different spin multiplicities. The average atomic binding energies, second-order energy differences and gaps of ground-state structures are calculated and discussed. The results show that FeB 3 , FeB 8 , FeB 12 and FeB 14 possess relatively higher stabilities. Moreover, there is a distinct hybridization between the d orbital of Fe and the p orbital of B for the ground-state cluster. The total magnetic moment for groundstate cluster is mainly provided by 3 d orbital of Fe atom, and exhibits the odd-even oscillation tendency with the increasing of cluster size. (authors)

Clustering on Membranes

DEFF Research Database (Denmark)

Johannes, Ludger; Pezeshkian, Weria; Ipsen, John H

2018-01-01

Clustering of extracellular ligands and proteins on the plasma membrane is required to perform specific cellular functions, such as signaling and endocytosis. Attractive forces that originate in perturbations of the membrane's physical properties contribute to this clustering, in addition to direct...... protein-protein interactions. However, these membrane-mediated forces have not all been equally considered, despite their importance. In this review, we describe how line tension, lipid depletion, and membrane curvature contribute to membrane-mediated clustering. Additional attractive forces that arise...... from protein-induced perturbation of a membrane's fluctuations are also described. This review aims to provide a survey of the current understanding of membrane-mediated clustering and how this supports precise biological functions....

Derivation of the density functional theory from the cluster expansion.

Science.gov (United States)

Hsu, J Y

2003-09-26

The density functional theory is derived from a cluster expansion by truncating the higher-order correlations in one and only one term in the kinetic energy. The formulation allows self-consistent calculation of the exchange correlation effect without imposing additional assumptions to generalize the local density approximation. The pair correlation is described as a two-body collision of bound-state electrons, and modifies the electron- electron interaction energy as well as the kinetic energy. The theory admits excited states, and has no self-interaction energy.

A functional bikaverin biosynthesis gene cluster in rare strains of Botrytis cinerea is positively controlled by VELVET.

Directory of Open Access Journals (Sweden)

Julia Schumacher

Full Text Available The gene cluster responsible for the biosynthesis of the red polyketidic pigment bikaverin has only been characterized in Fusarium ssp. so far. Recently, a highly homologous but incomplete and nonfunctional bikaverin cluster has been found in the genome of the unrelated phytopathogenic fungus Botrytis cinerea. In this study, we provided evidence that rare B. cinerea strains such as 1750 have a complete and functional cluster comprising the six genes orthologous to Fusarium fujikuroi ffbik1-ffbik6 and do produce bikaverin. Phylogenetic analysis confirmed that the whole cluster was acquired from Fusarium through a horizontal gene transfer (HGT. In the bikaverin-nonproducing strain B05.10, the genes encoding bikaverin biosynthesis enzymes are nonfunctional due to deleterious mutations (bcbik2-3 or missing (bcbik1 but interestingly, the genes encoding the regulatory proteins BcBIK4 and BcBIK5 do not harbor deleterious mutations which suggests that they may still be functional. Heterologous complementation of the F. fujikuroi Δffbik4 mutant confirmed that bcbik4 of strain B05.10 is indeed fully functional. Deletion of bcvel1 in the pink strain 1750 resulted in loss of bikaverin and overproduction of melanin indicating that the VELVET protein BcVEL1 regulates the biosynthesis of the two pigments in an opposite manner. Although strain 1750 itself expresses a truncated BcVEL1 protein (100 instead of 575 aa that is nonfunctional with regard to sclerotia formation, virulence and oxalic acid formation, it is sufficient to regulate pigment biosynthesis (bikaverin and melanin and fenhexamid HydR2 type of resistance. Finally, a genetic cross between strain 1750 and a bikaverin-nonproducing strain sensitive to fenhexamid revealed that the functional bikaverin cluster is genetically linked to the HydR2 locus.

Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists

International Nuclear Information System (INIS)

Mossman, David; Kim, Kyu-Tae; Scott, Rodney J

2010-01-01

DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. Aberrant epigenetic gene silencing in tumours is a frequent event, yet the factors which dictate which genes are targeted for inactivation are unknown. DNA methylation and histone acetylation can be modified with the chemical agents 5-aza-2'-deoxycytidine (5-aza-dC) and Trichostatin A (TSA) respectively. The aim of this study was to analyse de-methylation and re-methylation and its affect on gene expression in colorectal cancer cell lines treated with 5-aza-dC alone and in combination with TSA. We also sought to identify methylation patterns associated with long term reactivation of previously silenced genes. Colorectal cancer cell lines were treated with 5-aza-dC, with and without TSA, to analyse global methylation decreases by High Performance Liquid Chromatography (HPLC). Re-methylation was observed with removal of drug treatments. Expression arrays identified silenced genes with differing patterns of expression after treatment, such as short term reactivation or long term reactivation. Sodium bisulfite sequencing was performed on the CpG island associated with these genes and expression was verified with real time PCR. Treatment with 5-aza-dC was found to affect genomic methylation and to a lesser extent gene specific methylation. Reactivated genes which remained expressed 10 days post 5-aza-dC treatment featured hypomethylated CpG sites adjacent to the transcription start site (TSS). In contrast, genes with uniformly hypermethylated CpG islands were only temporarily reactivated. These results imply that 5-aza-dC induces strong de-methylation of the genome and initiates reactivation of transcriptionally inactive genes, but this does not require gene associated CpG island de-methylation to occur. In addition, for three of our selected genes, hypomethylation at the TSS of an epigenetically silenced gene is associated with the long term reversion of

A numerical study of spin-dependent organization of alkali-metal atomic clusters using density-functional method

International Nuclear Information System (INIS)

Liu Xuan; Ito, Haruhiko; Torikai, Eiko

2012-01-01

We calculate the different geometric isomers of spin clusters composed of a small number of alkali-metal atoms using the UB3LYP density-functional method. The electron density distribution of clusters changes according to the value of total spin. Steric structures as well as planar structures arise when the number of atoms increases. The lowest spin state is the most stable and Li n , Na n , K n , Rb n , and Cs n with n = 2–8 can be formed in higher spin states. In the highest spin state, the preparation of clusters depends on the kind and the number of constituent atoms. The interaction energy between alkali-metal atoms and rare-gas atoms is smaller than the binding energy of spin clusters. Consequently, it is possible to self-organize the alkali-metal-atom clusters on a non-wetting substrate coated with rare-gas atoms.

A numerical study of spin-dependent organization of alkali-metal atomic clusters using density-functional method

Energy Technology Data Exchange (ETDEWEB)

Liu Xuan, E-mail: liu.x.ad@m.titech.ac.jp; Ito, Haruhiko [Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology (Japan); Torikai, Eiko [Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi (Japan)

2012-08-15

We calculate the different geometric isomers of spin clusters composed of a small number of alkali-metal atoms using the UB3LYP density-functional method. The electron density distribution of clusters changes according to the value of total spin. Steric structures as well as planar structures arise when the number of atoms increases. The lowest spin state is the most stable and Li{sub n}, Na{sub n}, K{sub n}, Rb{sub n}, and Cs{sub n} with n = 2-8 can be formed in higher spin states. In the highest spin state, the preparation of clusters depends on the kind and the number of constituent atoms. The interaction energy between alkali-metal atoms and rare-gas atoms is smaller than the binding energy of spin clusters. Consequently, it is possible to self-organize the alkali-metal-atom clusters on a non-wetting substrate coated with rare-gas atoms.

Why do ultrasoft repulsive particles cluster and crystallize? Analytical results from density-functional theory.

Science.gov (United States)

Likos, Christos N; Mladek, Bianca M; Gottwald, Dieter; Kahl, Gerhard

2007-06-14

We demonstrate the accuracy of the hypernetted chain closure and of the mean-field approximation for the calculation of the fluid-state properties of systems interacting by means of bounded and positive pair potentials with oscillating Fourier transforms. Subsequently, we prove the validity of a bilinear, random-phase density functional for arbitrary inhomogeneous phases of the same systems. On the basis of this functional, we calculate analytically the freezing parameters of the latter. We demonstrate explicitly that the stable crystals feature a lattice constant that is independent of density and whose value is dictated by the position of the negative minimum of the Fourier transform of the pair potential. This property is equivalent with the existence of clusters, whose population scales proportionally to the density. We establish that regardless of the form of the interaction potential and of the location on the freezing line, all cluster crystals have a universal Lindemann ratio Lf=0.189 at freezing. We further make an explicit link between the aforementioned density functional and the harmonic theory of crystals. This allows us to establish an equivalence between the emergence of clusters and the existence of negative Fourier components of the interaction potential. Finally, we make a connection between the class of models at hand and the system of infinite-dimensional hard spheres, when the limits of interaction steepness and space dimension are both taken to infinity in a particularly described fashion.

Si clusters/defective graphene composites as Li-ion batteries anode materials: A density functional study

International Nuclear Information System (INIS)

Li, Meng; Liu, Yue-Jie; Zhao, Jing-xiang; Wang, Xiao-guang

2015-01-01

Highlights: • We study the interaction between Si clusters with pristine and defective graphene. • We find that the binding strength of Si clusters on graphene can be enhanced to different degrees after introducing various defects. • It is found that both graphene and Si cluster in the Si/graphene composites can preserve their Li uptake ability. - Abstract: Recently, the Si/graphene hybrid composites have attracted considerable attention due to their potential application for Li-ion batteries. How to effectively anchor Si clusters to graphene substrates to ensure their stability is an important factor to determine their performance for Li-ion batteries. In the present work, we have performed comprehensive density functional theory (DFT) calculations to investigate the geometric structures, stability, and electronic properties of the deposited Si clusters on defective graphenes as well as their potential applications for Li-ion batteries. The results indicate that the interfacial bonding between these Si clusters with the pristine graphene is quietly weak with a small adsorption energy (<−0.21 eV). Due to the presence of vacancy site, the binding strength of Si clusters on defective graphene is much stronger than that of pristine one, accompanying with a certain amount of charge transfer from Si clusters to graphene substrates. Moreover, the ability of Si/graphene hybrids for Li uptake is studied by calculating the adsorption of Li atoms. We find that both graphenes and Si clusters in the Si/graphene composites preserve their Li uptake ability, indicating that graphenes not only server as buffer materials for accommodating the expansion of Si cluster, but also provide additional intercalation sites for Li

Globular clusters and galaxy halos

International Nuclear Information System (INIS)

Van Den Bergh, S.

1984-01-01

Using semipartial correlation coefficients and bootstrap techniques, a study is made of the important features of globular clusters with respect to the total number of galaxy clusters and dependence of specific galaxy cluster on parent galaxy type, cluster radii, luminosity functions and cluster ellipticity. It is shown that the ellipticity of LMC clusters correlates significantly with cluster luminosity functions, but not with cluster age. The cluter luminosity value above which globulars are noticeably flattened may differ by a factor of about 100 from galaxy to galaxy. Both in the Galaxy and in M31 globulars with small core radii have a Gaussian distribution over luminosity, whereas clusters with large core radii do not. In the cluster systems surrounding the Galaxy, M31 and NGC 5128 the mean radii of globular clusters was found to increase with the distance from the nucleus. Central galaxies in rich clusters have much higher values for specific globular cluster frequency than do other cluster ellipticals, suggesting that such central galaxies must already have been different from normal ellipticals at the time they were formed

Structural, electronic, and magnetic properties of Y(n)O (n=2-14) clusters: Density functional study.

Science.gov (United States)

Yang, Zhi; Xiong, Shi-Jie

2008-09-28

The geometries stability, electronic properties, and magnetism of Y(n)O clusters up to n=14 are systematically studied with density functional theory. In the lowest-energy structures of Y(n)O clusters, the equilibrium site of the oxygen atom gradually moves from an outer site of the cluster, via a surface site, and finally, to an interior site as the number of the Y atoms increases from 2 to 14. Starting from n=12, the O atom falls into the center of the cluster with the Y atoms forming the outer frame. The results show that clusters with n=2, 4, 8, and 12 are more stable than their respective neighbors, and that the total magnetic moments of Y(n)O clusters are all quite small except Y(12)O cluster. The lowest-energy structure of Y(12)O cluster is a perfect icosahedron with a large magnetic moment 6mu(B). In addition, we find that the total magnetic moments are quenched for n=2, 6, and 8 due to the closed-shell electronic configuration. The calculated ionization potentials and electron affinities are in good agreement with the experimental results, which imply that the present theoretical treatments are satisfactory.

Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer.

Science.gov (United States)

Savio, Andrea J; Bapat, Bharati

2017-06-03

The MLH1 promoter polymorphism rs1800734 is associated with MLH1 CpG island hypermethylation and expression loss in colorectal cancer (CRC). Conversely, variant rs1800734 is associated with MLH1 shore, but not island, hypomethylation in peripheral blood mononuclear cell DNA. To explore these distinct patterns, MLH1 CpG island and shore methylation was assessed in CRC cell lines stratified by rs1800734 genotype. Cell lines containing the variant A allele demonstrated MLH1 shore hypomethylation compared to wild type (GG). There was significant enrichment of transcription factor AP4 at the MLH1 promoter in GG and GA cell lines, but not the AA cell line, by chromatin immunoprecipitation studies. Preferential binding to the G allele was confirmed by sequencing in the GA cell line. The enhancer-associated histone modification H3K4me1 was enriched at the MLH1 shore; however, H3K27ac was not, indicating the shore is an inactive enhancer. These results demonstrate the role of variant rs1800734 in altering transcription factor binding as well as epigenetics at regions beyond the MLH1 CpG island in which it is located.

Spectroscopic and functional characterization of iron-sulfur cluster-bound forms of Azotobacter vinelandii (Nif)IscA.

Science.gov (United States)

Mapolelo, Daphne T; Zhang, Bo; Naik, Sunil G; Huynh, Boi Hanh; Johnson, Michael K

2012-10-16

The mechanism of [4Fe-4S] cluster assembly on A-type Fe-S cluster assembly proteins, in general, and the specific role of (Nif)IscA in the maturation of nitrogen fixation proteins are currently unknown. To address these questions, in vitro spectroscopic studies (UV-visible absorption/CD, resonance Raman and Mössbauer) have been used to investigate the mechanism of [4Fe-4S] cluster assembly on Azotobacter vinelandii(Nif)IscA, and the ability of (Nif)IscA to accept clusters from NifU and to donate clusters to the apo form of the nitrogenase Fe-protein. The results show that (Nif)IscA can rapidly and reversibly cycle between forms containing one [2Fe-2S](2+) and one [4Fe-4S](2+) cluster per homodimer via DTT-induced two-electron reductive coupling of two [2Fe-2S](2+) clusters and O(2)-induced [4Fe-4S](2+) oxidative cleavage. This unique type of cluster interconversion in response to cellular redox status and oxygen levels is likely to be important for the specific role of A-type proteins in the maturation of [4Fe-4S] cluster-containing proteins under aerobic growth or oxidative stress conditions. Only the [4Fe-4S](2+)-(Nif)IscA was competent for rapid activation of apo-nitrogenase Fe protein under anaerobic conditions. Apo-(Nif)IscA was shown to accept clusters from [4Fe-4S] cluster-bound NifU via rapid intact cluster transfer, indicating a potential role as a cluster carrier for delivery of clusters assembled on NifU. Overall the results support the proposal that A-type proteins can function as carrier proteins for clusters assembled on U-type proteins and suggest that they are likely to supply [2Fe-2S] clusters rather than [4Fe-4S] for the maturation of [4Fe-4S] cluster-containing proteins under aerobic or oxidative stress growth conditions.

Studying the varied shapes of gold clusters by an elegant optimization algorithm that hybridizes the density functional tight-binding theory and the density functional theory

Science.gov (United States)

Yen, Tsung-Wen; Lim, Thong-Leng; Yoon, Tiem-Leong; Lai, S. K.

2017-11-01

We combined a new parametrized density functional tight-binding (DFTB) theory (Fihey et al. 2015) with an unbiased modified basin hopping (MBH) optimization algorithm (Yen and Lai 2015) and applied it to calculate the lowest energy structures of Au clusters. From the calculated topologies and their conformational changes, we find that this DFTB/MBH method is a necessary procedure for a systematic study of the structural development of Au clusters but is somewhat insufficient for a quantitative study. As a result, we propose an extended hybridized algorithm. This improved algorithm proceeds in two steps. In the first step, the DFTB theory is employed to calculate the total energy of the cluster and this step (through running DFTB/MBH optimization for given Monte-Carlo steps) is meant to efficiently bring the Au cluster near to the region of the lowest energy minimum since the cluster as a whole has explicitly considered the interactions of valence electrons with ions, albeit semi-quantitatively. Then, in the second succeeding step, the energy-minimum searching process will continue with a skilledly replacement of the energy function calculated by the DFTB theory in the first step by one calculated in the full density functional theory (DFT). In these subsequent calculations, we couple the DFT energy also with the MBH strategy and proceed with the DFT/MBH optimization until the lowest energy value is found. We checked that this extended hybridized algorithm successfully predicts the twisted pyramidal structure for the Au40 cluster and correctly confirms also the linear shape of C8 which our previous DFTB/MBH method failed to do so. Perhaps more remarkable is the topological growth of Aun: it changes from a planar (n =3-11) → an oblate-like cage (n =12-15) → a hollow-shape cage (n =16-18) and finally a pyramidal-like cage (n =19, 20). These varied forms of the cluster's shapes are consistent with those reported in the literature.

Modified genetic algorithms to model cluster structures in medium-size silicon clusters

International Nuclear Information System (INIS)

Bazterra, Victor E.; Ona, Ofelia; Caputo, Maria C.; Ferraro, Marta B.; Fuentealba, Patricio; Facelli, Julio C.

2004-01-01

This paper presents the results obtained using a genetic algorithm (GA) to search for stable structures of medium size silicon clusters. In this work the GA uses a semiempirical energy function to find the best cluster structures, which are further optimized using density-functional theory. For small clusters our results agree well with previously reported structures, but for larger ones different structures appear. This is the case of Si 36 where we report a different structure, with significant lower energy than those previously found using limited search approaches on common structural motifs. This demonstrates the need for global optimization schemes when searching for stable structures of medium-size silicon clusters

Multiple cluster axis II comorbidity and functional outcome in severe patients with borderline personality disorder.

Science.gov (United States)

Palomares, Nerea; McMaster, Antonia; Díaz-Marsá, Marina; de la Vega, Irene; Montes, Ana; Carrasco, José Luis

2016-11-01

Current literature suggests that personality disorder comorbidity negatively contributes to both the severity and prognosis of other disorders; however, little literature has been devoted to its influence on borderline personality disorder (BPD). The objective of the present work is to study comorbidity with other personality disorders in a severe clinical sample of patients with BPD, and its relationship with global functionality. A sample of 65 patients with severe borderline personality disorder was included in the study. Clinical and functionality measures were applied in order to study comorbidity of BPD with other disorders and its relationship with functionality. Associations with other comorbid PDs were analyzed with t-tests and linear correlations. Most patients (87%) presented comorbidity with other PDs. Almost half of the sample (42%) presented more than two PDs, and cluster A (paranoid) and C (obsessive and avoidant) PD were more frequent than cluster B (histrionic and antisocial). Only the presence of avoidant PD predicted a worse functional outcome in the long term (U Mann Withney ppersonality disorder might negatively predict for prognosis.

The CpG island methylator phenotype (CIMP) in colorectal cancer.

Science.gov (United States)

Nazemalhosseini Mojarad, Ehsan; Kuppen, Peter Jk; Aghdaei, Hamid Asadzadeh; Zali, Mohammad Reza

2013-01-01

It is clear that colorectal cancer (CRC) develops through multiple genetic and epigenetic pathways. These pathways may be determined on the basis of three molecular features: (i) mutations in DNA mismatch repair genes, leading to a DNA microsatellite instability (MSI) phenotype, (ii) mutations in APC and other genes that activate Wnt pathway, characterized by chromosomal instability (CIN) phenotype, and (iii) global genome hypermethylation, resulting in switch off of tumor suppressor genes, indicated as CpG island methylator phenotype (CIMP). Each of these pathways is characterized by specific pathological features, mechanisms of carcinogenesis and process of tumor development. The molecular aspects of these pathways have been used clinically in the diagnosis, screening and management of patients with colorectal cancer. In this review we especially describe various aspects of CIMP, one of the important and rather recently discovered pathways that lead to colorectal cancer.

Dynamical aspects of galaxy clustering

International Nuclear Information System (INIS)

Fall, S.M.

1980-01-01

Some recent work on the origin and evolution of galaxy clustering is reviewed, particularly within the context of the gravitational instability theory and the hot big-bang cosmological model. Statistical measures of clustering, including correlation functions and multiplicity functions, are explained and discussed. The close connection between galaxy formation and clustering is emphasized. Additional topics include the dependence of galaxy clustering on the spectrum of primordial density fluctuations and the mean mass density of the Universe. (author)

From the Cluster Temperature Function to the Mass Function at Low Z

Science.gov (United States)

Mushotzky, Richard (Technical Monitor); Markevitch, Maxim

2004-01-01

This XMM project consisted of three observations of the nearby, hot galaxy cluster Triangulum Australis, one of the cluster center and two offsets. The goal was to measure the radial gas temperature profile out to large radii and derive the total gravitating mass within the radius of average mass overdensity 500. The central pointing also provides data for a detailed two-dimensional gas temperature map of this interesting cluster. We have analyzed all three observations. The derivation of the temperature map using the central pointing is complete, and the paper is soon to be submitted. During the course of this study and of the analysis of archival XMM cluster observations, it became apparent that the commonly used XMM background flare screening techniques are often not accurate enough for studies of the cluster outer regions. The information on the cluster's total masses is contained at large off-center distances, and it is precisely the temperatures for those low-brightness regions that are most affected by the detector background anomalies. In particular, our two offset observations of the Triangulum have been contaminated by the background flares ("bad cosmic weather") to a degree where they could not be used for accurate spectral analysis. This forced us to expand the scope of our project. We needed to devise a more accurate method of screening and modeling the background flares, and to evaluate the uncertainty of the XMM background modeling. To do this, we have analyzed a large number of archival EPIC blank-field and closed-cover observations. As a result, we have derived stricter background screening criteria. It also turned out that mild flares affecting EPIC-pn can be modeled with an adequate accuracy. Such modeling has been used to derive our Triangulum temperature map. The results of our XMM background analysis, including the modeling recipes, are presented in a paper which is in final preparation and will be submitted soon. It will be useful not only

Diagnostics of subtropical plants functional state by cluster analysis

Directory of Open Access Journals (Sweden)

Oksana Belous

2016-05-01

Full Text Available The article presents an application example of statistical methods for data analysis on diagnosis of the adaptive capacity of subtropical plants varieties. We depicted selection indicators and basic physiological parameters that were defined as diagnostic. We used evaluation on a set of parameters of water regime, there are: determination of water deficit of the leaves, determining the fractional composition of water and detection parameters of the concentration of cell sap (CCS (for tea culture flushes. These settings are characterized by high liability and high responsiveness to the effects of many abiotic factors that determined the particular care in the selection of plant material for analysis and consideration of the impact on sustainability. On the basis of the experimental data calculated the coefficients of pair correlation between climatic factors and used physiological indicators. The result was a selection of physiological and biochemical indicators proposed to assess the adaptability and included in the basis of methodical recommendations on diagnostics of the functional state of the studied cultures. Analysis of complex studies involving a large number of indicators is quite difficult, especially does not allow to quickly identify the similarity of new varieties for their adaptive responses to adverse factors, and, therefore, to set general requirements to conditions of cultivation. Use of cluster analysis suggests that in the analysis of only quantitative data; define a set of variables used to assess varieties (and the more sampling, the more accurate the clustering will happen, be sure to ascertain the measure of similarity (or difference between objects. It is shown that the identification of diagnostic features, which are subjected to statistical processing, impact the accuracy of the varieties classification. Selection in result of the mono-clusters analysis (variety tea Kolhida; hazelnut Lombardsky red; variety kiwi Monty

Analysis of the Structures and Properties of (GaSb)n (n = 4-9) Clusters through Density Functional Theory.

Science.gov (United States)

Lu, Qi Liang; Luo, Qi Quan; Huang, Shou Guo; Li, Yi De; Wan, Jian Guo

2016-07-07

An optimization strategy combining global semiempirical quantum mechanical search with all-electron density functional theory was adopted to determine the lowest energy structure of (GaSb)n clusters up to n = 9. The growth pattern of the clusters differed from those of previously reported group III-V binary clusters. A cagelike configuration was found for cluster sizes n ≤ 7. The structure of (GaSb)6 deviated from that of other III-V clusters. Competition existed between core-shell and hollow cage structures of (GaSb)7. Novel noncagelike structures were energetically preferred over the cages for the (GaSb)8 and (GaSb)9 clusters. Electronic properties, such as vertical ionization potential, adiabatic electron affinities, HOMO-LUMO gaps, and average on-site charges on Ga or Sb atoms, as well as binding energies, were computed.

Range-clustering queries

NARCIS (Netherlands)

Abrahamsen, M.; de Berg, M.T.; Buchin, K.A.; Mehr, M.; Mehrabi, A.D.

2017-01-01

In a geometric k -clustering problem the goal is to partition a set of points in R d into k subsets such that a certain cost function of the clustering is minimized. We present data structures for orthogonal range-clustering queries on a point set S : given a query box Q and an integer k>2 , compute

Cluster-cluster correlations in the two-dimensional stationary Ising-model

International Nuclear Information System (INIS)

Klassmann, A.

1997-01-01

In numerical integration of the Cahn-Hillard equation, which describes Oswald rising in a two-phase matrix, N. Masbaum showed that spatial correlations between clusters scale with respect to the mean cluster size (itself a function of time). T. B. Liverpool showed by Monte Carlo simulations for the Ising model that the analogous correlations have a similar form. Both demonstrated that immediately around each cluster there is some depletion area followed by something like a ring of clusters of the same size as the original one. More precisely, it has been shown that the distribution of clusters around a given cluster looks like a sinus-curve decaying exponentially with respect to the distance to a constant value

Ensemble averaged structure–function relationship for nanocrystals: effective superparamagnetic Fe clusters with catalytically active Pt skin [Ensemble averaged structure-function relationship for composite nanocrystals: magnetic bcc Fe clusters with catalytically active fcc Pt skin

Energy Technology Data Exchange (ETDEWEB)

Petkov, Valeri [Central Michigan University, Mt. Pleasant, MI (United States); Prasai, Binay [Central Michigan University, Mt. Pleasant, MI (United States); Shastri, Sarvjit [Argonne National Lab. (ANL), Argonne, IL (United States). X-ray Science Division; Park, Hyun-Uk [Sungkyunkwan University, Suwon (Korea). Department of Chemistry; Kwon, Young-Uk [Sungkyunkwan University, Suwon (Korea). Department of Chemistry; Skumryev, Vassil [Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona (Spain); Universitat Autònoma de Barcelona (Spain). Department of Physics

2017-09-12

Practical applications require the production and usage of metallic nanocrystals (NCs) in large ensembles. Besides, due to their cluster-bulk solid duality, metallic NCs exhibit a large degree of structural diversity. This poses the question as to what atomic-scale basis is to be used when the structure–function relationship for metallic NCs is to be quantified precisely. In this paper, we address the question by studying bi-functional Fe core-Pt skin type NCs optimized for practical applications. In particular, the cluster-like Fe core and skin-like Pt surface of the NCs exhibit superparamagnetic properties and a superb catalytic activity for the oxygen reduction reaction, respectively. We determine the atomic-scale structure of the NCs by non-traditional resonant high-energy X-ray diffraction coupled to atomic pair distribution function analysis. Using the experimental structure data we explain the observed magnetic and catalytic behavior of the NCs in a quantitative manner. Lastly, we demonstrate that NC ensemble-averaged 3D positions of atoms obtained by advanced X-ray scattering techniques are a very proper basis for not only establishing but also quantifying the structure–function relationship for the increasingly complex metallic NCs explored for practical applications.

Function analysis of 5'-UTR of the cellulosomal xyl-doc cluster in Clostridium papyrosolvens.

Science.gov (United States)

Zou, Xia; Ren, Zhenxing; Wang, Na; Cheng, Yin; Jiang, Yuanyuan; Wang, Yan; Xu, Chenggang

2018-01-01

Anaerobic, mesophilic, and cellulolytic Clostridium papyrosolvens produces an efficient cellulolytic extracellular complex named cellulosome that hydrolyzes plant cell wall polysaccharides into simple sugars. Its genome harbors two long cellulosomal clusters: cip - cel operon encoding major cellulosome components (including scaffolding) and xyl - doc gene cluster encoding hemicellulases. Compared with works on cip - cel operon, there are much fewer studies on xyl - doc mainly due to its rare location in cellulolytic clostridia. Sequence analysis of xyl - doc revealed that it harbors a 5' untranslated region (5'-UTR) which potentially plays a role in the regulation of downstream gene expression. Here, we analyzed the function of 5'-UTR of xyl - doc cluster in C. papyrosolvens in vivo via transformation technology developed in this study. In this study, we firstly developed an electrotransformation method for C. papyrosolvens DSM 2782 before the analysis of 5'-UTR of xyl - doc cluster. In the optimized condition, a field with an intensity of 7.5-9.0 kV/cm was applied to a cuvette (0.2 cm gap) containing a mixture of plasmid and late cell suspended in exponential phase to form a 5 ms pulse in a sucrose-containing buffer. Afterwards, the putative promoter and the 5'-UTR of xyl - doc cluster were determined by sequence alignment. It is indicated that xyl - doc possesses a long conservative 5'-UTR with a complex secondary structure encompassing at least two perfect stem-loops which are potential candidates for controlling the transcriptional termination. In the last step, we employed an oxygen-independent flavin-based fluorescent protein (FbFP) as a quantitative reporter to analyze promoter activity and 5'-UTR function in vivo. It revealed that 5'-UTR significantly blocked transcription of downstream genes, but corn stover can relieve its suppression. In the present study, our results demonstrated that 5'-UTR of the cellulosomal xyl - doc cluster blocks the

CpG island protects Rous sarcoma virus-derived vectors integrated into nonpermissive cells from DNA methylation and transcriptional suppression

Czech Academy of Sciences Publication Activity Database

Hejnar, Jiří; Hájková, P.; Plachý, Jiří; Elleder, Daniel; Stepanets, Volodymyr; Svoboda, Jan

2001-01-01

Roč. 98, č. 2 (2001), s. 565-569 ISSN 0027-8424 R&D Projects: GA ČR GA312/97/P082; GA ČR GA312/98/0825 Keywords : CpG island * provirus silencing * DNA methylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.890, year: 2001

Body size, physical activity and risk of colorectal cancer with or without the CpG island methylator phenotype (CIMP)

NARCIS (Netherlands)

Hughes, L.A.E.; Simons, C.C.J.M.; Brandt, P.A. van den; Goldbohm, R.A.; Goeij, A.F. de; Bruïne, A.P. de; Engeland, M. van; Weijenberg, M.P.

2011-01-01

Background: We investigated how body size and physical activity influence the risk of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). Methods: In the Netherlands Cohort Study (n = 120,852), risk factors were self-reported at baseline in 1986. After 7.3 years of follow-up, 603

Statistical Issues in Galaxy Cluster Cosmology

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Mantz, Adam

2013-01-01

The number and growth of massive galaxy clusters are sensitive probes of cosmological structure formation. Surveys at various wavelengths can detect clusters to high redshift, but the fact that cluster mass is not directly observable complicates matters, requiring us to simultaneously constrain scaling relations of observable signals with mass. The problem can be cast as one of regression, in which the data set is truncated, the (cosmology-dependent) underlying population must be modeled, and strong, complex correlations between measurements often exist. Simulations of cosmological structure formation provide a robust prediction for the number of clusters in the Universe as a function of mass and redshift (the mass function), but they cannot reliably predict the observables used to detect clusters in sky surveys (e.g. X-ray luminosity). Consequently, observers must constrain observable-mass scaling relations using additional data, and use the scaling relation model in conjunction with the mass function to predict the number of clusters as a function of redshift and luminosity.

Deep UV Luminosity Functions at the Infall Region of the Coma Cluster

Science.gov (United States)

Hammer, D. M.; Hornschemeier, A. E.; Salim, S.; Smith, R.; Jenkins, L.; Mobasher, B.; Miller, N.; Ferguson, H.

2011-01-01

We have used deep GALEX observations at the infall region of the Coma cluster to measure the faintest UV luminosity functions (LFs) presented for a rich galaxy cluster thus far. The Coma UV LFs are measured to M(sub uv) = -10.5 in the GALEX FUV and NUV bands, or 3.5 mag fainter than previous studies, and reach the dwarf early-type galaxy population in Coma for the first time. The Schechter faint-end slopes (alpha approximately equal to -1.39 in both GALEX bands) are shallower than reported in previous Coma UV LF studies owing to a flatter LF at faint magnitudes. A Gaussian-plus-Schechter model provides a slightly better parametrization of the UV LFs resulting in a faint-end slope of alpha approximately equal to -1.15 in both GALEX bands. The two-component model gives faint-end slopes shallower than alpha = -1 (a turnover) for the LFs constructed separately for passive and star forming galaxies. The UV LFs for star forming galaxies show a turnover at M(sub UV) approximately equal to -14 owing to a deficit of dwarf star forming galaxies in Coma with stellar masses below M(sub *) = 10(sup 8) solar mass. A similar turnover is identified in recent UV LFs measured for the Virgo cluster suggesting this may be a common feature of local galaxy clusters, whereas the field UV LFs continue to rise at faint magnitudes. We did not identify an excess of passive galaxies as would be expected if the missing dwarf star forming galaxies were quenched inside the cluster. In fact, the LFs for both dwarf passive and star forming galaxies show the same turnover at faint magnitudes. We discuss the possible origin of the missing dwarf star forming galaxies in Coma and their expected properties based on comparisons to local field galaxies.

DEEP ULTRAVIOLET LUMINOSITY FUNCTIONS AT THE INFALL REGION OF THE COMA CLUSTER

International Nuclear Information System (INIS)

Hammer, D. M.; Hornschemeier, A. E.; Jenkins, L.; Salim, S.; Smith, R.; Mobasher, B.; Miller, N.; Ferguson, H.

2012-01-01

We have used deep GALEX observations at the infall region of the Coma cluster to measure the faintest ultraviolet (UV) luminosity functions (LFs) presented for a rich galaxy cluster thus far. The Coma UV LFs are measured to M UV = –10.5 in the GALEX FUV and NUV bands, or 3.5 mag fainter than previous studies, and reach the dwarf early-type galaxy population in Coma for the first time. The Schechter faint-end slopes (α ≈ –1.39 in both GALEX bands) are shallower than reported in previous Coma UV LF studies owing to a flatter LF at faint magnitudes. A Gaussian-plus-Schechter model provides a slightly better parameterization of the UV LFs resulting in a faint-end slope of α ≈ –1.15 in both GALEX bands. The two-component model gives faint-end slopes shallower than α = –1 (a turnover) for the LFs constructed separately for passive and star-forming galaxies. The UV LFs for star-forming galaxies show a turnover at M UV ≈ –14 owing to a deficit of dwarf star-forming galaxies in Coma with stellar masses below M * = 10 8 M ☉ . A similar turnover is identified in recent UV LFs measured for the Virgo cluster suggesting this may be a common feature of local galaxy clusters, whereas the field UV LFs continue to rise at faint magnitudes. We did not identify an excess of passive galaxies as would be expected if the missing dwarf star-forming galaxies were quenched inside the cluster. In fact, the LFs for both dwarf passive and star-forming galaxies show the same turnover at faint magnitudes. We discuss the possible origin of the missing dwarf star-forming galaxies in Coma and their expected properties based on comparisons to local field galaxies.

Structure and Electronic Properties of Neutral and Negatively Charged RhBn Clusters (n = 3-10): A Density Functional Theory Study.

Science.gov (United States)

Li, Peifang; Mei, Tingting; Lv, Linxia; Lu, Cheng; Wang, Weihua; Bao, Gang; Gutsev, Gennady L

2017-08-31

The geometrical structure and electronic properties of the neutral RhB n and singly negatively charged RhB n - clusters are obtained in the range of 3 ≤ n ≤ 10 using the unbiased CALYPSO structure search method and density functional theory (DFT). A combination of the PBE0 functional and the def2-TZVP basis set is used for determining global minima on potential energy surfaces of the Rh-doped B n clusters. The photoelectron spectra of the anions are simulated using the time-dependent density functional theory (TD-DFT) method. Good agreement between our simulated and experimentally obtained photoelectron spectra for RhB 9 - provides support to the validity of our theoretical method. The relative stabilities of the ground-state RhB n and RhB n - clusters are estimated using the calculated binding energies, second-order total energy differences, and HOMO-LUMO gaps. It is found that RhB 7 and RhB 8 - are the most stable species in the neutral and anionic series, respectively. The chemical bonding analysis reveals that the RhB 8 - cluster possesses two sets of delocalized σ and π bonds. In both cases, the Hückel 4N + 2 rule is fulfilled and this cluster possesses both σ and π aromaticities.

Subaru weak-lensing survey of dark matter subhalos in the Coma cluster: Subhalo mass function and statistical properties

International Nuclear Information System (INIS)

Okabe, Nobuhiro; Futamase, Toshifumi; Kuroshima, Risa; Kajisawa, Masaru

2014-01-01

We present a 4 deg 2 weak gravitational lensing survey of subhalos in the very nearby Coma cluster using the Subaru/Suprime-Cam. The large apparent size of cluster subhalos allows us to measure the mass of 32 subhalos detected in a model-independent manner, down to the order of 10 –3 of the virial mass of the cluster. Weak-lensing mass measurements of these shear-selected subhalos enable us to investigate subhalo properties and the correlation between subhalo masses and galaxy luminosities for the first time. The mean distortion profiles stacked over subhalos show a sharply truncated feature which is well-fitted by a Navarro-Frenk-White (NFW) mass model with the truncation radius, as expected due to tidal destruction by the main cluster. We also found that subhalo masses, truncation radii, and mass-to-light ratios decrease toward the cluster center. The subhalo mass function, dn/dln M sub , in the range of 2 orders of magnitude in mass, is well described by a single power law or a Schechter function. Best-fit power indices of 1.09 −0.32 +0.42 for the former model and 0.99 −0.23 +0.34 for the latter, are in remarkable agreement with slopes of ∼0.9-1.0 predicted by the cold dark matter paradigm. The tangential distortion signals in the radial range of 0.02-2 h –1 Mpc from the cluster center show a complex structure which is well described by a composition of three mass components of subhalos, the NFW mass distribution as a smooth component of the main cluster, and a lensing model from a large scale structure behind the cluster. Although the lensing signals are 1 order of magnitude lower than those for clusters at z ∼ 0.2, the total signal-to-noise ratio, S/N = 13.3, is comparable, or higher, because the enormous number of background source galaxies compensates for the low lensing efficiency of the nearby cluster.

Electronic structure and properties of designer clusters and cluster-assemblies

International Nuclear Information System (INIS)

Khanna, S.N.; Jena, P.

1995-01-01

Using self-consistent calculations based on density functional theory, we demonstrate that electronic shell filling and close atomic packing criteria can be used to design ultra-stable clusters. Interaction of these clusters with each other and with gas atoms is found to be weak confirming their chemical inertness. A crystal composed of these inert clusters is expected to have electronic properties that are markedly different from crystals where atoms are the building blocks. The recent observation of ferromagnetism in potassium clusters assembled in zeolite cages is discussed. (orig.)

Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias

Directory of Open Access Journals (Sweden)

Sofie Degerman

2014-07-01

Full Text Available We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs, islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis.

clusterMaker: a multi-algorithm clustering plugin for Cytoscape

Directory of Open Access Journals (Sweden)

Morris John H

2011-11-01

Full Text Available Abstract Background In the post-genomic era, the rapid increase in high-throughput data calls for computational tools capable of integrating data of diverse types and facilitating recognition of biologically meaningful patterns within them. For example, protein-protein interaction data sets have been clustered to identify stable complexes, but scientists lack easily accessible tools to facilitate combined analyses of multiple data sets from different types of experiments. Here we present clusterMaker, a Cytoscape plugin that implements several clustering algorithms and provides network, dendrogram, and heat map views of the results. The Cytoscape network is linked to all of the other views, so that a selection in one is immediately reflected in the others. clusterMaker is the first Cytoscape plugin to implement such a wide variety of clustering algorithms and visualizations, including the only implementations of hierarchical clustering, dendrogram plus heat map visualization (tree view, k-means, k-medoid, SCPS, AutoSOME, and native (Java MCL. Results Results are presented in the form of three scenarios of use: analysis of protein expression data using a recently published mouse interactome and a mouse microarray data set of nearly one hundred diverse cell/tissue types; the identification of protein complexes in the yeast Saccharomyces cerevisiae; and the cluster analysis of the vicinal oxygen chelate (VOC enzyme superfamily. For scenario one, we explore functionally enriched mouse interactomes specific to particular cellular phenotypes and apply fuzzy clustering. For scenario two, we explore the prefoldin complex in detail using both physical and genetic interaction clusters. For scenario three, we explore the possible annotation of a protein as a methylmalonyl-CoA epimerase within the VOC superfamily. Cytoscape session files for all three scenarios are provided in the Additional Files section. Conclusions The Cytoscape plugin cluster

Clustering and visualizing similarity networks of membrane proteins.

Science.gov (United States)

Hu, Geng-Ming; Mai, Te-Lun; Chen, Chi-Ming

2015-08-01

We proposed a fast and unsupervised clustering method, minimum span clustering (MSC), for analyzing the sequence-structure-function relationship of biological networks, and demonstrated its validity in clustering the sequence/structure similarity networks (SSN) of 682 membrane protein (MP) chains. The MSC clustering of MPs based on their sequence information was found to be consistent with their tertiary structures and functions. For the largest seven clusters predicted by MSC, the consistency in chain function within the same cluster is found to be 100%. From analyzing the edge distribution of SSN for MPs, we found a characteristic threshold distance for the boundary between clusters, over which SSN of MPs could be properly clustered by an unsupervised sparsification of the network distance matrix. The clustering results of MPs from both MSC and the unsupervised sparsification methods are consistent with each other, and have high intracluster similarity and low intercluster similarity in sequence, structure, and function. Our study showed a strong sequence-structure-function relationship of MPs. We discussed evidence of convergent evolution of MPs and suggested applications in finding structural similarities and predicting biological functions of MP chains based on their sequence information. © 2015 Wiley Periodicals, Inc.

CpG Island Methylation in Colorectal Cancer: Past, Present and Future

Directory of Open Access Journals (Sweden)

Karen Curtin

2011-01-01

Full Text Available The concept of a CpG island methylator phenotype, or CIMP, quickly became the focus of several colorectal cancer studies describing its clinical and pathological features after its introduction in 1999 by Toyota and colleagues. Further characterization of CIMP in tumors lead to widespread acceptance of the concept, as expressed by Shen and Issa in their 2005 editorial, “CIMP, at last.” Since that time, extensive research efforts have brought great insights into the epidemiology and prognosis of CIMP+ tumors and other epigenetic mechanisms underlying tumorigenesis. With the advances in technology and subsequent cataloging of the human methylome in cancer and normal tissue, new directions in research to understand CIMP and its role in complex biological systems yield hope for future epigenetically based diagnostics and treatments.

Cluster management.

Science.gov (United States)

Katz, R

1992-11-01

Cluster management is a management model that fosters decentralization of management, develops leadership potential of staff, and creates ownership of unit-based goals. Unlike shared governance models, there is no formal structure created by committees and it is less threatening for managers. There are two parts to the cluster management model. One is the formation of cluster groups, consisting of all staff and facilitated by a cluster leader. The cluster groups function for communication and problem-solving. The second part of the cluster management model is the creation of task forces. These task forces are designed to work on short-term goals, usually in response to solving one of the unit's goals. Sometimes the task forces are used for quality improvement or system problems. Clusters are groups of not more than five or six staff members, facilitated by a cluster leader. A cluster is made up of individuals who work the same shift. For example, people with job titles who work days would be in a cluster. There would be registered nurses, licensed practical nurses, nursing assistants, and unit clerks in the cluster. The cluster leader is chosen by the manager based on certain criteria and is trained for this specialized role. The concept of cluster management, criteria for choosing leaders, training for leaders, using cluster groups to solve quality improvement issues, and the learning process necessary for manager support are described.

Effectiveness of a clinical practice guideline implementation strategy for patients with anxiety disorders in primary care: cluster randomized trial.

Science.gov (United States)

Tello-Bernabé, Eugenia; Sanz-Cuesta, Teresa; del Cura-González, Isabel; de Santiago-Hernando, María L; Jurado-Sueiro, Montserrat; Fernández-Girón, Mercedes; García-de Blas, Francisca; Pensado-Freire, Higinio; Góngora-Maldonado, Francisco; de la Puente-Chamorro, María J; Rodríguez-Pasamontes, Carmen; Martín-Iglesias, Susana

2011-12-01

Anxiety is a common mental health problem seen in primary care. However, its management in clinical practice varies greatly. Clinical practice guidelines (CPGs) have the potential to reduce variations and improve the care received by patients by promoting interventions of proven benefit. However, uptake and adherence to their recommendations can be low. This study involves a community based on cluster randomized trial in primary healthcare centres in the Madrid Region (Spain). The project aims to determine whether the use of implementation strategy (including training session, information, opinion leader, reminders, audit, and feed-back) of CPG for patients with anxiety disorders in primary care is more effective than usual diffusion. The number of patients required is 296 (148 in each arm), all older than 18 years and diagnosed with generalized anxiety disorder, panic disorder, and panic attacks by the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). They are chosen by consecutive sampling. The main outcome variable is the change in two or more points into Goldberg anxiety scale at six and twelve months. Secondary outcome variables include quality of life (EuroQol 5D), and degree of compliance with the CPG recommendations on treatment, information, and referrals to mental health services. Main effectiveness will be analyzed by comparing the patients percentage improvement on the Goldberg scale between the intervention group and the control group. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. There is a need to identify effective implementation strategies for CPG for the management of anxiety disorders present in primary care. Ensuring the appropriate uptake of guideline recommendations can reduce clinical variation and improve the care patients receive. ISRCTN: ISRCTN83365316.

Effectiveness of a clinical practice guideline implementation strategy for patients with anxiety disorders in primary care: cluster randomized trial

Directory of Open Access Journals (Sweden)

Tello-Bernabé Eugenia

2011-12-01

Full Text Available Abstract Background Anxiety is a common mental health problem seen in primary care. However, its management in clinical practice varies greatly. Clinical practice guidelines (CPGs have the potential to reduce variations and improve the care received by patients by promoting interventions of proven benefit. However, uptake and adherence to their recommendations can be low. Method/design This study involves a community based on cluster randomized trial in primary healthcare centres in the Madrid Region (Spain. The project aims to determine whether the use of implementation strategy (including training session, information, opinion leader, reminders, audit, and feed-back of CPG for patients with anxiety disorders in primary care is more effective than usual diffusion. The number of patients required is 296 (148 in each arm, all older than 18 years and diagnosed with generalized anxiety disorder, panic disorder, and panic attacks by the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV. They are chosen by consecutive sampling. The main outcome variable is the change in two or more points into Goldberg anxiety scale at six and twelve months. Secondary outcome variables include quality of life (EuroQol 5D, and degree of compliance with the CPG recommendations on treatment, information, and referrals to mental health services. Main effectiveness will be analyzed by comparing the patients percentage improvement on the Goldberg scale between the intervention group and the control group. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. Discussion There is a need to identify effective implementation strategies for CPG for the management of anxiety disorders present in primary care. Ensuring the appropriate uptake of guideline recommendations can reduce clinical variation and improve the care

The Impact of Multipollutant Clusters on the Association Between Fine Particulate Air Pollution and Microvascular Function.

Science.gov (United States)

Ljungman, Petter L; Wilker, Elissa H; Rice, Mary B; Austin, Elena; Schwartz, Joel; Gold, Diane R; Koutrakis, Petros; Benjamin, Emelia J; Vita, Joseph A; Mitchell, Gary F; Vasan, Ramachandran S; Hamburg, Naomi M; Mittleman, Murray A

2016-03-01

Prior studies including the Framingham Heart Study have suggested associations between single components of air pollution and vascular function; however, underlying mixtures of air pollution may have distinct associations with vascular function. We used a k-means approach to construct five distinct pollution mixtures from elemental analyses of particle filters, air pollution monitoring data, and meteorology. Exposure was modeled as an interaction between fine particle mass (PM2.5), and concurrent pollution cluster. Outcome variables were two measures of microvascular function in the fingertip in the Framingham Offspring and Third Generation cohorts from 2003 to 2008. In 1,720 participants, associations between PM2.5 and baseline pulse amplitude tonometry differed by air pollution cluster (interaction P value 0.009). Higher PM2.5 on days with low mass concentrations but high proportion of ultrafine particles from traffic was associated with 18% (95% confidence interval: 4.6%, 33%) higher baseline pulse amplitude per 5 μg/m and days with high contributions of oil and wood combustion with 16% (95% confidence interval: 0.2%, 34%) higher baseline pulse amplitude. We observed no variation in associations of PM2.5 with hyperemic response to ischemia observed across air pollution clusters. PM2.5 exposure from air pollution mixtures with large contributions of local ultrafine particles from traffic, heating oil, and wood combustion was associated with higher baseline pulse amplitude but not hyperemic response. Our findings suggest little association between acute exposure to air pollution clusters reflective of select sources and hyperemic response to ischemia, but possible associations with excessive small artery pulsatility with potentially deleterious microvascular consequences.

Convex Clustering: An Attractive Alternative to Hierarchical Clustering

Science.gov (United States)

Chen, Gary K.; Chi, Eric C.; Ranola, John Michael O.; Lange, Kenneth

2015-01-01

The primary goal in cluster analysis is to discover natural groupings of objects. The field of cluster analysis is crowded with diverse methods that make special assumptions about data and address different scientific aims. Despite its shortcomings in accuracy, hierarchical clustering is the dominant clustering method in bioinformatics. Biologists find the trees constructed by hierarchical clustering visually appealing and in tune with their evolutionary perspective. Hierarchical clustering operates on multiple scales simultaneously. This is essential, for instance, in transcriptome data, where one may be interested in making qualitative inferences about how lower-order relationships like gene modules lead to higher-order relationships like pathways or biological processes. The recently developed method of convex clustering preserves the visual appeal of hierarchical clustering while ameliorating its propensity to make false inferences in the presence of outliers and noise. The solution paths generated by convex clustering reveal relationships between clusters that are hidden by static methods such as k-means clustering. The current paper derives and tests a novel proximal distance algorithm for minimizing the objective function of convex clustering. The algorithm separates parameters, accommodates missing data, and supports prior information on relationships. Our program CONVEXCLUSTER incorporating the algorithm is implemented on ATI and nVidia graphics processing units (GPUs) for maximal speed. Several biological examples illustrate the strengths of convex clustering and the ability of the proximal distance algorithm to handle high-dimensional problems. CONVEXCLUSTER can be freely downloaded from the UCLA Human Genetics web site at http://www.genetics.ucla.edu/software/ PMID:25965340

CpG oligodeoxynucleotide induces apoptosis and cell cycle arrest in A20 lymphoma cells via TLR9-mediated pathways.

Science.gov (United States)

Qi, Xu-Feng; Zheng, Li; Kim, Cheol-Su; Lee, Kyu-Jae; Kim, Dong-Heui; Cai, Dong-Qing; Qin, Jun-Wen; Yu, Yan-Hong; Wu, Zheng; Kim, Soo-Ki

2013-07-01

Recent studies have suggested that the anti-cancer activity of CpG-oligodeoxynucleotides (CpG-ODNs) is owing to their immunomodulatory effects in tumor-bearing host. The purpose of this study is to investigate the directly cytotoxic activity of KSK-CpG, a novel CpG-ODN with an alternative CpG motif, against A20 and EL4 lymphoma cells in comparison with previously used murine CpG motif (1826-CpG). To evaluate the potential cytotoxic effects of KSK-CpG on lymphoma cells, cell viability assay, confocal microscopy, flow cytometry, DNA fragmentation, Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) analysis were used. We found that KSK-CpG induced direct cytotoxicity in A20 lymphoma cells, but not in EL4 lymphoma cells, at least in part via TLR9-mediated pathways. Apoptotic cell death was demonstrated to play an important role in CpG-ODNs-induced cytotoxicity. In addition, both mitochondrial membrane potential decrease and G1-phase arrest were involved in KSK-CpG-induced apoptosis in A20 cells. The activities of apoptotic molecules such as caspase-3, PARP, and Bax were increased, but the activation of p27 Kip1 and ERK were decreased in KSK-CpG-treated A20 cells. Furthermore, autocrine IFN-γ partially contributed to apoptotic cell death in KSK-CpG-treated A20 cells. Collectively, our findings suggest that KSK-CpG induces apoptotic cell death in A20 lymphoma cells at least in part by inducing G1-phase arrest and autocrine IFN-γ via increasing TLR9 expression, without the need for immune system of tumor-bearing host. This new understanding supports the development of TLR9-targeted therapy with CpG-ODN as a direct therapeutic agent for treating B lymphoma. Copyright © 2013 Elsevier Ltd. All rights reserved.

Aberrant septin 9 DNA methylation in colorectal cancer is restricted to a single CpG island

International Nuclear Information System (INIS)

Wasserkort, Reinhold; Kalmar, Alexandra; Valcz, Gabor; Spisak, Sandor; Krispin, Manuel; Toth, Kinga; Tulassay, Zsolt; Sledziewski, Andrew Z; Molnar, Bela

2013-01-01

The septin 9 gene (SEPT9) codes for a GTP-binding protein associated with filamentous structures and cytoskeleton formation. SEPT9 plays a role in multiple cancers as either an oncogene or a tumor suppressor gene. Regulation of SEPT9 expression is complex and not well understood; however, hypermethylation of the gene was recently introduced as a biomarker for early detection of colorectal cancer (CRC) and has been linked to cancer of the breast and of the head and neck. Because the DNA methylation landscape of different regions of SEPT9 is poorly understood in cancer, we analyzed the methylation patterns of this gene in distinct cell populations from normal and diseased colon mucosa. Laser capture microdissection was performed to obtain homogeneous populations of epithelial and stromal cells from normal, adenomatous, and tumorous colon mucosa. Microdissected samples were analyzed using direct bisulfite sequencing to determine the DNA methylation status of eight regions within and near the SEPT9 gene. Septin-9 protein expression was assessed using immunohistochemistry (IHC). Regions analyzed in SEPT9 were unmethylated in normal tissue except for a methylation boundary detected downstream of the largest CpG island. In adenoma and tumor tissues, epithelial cells displayed markedly increased DNA methylation levels (>80%, p <0.0001) in only one of the CpG islands investigated. SEPT9 methylation in stromal cells increased in adenomatous and tumor tissues (≤50%, p <0.0001); however, methylation did not increase in stromal cells of normal tissue close to the tumor. IHC data indicated a significant decrease (p <0.01) in Septin-9 protein levels in epithelial cells derived from adenoma and tumor tissues; Septin-9 protein levels in stromal cells were low in all tissues. Hypermethylation of SEPT9 in adenoma and CRC specimens is confined to one of several CpG islands of this gene. Tumor-associated aberrant methylation originates in epithelial cells; stromal cells appear to

Alpha condensates and nonlocalized cluster structures

International Nuclear Information System (INIS)

Funaki, Yasuro

2014-01-01

We discuss a container structure for non-gaslike cluster states, in which single Tohsaki-Horiuchi-Schuck-ROpke (THSR) wave functions are shown to be almost 100% equivalent to the full solutions of the corresponding RGM/GCM equations, for the inversion doublet band states in 20 Ne, α-linear-chain states, and α + α + A cluster states in 9 Λ Be. The recognition of the fact that the THSR wave function describes well not only gaslike cluster states but also non-gaslike cluster states is a recent remarkable development of nuclear cluster physics. This fact tells us that the cluster structure is composed of cluster-mean-field motion under the constraint of inter-cluster Pauli repulsion, in which we call the cluster-mean-field potential the container. We demonstrate that the evolution of the cluster structure of a nucleus is governed by the size parameter of the cluster-mean-field potential (container), for 16 O nucleus

CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway.

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Rhee, Ye-Young; Kim, Kyung-Ju; Kang, Gyeong Hoon

2017-01-15

The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway.

CpG Type A Induction of an Early Protective Environment in Experimental Multiple Sclerosis

Directory of Open Access Journals (Sweden)

James Crooks

2017-01-01

Full Text Available Experimental autoimmune encephalomyelitis (EAE is an inflammatory, demyelinating disease of the CNS that mimics human multiple sclerosis (MS, and it is thought to be driven by Th1 and Th17 myelin-reactive cells. Although adaptive immunity is clearly pivotal in the pathogenesis of EAE, with an essential role of CD4+ T cells, little is known of early, innate responses in this experimental setting. CpG-rich oligodeoxynucleotides (ODNs, typically found in microbial genomes, are potent activators of TLR9 in plasmacytoid dendritic cells (pDCs. In this study, we compared the effects of two types of CpG, namely, type A and type B, on EAE. We found that treatment with CpG type A ODN (CpG-A, known to induce high amounts of IFN-α in pDCs, significantly reduced disease severity in EAE, relative to controls (12.63±1.86 versus 23.49±1.46, resp.; p=0.001. Treatment also delayed onset of neurological deficits and reduced spinal cord demyelination, while increasing the percentage of splenic regulatory (Foxp3+ CD4+ T cells. CpG-A likewise reduced the levels of IL-17 and IFN-γ in the CNS. Mechanistic insight into those events showed that CpG-A promoted a regulatory phenotype in pDCs. Moreover, adoptive transfer of pDCs isolated from CpG-A-treated mice inhibited CNS inflammation and induced disease remission in acute-phase EAE. Our data thus identify a link between TLR9 activation by specific ligands and the induction of tolerance via innate immunity mechanisms.

Different definitions of CpG island methylator phenotype and outcomes of colorectal cancer: a systematic review

OpenAIRE

Jia, Min; Gao, Xu; Zhang, Yan; Hoffmeister, Michael; Brenner, Hermann

2016-01-01

Contradictory results were reported for the prognostic role of CpG island methylator phenotype (CIMP) among colorectal cancer (CRC) patients. Differences in the definitions of CIMP were the most common explanation for these discrepancies. The aim of this systematic review was to give an overview of the published studies on CRC prognosis according to the different definitions of CIMP. A systematic literature search was performed in MEDLINE and ISI Web of Science for articles published until 3 ...

Bacterial xylose isomerases from the mammal gut Bacteroidetes cluster function in Saccharomyces cerevisiae for effective xylose fermentation.

Science.gov (United States)

Peng, Bingyin; Huang, Shuangcheng; Liu, Tingting; Geng, Anli

2015-05-17

Xylose isomerase (XI) catalyzes the conversion of xylose to xylulose, which is the key step for anaerobic ethanolic fermentation of xylose. Very few bacterial XIs can function actively in Saccharomyces cerevisiae. Here, we illustrate a group of XIs that would function for xylose fermentation in S. cerevisiae through phylogenetic analysis, recombinant yeast strain construction, and xylose fermentation. Phylogenetic analysis of deposited XI sequences showed that XI evolutionary relationship was highly consistent with the bacterial taxonomic orders and quite a few functional XIs in S. cerevisiae were clustered with XIs from mammal gut Bacteroidetes group. An XI from Bacteroides valgutus in this cluster was actively expressed in S. cerevisiae with an activity comparable to the fungal XI from Piromyces sp. Two XI genes were isolated from the environmental metagenome and they were clustered with XIs from environmental Bacteroidetes group. These two XIs could not be expressed in yeast with activity. With the XI from B. valgutus expressed in S. cerevisiae, background yeast strains were optimized by pentose metabolizing pathway enhancement and adaptive evolution in xylose medium. Afterwards, more XIs from the mammal gut Bacteroidetes group, including those from B. vulgatus, Tannerella sp. 6_1_58FAA_CT1, Paraprevotella xylaniphila and Alistipes sp. HGB5, were individually transformed into S. cerevisiae. The known functional XI from Orpinomyces sp. ukk1, a mammal gut fungus, was used as the control. All the resulting recombinant yeast strains were able to ferment xylose. The respiration-deficient strains harboring B. vulgatus and Alistipes sp. HGB5 XI genes respectively obtained specific xylose consumption rate of 0.662 and 0.704 g xylose gcdw(-1) h(-1), and ethanol specific productivity of 0.277 and 0.283 g ethanol gcdw(-1) h(-1), much comparable to those obtained by the control strain carrying Orpinomyces sp. ukk1 XI gene. This study demonstrated that XIs clustered in the

Density functional study of TaSin (n = 1-3, 12) clusters adsorbed to graphene surface

International Nuclear Information System (INIS)

Guo Ping; Zheng Lin; Zheng Jiming; Zhang Ruizhi; Yang Luna; Ren, Zhaoyu

2011-01-01

A plane-wave density functional theory (DFT) calculations have been performed to investigate structural and electronic properties of TaSi n (n = 1-3, 12) clusters supported by graphene surface. The resulting adsorption structures are described and discussed in terms of stability, bonding, and electron transfer between the cluster and the graphene. The TaSi n clusters on graphene surface favor their free-standing ground-state structures. Especially in the cases of the linear TaSi 2 and the planar TaSi 3 , the graphene surface may catalyze the transition of the TaSi n clusters from an isomer of lower dimensionality into the ground-state structure. The adsorption site and configuration of TaSi n on graphene surface are dominated by the interaction between Ta atom and graphene. Ta atom prefers to adsorb on the hollow site of graphene, and Si atoms tend to locate on the bridge site. Further, the electron transfer is found to proceed from the cluster to the surface for n = 1 and 2, while its direction reverses as n > 2. For the case of TaSi, chemisorption is shown to prevail over physisorption as the dominant mode of surface-adsorbate interaction by charge density analysis.

Evolution of the cluster optical galaxy luminosity function in the CFHTLS: breaking the degeneracy between mass and redshift

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Sarron, F.; Martinet, N.; Durret, F.; Adami, C.

2018-06-01

Obtaining large samples of galaxy clusters is important for cosmology: cluster counts as a function of redshift and mass can constrain the parameters of our Universe. They are also useful in order to understand the formation and evolution of clusters. We develop an improved version of the Adami & MAzure Cluster FInder (AMACFI), now the Adami, MAzure & Sarron Cluster FInder (AMASCFI), and apply it to the 154 deg2 of the Canada-France-Hawaii Telescope Legacy Survey (CFHTLS) to obtain a large catalogue of 1371 cluster candidates with mass M200 > 1014 M⊙ and redshift z ≤ 0.7. We derive the selection function of the algorithm from the Millennium simulation, and cluster masses from a richness-mass scaling relation built from matching our candidates with X-ray detections. We study the evolution of these clusters with mass and redshift by computing the i'-band galaxy luminosity functions (GLFs) for the early-type (ETGs) and late-type galaxies (LTGs). This sample is 90% pure and 70% complete, and therefore our results are representative of a large fraction of the cluster population in these redshift and mass ranges. We find an increase in both the ETG and LTG faint populations with decreasing redshift (with Schechter slopes αETG = -0.65 ± 0.03 and αLTG = -0.95 ± 0.04 at z = 0.6, and αETG = -0.79 ± 0.02 and αLTG = -1.26 ± 0.03 at z = 0.2) and also a decrease in the LTG (but not the ETG) bright end. Our large sample allows us to break the degeneracy between mass and redshift, finding that the redshift evolution is more pronounced in high-mass clusters, but that there is no significant dependence of the faint end on mass for a given redshift. These results show that the cluster red sequence is mainly formed at redshift z > 0.7, and that faint ETGs continue to enrich the red sequence through quenching of brighter LTGs at z ≤ 0.7. The efficiency of this quenching is higher in large-mass clusters, while the accretion rate of faint LTGs is lower as the more massive

Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

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Frank Georgy A

2007-03-01

Full Text Available Abstract Background High risk type human papilloma viruses (HR-HPV induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16ink4a drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16ink4a overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16ink4a overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas Methods Methylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16ink4a was analyzed by RT-PCR and by immunohistochemical technique. Results The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands. The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16ink4a cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors. Conclusion Hypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical

A Resting-State Brain Functional Network Study in MDD Based on Minimum Spanning Tree Analysis and the Hierarchical Clustering

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Xiaowei Li

2017-01-01

Full Text Available A large number of studies demonstrated that major depressive disorder (MDD is characterized by the alterations in brain functional connections which is also identifiable during the brain’s “resting-state.” But, in the present study, the approach of constructing functional connectivity is often biased by the choice of the threshold. Besides, more attention was paid to the number and length of links in brain networks, and the clustering partitioning of nodes was unclear. Therefore, minimum spanning tree (MST analysis and the hierarchical clustering were first used for the depression disease in this study. Resting-state electroencephalogram (EEG sources were assessed from 15 healthy and 23 major depressive subjects. Then the coherence, MST, and the hierarchical clustering were obtained. In the theta band, coherence analysis showed that the EEG coherence of the MDD patients was significantly higher than that of the healthy controls especially in the left temporal region. The MST results indicated the higher leaf fraction in the depressed group. Compared with the normal group, the major depressive patients lost clustering in frontal regions. Our findings suggested that there was a stronger brain interaction in the MDD group and a left-right functional imbalance in the frontal regions for MDD controls.

Determination of the structures of small gold clusters on stepped magnesia by density functional calculations.

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Damianos, Konstantina; Ferrando, Riccardo

2012-02-21

The structural modifications of small supported gold clusters caused by realistic surface defects (steps) in the MgO(001) support are investigated by computational methods. The most stable gold cluster structures on a stepped MgO(001) surface are searched for in the size range up to 24 Au atoms, and locally optimized by density-functional calculations. Several structural motifs are found within energy differences of 1 eV: inclined leaflets, arched leaflets, pyramidal hollow cages and compact structures. We show that the interaction with the step clearly modifies the structures with respect to adsorption on the flat defect-free surface. We find that leaflet structures clearly dominate for smaller sizes. These leaflets are either inclined and quasi-horizontal, or arched, at variance with the case of the flat surface in which vertical leaflets prevail. With increasing cluster size pyramidal hollow cages begin to compete against leaflet structures. Cage structures become more and more favourable as size increases. The only exception is size 20, at which the tetrahedron is found as the most stable isomer. This tetrahedron is however quite distorted. The comparison of two different exchange-correlation functionals (Perdew-Burke-Ernzerhof and local density approximation) show the same qualitative trends. This journal is © The Royal Society of Chemistry 2012

HOX Gene Promoter Prediction and Inter-genomic Comparison: An Evo-Devo Study

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Marla A. Endriga

2010-10-01

Full Text Available Homeobox genes direct the anterior-posterior axis of the body plan in eukaryotic organisms. Promoter regions upstream of the Hox genes jumpstart the transcription process. CpG islands found within the promoter regions can cause silencing of these promoters. The locations of the promoter regions and the CpG islands of Homeo sapiens sapiens (human, Pan troglodytes (chimpanzee, Mus musculus (mouse, and Rattus norvegicus (brown rat are compared and related to the possible influence on the specification of the mammalian body plan. The sequence of each gene in Hox clusters A-D of the mammals considered were retrieved from Ensembl and locations of promoter regions and CpG islands predicted using Exon Finder. The predicted promoter sequences were confirmed via BLAST and verified against the Eukaryotic Promoter Database. The significance of the locations was determined using the Kruskal-Wallis test. Among the four clusters, only promoter locations in cluster B showed significant difference. HOX B genes have been linked with the control of genes that direct the development of axial morphology, particularly of the vertebral column bones. The magnitude of variation among the body plans of closely-related species can thus be partially attributed to the promoter kind, location and number, and gene inactivation via CpG methylation.

Global survey of star clusters in the Milky Way. VI. Age distribution and cluster formation history

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Piskunov, A. E.; Just, A.; Kharchenko, N. V.; Berczik, P.; Scholz, R.-D.; Reffert, S.; Yen, S. X.

2018-06-01

Context. The all-sky Milky Way Star Clusters (MWSC) survey provides uniform and precise ages, along with other relevant parameters, for a wide variety of clusters in the extended solar neighbourhood. Aims: In this study we aim to construct the cluster age distribution, investigate its spatial variations, and discuss constraints on cluster formation scenarios of the Galactic disk during the last 5 Gyrs. Methods: Due to the spatial extent of the MWSC, we have considered spatial variations of the age distribution along galactocentric radius RG, and along Z-axis. For the analysis of the age distribution we used 2242 clusters, which all lie within roughly 2.5 kpc of the Sun. To connect the observed age distribution to the cluster formation history we built an analytical model based on simple assumptions on the cluster initial mass function and on the cluster mass-lifetime relation, fit it to the observations, and determined the parameters of the cluster formation law. Results: Comparison with the literature shows that earlier results strongly underestimated the number of evolved clusters with ages t ≳ 100 Myr. Recent studies based on all-sky catalogues agree better with our data, but still lack the oldest clusters with ages t ≳ 1 Gyr. We do not observe a strong variation in the age distribution along RG, though we find an enhanced fraction of older clusters (t > 1 Gyr) in the inner disk. In contrast, the distribution strongly varies along Z. The high altitude distribution practically does not contain clusters with t < 1 Gyr. With simple assumptions on the cluster formation history, the cluster initial mass function and the cluster lifetime we can reproduce the observations. The cluster formation rate and the cluster lifetime are strongly degenerate, which does not allow us to disentangle different formation scenarios. In all cases the cluster formation rate is strongly declining with time, and the cluster initial mass function is very shallow at the high mass end.

Direct atomic imaging and density functional theory study of the Au24Pd1 cluster catalyst.

Science.gov (United States)

Bruma, A; Negreiros, F R; Xie, S; Tsukuda, T; Johnston, R L; Fortunelli, A; Li, Z Y

2013-10-21

In this study we report a direct, atomic-resolution imaging of calcined Au24Pd1 clusters supported on multiwall carbon nanotubes by employing aberration-corrected scanning transmission electron microscopy. Using gold atoms as mass standards, we confirm the cluster size to be 25 ± 2, in agreement with the Au24Pd1(SR)18 precursor used in the synthesis. Concurrently, a Density-Functional/Basin-Hopping computational algorithm is employed to locate the low-energy configurations of free Au24Pd1 cluster. Cage structures surrounding a single core atom are found to be favored, with a slight preference for Pd to occupy the core site. The cluster shows a tendency toward elongated arrangements, consistent with experimental data. The degree of electron transfer from the Pd dopant to Au is quantified through a Löwdin charge analysis, suggesting that Pd may act as an electron promoter to the surrounding Au atoms when they are involved in catalytic reactions.

Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice

DEFF Research Database (Denmark)

Matheu, Victor; Treschow, Alexandra; Teige, Ingrid

2005-01-01

BACKGROUND: CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects o...

The core element of a CpG island protects avian sarcoma and leukosis virus-derived vectors from transcriptional silencing

Czech Academy of Sciences Publication Activity Database

Šenigl, Filip; Plachý, Jiří; Hejnar, Jiří

2008-01-01

Roč. 82, č. 16 (2008), s. 7818-7827 ISSN 0022-538X R&D Projects: GA ČR GA204/05/0939; GA ČR GA523/07/1171 Institutional research plan: CEZ:AV0Z50520514 Keywords : anti-methylation protection * retroviral vector * CpG island Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.308, year: 2008

LMC clusters: young

International Nuclear Information System (INIS)

Freeman, K.C.

1980-01-01

The young globular clusters of the LMC have ages of 10 7 -10 8 y. Their masses and structure are similar to those of the smaller galactic globular clusters. Their stellar mass functions (in the mass range 6 solar masses to 1.2 solar masses) vary greatly from cluster to cluster, although the clusters are similar in total mass, age, structure and chemical composition. It would be very interesting to know why these clusters are forming now in the LMC and not in the Galaxy. The author considers the 'young globular' or 'blue populous' clusters of the LMC. The ages of these objects are 10 7 to 10 8 y, and their masses are 10 4 to 10 5 solar masses, so they are populous enough to be really useful for studying the evolution of massive stars. The author concentrates on the structure and stellar content of these young clusters. (Auth.)

Accurate Energies and Structures for Large Water Clusters Using the X3LYP Hybrid Density Functional

OpenAIRE

Su, Julius T.; Xu, Xin; Goddard, William A., III

2004-01-01

We predict structures and energies of water clusters containing up to 19 waters with X3LYP, an extended hybrid density functional designed to describe noncovalently bound systems as accurately as covalent systems. Our work establishes X3LYP as the most practical ab initio method today for calculating accurate water cluster structures and energies. We compare X3LYP/aug-cc-pVTZ energies to the most accurate theoretical values available (n = 2−6, 8), MP2 with basis set superposition error (BSSE)...

The Effect of Scalp Point Cluster-Needling on Learning and Memory Function and Neurotransmitter Levels in Rats with Vascular Dementia

OpenAIRE

Yang, Junli; Litscher, Gerhard; Li, Haitao; Guo, Wenhai; Liang, Zhang; Zhang, Ting; Wang, Weihua; Li, Xiaoyan; Zhou, Yao; Zhao, Bing; Rong, Qi; Sheng, Zemin; Gaischek, Ingrid; Litscher, Daniela; Wang, Lu

2014-01-01

We observed the effect of scalp point cluster-needling treatment on learning and memory function and neurotransmitter levels in rats with vascular dementia (VD). Permanent ligation of the bilateral carotid arteries was used to create the VD rat model. A Morris water maze was used to measure the rats' learning and memory function, and the changes in neurotransmitter levels in the rats' hippocampus were analyzed. The results show that scalp point cluster-needling can increase the VD rat model's...

Cluster synchronization induced by one-node clusters in networks with asymmetric negative couplings

International Nuclear Information System (INIS)

Zhang, Jianbao; Ma, Zhongjun; Zhang, Gang

2013-01-01

This paper deals with the problem of cluster synchronization in networks with asymmetric negative couplings. By decomposing the coupling matrix into three matrices, and employing Lyapunov function method, sufficient conditions are derived for cluster synchronization. The conditions show that the couplings of multi-node clusters from one-node clusters have beneficial effects on cluster synchronization. Based on the effects of the one-node clusters, an effective and universal control scheme is put forward for the first time. The obtained results may help us better understand the relation between cluster synchronization and cluster structures of the networks. The validity of the control scheme is confirmed through two numerical simulations, in a network with no cluster structure and in a scale-free network

Cluster synchronization induced by one-node clusters in networks with asymmetric negative couplings

Science.gov (United States)

Zhang, Jianbao; Ma, Zhongjun; Zhang, Gang

2013-12-01

This paper deals with the problem of cluster synchronization in networks with asymmetric negative couplings. By decomposing the coupling matrix into three matrices, and employing Lyapunov function method, sufficient conditions are derived for cluster synchronization. The conditions show that the couplings of multi-node clusters from one-node clusters have beneficial effects on cluster synchronization. Based on the effects of the one-node clusters, an effective and universal control scheme is put forward for the first time. The obtained results may help us better understand the relation between cluster synchronization and cluster structures of the networks. The validity of the control scheme is confirmed through two numerical simulations, in a network with no cluster structure and in a scale-free network.

Perceptions of firms within a cluster regarding the cluster's function and success: Amish furniture manufacturing in Ohio

Science.gov (United States)

Matthew S. Bumgardner; Gary W. Graham; P. Charles Goebel; Robert L. Romig

2011-01-01

The Amish-based furniture manufacturing cluster in and around Holmes County, OH, is home to some 400 shops and has become an important regional driver of demand for hardwood products. The cluster has expanded even as the broader domestic furniture industry has declined. Clustering dynamics are seen as important to the success, but little information has been available...

Subaru Weak-lensing Survey of Dark Matter Subhalos in the Coma Cluster: Subhalo Mass Function and Statistical Properties

Science.gov (United States)

Okabe, Nobuhiro; Futamase, Toshifumi; Kajisawa, Masaru; Kuroshima, Risa

2014-04-01

We present a 4 deg2 weak gravitational lensing survey of subhalos in the very nearby Coma cluster using the Subaru/Suprime-Cam. The large apparent size of cluster subhalos allows us to measure the mass of 32 subhalos detected in a model-independent manner, down to the order of 10-3 of the virial mass of the cluster. Weak-lensing mass measurements of these shear-selected subhalos enable us to investigate subhalo properties and the correlation between subhalo masses and galaxy luminosities for the first time. The mean distortion profiles stacked over subhalos show a sharply truncated feature which is well-fitted by a Navarro-Frenk-White (NFW) mass model with the truncation radius, as expected due to tidal destruction by the main cluster. We also found that subhalo masses, truncation radii, and mass-to-light ratios decrease toward the cluster center. The subhalo mass function, dn/dln M sub, in the range of 2 orders of magnitude in mass, is well described by a single power law or a Schechter function. Best-fit power indices of 1.09^{+0.42}_{-0.32} for the former model and 0.99_{-0.23}^{+0.34} for the latter, are in remarkable agreement with slopes of ~0.9-1.0 predicted by the cold dark matter paradigm. The tangential distortion signals in the radial range of 0.02-2 h -1 Mpc from the cluster center show a complex structure which is well described by a composition of three mass components of subhalos, the NFW mass distribution as a smooth component of the main cluster, and a lensing model from a large scale structure behind the cluster. Although the lensing signals are 1 order of magnitude lower than those for clusters at z ~ 0.2, the total signal-to-noise ratio, S/N = 13.3, is comparable, or higher, because the enormous number of background source galaxies compensates for the low lensing efficiency of the nearby cluster. Based on data collected from the Subaru Telescope and obtained from SMOKA, operated by the Astronomy Data Center, National Astronomical Observatory of

A stable nanoparticulate DDA/MMG formulation acts synergistically with CpG ODN 1826 to enhance the CD4(+) T-cell response

DEFF Research Database (Denmark)

Karlsen, Kasper; Korsholm, Karen Smith; Mortensen, Rasmus

2014-01-01

AIM: To combine the dimethyldioctadecyl ammonium/monomycoloyl glycerol (DDA/MMG) liposomal vaccine adjuvant with the Toll-like receptor (TLR) ligands poly(I:C) (TLR3), flagellin (TLR5) or CpG oligodeoxynucleotide 1826 (TLR9) and investigate their physicochemical properties as well as their CD4(+)...

Genome-wide CpG island methylation analysis implicates novel genes in the pathogenesis of renal cell carcinoma

OpenAIRE

Ricketts, Christopher J.; Morris, Mark R.; Gentle, Dean; Brown, Michael; Wake, Naomi; Woodward, Emma R.; Clarke, Noel; Latif, Farida; Maher, Eamonn R.

2012-01-01

In order to identify novel candidate tumor suppressor genes (TSGs) implicated in renal cell carcinoma (RCC), we performed genome-wide methylation profiling of RCC using the HumanMethylation27 BeadChips to assess methylation at >14,000 genes. Two hundred and twenty hypermethylated probes representing 205 loci/genes were identified in genomic CpG islands. A subset of TSGs investigated in detail exhibited frequent tumor methylation, promoter methylation associated transcriptional silencing an...

[Clustered regularly interspaced short palindromic repeats: structure, function and application--a review].

Science.gov (United States)

Cui, Yujun; Li, Yanjun; Yan, Yanfeng; Yang, Ruifu

2008-11-01

CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats), the basis of spoligotyping technology, can provide prokaryotes with heritable adaptive immunity against phages' invasion. Studies on CRISPR loci and their associated elements, including various CAS (CRISPR-associated) proteins and leader sequences, are still in its infant period. We introduce the brief history', structure, function, bioinformatics research and application of this amazing immunity system in prokaryotic organism for inspiring more scientists to find their interest in this developing topic.

Immortalization of T-cells is accompanied by gradual changes in CpG methylation resulting in a profile resembling a subset of T-cell leukemias.

Science.gov (United States)

Degerman, Sofie; Landfors, Mattias; Siwicki, Jan Konrad; Revie, John; Borssén, Magnus; Evelönn, Emma; Forestier, Erik; Chrzanowska, Krystyna H; Rydén, Patrik; Keith, W Nicol; Roos, Göran

2014-07-01

We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs), islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

Computational Investigation of the Geometrical and Electronic Structures of VGen-/0 (n = 1-4) Clusters by Density Functional Theory and Multiconfigurational CASSCF/CASPT2 Method.

Science.gov (United States)

Tran, Van Tan; Nguyen, Minh Thao; Tran, Quoc Tri

2017-10-12

Density functional theory and the multiconfigurational CASSCF/CASPT2 method have been employed to study the low-lying states of VGe n -/0 (n = 1-4) clusters. For VGe -/0 and VGe 2 -/0 clusters, the relative energies and geometrical structures of the low-lying states are reported at the CASSCF/CASPT2 level. For the VGe 3 -/0 and VGe 4 -/0 clusters, the computational results show that due to the large contribution of the Hartree-Fock exact exchange, the hybrid B3LYP, B3PW91, and PBE0 functionals overestimate the energies of the high-spin states as compared to the pure GGA BP86 and PBE functionals and the CASPT2 method. On the basis of the pure GGA BP86 and PBE functionals and the CASSCF/CASPT2 results, the ground states of anionic and neutral clusters are defined, the relative energies of the excited states are computed, and the electron detachment energies of the anionic clusters are evaluated. The computational results are employed to give new assignments for all features in the photoelectron spectra of VGe 3 - and VGe 4 - clusters.

EG-09EPIGENETIC PROFILING REVEALS A CpG HYPERMETHYLATION PHENOTYPE (CIMP) ASSOCIATED WITH WORSE PROGRESSION-FREE SURVIVAL IN MENINGIOMA

Science.gov (United States)

Olar, Adriana; Wani, Khalida; Mansouri, Alireza; Zadeh, Gelareh; Wilson, Charmaine; DeMonte, Franco; Fuller, Gregory; Jones, David; Pfister, Stefan; von Deimling, Andreas; Sulman, Erik; Aldape, Kenneth

2014-01-01

BACKGROUND: Methylation profiling of solid tumors has revealed biologic subtypes, often with clinical implications. Methylation profiles of meningioma and their clinical implications are not well understood. METHODS: Ninety-two meningioma samples (n = 44 test set and n = 48 validation set) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised clustering and analyses for recurrence-free survival (RFS) were performed. RESULTS: Unsupervised clustering of the test set using approximately 900 highly variable markers identified two clearly defined methylation subgroups. One of the groups (n = 19) showed global hypermethylation of a set of markers, analogous to CpG island methylator phenotype (CIMP). These findings were reproducible in the validation set, with 18/48 samples showing the CIMP-positive phenotype. Importantly, of 347 highly variable markers common to both the test and validation set analyses, 107 defined CIMP in the test set and 94 defined CIMP in the validation set, with an overlap of 83 markers between the two datasets. This number is much greater than expected by chance indicating reproducibly of the hypermethylated markers that define CIMP in meningioma. With respect to clinical correlation, the 37 CIMP-positive cases displayed significantly shorter RFS compared to the 55 non-CIMP cases (hazard ratio 2.9, p = 0.013). In an effort to develop a preliminary outcome predictor, a 155-marker subset correlated with RFS was identified in the test dataset. When interrogated in the validation dataset, this 155-marker subset showed a statistical trend (p < 0.1) towards distinguishing survival groups. CONCLUSIONS: This study defines the existence of a CIMP phenotype in meningioma, which involves a substantial proportion (37/92, 40%) of samples with clinical implications. Ongoing work will expand this cohort and examine identification of additional biologic differences (mutational and DNA copy number analysis) to further characterize the aberrant

Density functional study of photoabsorption in metallic clusters using an exchange-correlation potential with correct long-range behaviour

Energy Technology Data Exchange (ETDEWEB)

Torres, M.B. [Dpto. de Matematicas y Computacion, Universidad de Burgos, Burgos (Spain); Balbas, L.C. [Dpto. de Fisica Teorica, Universidad de Valladolid, Valladolid (Spain)

2002-06-17

The atomic exchange-correlation (xc) potential with the correct -1/r asymptotic behaviour constructed by Parr and Ghosh (Parr R G and Ghosh S K 1995 Phys. Rev. A 51 3564) is adapted here to study, within time density functional theory, the linear response to external fields of (i) neutral and charged sodium clusters, and (ii) doped clusters of the type Na{sub n}Pb (n=4, 6, 16). The resulting photoabsorption cross sections are compared to experimental results, when available, and to results from previous calculations using local and non-local xc functionals. The calculated static polarizabilities and plasmon frequencies are closer to the experimental values than previous results. (author)

Structure and physical properties of silicon clusters and of vacancy clusters in bulk silicon

International Nuclear Information System (INIS)

Sieck, A.

2000-01-01

In this thesis the growth-pattern of free silicon clusters and vacancy clusters in bulk silicon is investigated. The aim is to describe and to better understand the cluster to bulk transition. Silicon structures in between clusters and solids feature new interesting physical properties. The structure and physical properties of silicon clusters can be revealed by a combination of theory and experiment, only. Low-energy clusters are determined with different optimization techniques and a density-functional based tight-binding method. Additionally, infrared and Raman spectra, and polarizabilities calculated within self-consistent field density-functional theory are provided for the smaller clusters. For clusters with 25 to 35 atoms an analysis of the shape of the clusters and the related mobilities in a buffer gas is given. Finally, the clusters observed in low-temperature experiments are identified via the best match between calculated properties and experimental data. Silicon clusters with 10 to 15 atoms have a tricapped trigonal prism as a common subunit. Clusters with up to about 25 atoms follow a prolate growth-path. In the range from 24 to 30 atoms the geometry of the clusters undergoes a transition towards compact spherical structures. Low-energy clusters with up to 240 atoms feature a bonding pattern strikingly different from the tetrahedral bonding in the solid. It follows that structures with dimensions of several Angstroem have electrical and optical properties different from the solid. The calculated stabilities and positron-lifetimes of vacancy clusters in bulk silicon indicate the positron-lifetimes of about 435 ps detected in irradiated silicon to be related to clusters of 9 or 10 vacancies. The vacancies in these clusters form neighboring hexa-rings and, therefore, minimize the number of dangling bonds. (orig.)

Systematic CpT (ApG) Depletion and CpG Excess Are Unique Genomic Signatures of Large DNA Viruses Infecting Invertebrates

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Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal

2014-01-01

Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts. PMID:25369195

The Impact of Multi-pollutant Clusters on the Association between Fine Particulate Air Pollution and Microvascular Function

Science.gov (United States)

Ljungman, Petter L.; Wilker, Elissa H.; Rice, Mary B.; Austin, Elena; Schwartz, Joel; Gold, Diane R.; Koutrakis, Petros; Benjamin, Emelia J.; Vita, Joseph A.; Mitchell, Gary F.; Vasan, Ramachandran S.

2016-01-01

Background Prior studies including the Framingham Heart Study have suggested associations between single components of air pollution and vascular function; however, underlying mixtures of air pollution may have distinct associations with vascular function. Methods We used a k-means approach to construct five distinct pollution mixtures from elemental analyses of particle filters, air pollution monitoring data, and meteorology. Exposure was modeled as an interaction between fine particle mass (PM2.5), and concurrent pollution cluster. Outcome variables were two measures of microvascular function in the fingertip in the Framingham Offspring and Third Generation cohorts from 2003-2008. Results In 1,720 participants, associations between PM2.5 and baseline pulse amplitude tonometry differed by air pollution cluster (interaction p value 0.009). Higher PM2.5 on days with low mass concentrations but high proportion of ultrafine particles from traffic was associated with 18% (95% CI 4.6%; 33%) higher baseline pulse amplitude per 5 μg/m3 and days with high contributions of oil and wood combustion with 16% (95% CI 0.2%; 34%) higher baseline pulse amplitude. We observed no variation in associations of PM2.5 with hyperemic response to ischemia observed across air pollution clusters. Conclusions PM2.5 exposure from air pollution mixtures with large contributions of local ultrafine particles from traffic, heating oil and wood combustion was associated with higher baseline pulse amplitude but not PAT ratio. Our findings suggest little association between acute exposure to air pollution clusters reflective of select sources and hyperemic response to ischemia, but possible associations with excessive small artery pulsatility with potentially deleterious microvascular consequences. PMID:26562062

The cluster index of regularly varying sequences with applications to limit theory for functions of multivariate Markov chains

DEFF Research Database (Denmark)

Mikosch, Thomas Valentin; Wintenberger, Olivier

2014-01-01

We introduce the cluster index of a multivariate stationary sequence and characterize the index in terms of the spectral tail process. This index plays a major role in limit theory for partial sums of sequences. We illustrate the use of the cluster index by characterizing infinite variance stable...... limit distributions and precise large deviation results for sums of multivariate functions acting on a stationary Markov chain under a drift condition....

Comparative mapping of GABA-immunoreactive neurons in the central nervous systems of nudibranch molluscs.

Science.gov (United States)

Gunaratne, Charuni A; Sakurai, Akira; Katz, Paul S

2014-03-01

The relative simplicity of certain invertebrate nervous systems, such as those of gastropod molluscs, allows behaviors to be dissected at the level of small neural circuits composed of individually identifiable neurons. Elucidating the neurotransmitter phenotype of neurons in neural circuits is important for understanding how those neural circuits function. In this study, we examined the distribution of γ-aminobutyric-acid;-immunoreactive (GABA-ir) neurons in four species of sea slugs (Mollusca, Gastropoda, Opisthobranchia, Nudibranchia): Tritonia diomedea, Melibe leonina, Dendronotus iris, and Hermissenda crassicornis. We found consistent patterns of GABA immunoreactivity in the pedal and cerebral-pleural ganglia across species. In particular, there were bilateral clusters in the lateral and medial regions of the dorsal surface of the cerebral ganglia as well as a cluster on the ventral surface of the pedal ganglia. There were also individual GABA-ir neurons that were recognizable across species. The invariant presence of these individual neurons and clusters suggests that they are homologous, although there were interspecies differences in the numbers of neurons in the clusters. The GABAergic system was largely restricted to the central nervous system, with the majority of axons confined to ganglionic connectives and commissures, suggesting a central, integrative role for GABA. GABA was a candidate inhibitory neurotransmitter for neurons in central pattern generator (CPG) circuits underlying swimming behaviors in these species, however none of the known swim CPG neurons were GABA-ir. Although the functions of these GABA-ir neurons are not known, it is clear that their presence has been strongly conserved across nudibranchs. Copyright © 2013 Wiley Periodicals, Inc.

Synergy between pair coupled cluster doubles and pair density functional theory

Energy Technology Data Exchange (ETDEWEB)

Garza, Alejandro J.; Bulik, Ireneusz W. [Department of Chemistry, Rice University, Houston, Texas 77251-1892 (United States); Henderson, Thomas M. [Department of Chemistry and Department of Physics and Astronomy, Rice University, Houston, Texas 77251-1892 (United States); Scuseria, Gustavo E. [Department of Chemistry and Department of Physics and Astronomy, Rice University, Houston, Texas 77251-1892 (United States); Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589 (Saudi Arabia)

2015-01-28

Pair coupled cluster doubles (pCCD) has been recently studied as a method capable of accounting for static correlation with low polynomial cost. We present three combinations of pCCD with Kohn–Sham functionals of the density and on-top pair density (the probability of finding two electrons on top of each other) to add dynamic correlation to pCCD without double counting. With a negligible increase in computational cost, these pCCD+DFT blends greatly improve upon pCCD in the description of typical problems where static and dynamic correlations are both important. We argue that—as a black-box method with low scaling, size-extensivity, size-consistency, and a simple quasidiagonal two-particle density matrix—pCCD is an excellent match for pair density functionals in this type of fusion of multireference wavefunctions with DFT.

A comparison of density functional theory and coupled cluster methods for the calculation of electric dipole polarizability gradients of methane

DEFF Research Database (Denmark)

Paidarová, Ivana; Sauer, Stephan P. A.

2012-01-01

We have compared the performance of density functional theory (DFT) using five different exchange-correlation functionals with four coupled cluster theory based wave function methods in the calculation of geometrical derivatives of the polarizability tensor of methane. The polarizability gradient...

Isocitrate dehydrogenase 1 R132C mutation occurs exclusively in microsatellite stable colorectal cancers with the CpG island methylator phenotype.

Science.gov (United States)

Whitehall, V L J; Dumenil, T D; McKeone, D M; Bond, C E; Bettington, M L; Buttenshaw, R L; Bowdler, L; Montgomery, G W; Wockner, L F; Leggett, B A

2014-11-01

The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features.

A Proteomic Approach to Investigating Gene Cluster Expression and Secondary Metabolite Functionality in Aspergillus fumigatus

Science.gov (United States)

Owens, Rebecca A.; Hammel, Stephen; Sheridan, Kevin J.; Jones, Gary W.; Doyle, Sean

2014-01-01

A combined proteomics and metabolomics approach was utilised to advance the identification and characterisation of secondary metabolites in Aspergillus fumigatus. Here, implementation of a shotgun proteomic strategy led to the identification of non-redundant mycelial proteins (n = 414) from A. fumigatus including proteins typically under-represented in 2-D proteome maps: proteins with multiple transmembrane regions, hydrophobic proteins and proteins with extremes of molecular mass and pI. Indirect identification of secondary metabolite cluster expression was also achieved, with proteins (n = 18) from LaeA-regulated clusters detected, including GliT encoded within the gliotoxin biosynthetic cluster. Biochemical analysis then revealed that gliotoxin significantly attenuates H2O2-induced oxidative stress in A. fumigatus (p>0.0001), confirming observations from proteomics data. A complementary 2-D/LC-MS/MS approach further elucidated significantly increased abundance (pproteome and experimental strategies, plus mechanistic data pertaining to gliotoxin functionality in the organism. PMID:25198175

A polyethylenimine-modified carboxyl-poly(styrene/acrylamide copolymer nanosphere for co-delivering of CpG and TGF-β receptor I inhibitor with remarkable additive tumor regression effect against liver cancer in mice

Directory of Open Access Journals (Sweden)

Liang SY

2016-12-01

Full Text Available Shuyan Liang,* Jun Hu,* Yuanyuan Xie, Qing Zhou, Yanhong Zhu, Xiangliang Yang National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Cancer immunotherapy based on nanodelivery systems has shown potential for treatment of various malignancies, owing to the benefits of tumor targeting of nanoparticles. However, induction of a potent T-cell immune response against tumors still remains a challenge. In this study, polyethylenimine-modified carboxyl-styrene/acrylamide (PS copolymer nanospheres were developed as a delivery system of unmethylated cytosine-phosphate-guanine (CpG oligodeoxynucleotides and transforming growth factor-beta (TGF-β receptor I inhibitors for cancer immunotherapy. TGF-β receptor I inhibitors (LY2157299, LY were encapsulated to the PS via hydrophobic interaction, while CpG oligodeoxynucleotides were loaded onto the PS through electrostatic interaction. Compared to the control group, tumor inhibition in the PS-LY/CpG group was up to 99.7% without noticeable toxicity. The tumor regression may be attributed to T-cell activation and amplification in mouse models. The results highlight the additive effect of CpG and TGF-β receptor I inhibitors co-delivered in cancer immunotherapy. Keywords: CpG, TGF-β receptor I inhibitor, Pst-AAm copolymer nanosphere, immunotherapy

Functional clustering in hippocampal cultures: relating network structure and dynamics

International Nuclear Information System (INIS)

Feldt, S; Dzakpasu, R; Olariu, E; Żochowski, M; Wang, J X; Shtrahman, E

2010-01-01

In this work we investigate the relationship between gross anatomic structural network properties, neuronal dynamics and the resultant functional structure in dissociated rat hippocampal cultures. Specifically, we studied cultures as they developed under two conditions: the first supporting glial cell growth (high glial group), and the second one inhibiting it (low glial group). We then compared structural network properties and the spatio-temporal activity patterns of the neurons. Differences in dynamics between the two groups could be linked to the impact of the glial network on the neuronal network as the cultures developed. We also implemented a recently developed algorithm called the functional clustering algorithm (FCA) to obtain the resulting functional network structure. We show that this new algorithm is useful for capturing changes in functional network structure as the networks evolve over time. The FCA detects changes in functional structure that are consistent with expected dynamical differences due to the impact of the glial network. Cultures in the high glial group show an increase in global synchronization as the cultures age, while those in the low glial group remain locally synchronized. We additionally use the FCA to quantify the amount of synchronization present in the cultures and show that the total level of synchronization in the high glial group is stronger than in the low glial group. These results indicate an interdependence between the glial and neuronal networks present in dissociated cultures

Simulating star clusters with the AMUSE software framework. I. Dependence of cluster lifetimes on model assumptions and cluster dissolution modes

International Nuclear Information System (INIS)

Whitehead, Alfred J.; McMillan, Stephen L. W.; Vesperini, Enrico; Portegies Zwart, Simon

2013-01-01

We perform a series of simulations of evolving star clusters using the Astrophysical Multipurpose Software Environment (AMUSE), a new community-based multi-physics simulation package, and compare our results to existing work. These simulations model a star cluster beginning with a King model distribution and a selection of power-law initial mass functions and contain a tidal cutoff. They are evolved using collisional stellar dynamics and include mass loss due to stellar evolution. After studying and understanding that the differences between AMUSE results and results from previous studies are understood, we explored the variation in cluster lifetimes due to the random realization noise introduced by transforming a King model to specific initial conditions. This random realization noise can affect the lifetime of a simulated star cluster by up to 30%. Two modes of star cluster dissolution were identified: a mass evolution curve that contains a runaway cluster dissolution with a sudden loss of mass, and a dissolution mode that does not contain this feature. We refer to these dissolution modes as 'dynamical' and 'relaxation' dominated, respectively. For Salpeter-like initial mass functions, we determined the boundary between these two modes in terms of the dynamical and relaxation timescales.

Cluster structure of 20Ne and 40Ca

International Nuclear Information System (INIS)

Taniguchi, Yasutaka

2004-01-01

A d-constraint for calculating the wave functions of various kinds of configurations of cluster structure and optimizing the inside wave functions of the cluster was developed. The wave functions of various kinds of cluster structures were calculated by constraining and energy variation of the antisymmetrized molecular dynamics wave functions. The cluster structure of nucleus was reproduced by linear combination of the above wave functions by the generator coordinate method. By superposition of both wave functions calculated using d-constraint and β-constraint, K π =O 3 + rotation band of 20 Ne was reproduced. The excitation energies of 20 Ne were calculated. The result of calculation energies of α- 36 Ar structure of 40 Ca are higher values than expected them. Framework, AMD wave function, constraint, calculation results and discussions are stated. (S.Y.)

The CpG island encompassing the promoter and first exon of human DNMT3L gene is a PcG/TrX response element (PRE).

Science.gov (United States)

Basu, Amitava; Dasari, Vasanthi; Mishra, Rakesh K; Khosla, Sanjeev

2014-01-01

DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that can read the histone code and translate it into DNA methylation. It plays an important role in the initiation of genomic imprints during gametogenesis and in nuclear reprogramming. With important functions attributed to it, it is imperative that the DNMT3L expression is tightly controlled. Previously, we had identified a CpG island within the human DNMT3L promoter and first exon that showed loss of DNA methylation in cancer samples. Here we show that this Differentially Methylated CpG island within DNMT3L (DNMT3L DMC) acts to repress transcription, is a Polycomb/Trithorax Response Element (PRE) and interacts with both PRC1 and PRC2 Polycomb repressive complexes. In addition, it adopts inactive chromatin conformation and is associated with other inactive chromatin-specific proteins like SUV39H1 and HP1. The presence of DNMT3L DMC also influences the adjacent promoter to adopt repressive histone post-translational modifications. Due to its association with multiple layers of repressive epigenetic modifications, we believe that PRE within the DNMT3L DMC is responsible for the tight regulation of DNMT3L expression and the aberrant epigenetic modifications of this region leading to DNMT3L overexpression could be the reason of nuclear programming during carcinogenesis.

The CpG island encompassing the promoter and first exon of human DNMT3L gene is a PcG/TrX response element (PRE.

Directory of Open Access Journals (Sweden)

Amitava Basu

Full Text Available DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that can read the histone code and translate it into DNA methylation. It plays an important role in the initiation of genomic imprints during gametogenesis and in nuclear reprogramming. With important functions attributed to it, it is imperative that the DNMT3L expression is tightly controlled. Previously, we had identified a CpG island within the human DNMT3L promoter and first exon that showed loss of DNA methylation in cancer samples. Here we show that this Differentially Methylated CpG island within DNMT3L (DNMT3L DMC acts to repress transcription, is a Polycomb/Trithorax Response Element (PRE and interacts with both PRC1 and PRC2 Polycomb repressive complexes. In addition, it adopts inactive chromatin conformation and is associated with other inactive chromatin-specific proteins like SUV39H1 and HP1. The presence of DNMT3L DMC also influences the adjacent promoter to adopt repressive histone post-translational modifications. Due to its association with multiple layers of repressive epigenetic modifications, we believe that PRE within the DNMT3L DMC is responsible for the tight regulation of DNMT3L expression and the aberrant epigenetic modifications of this region leading to DNMT3L overexpression could be the reason of nuclear programming during carcinogenesis.

Color Gradients Within Globular Clusters: Restricted Numerical Simulation

Directory of Open Access Journals (Sweden)

Young-Jong Sohn

1997-06-01

Full Text Available The results of a restricted numerical simulation for the color gradients within globular clusters have been presented. The standard luminosity function of M3 and Salpeter's initial mass functions were used to generate model clusters as a fundamental population. Color gradients with the sample clusters for both King and power law cusp models of surface brightness distributions are discussed in the case of using the standard luminosity function. The dependence of color gradients on several parameters for the simulations with Salpeter's initial mass functions, such as slope of initial mass functions, cluster ages, metallicities, concentration parameters of King model, and slopes of power law, are also discussed. No significant radial color gradients are shown to the sample clusters which are regenerated by a random number generation technique with various parameters in both of King and power law cusp models of surface brightness distributions. Dynamical mass segregation and stellar evolution of horizontal branch stars and blue stragglers should be included for the general case of model simulations to show the observed radial color gradients within globular clusters.

Cluster growth kinetics

International Nuclear Information System (INIS)

Dubovik, V.M.; Gal'perin, A.G.; Rikhvitskij, V.S.; Lushnikov, A.A.

2000-01-01

Processes of some traffic blocking coming into existence are considered as probabilistic ones. We study analytic solutions for models for the dynamics of both cluster growth and cluster growth with fragmentation in the systems of finite number of objects. Assuming rates constancy of both coalescence and fragmentation, the models under consideration are linear on the probability functions

Monoxides of small terbium clusters: A density functional theory investigation

Energy Technology Data Exchange (ETDEWEB)

Zhang, G. L.; Yuan, H. K., E-mail: yhk10@swu.edu.cn; Chen, H.; Kuang, A. L.; Li, Y.; Wang, J. Z.; Chen, J. [School of Physical Science and Technology, Southwest University, Chongqing 400715 (China)

2014-12-28

To investigate the effect of oxygen atom on the geometrical structures, electronic, and magnetic properties of small terbium clusters, we carried out the first-principles calculations on Tb{sub n}O (n = 1-14) clusters. The capping of an oxygen atom on one trigonal-facet of Tb{sub n} structures is always favored energetically, which can significantly improve the structural stability. The far-infrared vibrational spectroscopies are found to be different from those of corresponding bare clusters, providing a distinct signal to detect the characteristic structures of Tb{sub n}O clusters. The primary effect of oxygen atom on magnetic properties is to change the magnetic orderings among Tb atoms and to reduce small of local magnetic moments of the O-coordinated Tb atoms, both of which serve as the key reasons for the experimental magnetic evolution of an oscillating behavior. These calculations are consistent with, and help to account for, the experimentally observed magnetic properties of monoxide Tb{sub n}O clusters [C. N. Van Dijk et al., J. Appl. Phys. 107, 09B526 (2010)].

COSMOLOGICAL CONSTRAINTS FROM GALAXY CLUSTERING AND THE MASS-TO-NUMBER RATIO OF GALAXY CLUSTERS

International Nuclear Information System (INIS)

Tinker, Jeremy L.; Blanton, Michael R.; Sheldon, Erin S.; Wechsler, Risa H.; Becker, Matthew R.; Rozo, Eduardo; Zu, Ying; Weinberg, David H.; Zehavi, Idit; Busha, Michael T.; Koester, Benjamin P.

2012-01-01

We place constraints on the average density (Ω m ) and clustering amplitude (σ 8 ) of matter using a combination of two measurements from the Sloan Digital Sky Survey: the galaxy two-point correlation function, w p (r p ), and the mass-to-galaxy-number ratio within galaxy clusters, M/N, analogous to cluster M/L ratios. Our w p (r p ) measurements are obtained from DR7 while the sample of clusters is the maxBCG sample, with cluster masses derived from weak gravitational lensing. We construct nonlinear galaxy bias models using the Halo Occupation Distribution (HOD) to fit both w p (r p ) and M/N for different cosmological parameters. HOD models that match the same two-point clustering predict different numbers of galaxies in massive halos when Ω m or σ 8 is varied, thereby breaking the degeneracy between cosmology and bias. We demonstrate that this technique yields constraints that are consistent and competitive with current results from cluster abundance studies, without the use of abundance information. Using w p (r p ) and M/N alone, we find Ω 0.5 m σ 8 = 0.465 ± 0.026, with individual constraints of Ω m = 0.29 ± 0.03 and σ 8 = 0.85 ± 0.06. Combined with current cosmic microwave background data, these constraints are Ω m = 0.290 ± 0.016 and σ 8 = 0.826 ± 0.020. All errors are 1σ. The systematic uncertainties that the M/N technique are most sensitive to are the amplitude of the bias function of dark matter halos and the possibility of redshift evolution between the SDSS Main sample and the maxBCG cluster sample. Our derived constraints are insensitive to the current level of uncertainties in the halo mass function and in the mass-richness relation of clusters and its scatter, making the M/N technique complementary to cluster abundances as a method for constraining cosmology with future galaxy surveys.

COSMOLOGICAL CONSTRAINTS FROM GALAXY CLUSTERING AND THE MASS-TO-NUMBER RATIO OF GALAXY CLUSTERS

Energy Technology Data Exchange (ETDEWEB)

Tinker, Jeremy L.; Blanton, Michael R. [Center for Cosmology and Particle Physics, Department of Physics, New York University, New York, NY 10013 (United States); Sheldon, Erin S. [Brookhaven National Laboratory, Upton, NY 11973 (United States); Wechsler, Risa H. [Kavli Institute for Particle Astrophysics and Cosmology, Physics Department, and SLAC National Accelerator Laboratory, Stanford University, Stanford, CA 94305 (United States); Becker, Matthew R.; Rozo, Eduardo [Kavli Institute for Cosmological Physics, University of Chicago, Chicago, IL 60637 (United States); Zu, Ying; Weinberg, David H. [Department of Astronomy, Ohio State University, Columbus, OH 43210 (United States); Zehavi, Idit [Department of Astronomy and CERCA, Case Western Reserve University, Cleveland, OH 44106 (United States); Busha, Michael T. [Institute for Theoretical Physics, Department of Physics, University of Zurich, CH-8057 Zurich (Switzerland); Koester, Benjamin P. [Department of Astronomy and Astrophysics, University of Chicago, Chicago, IL 6037 (United States)

2012-01-20

We place constraints on the average density ({Omega}{sub m}) and clustering amplitude ({sigma}{sub 8}) of matter using a combination of two measurements from the Sloan Digital Sky Survey: the galaxy two-point correlation function, w{sub p} (r{sub p} ), and the mass-to-galaxy-number ratio within galaxy clusters, M/N, analogous to cluster M/L ratios. Our w{sub p} (r{sub p} ) measurements are obtained from DR7 while the sample of clusters is the maxBCG sample, with cluster masses derived from weak gravitational lensing. We construct nonlinear galaxy bias models using the Halo Occupation Distribution (HOD) to fit both w{sub p} (r{sub p} ) and M/N for different cosmological parameters. HOD models that match the same two-point clustering predict different numbers of galaxies in massive halos when {Omega}{sub m} or {sigma}{sub 8} is varied, thereby breaking the degeneracy between cosmology and bias. We demonstrate that this technique yields constraints that are consistent and competitive with current results from cluster abundance studies, without the use of abundance information. Using w{sub p} (r{sub p} ) and M/N alone, we find {Omega}{sup 0.5}{sub m}{sigma}{sub 8} = 0.465 {+-} 0.026, with individual constraints of {Omega}{sub m} = 0.29 {+-} 0.03 and {sigma}{sub 8} = 0.85 {+-} 0.06. Combined with current cosmic microwave background data, these constraints are {Omega}{sub m} = 0.290 {+-} 0.016 and {sigma}{sub 8} = 0.826 {+-} 0.020. All errors are 1{sigma}. The systematic uncertainties that the M/N technique are most sensitive to are the amplitude of the bias function of dark matter halos and the possibility of redshift evolution between the SDSS Main sample and the maxBCG cluster sample. Our derived constraints are insensitive to the current level of uncertainties in the halo mass function and in the mass-richness relation of clusters and its scatter, making the M/N technique complementary to cluster abundances as a method for constraining cosmology with future galaxy

Clustering Coefficients for Correlation Networks

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Naoki Masuda

2018-03-01

Full Text Available Graph theory is a useful tool for deciphering structural and functional networks of the brain on various spatial and temporal scales. The clustering coefficient quantifies the abundance of connected triangles in a network and is a major descriptive statistics of networks. For example, it finds an application in the assessment of small-worldness of brain networks, which is affected by attentional and cognitive conditions, age, psychiatric disorders and so forth. However, it remains unclear how the clustering coefficient should be measured in a correlation-based network, which is among major representations of brain networks. In the present article, we propose clustering coefficients tailored to correlation matrices. The key idea is to use three-way partial correlation or partial mutual information to measure the strength of the association between the two neighboring nodes of a focal node relative to the amount of pseudo-correlation expected from indirect paths between the nodes. Our method avoids the difficulties of previous applications of clustering coefficient (and other measures in defining correlational networks, i.e., thresholding on the correlation value, discarding of negative correlation values, the pseudo-correlation problem and full partial correlation matrices whose estimation is computationally difficult. For proof of concept, we apply the proposed clustering coefficient measures to functional magnetic resonance imaging data obtained from healthy participants of various ages and compare them with conventional clustering coefficients. We show that the clustering coefficients decline with the age. The proposed clustering coefficients are more strongly correlated with age than the conventional ones are. We also show that the local variants of the proposed clustering coefficients (i.e., abundance of triangles around a focal node are useful in characterizing individual nodes. In contrast, the conventional local clustering coefficients

Clustering Coefficients for Correlation Networks.

Science.gov (United States)

Masuda, Naoki; Sakaki, Michiko; Ezaki, Takahiro; Watanabe, Takamitsu

2018-01-01

Graph theory is a useful tool for deciphering structural and functional networks of the brain on various spatial and temporal scales. The clustering coefficient quantifies the abundance of connected triangles in a network and is a major descriptive statistics of networks. For example, it finds an application in the assessment of small-worldness of brain networks, which is affected by attentional and cognitive conditions, age, psychiatric disorders and so forth. However, it remains unclear how the clustering coefficient should be measured in a correlation-based network, which is among major representations of brain networks. In the present article, we propose clustering coefficients tailored to correlation matrices. The key idea is to use three-way partial correlation or partial mutual information to measure the strength of the association between the two neighboring nodes of a focal node relative to the amount of pseudo-correlation expected from indirect paths between the nodes. Our method avoids the difficulties of previous applications of clustering coefficient (and other) measures in defining correlational networks, i.e., thresholding on the correlation value, discarding of negative correlation values, the pseudo-correlation problem and full partial correlation matrices whose estimation is computationally difficult. For proof of concept, we apply the proposed clustering coefficient measures to functional magnetic resonance imaging data obtained from healthy participants of various ages and compare them with conventional clustering coefficients. We show that the clustering coefficients decline with the age. The proposed clustering coefficients are more strongly correlated with age than the conventional ones are. We also show that the local variants of the proposed clustering coefficients (i.e., abundance of triangles around a focal node) are useful in characterizing individual nodes. In contrast, the conventional local clustering coefficients were strongly

Clustering Coefficients for Correlation Networks

Science.gov (United States)

Masuda, Naoki; Sakaki, Michiko; Ezaki, Takahiro; Watanabe, Takamitsu

2018-01-01

Graph theory is a useful tool for deciphering structural and functional networks of the brain on various spatial and temporal scales. The clustering coefficient quantifies the abundance of connected triangles in a network and is a major descriptive statistics of networks. For example, it finds an application in the assessment of small-worldness of brain networks, which is affected by attentional and cognitive conditions, age, psychiatric disorders and so forth. However, it remains unclear how the clustering coefficient should be measured in a correlation-based network, which is among major representations of brain networks. In the present article, we propose clustering coefficients tailored to correlation matrices. The key idea is to use three-way partial correlation or partial mutual information to measure the strength of the association between the two neighboring nodes of a focal node relative to the amount of pseudo-correlation expected from indirect paths between the nodes. Our method avoids the difficulties of previous applications of clustering coefficient (and other) measures in defining correlational networks, i.e., thresholding on the correlation value, discarding of negative correlation values, the pseudo-correlation problem and full partial correlation matrices whose estimation is computationally difficult. For proof of concept, we apply the proposed clustering coefficient measures to functional magnetic resonance imaging data obtained from healthy participants of various ages and compare them with conventional clustering coefficients. We show that the clustering coefficients decline with the age. The proposed clustering coefficients are more strongly correlated with age than the conventional ones are. We also show that the local variants of the proposed clustering coefficients (i.e., abundance of triangles around a focal node) are useful in characterizing individual nodes. In contrast, the conventional local clustering coefficients were strongly

Cluster algebras in mathematical physics

International Nuclear Information System (INIS)

Francesco, Philippe Di; Gekhtman, Michael; Kuniba, Atsuo; Yamazaki, Masahito

2014-01-01

This special issue of Journal of Physics A: Mathematical and Theoretical contains reviews and original research articles on cluster algebras and their applications to mathematical physics. Cluster algebras were introduced by S Fomin and A Zelevinsky around 2000 as a tool for studying total positivity and dual canonical bases in Lie theory. Since then the theory has found diverse applications in mathematics and mathematical physics. Cluster algebras are axiomatically defined commutative rings equipped with a distinguished set of generators (cluster variables) subdivided into overlapping subsets (clusters) of the same cardinality subject to certain polynomial relations. A cluster algebra of rank n can be viewed as a subring of the field of rational functions in n variables. Rather than being presented, at the outset, by a complete set of generators and relations, it is constructed from the initial seed via an iterative procedure called mutation producing new seeds successively to generate the whole algebra. A seed consists of an n-tuple of rational functions called cluster variables and an exchange matrix controlling the mutation. Relations of cluster algebra type can be observed in many areas of mathematics (Plücker and Ptolemy relations, Stokes curves and wall-crossing phenomena, Feynman integrals, Somos sequences and Hirota equations to name just a few examples). The cluster variables enjoy a remarkable combinatorial pattern; in particular, they exhibit the Laurent phenomenon: they are expressed as Laurent polynomials rather than more general rational functions in terms of the cluster variables in any seed. These characteristic features are often referred to as the cluster algebra structure. In the last decade, it became apparent that cluster structures are ubiquitous in mathematical physics. Examples include supersymmetric gauge theories, Poisson geometry, integrable systems, statistical mechanics, fusion products in infinite dimensional algebras, dilogarithm

Mean Occupation Function of High-redshift Quasars from the Planck Cluster Catalog

Science.gov (United States)

Chakraborty, Priyanka; Chatterjee, Suchetana; Dutta, Alankar; Myers, Adam D.

2018-06-01

We characterize the distribution of quasars within dark matter halos using a direct measurement technique for the first time at redshifts as high as z ∼ 1. Using the Planck Sunyaev-Zeldovich (SZ) catalog for galaxy groups and the Sloan Digital Sky Survey (SDSS) DR12 quasar data set, we assign host clusters/groups to the quasars and make a measurement of the mean number of quasars within dark matter halos as a function of halo mass. We find that a simple power-law fit of {log} =(2.11+/- 0.01) {log}(M)-(32.77+/- 0.11) can be used to model the quasar fraction in dark matter halos. This suggests that the quasar fraction increases monotonically as a function of halo mass even to redshifts as high as z ∼ 1.

Reproducibility of Cognitive Profiles in Psychosis Using Cluster Analysis.

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Lewandowski, Kathryn E; Baker, Justin T; McCarthy, Julie M; Norris, Lesley A; Öngür, Dost

2018-04-01

Cognitive dysfunction is a core symptom dimension that cuts across the psychoses. Recent findings support classification of patients along the cognitive dimension using cluster analysis; however, data-derived groupings may be highly determined by sampling characteristics and the measures used to derive the clusters, and so their interpretability must be established. We examined cognitive clusters in a cross-diagnostic sample of patients with psychosis and associations with clinical and functional outcomes. We then compared our findings to a previous report of cognitive clusters in a separate sample using a different cognitive battery. Participants with affective or non-affective psychosis (n=120) and healthy controls (n=31) were administered the MATRICS Consensus Cognitive Battery, and clinical and community functioning assessments. Cluster analyses were performed on cognitive variables, and clusters were compared on demographic, cognitive, and clinical measures. Results were compared to findings from our previous report. A four-cluster solution provided a good fit to the data; profiles included a neuropsychologically normal cluster, a globally impaired cluster, and two clusters of mixed profiles. Cognitive burden was associated with symptom severity and poorer community functioning. The patterns of cognitive performance by cluster were highly consistent with our previous findings. We found evidence of four cognitive subgroups of patients with psychosis, with cognitive profiles that map closely to those produced in our previous work. Clusters were associated with clinical and community variables and a measure of premorbid functioning, suggesting that they reflect meaningful groupings: replicable, and related to clinical presentation and functional outcomes. (JINS, 2018, 24, 382-390).

Simulation of resonance hyper-Rayleigh scattering of molecules and metal clusters using a time-dependent density functional theory approach.

Science.gov (United States)

Hu, Zhongwei; Autschbach, Jochen; Jensen, Lasse

2014-09-28

Resonance hyper-Rayleigh scattering (HRS) of molecules and metal clusters have been simulated based on a time-dependent density functional theory approach. The resonance first-order hyperpolarizability (β) is obtained by implementing damped quadratic response theory using the (2n + 1) rule. To test this implementation, the prototypical dipolar molecule para-nitroaniline (p-NA) and the octupolar molecule crystal violet are used as benchmark systems. Moreover, small silver clusters Ag 8 and Ag 20 are tested with a focus on determining the two-photon resonant enhancement arising from the strong metal transition. Our results show that, on a per atom basis, the small silver clusters possess two-photon enhanced HRS comparable to that of larger nanoparticles. This finding indicates the potential interest of using small metal clusters for designing new nonlinear optical materials.

Description of an α-cluster tail in 8Be and 20Ne: Delocalization of the α cluster by quantum penetration

Science.gov (United States)

Kanada-En'yo, Yoshiko

2014-10-01

We analyze the α-cluster wave functions in cluster states of ^8Be and ^{20}Ne by comparing the exact relative wave function obtained by the generator coordinate method (GCM) with various types of trial functions. For the trial functions, we adopt the fixed range shifted Gaussian of the Brink-Bloch (BB) wave function, the spherical Gaussian with the adjustable range parameter of the spherical Tohsaki-Horiuchi-Schuck-Röpke (sTHSR), the deformed Gaussian of the deformed THSR (dTHSR), and a function with the Yukawa tail (YT). The quality of the description of the exact wave function with a trial function is judged by the squared overlap between the trial function and the GCM wave function. A better result is obtained with the sTHSR wave function than the BB wave function, and further improvement can be made with the dTHSR wave function because these wave functions can describe the outer tail better. The YT wave function gives almost an equal quality to or even better quality than the dTHSR wave function, indicating that the outer tail of α-cluster states is characterized by the Yukawa-like tail rather than the Gaussian tail. In weakly bound α-cluster states with small α separation energy and the low centrifugal and Coulomb barriers, the outer tail part is the slowly damping function described well by the quantum penetration through the effective barrier. This outer tail characterizes the almost zero-energy free α gas behavior, i.e., the delocalization of the cluster.

Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort.

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Jukka S Alasaari

Full Text Available Shift-working nurses are exposed to a stressful work environment, which puts them at an increased risk for burnout and depression. We explored the effect of environmental stress on serotonin transporter gene (SLC6A4 promoter methylation among nurses from high and low work stress environments.Using bisulfite sequencing, we investigated the methylation status of five CpG residues of a CpG-rich region in the promoter of SLC6A4 by comparing female shift working nurses from a high work stress environment (n = 24 to low work stress environment (n = 25. We also analyzed the association of 5-HTTLPR polymorphism at 5' end of SLC6A4. Work stress was assessed by the Karasek's Model and possible signs of burnout or depression were measured by the Maslach Burnout Index General Survey and Beck Depression Index. Methylation levels were assessed by bisulfite sequencing of DNA extracted from peripheral blood leucocytes. Restriction enzyme treatment followed by standard PCR was used to identify 5-HTTLPR genotypes.We found that nurses in the high stress environment had significantly lower promoter methylation levels at all five CpG residues compared to nurses in the low stress environment (p<0.01. There was no significant interaction of 5-HTTLPR genotype and work stress with methylation (p = 0.58. In unadjusted (bivariate analysis, burnout was not significantly associated to methylation levels. However, when mutually adjusted for both, burnout and work stress were significant contributors (p = 0.038 and p<0.0001 respectively to methylation levels.Our findings show that environmental stress is concurrent with decreased methylation of the SLC6A4 promoter. This may lead to increased transcriptional activity of the gene, increased reuptake of serotonin from synaptic clefts, and termination of the activity of serotonin. This could present a possible coping mechanism for environmental stress in humans that could eventually increase risk for disturbed functional

Quantum annealing for combinatorial clustering

Science.gov (United States)

Kumar, Vaibhaw; Bass, Gideon; Tomlin, Casey; Dulny, Joseph

2018-02-01

Clustering is a powerful machine learning technique that groups "similar" data points based on their characteristics. Many clustering algorithms work by approximating the minimization of an objective function, namely the sum of within-the-cluster distances between points. The straightforward approach involves examining all the possible assignments of points to each of the clusters. This approach guarantees the solution will be a global minimum; however, the number of possible assignments scales quickly with the number of data points and becomes computationally intractable even for very small datasets. In order to circumvent this issue, cost function minima are found using popular local search-based heuristic approaches such as k-means and hierarchical clustering. Due to their greedy nature, such techniques do not guarantee that a global minimum will be found and can lead to sub-optimal clustering assignments. Other classes of global search-based techniques, such as simulated annealing, tabu search, and genetic algorithms, may offer better quality results but can be too time-consuming to implement. In this work, we describe how quantum annealing can be used to carry out clustering. We map the clustering objective to a quadratic binary optimization problem and discuss two clustering algorithms which are then implemented on commercially available quantum annealing hardware, as well as on a purely classical solver "qbsolv." The first algorithm assigns N data points to K clusters, and the second one can be used to perform binary clustering in a hierarchical manner. We present our results in the form of benchmarks against well-known k-means clustering and discuss the advantages and disadvantages of the proposed techniques.

CLASH-VLT: The stellar mass function and stellar mass density profile of the z=0.44 cluster of galaxies MACS J1206.2-0847

CERN Document Server

Annunziatella, M; Mercurio, A.; Nonino, M.; Rosati, P.; Balestra, I.; Presotto, V.; Girardi, M.; Gobat, R.; Grillo, C.; Medezinski, E.; Kelson, D.; Postman, M.; Scodeggio, M.; Brescia, M.; Sartoris, B.; Demarco, R.; Fritz, A.; Koekemoer, A.; Lemze, D.; Lombardi, M.; Bradley, L.; Coe, D.; Donahue, M.; Regös, E.; Umetsu, K.; Vanzella, E.; Infante, L.; Kuchner, U.; Maier, C.; Verdugo, M.; Ziegler, B.

2014-01-01

Context. The study of the galaxy stellar mass function (SMF) in relation to the galaxy environment and the stellar mass density profile, rho(r), is a powerful tool to constrain models of galaxy evolution. Aims. We determine the SMF of the z=0.44 cluster of galaxies MACS J1206.2-0847 separately for passive and star-forming (SF) galaxies, in different regions of the cluster, from the center out to approximately 2 virial radii. We also determine rho(r) to compare it to the number density and total mass density profiles. Methods. We use the dataset from the CLASH-VLT survey. Stellar masses are obtained by SED fitting on 5-band photometric data obtained at the Subaru telescope. We identify 1363 cluster members down to a stellar mass of 10^9.5 Msolar. Results. The whole cluster SMF is well fitted by a double Schechter function. The SMFs of cluster SF and passive galaxies are statistically different. The SMF of the SF cluster galaxies does not depend on the environment. The SMF of the passive population has a signif...

MD simulation of cluster formation during sputtering

International Nuclear Information System (INIS)

Muramoto, T.; Okai, M.; Yamashita, Y.; Yorizane, K.; Yamamura, Y.

2001-01-01

The cluster ejection due to cluster impact on a solid surface is studied through molecular dynamics (MD) simulations. Simulations are performed for Cu cluster impacts on the Cu(1 1 1) surface for cluster energy 100 eV/atom, and for clusters of 6, 13, 28 and 55 atoms. Interatomic interactions are described by the AMLJ-EAM potential. The vibration energy spectrum is independent of the incident cluster size and energy. This comes from the fact that sputtered clusters become stable through the successive fragmentation of nascent large sputtered clusters. The vibration energy spectra for large sputtered clusters have a peak, whose energy corresponds to the melting temperature of Cu. The exponent of the power-law fit of the abundance distribution and the total sputtering yield for the cluster impacts are higher than that for the monatomic ion impacts with the same total energy, where the exponent δ is given by Y n ∝n δ and Y n is the yield of sputtered n-atom cluster. The exponent δ follows a unified function of the total sputtering yield, which is a monotonic increase function, and it is nearly equal to δ ∼ -3 for larger yield

clusters

Indian Academy of Sciences (India)

2017-09-27

Sep 27, 2017 ... Author for correspondence (zh4403701@126.com). MS received 15 ... lic clusters using density functional theory (DFT)-GGA of the DMOL3 package. ... In the process of geometric optimization, con- vergence thresholds ..... and Postgraduate Research & Practice Innovation Program of. Jiangsu Province ...

Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history.

Science.gov (United States)

Weisenberger, Daniel J; Levine, A Joan; Long, Tiffany I; Buchanan, Daniel D; Walters, Rhiannon; Clendenning, Mark; Rosty, Christophe; Joshi, Amit D; Stern, Mariana C; LeMarchand, Loic; Lindor, Noralane M; Daftary, Darshana; Gallinger, Steven; Selander, Teresa; Bapat, Bharati; Newcomb, Polly A; Campbell, Peter T; Casey, Graham; Ahnen, Dennis J; Baron, John A; Haile, Robert W; Hopper, John L; Young, Joanne P; Laird, Peter W; Siegmund, Kimberly D

2015-03-01

The CpG island methylator phenotype (CIMP) represents a subset of colorectal cancers characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not known. We measured the CIMP status of 3,119 primary population-based colorectal cancer tumors from the multinational Colon Cancer Family Registry. Etiologic heterogeneity was assessed by a case-case study comparing risk factor frequency of colorectal cancer cases with CIMP and non-CIMP tumors using logistic regression to estimate the case-case odds ratio (ccOR). We found associations between tumor CIMP status and MSI-H (ccOR = 7.6), BRAF V600E mutation (ccOR = 59.8), proximal tumor site (ccOR = 9; all P CIMP status for both males and females (P = 0.0001 and P = 0.02, respectively), use of multivitamin or calcium supplements did not. Only for female colorectal cancer was CIMP status associated with increased pack-years of smoking (Ptrend CIMP status, and the associations of smoking and obesity with tumor subtype were evident only for females. Differences in the associations of a unique DNA methylation-based subgroup of colorectal cancer with important lifestyle and environmental exposures increase understanding of the molecular pathologic epidemiology of this heavily methylated subset of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 512-9. ©2015 AACR. ©2015 American Association for Cancer Research.

CpGislandEVO: A Database and Genome Browser for Comparative Evolutionary Genomics of CpG Islands

Directory of Open Access Journals (Sweden)

Guillermo Barturen

2013-01-01

Full Text Available Hypomethylated, CpG-rich DNA segments (CpG islands, CGIs are epigenome markers involved in key biological processes. Aberrant methylation is implicated in the appearance of several disorders as cancer, immunodeficiency, or centromere instability. Furthermore, methylation differences at promoter regions between human and chimpanzee strongly associate with genes involved in neurological/psychological disorders and cancers. Therefore, the evolutionary comparative analyses of CGIs can provide insights on the functional role of these epigenome markers in both health and disease. Given the lack of specific tools, we developed CpGislandEVO. Briefly, we first compile a database of statistically significant CGIs for the best assembled mammalian genome sequences available to date. Second, by means of a coupled browser front-end, we focus on the CGIs overlapping orthologous genes extracted from OrthoDB, thus ensuring the comparison between CGIs located on truly homologous genome segments. This allows comparing the main compositional features between homologous CGIs. Finally, to facilitate nucleotide comparisons, we lifted genome coordinates between assemblies from different species, which enables the analysis of sequence divergence by direct count of nucleotide substitutions and indels occurring between homologous CGIs. The resulting CpGislandEVO database, linking together CGIs and single-cytosine DNA methylation data from several mammalian species, is freely available at our website.

A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps

OpenAIRE

HOKAZONO, KOJI; UEKI, TAKASHI; NAGAYOSHI, KINUKO; NISHIOKA, YASUNOBU; HATAE, TATSUNOBU; KOGA, YUTAKA; HIRAHASHI, MINAKO; ODA, YOSHINAO; TANAKA, MASAO

2014-01-01

A subset of colorectal cancers (CRCs) harbor the CpG island methylator phenotype (CIMP), with concurrent multiple promoter hypermethylation of tumor-related genes. A serrated pathway in which CIMP is developed from serrated polyps is proposed. The present study characterized CIMP and morphologically examined precursor lesions of CIMP. In total, 104 CRCs treated between January 1996 and December 2004 were examined. Aberrant promoter methylation of 15 cancer-related genes was analyzed. CIMP sta...

The cylindrical K-function and Poisson line cluster point processes

DEFF Research Database (Denmark)

Møller, Jesper; Safavimanesh, Farzaneh; Rasmussen, Jakob G.

Poisson line cluster point processes, is also introduced. Parameter estimation based on moment methods or Bayesian inference for this model is discussed when the underlying Poisson line process and the cluster memberships are treated as hidden processes. To illustrate the methodologies, we analyze two...

Quantification of the clustering properties of nuclear states

International Nuclear Information System (INIS)

Beck, R.; Dickmann, F.

1985-05-01

The amount of particular type of clustering in a nuclear state is defined in this paper as the norm square of the projection of the wave function onto the particular cluster model subspace. It is pointed out that, although the clusters can not be localized in space by measurement, the amount of clustering characterizes the cluster formation in close analogy with a quantum mechanical probability. The cluster model component of the wave function is proved to have a variational property. This facilitates the computation of the amount of clustering. The model dependence of the amounts of various clusterings and their relationship to the corresponding spectroscopic factors are studied via numerical examples for two models of sup(6)Li. It is concluded that, in a relative sense, the spectroscopic factor, which is more directly related to experiment, is also characteristic of the clustering contents of different states of the same nucleus, but it can not be used for comparisons between different nuclei or clusterings. (author)

Expression of Toll-like receptor 9 and response to bacterial CpG oligodeoxynucleotides in human intestinal epithelium

DEFF Research Database (Denmark)

Pedersen, G; Andresen, Lars; Matthiessen, M W

2005-01-01

Recognition of repeat CpG motifs, which are common in bacterial, but not in mammalian, DNA, through Toll-like receptor (TLR)9 is an integral part of the innate immune system. As the role of TLR9 in the human gut is unknown, we determined the spectrum of TLR9 expression in normal and inflamed colo...... in vitro despite spontaneous TLR9 gene expression. This suggests that the human epithelium is able to avoid inappropriate immune responses to luminal bacterial products through modulation of the TLR9 pathway....

Non-specific filtering of beta-distributed data.

Science.gov (United States)

Wang, Xinhui; Laird, Peter W; Hinoue, Toshinori; Groshen, Susan; Siegmund, Kimberly D

2014-06-19

Non-specific feature selection is a dimension reduction procedure performed prior to cluster analysis of high dimensional molecular data. Not all measured features are expected to show biological variation, so only the most varying are selected for analysis. In DNA methylation studies, DNA methylation is measured as a proportion, bounded between 0 and 1, with variance a function of the mean. Filtering on standard deviation biases the selection of probes to those with mean values near 0.5. We explore the effect this has on clustering, and develop alternate filter methods that utilize a variance stabilizing transformation for Beta distributed data and do not share this bias. We compared results for 11 different non-specific filters on eight Infinium HumanMethylation data sets, selected to span a variety of biological conditions. We found that for data sets having a small fraction of samples showing abnormal methylation of a subset of normally unmethylated CpGs, a characteristic of the CpG island methylator phenotype in cancer, a novel filter statistic that utilized a variance-stabilizing transformation for Beta distributed data outperformed the common filter of using standard deviation of the DNA methylation proportion, or its log-transformed M-value, in its ability to detect the cancer subtype in a cluster analysis. However, the standard deviation filter always performed among the best for distinguishing subgroups of normal tissue. The novel filter and standard deviation filter tended to favour features in different genome contexts; for the same data set, the novel filter always selected more features from CpG island promoters and the standard deviation filter always selected more features from non-CpG island intergenic regions. Interestingly, despite selecting largely non-overlapping sets of features, the two filters did find sample subsets that overlapped for some real data sets. We found two different filter statistics that tended to prioritize features with

Structure and bonding in clusters

International Nuclear Information System (INIS)

Kumar, V.

1991-10-01

We review here the recent progress made in the understanding of the electronic and atomic structure of small clusters of s-p bonded materials using the density functional molecular dynamics technique within the local density approximation. Starting with a brief description of the method, results are presented for alkali metal clusters, clusters of divalent metals such as Mg and Be which show a transition from van der Waals or weak chemical bonding to metallic behaviour as the cluster size grows and clusters of Al, Sn and Sb. In the case of semiconductors, we discuss results for Si, Ge and GaAs clusters. Clusters of other materials such as P, C, S, and Se are also briefly discussed. From these and other available results we suggest the possibility of unique structures for the magic clusters. (author). 69 refs, 7 figs, 1 tab

Are pelvic adhesions associated with pain, physical, emotional and functional characteristics of women presenting with chronic pelvic pain? A cluster analysis.

Science.gov (United States)

Cheong, Ying; Saran, Mili; Hounslow, James William; Reading, Isabel Claire

2018-01-08

Chronic pelvic pain is a debilitating condition. It is unknown if there is a clinical phenotype for adhesive disorders. This study aimed to determine if the presence or absence, nature, severity and extent of adhesions correlated with demographic and patient reported clinical characteristics of women presenting with CPP. Women undergoing a laparoscopy for the investigation of chronic pelvic pain were recruited prospectively; their pain and phenotypic characteristics were entered into a hierarchical cluster analysis. The groups with differing baseline clinical and operative characteristics in terms of adhesions involvement were analyzed. Sixty two women were recruited where 37 had adhesions. A low correlation was found between women's reported current pain scores and that of most severe (r = 0.34) or average pain experienced (r = 0.44) in the last 6 months. Three main groups of women with CPP were identified: Cluster 1 (n = 35) had moderate severity of pain, with poor average and present pain intensity; Cluster 2 (n = 14) had a long duration of symptoms/diagnosis, the worst current pain and worst physical, emotional and social functions; Cluster 3 (n = 11) had the shortest duration of pain and showed the best evidence of coping with low (good) physical, social and emotional scores. This cluster also had the highest proportion of women with adhesions (82%) compared to 51% in Cluster 1 and 71% in Cluster 2. In this study, we found that there is little or no correlation between patient-reported pain, physical, emotional and functional characteristics scores with the presence or absence of intra-abdominal/pelvic adhesions found during investigative laparoscopy. Most women who had adhesions had the lowest reported current pain scores.

Epigenetic Loss of MLH1 Expression in Normal Human Hematopoietic Stem Cell Clones is Defined by the Promoter CpG Methylation Pattern Observed by High-Throughput Methylation Specific Sequencing.

Science.gov (United States)

Kenyon, Jonathan; Nickel-Meester, Gabrielle; Qing, Yulan; Santos-Guasch, Gabriela; Drake, Ellen; PingfuFu; Sun, Shuying; Bai, Xiaodong; Wald, David; Arts, Eric; Gerson, Stanton L

Normal human hematopoietic stem and progenitor cells (HPC) lose expression of MLH1 , an important mismatch repair (MMR) pathway gene, with age. Loss of MMR leads to replication dependent mutational events and microsatellite instability observed in secondary acute myelogenous leukemia and other hematologic malignancies. Epigenetic CpG methylation upstream of the MLH1 promoter is a contributing factor to acquired loss of MLH1 expression in tumors of the epithelia and proximal mucosa. Using single molecule high-throughput bisulfite sequencing we have characterized the CpG methylation landscape from -938 to -337 bp upstream of the MLH1 transcriptional start site (position +0), from 30 hematopoietic colony forming cell clones (CFC) either expressing or not expressing MLH1 . We identify a correlation between MLH1 promoter methylation and loss of MLH1 expression. Additionally, using the CpG site methylation frequencies obtained in this study we were able to generate a classification algorithm capable of sorting the expressing and non-expressing CFC. Thus, as has been previously described for many tumor cell types, we report for the first time a correlation between the loss of MLH1 expression and increased MLH1 promoter methylation in CFC derived from CD34 + selected hematopoietic stem and progenitor cells.

Thermodynamically accessible titanium clusters TiN, N = 2-32.

Science.gov (United States)

Lazauskas, Tomas; Sokol, Alexey A; Buckeridge, John; Catlow, C Richard A; Escher, Susanne G E T; Farrow, Matthew R; Mora-Fonz, David; Blum, Volker W; Phaahla, Tshegofatso M; Chauke, Hasani R; Ngoepe, Phuti E; Woodley, Scott M

2018-05-10

We have performed a genetic algorithm search on the tight-binding interatomic potential energy surface (PES) for small TiN (N = 2-32) clusters. The low energy candidate clusters were further refined using density functional theory (DFT) calculations with the PBEsol exchange-correlation functional and evaluated with the PBEsol0 hybrid functional. The resulting clusters were analysed in terms of their structural features, growth mechanism and surface area. The results suggest a growth mechanism that is based on forming coordination centres by interpenetrating icosahedra, icositetrahedra and Frank-Kasper polyhedra. We identify centres of coordination, which act as centres of bulk nucleation in medium sized clusters and determine the morphological features of the cluster.

UET: a database of evolutionarily-predicted functional determinants of protein sequences that cluster as functional sites in protein structures.

Science.gov (United States)

Lua, Rhonald C; Wilson, Stephen J; Konecki, Daniel M; Wilkins, Angela D; Venner, Eric; Morgan, Daniel H; Lichtarge, Olivier

2016-01-04

The structure and function of proteins underlie most aspects of biology and their mutational perturbations often cause disease. To identify the molecular determinants of function as well as targets for drugs, it is central to characterize the important residues and how they cluster to form functional sites. The Evolutionary Trace (ET) achieves this by ranking the functional and structural importance of the protein sequence positions. ET uses evolutionary distances to estimate functional distances and correlates genotype variations with those in the fitness phenotype. Thus, ET ranks are worse for sequence positions that vary among evolutionarily closer homologs but better for positions that vary mostly among distant homologs. This approach identifies functional determinants, predicts function, guides the mutational redesign of functional and allosteric specificity, and interprets the action of coding sequence variations in proteins, people and populations. Now, the UET database offers pre-computed ET analyses for the protein structure databank, and on-the-fly analysis of any protein sequence. A web interface retrieves ET rankings of sequence positions and maps results to a structure to identify functionally important regions. This UET database integrates several ways of viewing the results on the protein sequence or structure and can be found at http://mammoth.bcm.tmc.edu/uet/. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cosmology with EMSS Clusters of Galaxies

Science.gov (United States)

Donahue, Megan; Voit, G. Mark

1999-01-01

We use ASCA observations of the Extended Medium Sensitivity Survey sample of clusters of galaxies to construct the first z = 0.5 - 0.8 cluster temperature function. This distant cluster temperature function, when compared to local z approximately 0 and to a similar moderate redshift (z = 0.3 - 0.4) temperature function strongly constrains the matter density of the universe. Best fits to the distributions of temperatures and redshifts of these cluster samples results in Omega(sub M) = 0.45 +/- 0.1 if Lambda = 0 and Omega = 0.27 +/- 0.1 if Lambda + Omega(sub M) = 1. The uncertainties are 1sigma statistical. We examine the systematics of our approach and find that systematics, stemming mainly from model assumptions and not measurement errors, are about the same size as the statistical uncertainty +/- 0.1. In this poster proceedings, we clarify the issue of a8 as reported in our paper Donahue & Voit (1999), since this was a matter of discussion at the meeting.

Ages of young star clusters, massive blue stragglers, and the upper mass limit of stars: Analyzing age-dependent stellar mass functions

Energy Technology Data Exchange (ETDEWEB)

Schneider, F. R. N.; Izzard, R. G.; Langer, N.; Stolte, A.; Hußmann, B. [Argelander-Institut für Astronomie der Universität Bonn, Auf dem Hügel 71, D-53121 Bonn (Germany); De Mink, S. E. [Observatories of the Carnegie Institution for Science, 813 Santa Barbara St, Pasadena, CA 91101 (United States); De Koter, A.; Sana, H. [Astronomical Institute " Anton Pannekoek" , Amsterdam University, Science Park 904, 1098 XH, Amsterdam (Netherlands); Gvaramadze, V. V. [Sternberg Astronomical Institute, Lomonosov Moscow State University, Universitetskij Pr. 13, Moscow 119992 (Russian Federation); Liermann, A., E-mail: fschneid@astro.uni-bonn.de [Max Planck Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany)

2014-01-10

Massive stars rapidly change their masses through strong stellar winds and mass transfer in binary systems. The latter aspect is important for populations of massive stars as more than 70% of all O stars are expected to interact with a binary companion during their lifetime. We show that such mass changes leave characteristic signatures in stellar mass functions of young star clusters that can be used to infer their ages and to identify products of binary evolution. We model the observed present-day mass functions of the young Galactic Arches and Quintuplet star clusters using our rapid binary evolution code. We find that the shaping of the mass function by stellar wind mass loss allows us to determine the cluster ages as 3.5 ± 0.7 Myr and 4.8 ± 1.1 Myr, respectively. Exploiting the effects of binary mass exchange on the cluster mass function, we find that the most massive stars in both clusters are rejuvenated products of binary mass transfer, i.e., the massive counterpart of classical blue straggler stars. This resolves the problem of an apparent age spread among the most luminous stars exceeding the expected duration of star formation in these clusters. We perform Monte Carlo simulations to probe stochastic sampling, which support the idea of the most massive stars being rejuvenated binary products. We find that the most massive star is expected to be a binary product after 1.0 ± 0.7 Myr in Arches and after 1.7 ± 1.0 Myr in Quintuplet. Today, the most massive 9 ± 3 stars in Arches and 8 ± 3 in Quintuplet are expected to be such objects. Our findings have strong implications for the stellar upper mass limit and solve the discrepancy between the claimed 150 M {sub ☉} limit and observations of four stars with initial masses of 165-320 M {sub ☉} in R136 and of supernova 2007bi, which is thought to be a pair-instability supernova from an initial 250 M {sub ☉} star. Using the stellar population of R136, we revise the upper mass limit to values in the range

Ages of young star clusters, massive blue stragglers, and the upper mass limit of stars: Analyzing age-dependent stellar mass functions

International Nuclear Information System (INIS)

Schneider, F. R. N.; Izzard, R. G.; Langer, N.; Stolte, A.; Hußmann, B.; De Mink, S. E.; Anton Pannekoek, Amsterdam University, Science Park 904, 1098 XH, Amsterdam (Netherlands))" data-affiliation=" (Astronomical Institute Anton Pannekoek, Amsterdam University, Science Park 904, 1098 XH, Amsterdam (Netherlands))" >De Koter, A.; Anton Pannekoek, Amsterdam University, Science Park 904, 1098 XH, Amsterdam (Netherlands))" data-affiliation=" (Astronomical Institute Anton Pannekoek, Amsterdam University, Science Park 904, 1098 XH, Amsterdam (Netherlands))" >Sana, H.; Gvaramadze, V. V.; Liermann, A.

2014-01-01

Massive stars rapidly change their masses through strong stellar winds and mass transfer in binary systems. The latter aspect is important for populations of massive stars as more than 70% of all O stars are expected to interact with a binary companion during their lifetime. We show that such mass changes leave characteristic signatures in stellar mass functions of young star clusters that can be used to infer their ages and to identify products of binary evolution. We model the observed present-day mass functions of the young Galactic Arches and Quintuplet star clusters using our rapid binary evolution code. We find that the shaping of the mass function by stellar wind mass loss allows us to determine the cluster ages as 3.5 ± 0.7 Myr and 4.8 ± 1.1 Myr, respectively. Exploiting the effects of binary mass exchange on the cluster mass function, we find that the most massive stars in both clusters are rejuvenated products of binary mass transfer, i.e., the massive counterpart of classical blue straggler stars. This resolves the problem of an apparent age spread among the most luminous stars exceeding the expected duration of star formation in these clusters. We perform Monte Carlo simulations to probe stochastic sampling, which support the idea of the most massive stars being rejuvenated binary products. We find that the most massive star is expected to be a binary product after 1.0 ± 0.7 Myr in Arches and after 1.7 ± 1.0 Myr in Quintuplet. Today, the most massive 9 ± 3 stars in Arches and 8 ± 3 in Quintuplet are expected to be such objects. Our findings have strong implications for the stellar upper mass limit and solve the discrepancy between the claimed 150 M ☉ limit and observations of four stars with initial masses of 165-320 M ☉ in R136 and of supernova 2007bi, which is thought to be a pair-instability supernova from an initial 250 M ☉ star. Using the stellar population of R136, we revise the upper mass limit to values in the range 200-500 M ☉ .

Ages of Young Star Clusters, Massive Blue Stragglers, and the Upper Mass Limit of Stars: Analyzing Age-dependent Stellar Mass Functions

Science.gov (United States)

Schneider, F. R. N.; Izzard, R. G.; de Mink, S. E.; Langer, N.; Stolte, A.; de Koter, A.; Gvaramadze, V. V.; Hußmann, B.; Liermann, A.; Sana, H.

2014-01-01

Massive stars rapidly change their masses through strong stellar winds and mass transfer in binary systems. The latter aspect is important for populations of massive stars as more than 70% of all O stars are expected to interact with a binary companion during their lifetime. We show that such mass changes leave characteristic signatures in stellar mass functions of young star clusters that can be used to infer their ages and to identify products of binary evolution. We model the observed present-day mass functions of the young Galactic Arches and Quintuplet star clusters using our rapid binary evolution code. We find that the shaping of the mass function by stellar wind mass loss allows us to determine the cluster ages as 3.5 ± 0.7 Myr and 4.8 ± 1.1 Myr, respectively. Exploiting the effects of binary mass exchange on the cluster mass function, we find that the most massive stars in both clusters are rejuvenated products of binary mass transfer, i.e., the massive counterpart of classical blue straggler stars. This resolves the problem of an apparent age spread among the most luminous stars exceeding the expected duration of star formation in these clusters. We perform Monte Carlo simulations to probe stochastic sampling, which support the idea of the most massive stars being rejuvenated binary products. We find that the most massive star is expected to be a binary product after 1.0 ± 0.7 Myr in Arches and after 1.7 ± 1.0 Myr in Quintuplet. Today, the most massive 9 ± 3 stars in Arches and 8 ± 3 in Quintuplet are expected to be such objects. Our findings have strong implications for the stellar upper mass limit and solve the discrepancy between the claimed 150 M ⊙ limit and observations of four stars with initial masses of 165-320 M ⊙ in R136 and of supernova 2007bi, which is thought to be a pair-instability supernova from an initial 250 M ⊙ star. Using the stellar population of R136, we revise the upper mass limit to values in the range 200-500 M ⊙.

Transcriptional interference networks coordinate the expression of functionally related genes clustered in the same genomic loci.

Science.gov (United States)

Boldogköi, Zsolt

2012-01-01

The regulation of gene expression is essential for normal functioning of biological systems in every form of life. Gene expression is primarily controlled at the level of transcription, especially at the phase of initiation. Non-coding RNAs are one of the major players at every level of genetic regulation, including the control of chromatin organization, transcription, various post-transcriptional processes, and translation. In this study, the Transcriptional Interference Network (TIN) hypothesis was put forward in an attempt to explain the global expression of antisense RNAs and the overall occurrence of tandem gene clusters in the genomes of various biological systems ranging from viruses to mammalian cells. The TIN hypothesis suggests the existence of a novel layer of genetic regulation, based on the interactions between the transcriptional machineries of neighboring genes at their overlapping regions, which are assumed to play a fundamental role in coordinating gene expression within a cluster of functionally linked genes. It is claimed that the transcriptional overlaps between adjacent genes are much more widespread in genomes than is thought today. The Waterfall model of the TIN hypothesis postulates a unidirectional effect of upstream genes on the transcription of downstream genes within a cluster of tandemly arrayed genes, while the Seesaw model proposes a mutual interdependence of gene expression between the oppositely oriented genes. The TIN represents an auto-regulatory system with an exquisitely timed and highly synchronized cascade of gene expression in functionally linked genes located in close physical proximity to each other. In this study, we focused on herpesviruses. The reason for this lies in the compressed nature of viral genes, which allows a tight regulation and an easier investigation of the transcriptional interactions between genes. However, I believe that the same or similar principles can be applied to cellular organisms too.

Transcriptional interference networks coordinate the expression of functionally-related genes clustered in the same genomic loci

Directory of Open Access Journals (Sweden)

Zsolt eBoldogkoi

2012-07-01

Full Text Available The regulation of gene expression is essential for normal functioning of biological systems in every form of life. Gene expression is primarily controlled at the level of transcription, especially at the phase of initiation. Non-coding RNAs are one of the major players at every level of genetic regulation, including the control of chromatin organisation, transcription, various post-transcriptional processes and translation. In this study, the Transcriptional Interference Network (TIN hypothesis was put forward in an attempt to explain the global expression of antisense RNAs and the overall occurrence of tandem gene clusters in the genomes of various biological systems ranging from viruses to mammalian cells. The TIN hypothesis suggests the existence of a novel layer of genetic regulation, based on the interactions between the transcriptional machineries of neighbouring genes at their overlapping regions, which are assumed to play a fundamental role in coordinating gene expression within a cluster of functionally-linked genes. It is claimed that the transcriptional overlaps between adjacent genes are much more widespread in genomes than is thought today. The Waterfall model of the TIN hypothesis postulates a unidirectional effect of upstream genes on the transcription of downstream genes within a cluster of tandemly-arrayed genes, while the Seesaw model proposes a mutual interdependence of gene expression between the oppositely-oriented genes. The TIN represents an auto-regulatory system with an exquisitely timed and highly synchronised cascade of gene expression in functionally-linked genes located in close physical proximity to each other. In this study, we focused on herpesviruses. The reason for this lies in the compressed nature of viral genes, which allows a tight regulation and an easier investigation of the transcriptional interactions between genes. However, I believe that the same or similar principles can be applied to cellular

No association of CpG island methylator phenotype and colorectal cancer survival: population-based study.

Science.gov (United States)

Jia, Min; Jansen, Lina; Walter, Viola; Tagscherer, Katrin; Roth, Wilfried; Herpel, Esther; Kloor, Matthias; Bläker, Hendrik; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael

2016-11-22

Previous studies have shown adverse effects of CpG island methylator phenotype (CIMP) on colorectal cancer (CRC) prognosis. However, sample sizes were often limited and only few studies were able to adjust for relevant molecular features associated with CIMP. The aim of this study was to investigate the impact of CIMP on CRC survival in a large population-based study with comprehensive adjustment. The CIMP status and other molecular tumour features were analysed in 1385 CRC patients diagnosed between 2003 and 2010. Detailed information were obtained from standardised personal interviews and medical records. During follow-up (median: 4.9 years), we assessed vital status, cause of death and therapy details. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of survival after CRC. The CIMP-H occurred more frequently in patients with older age, female gender, cancer in the proximal colon, BRAF mutation and microsatellite instability-high (MSI-H). However, CIMP status was not associated with CRC prognosis in CRC patients (HR=1.00; 95% CI=0.72-1.40 for overall survival; HR=0.96; 95% CI=0.65-1.41 for disease-specific survival) or in any of the subgroups. Although CIMP status was associated with the presence of MSI-H and BRAF mutation, the prognostic effects of MSI-H (HR=0.49; 95% CI=0.27-0.90) and BRAF mutation (HR=1.78; 95% CI=1.10-2.84) were independent of CIMP status. Similar benefit of chemotherapy was found for CRC outcomes in both the CIMP-low/negative group and the CIMP-high group. CpG island methylator phenotype was not associated with CRC prognosis after adjusting for other important clinical factors and associated mutations.

DATA CLASSIFICATION WITH NEURAL CLASSIFIER USING RADIAL BASIS FUNCTION WITH DATA REDUCTION USING HIERARCHICAL CLUSTERING

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M. Safish Mary

2012-04-01

Full Text Available Classification of large amount of data is a time consuming process but crucial for analysis and decision making. Radial Basis Function networks are widely used for classification and regression analysis. In this paper, we have studied the performance of RBF neural networks to classify the sales of cars based on the demand, using kernel density estimation algorithm which produces classification accuracy comparable to data classification accuracy provided by support vector machines. In this paper, we have proposed a new instance based data selection method where redundant instances are removed with help of a threshold thus improving the time complexity with improved classification accuracy. The instance based selection of the data set will help reduce the number of clusters formed thereby reduces the number of centers considered for building the RBF network. Further the efficiency of the training is improved by applying a hierarchical clustering technique to reduce the number of clusters formed at every step. The paper explains the algorithm used for classification and for conditioning the data. It also explains the complexities involved in classification of sales data for analysis and decision-making.

Structures, stability, magnetic moments and growth strategies of the Fe_nN (n = 1–7) clusters: All-electron density functional theory calculations

International Nuclear Information System (INIS)

Li, Zhi; Zhao, Zhen

2017-01-01

The geometries, electronic properties, magnetic moments and growth strategies of the Fe_nN (n = 1–7) clusters are investigated using all-electron density functional theory. The results show that N doping significantly distorts the Fe_n clusters. Fe_4N and Fe_6N clusters are more stable structures than other considered Fe_nN clusters. Local peaks of HOMO-LUMO gap curve are found at n = 3, 7, implying that the chemical stability of the Fe_3N and Fe_7N clusters is higher. Fe_2N, Fe_4N and Fe_6N clusters have larger magnetic moments compared to other considered Fe_nN (n = 1–7) clusters. It can be seen that the Fe_5 clusters are easier to adsorb a Fe atom while the Fe_4 clusters are easier to adsorb a N atom. The considered Fe_mN clusters prefer to adsorb a Fe atom and larger Fe_mN clusters are easier to grow. - Highlights: • The structural stability of the Fe_4N and Fe_6N clusters is higher. • The chemical stability of the Fe_3N and Fe_7N clusters is higher. • Fe_5 clusters are easier to adsorb a Fe atom while Fe_4 clusters are easier to adsorb a N atom. • Fe_nN clusters prefer to adsorb a Fe atom.

Association between the CpG island methylator phenotype and its prognostic significance in primary pulmonary adenocarcinoma.

Science.gov (United States)

Koh, Young Wha; Chun, Sung-Min; Park, Young-Soo; Song, Joon Seon; Lee, Geon Kook; Khang, Shin Kwang; Jang, Se Jin

2016-08-01

Aberrant methylation of promoter CpG islands is one of the most important inactivation mechanisms for tumor suppressor and tumor-related genes. Previous studies using genome-wide DNA methylation microarray analysis have suggested the existence of a CpG island methylator phenotype (CIMP) in lung adenocarcinomas. Although the biological behavior of these tumors varies according to tumor stage, no large-scale study has examined the CIMP in lung adenocarcinoma patients according to tumor stage. Furthermore, there have been no reported results regarding the clinical significance of each of the six CIMP markers. To examine the CIMP in patients with pulmonary adenocarcinoma after a surgical resection, we performed methylation analysis of six genes (CCNA1, ACAN, GFRA1, EDARADD, MGC45800, and p16 (INK4A)) in 230 pulmonary adenocarcinoma cases using the SEQUENOM MassARRAY platform. Fifty-four patients (28 %, 54/191) were in the CIMP-high (CIMP-H) group associated with high nodal stage (P = 0.007), the presence of micropapillary or solid histology (P = 0.003), and the absence of an epidermal growth factor receptor (EGFR) mutation (P = 0.002). By multivariate analysis, CIMP was an independent prognostic marker for overall survival (OS) and disease-specific survival (P = 0.03 and P = 0.43, respectively). In the stage I subgroups alone, CIMP-H patients had lower OS rates than the CIMP-low (CIMP-L) group (P = 0.041). Of the six CIMP markers, ACAN alone was significantly associated with patient survival. CIMP predicted the risk of progression independently of clinicopathological variables and enables the stratification of pulmonary adenocarcinoma patients, particularly among stage I cases.

Identification of Voxels Confounded by Venous Signals Using Resting-State fMRI Functional Connectivity Graph Clustering

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Klaudius eKalcher

2015-12-01

Full Text Available Identifying venous voxels in fMRI datasets is important to increase the specificity of fMRI analyses to microvasculature in the vicinity of the neural processes triggering the BOLD response. This is, however, difficult to achieve in particular in typical studies where magnitude images of BOLD EPI are the only data available. In this study, voxelwise functional connectivity graphs were computed on minimally preprocessed low TR (333 ms multiband resting-state fMRI data, using both high positive and negative correlations to define edges between nodes (voxels. A high correlation threshold for binarization ensures that most edges in the resulting sparse graph reflect the high coherence of signals in medium to large veins. Graph clustering based on the optimization of modularity was then employed to identify clusters of coherent voxels in this graph, and all clusters of 50 or more voxels were then interpreted as corresponding to medium to large veins. Indeed, a comparison with SWI reveals that 75.6 ± 5.9% of voxels within these large clusters overlap with veins visible in the SWI image or lie outside the brain parenchyma. Some of the remainingdifferences between the two modalities can be explained by imperfect alignment or geometric distortions between the two images. Overall, the graph clustering based method for identifying venous voxels has a high specificity as well as the additional advantages of being computed in the same voxel grid as the fMRI dataset itself and not needingany additional data beyond what is usually acquired (and exported in standard fMRI experiments.

Clustering of noise-induced oscillations

DEFF Research Database (Denmark)

Sosnovtseva, Olga; Fomin, A I; Postnov, D E

2001-01-01

The subject of our study is clustering in a population of excitable systems driven by Gaussian white noise and with randomly distributed coupling strength. The cluster state is frequency-locked state in which all functional units run at the same noise-induced frequency. Cooperative dynamics...

Globular clusters - Fads and fallacies

International Nuclear Information System (INIS)

White, R.E.

1991-01-01

The types of globular clusters observed in the Milky Way Galaxy are described together with their known characteristics, with special attention given to correcting the erroneous statements made earlier about globular clusters. Among these are the following statements: the Galaxy is surrounded by many hundreds of globular clusters; all globular clusters are located toward the Galactic center, all globular clusters are metal poor and move about the Galaxy in highly elliptical paths; all globular clusters contain RR Lyrae-type variable stars, and the RR Lyrae stars found outside of globulars have come from cluster dissolution or ejection; all of the stars in a given cluster were born at the same time and have the same chemical composition; X-ray globulars are powered by central black holes; and the luminosity functions for globular clusters are well defined and well determined. Consideration is given to the fact that globular clusters in the Magellanic Clouds differ from those in the Milky Way by their age distribution and that the globulars of the SMC differ from those of the LMC

Persistence drives gene clustering in bacterial genomes

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Rocha Eduardo PC

2008-01-01

Full Text Available Abstract Background Gene clustering plays an important role in the organization of the bacterial chromosome and several mechanisms have been proposed to explain its extent. However, the controversies raised about the validity of each of these mechanisms remind us that the cause of this gene organization remains an open question. Models proposed to explain clustering did not take into account the function of the gene products nor the likely presence or absence of a given gene in a genome. However, genomes harbor two very different categories of genes: those genes present in a majority of organisms – persistent genes – and those present in very few organisms – rare genes. Results We show that two classes of genes are significantly clustered in bacterial genomes: the highly persistent and the rare genes. The clustering of rare genes is readily explained by the selfish operon theory. Yet, genes persistently present in bacterial genomes are also clustered and we try to understand why. We propose a model accounting specifically for such clustering, and show that indispensability in a genome with frequent gene deletion and insertion leads to the transient clustering of these genes. The model describes how clusters are created via the gene flux that continuously introduces new genes while deleting others. We then test if known selective processes, such as co-transcription, physical interaction or functional neighborhood, account for the stabilization of these clusters. Conclusion We show that the strong selective pressure acting on the function of persistent genes, in a permanent state of flux of genes in bacterial genomes, maintaining their size fairly constant, that drives persistent genes clustering. A further selective stabilization process might contribute to maintaining the clustering.

Functional connectivity analysis of the neural bases of emotion regulation: A comparison of independent component method with density-based k-means clustering method.

Science.gov (United States)

Zou, Ling; Guo, Qian; Xu, Yi; Yang, Biao; Jiao, Zhuqing; Xiang, Jianbo

2016-04-29

Functional magnetic resonance imaging (fMRI) is an important tool in neuroscience for assessing connectivity and interactions between distant areas of the brain. To find and characterize the coherent patterns of brain activity as a means of identifying brain systems for the cognitive reappraisal of the emotion task, both density-based k-means clustering and independent component analysis (ICA) methods can be applied to characterize the interactions between brain regions involved in cognitive reappraisal of emotion. Our results reveal that compared with the ICA method, the density-based k-means clustering method provides a higher sensitivity of polymerization. In addition, it is more sensitive to those relatively weak functional connection regions. Thus, the study concludes that in the process of receiving emotional stimuli, the relatively obvious activation areas are mainly distributed in the frontal lobe, cingulum and near the hypothalamus. Furthermore, density-based k-means clustering method creates a more reliable method for follow-up studies of brain functional connectivity.

Reactions of mixed silver-gold cluster cations AgmAun+ (m+n=4,5,6) with CO: Radiative association kinetics and density functional theory computations

International Nuclear Information System (INIS)

Neumaier, Marco; Weigend, Florian; Hampe, Oliver; Kappes, Manfred M.

2006-01-01

Near thermal energy reactive collisions of small mixed metal cluster cations Ag m Au n + (m+n=4, 5, and 6) with carbon monoxide have been studied in the room temperature Penning trap of a Fourier transform ion-cyclotron-resonance mass spectrometer as a function of cluster size and composition. The tetrameric species AgAu 3 + and Ag 2 Au 2 + are found to react dissociatively by way of Au or Ag atom loss, respectively, to form the cluster carbonyl AgAu 2 CO + . In contrast, measurements on a selection of pentamers and hexamers show that CO is added with absolute rate constants that decrease with increasing silver content. Experimentally determined absolute rate constants for CO adsorption were analyzed using the radiative association kinetics model to obtain cluster cation-CO binding energies ranging from 0.77 to 1.09 eV. High-level ab initio density functional theory (DFT) computations identifying the lowest-energy cluster isomers and the respective CO adsorption energies are in good agreement with the experimental findings clearly showing that CO binds in a ''head-on'' fashion to a gold atom in the mixed clusters. DFT exploration of reaction pathways in the case of Ag 2 Au 2 + suggests that exoergicities are high enough to access the minimum energy products for all reactive clusters probed

Reactions of mixed silver-gold cluster cations AgmAun+ (m+n=4,5,6) with CO: Radiative association kinetics and density functional theory computations

Science.gov (United States)

Neumaier, Marco; Weigend, Florian; Hampe, Oliver; Kappes, Manfred M.

2006-09-01

Near thermal energy reactive collisions of small mixed metal cluster cations AgmAun+ (m +n=4, 5, and 6) with carbon monoxide have been studied in the room temperature Penning trap of a Fourier transform ion-cyclotron-resonance mass spectrometer as a function of cluster size and composition. The tetrameric species AgAu3+ and Ag2Au2+ are found to react dissociatively by way of Au or Ag atom loss, respectively, to form the cluster carbonyl AgAu2CO+. In contrast, measurements on a selection of pentamers and hexamers show that CO is added with absolute rate constants that decrease with increasing silver content. Experimentally determined absolute rate constants for CO adsorption were analyzed using the radiative association kinetics model to obtain cluster cation-CO binding energies ranging from 0.77to1.09eV. High-level ab initio density functional theory (DFT) computations identifying the lowest-energy cluster isomers and the respective CO adsorption energies are in good agreement with the experimental findings clearly showing that CO binds in a "head-on" fashion to a gold atom in the mixed clusters. DFT exploration of reaction pathways in the case of Ag2Au2+ suggests that exoergicities are high enough to access the minimum energy products for all reactive clusters probed.

Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

International Nuclear Information System (INIS)

Ang, Pei Woon; Soong, Richie; Loh, Marie; Liem, Natalia; Lim, Pei Li; Grieu, Fabienne; Vaithilingam, Aparna; Platell, Cameron; Yong, Wei Peng; Iacopetta, Barry

2010-01-01

Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate ® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P < 0.001). Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups

Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

Directory of Open Access Journals (Sweden)

Vaithilingam Aparna

2010-05-01

Full Text Available Abstract Background Most previous studies of the CpG island methylator phenotype (CIMP in colorectal cancer (CRC have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. Methods DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI, methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. Results A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases, CIMP-mid (CIMP-M, 14% and CIMP-high (CIMP-H, 65%. In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P Conclusions Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups.

Maximum-entropy clustering algorithm and its global convergence analysis

Institute of Scientific and Technical Information of China (English)

无

2001-01-01

Constructing a batch of differentiable entropy functions touniformly approximate an objective function by means of the maximum-entropy principle, a new clustering algorithm, called maximum-entropy clustering algorithm, is proposed based on optimization theory. This algorithm is a soft generalization of the hard C-means algorithm and possesses global convergence. Its relations with other clustering algorithms are discussed.

A Novel Cluster Head Selection Algorithm Based on Fuzzy Clustering and Particle Swarm Optimization.

Science.gov (United States)

Ni, Qingjian; Pan, Qianqian; Du, Huimin; Cao, Cen; Zhai, Yuqing

2017-01-01

An important objective of wireless sensor network is to prolong the network life cycle, and topology control is of great significance for extending the network life cycle. Based on previous work, for cluster head selection in hierarchical topology control, we propose a solution based on fuzzy clustering preprocessing and particle swarm optimization. More specifically, first, fuzzy clustering algorithm is used to initial clustering for sensor nodes according to geographical locations, where a sensor node belongs to a cluster with a determined probability, and the number of initial clusters is analyzed and discussed. Furthermore, the fitness function is designed considering both the energy consumption and distance factors of wireless sensor network. Finally, the cluster head nodes in hierarchical topology are determined based on the improved particle swarm optimization. Experimental results show that, compared with traditional methods, the proposed method achieved the purpose of reducing the mortality rate of nodes and extending the network life cycle.

Analysis of RET promoter CpG island methylation using methylation-specific PCR (MSP), pyrosequencing, and methylation-sensitive high-resolution melting (MS-HRM): impact on stage II colon cancer patient outcome.

Science.gov (United States)

Draht, Muriel X G; Smits, Kim M; Jooste, Valérie; Tournier, Benjamin; Vervoort, Martijn; Ramaekers, Chantal; Chapusot, Caroline; Weijenberg, Matty P; van Engeland, Manon; Melotte, Veerle

2016-01-01

Already since the 1990s, promoter CpG island methylation markers have been considered promising diagnostic, prognostic, and predictive cancer biomarkers. However, so far, only a limited number of DNA methylation markers have been introduced into clinical practice. One reason why the vast majority of methylation markers do not translate into clinical applications is lack of independent validation of methylation markers, often caused by differences in methylation analysis techniques. We recently described RET promoter CpG island methylation as a potential prognostic marker in stage II colorectal cancer (CRC) patients of two independent series. In the current study, we analyzed the RET promoter CpG island methylation of 241 stage II colon cancer patients by direct methylation-specific PCR (MSP), nested-MSP, pyrosequencing, and methylation-sensitive high-resolution melting (MS-HRM). All primers were designed as close as possible to the same genomic region. In order to investigate the effect of different DNA methylation assays on patient outcome, we assessed the clinical sensitivity and specificity as well as the association of RET methylation with overall survival for three and five years of follow-up. Using direct-MSP and nested-MSP, 12.0 % (25/209) and 29.6 % (71/240) of the patients showed RET promoter CpG island methylation. Methylation frequencies detected by pyrosequencing were related to the threshold for positivity that defined RET methylation. Methylation frequencies obtained by pyrosequencing (threshold for positivity at 20 %) and MS-HRM were 13.3 % (32/240) and 13.8 % (33/239), respectively. The pyrosequencing threshold for positivity of 20 % showed the best correlation with MS-HRM and direct-MSP results. Nested-MSP detected RET promoter CpG island methylation in deceased patients with a higher sensitivity (33.1 %) compared to direct-MSP (10.7 %), pyrosequencing (14.4 %), and MS-HRM (15.4 %). While RET methylation frequencies detected by nested

Quantum size correction to the work function and centroid of excess charge in positively ionized simple metal clusters

International Nuclear Information System (INIS)

Payami, M.

2004-01-01

In this work, we have shown the important role of the finite-size correction to the work function in predicting the correct position of the centroid of excess charge in positively charged simple metal clusters with different r s values (2≤ r s ≥ 7). For this purpose, firstly we have calculated the self-consistent Kohn-Sham energies of neutral and singly-ionized clusters with sizes 2≤ N ≥100 in the framework of local spin-density approximation and stabilized jellium model as well as simple jellium model with rigid jellium. Secondly, we have fitted our results to the asymptotic ionization formulas both with and without the size correction to the work function. The results of fittings show that the formula containing the size correction predict a correct position of the centroid inside the jellium while the other predicts a false position, outside the jellium sphere

Cluster processing business level monitor

International Nuclear Information System (INIS)

Muniz, Francisco J.

2017-01-01

This article describes a Cluster Processing Monitor. Several applications with this functionality can be freely found doing a search in the Google machine. However, those applications may offer more features that are needed on the Processing Monitor being proposed. Therefore, making the monitor output evaluation difficult to be understood by the user, at-a-glance. In addition, such monitors may add unnecessary processing cost to the Cluster. For these reasons, a completely new Cluster Processing Monitor module was designed and implemented. In the CDTN, Clusters are broadly used, mainly, in deterministic methods (CFD) and non-deterministic methods (Monte Carlo). (author)

Cluster processing business level monitor

Energy Technology Data Exchange (ETDEWEB)

Muniz, Francisco J., E-mail: muniz@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2017-07-01

This article describes a Cluster Processing Monitor. Several applications with this functionality can be freely found doing a search in the Google machine. However, those applications may offer more features that are needed on the Processing Monitor being proposed. Therefore, making the monitor output evaluation difficult to be understood by the user, at-a-glance. In addition, such monitors may add unnecessary processing cost to the Cluster. For these reasons, a completely new Cluster Processing Monitor module was designed and implemented. In the CDTN, Clusters are broadly used, mainly, in deterministic methods (CFD) and non-deterministic methods (Monte Carlo). (author)

ABOUT THE TYPES OF REGIONAL INNOVATION CLUSTERS

Directory of Open Access Journals (Sweden)

Aleksandr S. Voronov

2016-01-01

Full Text Available This article describes the main characteristics of innovation clusters, analyzed the develop-ment plans of the cluster areas of growth on the basis of innovation in the various subjects of the federation, it proposed the principle of clustering of the «nuclear» type, dened by problems in the functioning of specialized distributed clusters on the basis of the organi-zational and marketing innovations, proposed scheme for sustainable innovation develop-ment of specialized distributed cluster.

CHANDRA CLUSTER COSMOLOGY PROJECT III: COSMOLOGICAL PARAMETER CONSTRAINTS

International Nuclear Information System (INIS)

Vikhlinin, A.; Forman, W. R.; Jones, C.; Murray, S. S.; Kravtsov, A. V.; Burenin, R. A.; Voevodkin, A.; Ebeling, H.; Hornstrup, A.; Nagai, D.; Quintana, H.

2009-01-01

Chandra observations of large samples of galaxy clusters detected in X-rays by ROSAT provide a new, robust determination of the cluster mass functions at low and high redshifts. Statistical and systematic errors are now sufficiently small, and the redshift leverage sufficiently large for the mass function evolution to be used as a useful growth of a structure-based dark energy probe. In this paper, we present cosmological parameter constraints obtained from Chandra observations of 37 clusters with (z) = 0.55 derived from 400 deg 2 ROSAT serendipitous survey and 49 brightest z ∼ 0.05 clusters detected in the All-Sky Survey. Evolution of the mass function between these redshifts requires Ω Λ > 0 with a ∼5σ significance, and constrains the dark energy equation-of-state parameter to w 0 = -1.14 ± 0.21, assuming a constant w and a flat universe. Cluster information also significantly improves constraints when combined with other methods. Fitting our cluster data jointly with the latest supernovae, Wilkinson Microwave Anisotropy Probe, and baryonic acoustic oscillation measurements, we obtain w 0 = -0.991 ± 0.045 (stat) ±0.039 (sys), a factor of 1.5 reduction in statistical uncertainties, and nearly a factor of 2 improvement in systematics compared with constraints that can be obtained without clusters. The joint analysis of these four data sets puts a conservative upper limit on the masses of light neutrinos Σm ν M h and σ 8 from the low-redshift cluster mass function.

From Lipid Homeostasis to Differentiation: Old and New Functions of the Zinc Cluster Proteins Ecm22, Upc2, Sut1 and Sut2

Directory of Open Access Journals (Sweden)

Ifeoluwapo Matthew Joshua

2017-04-01

Full Text Available Zinc cluster proteins are a large family of transcriptional regulators with a wide range of biological functions. The zinc cluster proteins Ecm22, Upc2, Sut1 and Sut2 have initially been identified as regulators of sterol import in the budding yeast Saccharomyces cerevisiae. These proteins also control adaptations to anaerobic growth, sterol biosynthesis as well as filamentation and mating. Orthologs of these zinc cluster proteins have been identified in several species of Candida. Upc2 plays a critical role in antifungal resistance in these important human fungal pathogens. Upc2 is therefore an interesting potential target for novel antifungals. In this review we discuss the functions, mode of actions and regulation of Ecm22, Upc2, Sut1 and Sut2 in budding yeast and Candida.

Clustering of galaxies with f(R) gravity

Science.gov (United States)

Capozziello, Salvatore; Faizal, Mir; Hameeda, Mir; Pourhassan, Behnam; Salzano, Vincenzo; Upadhyay, Sudhaker

2018-02-01

Based on thermodynamics, we discuss the galactic clustering of expanding Universe by assuming the gravitational interaction through the modified Newton's potential given by f(R) gravity. We compute the corrected N-particle partition function analytically. The corrected partition function leads to more exact equations of state of the system. By assuming that the system follows quasi-equilibrium, we derive the exact distribution function that exhibits the f(R) correction. Moreover, we evaluate the critical temperature and discuss the stability of the system. We observe the effects of correction of f(R) gravity on the power-law behaviour of particle-particle correlation function also. In order to check the feasibility of an f(R) gravity approach to the clustering of galaxies, we compare our results with an observational galaxy cluster catalogue.

Cluster synchronization in networks of identical oscillators with α-function pulse coupling.

Science.gov (United States)

Chen, Bolun; Engelbrecht, Jan R; Mirollo, Renato

2017-02-01

We study a network of N identical leaky integrate-and-fire model neurons coupled by α-function pulses, weighted by a coupling parameter K. Studies of the dynamics of this system have mostly focused on the stability of the fully synchronized and the fully asynchronous splay states, which naturally depends on the sign of K, i.e., excitation vs inhibition. We find that there is also a rich set of attractors consisting of clusters of fully synchronized oscillators, such as fixed (N-1,1) states, which have synchronized clusters of sizes N-1 and 1, as well as splay states of clusters with equal sizes greater than 1. Additionally, we find limit cycles that clarify the stability of previously observed quasiperiodic behavior. Our framework exploits the neutrality of the dynamics for K=0 which allows us to implement a dimensional reduction strategy that simplifies the dynamics to a continuous flow on a codimension 3 subspace with the sign of K determining the flow direction. This reduction framework naturally incorporates a hierarchy of partially synchronized subspaces in which the new attracting states lie. Using high-precision numerical simulations, we describe completely the sequence of bifurcations and the stability of all fixed points and limit cycles for N=2-4. The set of possible attracting states can be used to distinguish different classes of neuron models. For instance from our previous work [Chaos 24, 013114 (2014)CHAOEH1054-150010.1063/1.4858458] we know that of the types of partially synchronized states discussed here, only the (N-1,1) states can be stable in systems of identical coupled sinusoidal (i.e., Kuramoto type) oscillators, such as θ-neuron models. Upon introducing a small variation in individual neuron parameters, the attracting fixed points we discuss here generalize to equivalent fixed points in which neurons need not fire coincidently.

Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

Science.gov (United States)

Kim, Mi Ae; Shin, Seung Woo; Park, Jong Sook; Uh, Soo Taek; Chang, Hun Soo; Bae, Da Jeong; Cho, You Sook; Park, Hae Sim; Yoon, Ho Joo; Choi, Byoung Whui; Kim, Yong Hoon; Park, Choon Sik

2017-11-01

Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease

Orbit Clustering Based on Transfer Cost

Science.gov (United States)

Gustafson, Eric D.; Arrieta-Camacho, Juan J.; Petropoulos, Anastassios E.

2013-01-01

We propose using cluster analysis to perform quick screening for combinatorial global optimization problems. The key missing component currently preventing cluster analysis from use in this context is the lack of a useable metric function that defines the cost to transfer between two orbits. We study several proposed metrics and clustering algorithms, including k-means and the expectation maximization algorithm. We also show that proven heuristic methods such as the Q-law can be modified to work with cluster analysis.

Dietary Patterns Derived by Cluster Analysis are Associated with Cognitive Function among Korean Older Adults.

Science.gov (United States)

Kim, Jihye; Yu, Areum; Choi, Bo Youl; Nam, Jung Hyun; Kim, Mi Kyung; Oh, Dong Hoon; Yang, Yoon Jung

2015-05-29

The objective of this study was to investigate major dietary patterns among older Korean adults through cluster analysis and to determine an association between dietary patterns and cognitive function. This is a cross-sectional study. The data from the Korean Multi-Rural Communities Cohort Study was used. Participants included 765 participants aged 60 years and over. A quantitative food frequency questionnaire with 106 items was used to investigate dietary intake. The Korean version of the MMSE-KC (Mini-Mental Status Examination-Korean version) was used to assess cognitive function. Two major dietary patterns were identified using K-means cluster analysis. The "MFDF" dietary pattern indicated high consumption of Multigrain rice, Fish, Dairy products, Fruits and fruit juices, while the "WNC" dietary pattern referred to higher intakes of White rice, Noodles, and Coffee. Means of the total MMSE-KC and orientation score of the participants in the MFDF dietary pattern were higher than those of the WNC dietary pattern. Compared with the WNC dietary pattern, the MFDF dietary pattern showed a lower risk of cognitive impairment after adjusting for covariates (OR 0.64, 95% CI 0.44-0.94). The MFDF dietary pattern, with high consumption of multigrain rice, fish, dairy products, and fruits may be related to better cognition among Korean older adults.

METHOD OF CONSTRUCTION OF GENETIC DATA CLUSTERS

Directory of Open Access Journals (Sweden)

N. A. Novoselova

2016-01-01

Full Text Available The paper presents a method of construction of genetic data clusters (functional modules using the randomized matrices. To build the functional modules the selection and analysis of the eigenvalues of the gene profiles correlation matrix is performed. The principal components, corresponding to the eigenvalues, which are significantly different from those obtained for the randomly generated correlation matrix, are used for the analysis. Each selected principal component forms gene cluster. In a comparative experiment with the analogs the proposed method shows the advantage in allocating statistically significant different-sized clusters, the ability to filter non- informative genes and to extract the biologically interpretable functional modules matching the real data structure.

Coupled-cluster representation of Green function employing modified spectral resolutions of similarity transformed Hamiltonians

Energy Technology Data Exchange (ETDEWEB)

Kowalski, K., E-mail: karol.kowalski@pnnl.gov; Bhaskaran-Nair, K.; Shelton, W. A. [William R. Wiley Environmental Molecular Sciences Laboratory, Battelle, Pacific Northwest National Laboratory, K8-91, P.O. Box 999, Richland, Washington 99352 (United States)

2014-09-07

In this paper we discuss a new formalism for producing an analytic coupled-cluster (CC) Green's function for an N-electron system by shifting the poles of similarity transformed Hamiltonians represented in N − 1 and N + 1 electron Hilbert spaces. Simple criteria are derived for the states in N − 1 and N + 1 electron spaces that are then corrected in the spectral resolution of the corresponding matrix representations of the similarity transformed Hamiltonian. The accurate description of excited state processes within a Green's function formalism would be of significant importance to a number of scientific communities ranging from physics and chemistry to engineering and the biological sciences. This is because the Green's function methodology provides a direct path for not only calculating properties whose underlying origins come from coupled many-body interactions but also provides a straightforward path for calculating electron transport, response, and correlation functions that allows for a direct link with experiment. As a special case of this general formulation, we discuss the application of this technique for Green's function defined by the CC with singles and doubles representation of the ground-state wave function.

Coupled-cluster representation of Green function employing modified spectral resolutions of similarity transformed Hamiltonians

Energy Technology Data Exchange (ETDEWEB)

Kowalski, K. [William R. Wiley Environmental Molecular Sciences Laboratory, Battelle, Pacific Northwest National Laboratory, K8-91, P.O. Box 999, Richland, Washington 99352, USA; Bhaskaran-Nair, K. [William R. Wiley Environmental Molecular Sciences Laboratory, Battelle, Pacific Northwest National Laboratory, K8-91, P.O. Box 999, Richland, Washington 99352, USA; Shelton, W. A. [William R. Wiley Environmental Molecular Sciences Laboratory, Battelle, Pacific Northwest National Laboratory, K8-91, P.O. Box 999, Richland, Washington 99352, USA

2014-09-07

In this paper we discuss a new formalism for producing an analytic coupled-cluster (CC) Green's function for an N-electron system by shifting the poles of similarity transformed Hamiltonians represented in N - 1 and N + 1 electron Hilbert spaces. Simple criteria are derived for the states in N - 1 and N + 1 electron spaces that are then corrected in the spectral resolution of the corresponding matrix representations of the similarity transformed Hamiltonian. The accurate description of excited state processes within a Green's function formalism would be of significant importance to a number of scientific communities ranging from physics and chemistry to engineering and the biological sciences. This is because the Green's function methodology provides a direct path for not only calculating properties whose underlying origins come from coupled many-body interactions but also provides a straightforward path for calculating electron transport, response, and correlation functions that allows for a direct link with experiment. Finally, as a special case of this general formulation, we discuss the application of this technique for Green's function defined by the CC with singles and doubles representation of the ground-state wave function.

Coupled-cluster representation of Green function employing modified spectral resolutions of similarity transformed Hamiltonians

International Nuclear Information System (INIS)

Kowalski, K.; Bhaskaran-Nair, K.; Shelton, W. A.

2014-01-01

In this paper we discuss a new formalism for producing an analytic coupled-cluster (CC) Green's function for an N-electron system by shifting the poles of similarity transformed Hamiltonians represented in N − 1 and N + 1 electron Hilbert spaces. Simple criteria are derived for the states in N − 1 and N + 1 electron spaces that are then corrected in the spectral resolution of the corresponding matrix representations of the similarity transformed Hamiltonian. The accurate description of excited state processes within a Green's function formalism would be of significant importance to a number of scientific communities ranging from physics and chemistry to engineering and the biological sciences. This is because the Green's function methodology provides a direct path for not only calculating properties whose underlying origins come from coupled many-body interactions but also provides a straightforward path for calculating electron transport, response, and correlation functions that allows for a direct link with experiment. As a special case of this general formulation, we discuss the application of this technique for Green's function defined by the CC with singles and doubles representation of the ground-state wave function

Fatigue Feature Extraction Analysis based on a K-Means Clustering Approach

Directory of Open Access Journals (Sweden)

M.F.M. Yunoh

2015-06-01

Full Text Available This paper focuses on clustering analysis using a K-means approach for fatigue feature dataset extraction. The aim of this study is to group the dataset as closely as possible (homogeneity for the scattered dataset. Kurtosis, the wavelet-based energy coefficient and fatigue damage are calculated for all segments after the extraction process using wavelet transform. Kurtosis, the wavelet-based energy coefficient and fatigue damage are used as input data for the K-means clustering approach. K-means clustering calculates the average distance of each group from the centroid and gives the objective function values. Based on the results, maximum values of the objective function can be seen in the two centroid clusters, with a value of 11.58. The minimum objective function value is found at 8.06 for five centroid clusters. It can be seen that the objective function with the lowest value for the number of clusters is equal to five; which is therefore the best cluster for the dataset.

Clusters of Insomnia Disorder: An Exploratory Cluster Analysis of Objective Sleep Parameters Reveals Differences in Neurocognitive Functioning, Quantitative EEG, and Heart Rate Variability.

Science.gov (United States)

Miller, Christopher B; Bartlett, Delwyn J; Mullins, Anna E; Dodds, Kirsty L; Gordon, Christopher J; Kyle, Simon D; Kim, Jong Won; D'Rozario, Angela L; Lee, Rico S C; Comas, Maria; Marshall, Nathaniel S; Yee, Brendon J; Espie, Colin A; Grunstein, Ronald R

2016-11-01

To empirically derive and evaluate potential clusters of Insomnia Disorder through cluster analysis from polysomnography (PSG). We hypothesized that clusters would differ on neurocognitive performance, sleep-onset measures of quantitative ( q )-EEG and heart rate variability (HRV). Research volunteers with Insomnia Disorder (DSM-5) completed a neurocognitive assessment and overnight PSG measures of total sleep time (TST), wake time after sleep onset (WASO), and sleep onset latency (SOL) were used to determine clusters. From 96 volunteers with Insomnia Disorder, cluster analysis derived at least two clusters from objective sleep parameters: Insomnia with normal objective sleep duration (I-NSD: n = 53) and Insomnia with short sleep duration (I-SSD: n = 43). At sleep onset, differences in HRV between I-NSD and I-SSD clusters suggest attenuated parasympathetic activity in I-SSD (P insomnia clusters derived from cluster analysis differ in sleep onset HRV. Preliminary data suggest evidence for three clusters in insomnia with differences for sustained attention and sleep-onset q -EEG. Insomnia 100 sleep study: Australia New Zealand Clinical Trials Registry (ANZCTR) identification number 12612000049875. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=347742. © 2016 Associated Professional Sleep Societies, LLC.

The Voronoi Tessellation cluster finder in 2+1 dimensions

Energy Technology Data Exchange (ETDEWEB)

Soares-Santos, Marcelle; /Fermilab /Sao Paulo U.; de Carvalho, Reinaldo R.; /Sao Jose, INPE; Annis, James; /Fermilab; Gal, Roy R.; /Hawaii U.; La Barbera, Francesco; /Capodimonte Observ.; Lopes, Paulo A.A.; /Valongo Observ.; Wechsler, Risa H.; Busha, Michael T.; Gerke, Brian F.; /SLAC /KIPAC, Menlo Park

2010-11-01

We present a detailed description of the Voronoi Tessellation (VT) cluster finder algorithm in 2+1 dimensions, which improves on past implementations of this technique. The need for cluster finder algorithms able to produce reliable cluster catalogs up to redshift 1 or beyond and down to 10{sup 13.5} solar masses is paramount especially in light of upcoming surveys aiming at cosmological constraints from galaxy cluster number counts. We build the VT in photometric redshift shells and use the two-point correlation function of the galaxies in the field to both determine the density threshold for detection of cluster candidates and to establish their significance. This allows us to detect clusters in a self-consistent way without any assumptions about their astrophysical properties. We apply the VT to mock catalogs which extend to redshift 1.4 reproducing the {Lambda}CDM cosmology and the clustering properties observed in the Sloan Digital Sky Survey data. An objective estimate of the cluster selection function in terms of the completeness and purity as a function of mass and redshift is as important as having a reliable cluster finder. We measure these quantities by matching the VT cluster catalog with the mock truth table. We show that the VT can produce a cluster catalog with completeness and purity >80% for the redshift range up to {approx}1 and mass range down to {approx}10{sup 13.5} solar masses.

The Voronoi Tessellation Cluster Finder in 2 1 Dimensions

Energy Technology Data Exchange (ETDEWEB)

Soares-Santos, Marcelle; /Fermilab /Sao Paulo U.; de Carvalho, Reinaldo R.; /Sao Jose, INPE; Annis, James; /Fermilab; Gal, Roy R.; /Hawaii U.; La Barbera, Francesco; /Capodimonte Observ.; Lopes, Paulo A.A.; /Valongo Observ.; Wechsler, Risa H.; Busha, Michael T.; Gerke, Brian F.; /SLAC /KIPAC, Menlo Park

2011-06-23

We present a detailed description of the Voronoi Tessellation (VT) cluster finder algorithm in 2+1 dimensions, which improves on past implementations of this technique. The need for cluster finder algorithms able to produce reliable cluster catalogs up to redshift 1 or beyond and down to 10{sup 13.5} solar masses is paramount especially in light of upcoming surveys aiming at cosmological constraints from galaxy cluster number counts. We build the VT in photometric redshift shells and use the two-point correlation function of the galaxies in the field to both determine the density threshold for detection of cluster candidates and to establish their significance. This allows us to detect clusters in a self-consistent way without any assumptions about their astrophysical properties. We apply the VT to mock catalogs which extend to redshift 1.4 reproducing the ?CDM cosmology and the clustering properties observed in the Sloan Digital Sky Survey data. An objective estimate of the cluster selection function in terms of the completeness and purity as a function of mass and redshift is as important as having a reliable cluster finder. We measure these quantities by matching the VT cluster catalog with the mock truth table. We show that the VT can produce a cluster catalog with completeness and purity >80% for the redshift range up to {approx}1 and mass range down to {approx}10{sup 13.5} solar masses.

THE VORONOI TESSELLATION CLUSTER FINDER IN 2+1 DIMENSIONS

International Nuclear Information System (INIS)

Soares-Santos, Marcelle; Annis, James; De Carvalho, Reinaldo R.; Gal, Roy R.; La Barbera, Francesco; Lopes, Paulo A. A.; Wechsler, Risa H.; Busha, Michael T.; Gerke, Brian F.

2011-01-01

We present a detailed description of the Voronoi Tessellation (VT) cluster finder algorithm in 2+1 dimensions, which improves on past implementations of this technique. The need for cluster finder algorithms able to produce reliable cluster catalogs up to redshift 1 or beyond and down to 10 13.5 solar masses is paramount especially in light of upcoming surveys aiming at cosmological constraints from galaxy cluster number counts. We build the VT in photometric redshift shells and use the two-point correlation function of the galaxies in the field to both determine the density threshold for detection of cluster candidates and to establish their significance. This allows us to detect clusters in a self-consistent way without any assumptions about their astrophysical properties. We apply the VT to mock catalogs which extend to redshift 1.4 reproducing the ΛCDM cosmology and the clustering properties observed in the Sloan Digital Sky Survey data. An objective estimate of the cluster selection function in terms of the completeness and purity as a function of mass and redshift is as important as having a reliable cluster finder. We measure these quantities by matching the VT cluster catalog with the mock truth table. We show that the VT can produce a cluster catalog with completeness and purity >80% for the redshift range up to ∼1 and mass range down to ∼10 13.5 solar masses.

Quantum size correction to the work function and the centroid of excess charge in positively ionized simple metal clusters

Directory of Open Access Journals (Sweden)

M. Payami

2003-12-01

Full Text Available  In this work, we have shown the important role of the finite-size correction to the work function in predicting the correct position of the centroid of excess charge in positively charged simple metal clusters with different values . For this purpose, firstly we have calculated the self-consistent Kohn-Sham energies of neutral and singly-ionized clusters with sizes in the framework of local spin-density approximation and stabilized jellium model (SJM as well as simple jellium model (JM with rigid jellium. Secondly, we have fitted our results to the asymptotic ionization formulas both with and without the size correction to the work function. The results of fittings show that the formula containing the size correction predict a correct position of the centroid inside the jellium while the other predicts a false position, outside the jellium sphere.

A First Estimate of the X-Ray Binary Frequency as a Function of Star Cluster Mass in a Single Galactic System

Science.gov (United States)

Clark, D. M.; Eikenberry, S. S.; Brandl, B. R.; Wilson, J. C.; Carson, J. C.; Henderson, C. P.; Hayward, T. L.; Barry, D. J.; Ptak, A. F.; Colbert, E. J. M.

2008-05-01

We use the previously identified 15 infrared star cluster counterparts to X-ray point sources in the interacting galaxies NGC 4038/4039 (the Antennae) to study the relationship between total cluster mass and X-ray binary number. This significant population of X-Ray/IR associations allows us to perform, for the first time, a statistical study of X-ray point sources and their environments. We define a quantity, η, relating the fraction of X-ray sources per unit mass as a function of cluster mass in the Antennae. We compute cluster mass by fitting spectral evolutionary models to Ks luminosity. Considering that this method depends on cluster age, we use four different age distributions to explore the effects of cluster age on the value of η and find it varies by less than a factor of 4. We find a mean value of η for these different distributions of η = 1.7 × 10-8 M-1⊙ with ση = 1.2 × 10-8 M-1⊙. Performing a χ2 test, we demonstrate η could exhibit a positive slope, but that it depends on the assumed distribution in cluster ages. While the estimated uncertainties in η are factors of a few, we believe this is the first estimate made of this quantity to "order of magnitude" accuracy. We also compare our findings to theoretical models of open and globular cluster evolution, incorporating the X-ray binary fraction per cluster.

Cosmological constraints from the evolution of the cluster baryon mass function at z similar to 0.5

DEFF Research Database (Denmark)

Vikhlinin, A.; Voevodkin, A.; Mullis, C.R.

2003-01-01

measurements of the gas masses for distant clusters, we find strong evolution of the baryon mass function between z > 0.4 and the present. The observed evolution defines a narrow band in the Omega(m)-Lambda plane, Omega(m) + 0.23Lambda = 0.41 +/- 0.10 at 68% confidence, which intersects with constraints from...

Small gold clusters on graphene, their mobility and clustering: a DFT study

International Nuclear Information System (INIS)

Amft, Martin; Sanyal, Biplab; Eriksson, Olle; Skorodumova, Natalia V

2011-01-01

Motivated by the experimentally observed high mobility of gold atoms on graphene and their tendency to form nanometer-sized clusters, we present a density functional theory study of the ground state structures of small gold clusters on graphene, their mobility and clustering. Our detailed analysis of the electronic structures identifies the opportunity to form strong gold-gold bonds and the graphene-mediated interaction of the pre-adsorbed fragments as the driving forces behind gold's tendency to aggregate on graphene. While clusters containing up to three gold atoms have one unambiguous ground state structure, both gas phase isomers of a cluster with four gold atoms can be found on graphene. In the gas phase the diamond-shaped Au 4 D cluster is the ground state structure, whereas the Y-shaped Au 4 Y becomes the actual ground state when adsorbed on graphene. As we show, both clusters can be produced on graphene by two distinct clustering processes. We also studied in detail the stepwise formation of a gold dimer out of two pre-adsorbed adatoms, as well as the formation of Au 3 . All reactions are exothermic and no further activation barriers, apart from the diffusion barriers, were found. The diffusion barriers of all studied clusters range from 4 to 36 meV only, and are substantially exceeded by the adsorption energies of - 0.1 to - 0.59 eV. This explains the high mobility of Au 1-4 on graphene along the C-C bonds.

X-ray cluster Abell 744

International Nuclear Information System (INIS)

Kurtz, M.J.; Huchra, J.P.; Beers, T.C.; Geller, M.J.; Gioia, I.M.

1985-01-01

X-ray and optical observations of the cluster of galaxies Abell 744 are presented. The X-ray flux (assuming H(0) = 100 km/s per Mpc) is about 9 x 10 to the 42nd erg/s. The X-ray source is extended, but shows no other structure. Photographic photometry (in Kron-Cousins R), calibrated by deep CCD frames, is presented for all galaxies brighter than 19th magnitude within 0.75 Mpc of the cluster center. The luminosity function is normal, and the isopleths show little evidence of substructure near the cluster center. The cluster has a dominant central galaxy, which is classified as a normal brightest-cluster elliptical on the basis of its luminosity profile. New redshifts were obtained for 26 galaxies in the vicinity of the cluster center; 20 appear to be cluster members. The spatial distribution of redshifts is peculiar; the dispersion within the 150 kpc core radius is much greater than outside. Abell 744 is similar to the nearby cluster Abell 1060. 31 references

Extensive polycistronism and antisense transcription in the mammalian Hox clusters.

Directory of Open Access Journals (Sweden)

Gaëll Mainguy

Full Text Available The Hox clusters play a crucial role in body patterning during animal development. They encode both Hox transcription factor and micro-RNA genes that are activated in a precise temporal and spatial sequence that follows their chromosomal order. These remarkable collinear properties confer functional unit status for Hox clusters. We developed the TranscriptView platform to establish high resolution transcriptional profiling and report here that transcription in the Hox clusters is far more complex than previously described in both human and mouse. Unannotated transcripts can represent up to 60% of the total transcriptional output of a cluster. In particular, we identified 14 non-coding Transcriptional Units antisense to Hox genes, 10 of which (70% have a detectable mouse homolog. Most of these Transcriptional Units in both human and mouse present conserved sizeable sequences (>40 bp overlapping Hox transcripts, suggesting that these Hox antisense transcripts are functional. Hox clusters also display at least seven polycistronic clusters, i.e., different genes being co-transcribed on long isoforms (up to 30 kb. This work provides a reevaluated framework for understanding Hox gene function and dys-function. Such extensive transcriptions may provide a structural explanation for Hox clustering.

Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer

Science.gov (United States)

Shigeyasu, Kunitoshi; Nagasaka, Takeshi; Mori, Yoshiko; Yokomichi, Naosuke; Kawai, Takashi; Fuji, Tomokazu; Kimura, Keisuke; Umeda, Yuzo; Kagawa, Shunsuke; Goel, Ajay; Fujiwara, Toshiyoshi

2015-01-01

Background To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown. Methods This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox’s proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1 methylation status in relation to overall survival (OS). Results By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088), better tumor differentiation (P = 0.0267) and CIMP-high and MLH1 3' methylated status (P = 0.0312). Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis. Conclusions CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer. PMID:26121593