Quadruplexes of human telomere dG{sub 3}(TTAG{sub 3}){sub 3} sequences containing guanine abasic sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skolakova, Petra; Bednarova, Klara; Vorlickova, Michaela

Research highlights: {yields} Loss of a guanine base does not hinder the formation of G-quadruplex of human telomere sequence. {yields} Each depurination strongly destabilizes the quadruplex of dG{sub 3}(TTAG{sub 3}){sub 3} in NaCl and KCl. {yields} Conformational change of the abasic analogs of dG{sub 3}(TTAG{sub 3}){sub 3} is inhibited in KCl. {yields} The effects abasic sites may affect telomere-end structures in vivo. -- Abstract: This study was performed to evaluate how the loss of a guanine base affects the structure and stability of the three-tetrad G-quadruplex of 5'-dG{sub 3}(TTAG{sub 3}){sub 3}, the basic quadruplex-forming unit of the human telomere DNA.more » None of the 12 possible abasic sites hindered the formation of quadruplexes, but all reduced the thermodynamic stability of the parent quadruplex in both NaCl and KCl. The base loss did not change the Na{sup +}-stabilized intramolecular antiparallel architecture, based on CD spectra, but held up the conformational change induced in dG{sub 3}(TTAG{sub 3}){sub 3} in physiological concentration of KCl. The reduced stability and the inhibited conformational transitions observed here in vitro for the first time may predict that unrepaired abasic sites in G-quadruplexes could lead to changes in the chromosome's terminal protection in vivo.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Shuangluo; Vashishtha, Ashwani; Bulkley, David

During DNA synthesis, base stacking and Watson-Crick (WC) hydrogen bonding increase the stability of nascent base pairs when they are in a ternary complex. To evaluate the contribution of base stacking to the incorporation efficiency of dNTPs when a DNA polymerase encounters an abasic site, we varied the penultimate base pairs (PBs) adjacent to the abasic site using all 16 possible combinations. We then determined pre-steady-state kinetic parameters with an RB69 DNA polymerase variant and solved nine structures of the corresponding ternary complexes. The efficiency of incorporation for incoming dNTPs opposite an abasic site varied between 2- and 210-fold dependingmore » on the identity of the PB. We propose that the A rule can be extended to encompass the fact that DNA polymerase can bypass dA/abasic sites more efficiently than other dN/abasic sites. Crystal structures of the ternary complexes show that the surface of the incoming base was stacked against the PB's interface and that the kinetic parameters for dNMP incorporation were consistent with specific features of base stacking, such as surface area and partial charge-charge interactions between the incoming base and the PB. Without a templating nucleotide residue, an incoming dNTP has no base with which it can hydrogen bond and cannot be desolvated, so that these surrounding water molecules become ordered and remain on the PB's surface in the ternary complex. When these water molecules are on top of a hydrophobic patch on the PB, they destabilize the ternary complex, and the incorporation efficiency of incoming dNTPs is reduced.« less

Preparation and Analysis of Oligonucleotides Containing the C4′-Oxidized Abasic Site and Related Mechanistic Probes

PubMed Central

Kim, Jaeseung; Kreller, Cortney R.; Greenberg, Marc M.

2005-01-01

The C4′-oxidized abasic site (C4-AP) is produced by a variety of DNA damaging agents. This alkali labile lesion can exist in up to four diastereomeric cyclic forms, in addition to the acyclic keto-aldehyde. Synthetic oligonucleotides containing the lesion were prepared from a stable photochemical precursor. Chemical integrity of the lesion containing oligonucleotides was probed using phosphodiesterase lability. Analysis of the 3′,5′-phosphate diester of the monomeric lesion released from single diastereomers of photolabile precursors by 1H NMR indicates that isomerization of the hemiacetal and/or hemiketal is rapid. The syntheses and characterization of oligonucleotides containing configurationally stable analogues of C4-AP, which serve as mechanistic probes for deciphering the structural basis of the biochemical and biological effects of the C4′-oxidized abasic lesion, are also described. PMID:16277338

Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis

PubMed Central

Lu, Duo; Silhan, Jan; MacDonald, James T.; Carpenter, Elisabeth P.; Jensen, Kirsten; Tang, Christoph M.; Baldwin, Geoff S.; Freemont, Paul S.

2012-01-01

Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cleaving the phosphodiester backbone 5′ to the abasic site. Despite extensive study, there is no structure of a bacterial AP endonuclease bound to substrate DNA. Furthermore, the structural mechanism for AP-site cleavage is incomplete. Here we report a detailed structural and biochemical study of the AP endonuclease from Neisseria meningitidis that has allowed us to capture structural intermediates providing more complete snapshots of the catalytic mechanism. Our data reveal subtle differences in AP-site recognition and kinetics between the human and bacterial enzymes that may reflect different evolutionary pressures. PMID:23035246

The psychological structure of humility.

PubMed

Weidman, Aaron C; Cheng, Joey T; Tracy, Jessica L

2018-01-01

Psychological inquiry into humility has advanced considerably over the past decade, yet this literature suffers from 2 notable limitations. First, there is no clear consensus among researchers about what humility is, and conceptualizations vary considerably across studies. Second, researchers have uniformly operationalized humility as a positive, socially desirable construct, while dismissing evidence from lay opinion and theological and philosophical traditions suggesting that humility may also have a darker side. To redress these issues, we conducted the first comprehensive, bottom-up analysis of the psychological structure of humility. Here we report 5 studies (total N = 1,479) that involve: (a) cluster analysis and categorization of humility-related words, generated by both lay persons and academic experts; (b) exploratory and confirmatory factor analyses of momentary and dispositional humility experiences; and (c) experimental induction of a momentary humility experience. Across these studies, we found converging evidence that humility can take 2 distinct forms, which we labeled "appreciative" and "self-abasing" humility. Appreciative humility tends to be elicited by personal success, involve action tendencies oriented toward celebrating others, and is positively associated with dispositions such as authentic pride, guilt, and prestige-based status. In contrast, self-abasing humility tends to be elicited by personal failure, involves negative self-evaluations and action tendencies oriented toward hiding from others' evaluations, and is associated with dispositions such as shame, low self-esteem, and submissiveness. Together, these findings provide a systematic and empirically grounded understanding of humility. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Bioconjugation of Oligodeoxynucleotides Carrying 1,4-Dicarbonyl Groups via Reductive Amination with Lysine Residues.

PubMed

Yang, Bo; Jinnouchi, Akiko; Usui, Kazuteru; Katayama, Tsutomu; Fujii, Masayuki; Suemune, Hiroshi; Aso, Mariko

2015-08-19

We evaluated the efficacy of bioconjugation of oligodeoxynucleotides (ODNs) containing 1,4-dicarbonyl groups, a C4'-oxidized abasic site (OAS), and a newly designed 2'-methoxy analogue, via reductive amination with lysine residues. Dicarbonyls, aldehyde and ketone at C1- and C4-positions of deoxyribose in the ring-opened form of OAS allowed efficient reaction with amines. Kinetic studies indicated that reductive amination of OAS-containing ODNs with a proximal amine on the complementary strand proceeded 10 times faster than the corresponding reaction of an ODN containing an abasic site with C1-aldehyde. Efficient reductive amination between the DNA-binding domain of Escherichia coli DnaA protein and ODNs carrying OAS in the DnaA-binding sequence proceeded at the lysine residue in proximity to the phosphate group at the 5'-position of the OAS, in contrast to unsuccessful conjugation with abasic site ODNs, even though they have similar aldehydes. Theoretical calculation indicated that the C1-aldehyde of OAS was more accessible to the target lysine than that of the abasic site. These results demonstrate the potential utility of cross-linking strategies that use dicarbonyl-containing ODNs for the study of protein-nucleic acid interactions. Conjugation with a lysine-containing peptide that lacked specific affinity for ODN was also successful, further highlighting the advantages of 1,4-dicarbonyls.

Reduced repair capacity of a DNA clustered damage site comprised of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 2-deoxyribonolactone results in an increased mutagenic potential of these lesions

DOE PAGES

Cunniffe, Siobhan; O’Neill, Peter; Greenberg, Marc M.; ...

2014-04-01

A signature of ionizing radiation is the induction of DNA clustered damaged sites. Non-double strand break (DSB) clustered damage has been shown to compromise the base excision repair pathway, extending the lifetimes of the lesions within the cluster, compared to isolated lesions. This increases the likelihood the lesions persist to replication and thus increasing the mutagenic potential of the lesions within the cluster. Lesions formed by ionizing radiation include 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 2-deoxyribonolactone (dL). dL poses an additional challenge to the cell as it is not repaired by the short-patch base excision repair pathway. Here we show recalcitrant dL repairmore » is reflected in mutations observed when DNA containing it and a proximal 8-oxodGuo is replicated in Escherichia coli. 8-oxodGuo in close proximity to dL on the opposing DNA strand results in an enhanced frequency of mutation of the lesions within the cluster and a 20 base sequence flanking the clustered damage site in an E. coli based plasmid assay. In vitro repair of a dL lesion is reduced when compared to the repair of an abasic (AP) site and a tetrahydrofuran (THF), and this is due mainly to a reduction in the activity of polymerase β, leading to retarded FEN1 and ligase 1 activities. This study has given insights in to the biological effects of clusters containing dL.« less

DNA polymerase θ contributes to the generation of C/G mutations during somatic hypermutation of Ig genes

PubMed Central

Masuda, Keiji; Ouchida, Rika; Takeuchi, Arata; Saito, Takashi; Koseki, Haruhiko; Kawamura, Kiyoko; Tagawa, Masatoshi; Tokuhisa, Takeshi; Azuma, Takachika; O-Wang, Jiyang

2005-01-01

Somatic hypermutation of Ig variable region genes is initiated by activation-induced cytidine deaminase; however, the activity of multiple DNA polymerases is required to ultimately introduce mutations. DNA polymerase η (Polη) has been implicated in mutations at A/T, but polymerases involved in C/G mutations have not been identified. We have generated mutant mice expressing DNA polymerase (Polθ) specifically devoid of polymerase activity. Compared with WT mice, Polq-inactive (Polq, the gene encoding Polθ) mice exhibited a reduced level of serum IgM and IgG1. The mutant mice mounted relatively normal primary and secondary immune responses to a T-dependent antigen, but the production of high-affinity specific antibodies was partially impaired. Analysis of the JH4 intronic sequences revealed a slight reduction in the overall mutation frequency in Polq-inactive mice. Remarkably, although mutations at A/T were unaffected, mutations at C/G were significantly decreased, indicating an important, albeit not exclusive, role for Polθ activity. The reduction of C/G mutations was particularly focused on the intrinsic somatic hypermutation hotspots and both transitions and transversions were similarly reduced. These findings, together with the recent observation that Polθ efficiently catalyzes the bypass of abasic sites, lead us to propose that Polθ introduces mutations at C/G by replicating over abasic sites generated via uracil-DNA glycosylase. PMID:16172387

Non-Covalent Fluorescent Labeling of Hairpin DNA Probe Coupled with Hybridization Chain Reaction for Sensitive DNA Detection.

PubMed

Song, Luna; Zhang, Yonghua; Li, Junling; Gao, Qiang; Qi, Honglan; Zhang, Chengxiao

2016-04-01

An enzyme-free signal amplification-based assay for DNA detection was developed using fluorescent hairpin DNA probes coupled with hybridization chain reaction (HCR). The hairpin DNAs were designed to contain abasic sites in the stem moiety. Non-covalent labeling of the hairpin DNAs was achieved when a fluorescent ligand was bound to the abasic sites through hydrogen bonding with the orphan cytosine present on the complementary strand, accompanied by quench of ligand fluorescence. As a result, the resultant probes, the complex formed between the hairpin DNA and ligand, showed almost no fluorescence. Upon hybridization with target DNA, the probe underwent a dehybridization of the stem moiety containing an abasic site. The release of ligand from the abasic site to the solution resulted in an effective fluorescent enhancement, which can be used as a signal. Compared with a sensing system without HCR, a 20-fold increase in the sensitivity was achieved using the sensing system with HCR. The fluorescent intensity of the sensing system increased with the increase in target DNA concentration from 0.5 nM to 100 nM. A single mismatched target ss-DNA could be effectively discriminated from complementary target DNA. Genotyping of a G/C single-nucleotide polymorphism of polymerase chain reaction (PCR) products was successfully demonstrated with the sensing system. Therefore, integrating HCR strategy with non-covalent labeling of fluorescent hairpin DNA probes provides a sensitive and cost-effective DNA assay. © The Author(s) 2016.

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages

PubMed Central

Greinert, R.; Volkmer, B.; Henning, S.; Breitbart, E. W.; Greulich, K. O.; Cardoso, M. C.; Rapp, Alexander

2012-01-01

UVA (320–400 nm) represents the main spectral component of solar UV radiation, induces pre-mutagenic DNA lesions and is classified as Class I carcinogen. Recently, discussion arose whether UVA induces DNA double-strand breaks (dsbs). Only few reports link the induction of dsbs to UVA exposure and the underlying mechanisms are poorly understood. Using the Comet-assay and γH2AX as markers for dsb formation, we demonstrate the dose-dependent dsb induction by UVA in G1-synchronized human keratinocytes (HaCaT) and primary human skin fibroblasts. The number of γH2AX foci increases when a UVA dose is applied in fractions (split dose), with a 2-h recovery period between fractions. The presence of the anti-oxidant Naringin reduces dsb formation significantly. Using an FPG-modified Comet-assay as well as warm and cold repair incubation, we show that dsbs arise partially during repair of bi-stranded, oxidative, clustered DNA lesions. We also demonstrate that on stretched chromatin fibres, 8-oxo-G and abasic sites occur in clusters. This suggests a replication-independent formation of UVA-induced dsbs through clustered single-strand breaks via locally generated reactive oxygen species. Since UVA is the main component of solar UV exposure and is used for artificial UV exposure, our results shine new light on the aetiology of skin cancer. PMID:22941639

Lesion bypass activity of DNA polymerase θ (POLQ) is an intrinsic property of the pol domain and depends on unique sequence inserts.

PubMed

Hogg, Matthew; Seki, Mineaki; Wood, Richard D; Doublié, Sylvie; Wallace, Susan S

2011-01-21

DNA polymerase θ (POLQ, polθ) is a large, multidomain DNA polymerase encoded in higher eukaryotic genomes. It is important for maintaining genetic stability in cells and helping protect cells from DNA damage caused by ionizing radiation. POLQ contains an N-terminal helicase-like domain, a large central domain of indeterminate function, and a C-terminal polymerase domain with sequence similarity to the A-family of DNA polymerases. The enzyme has several unique properties, including low fidelity and the ability to insert and extend past abasic sites and thymine glycol lesions. It is not known whether the abasic site bypass activity is an intrinsic property of the polymerase domain or whether helicase activity is also required. Three "insertion" sequence elements present in POLQ are not found in any other A-family DNA polymerase, and it has been proposed that they may lend some unique properties to POLQ. Here, we analyzed the activity of the DNA polymerase in the absence of each sequence insertion. We found that the pol domain is capable of highly efficient bypass of abasic sites in the absence of the helicase-like or central domains. Insertion 1 increases the processivity of the polymerase but has little, if any, bearing on the translesion synthesis properties of the enzyme. However, removal of insertions 2 and 3 reduces activity on undamaged DNA and completely abrogates the ability of the enzyme to bypass abasic sites or thymine glycol lesions. Copyright © 2010 Elsevier Ltd. All rights reserved.

Abasic pivot substitution harnesses target specificity of RNA interference

PubMed Central

Lee, Hye-Sook; Seok, Heeyoung; Lee, Dong Ha; Ham, Juyoung; Lee, Wooje; Youm, Emilia Moonkyung; Yoo, Jin Seon; Lee, Yong-Seung; Jang, Eun-Sook; Chi, Sung Wook

2015-01-01

Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA–target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at ∼80–100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome-wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications. PMID:26679372

Conformational dynamics of abasic DNA upon interactions with AP endonuclease 1 revealed by stopped-flow fluorescence analysis.

PubMed

Kanazhevskaya, Lyubov Yu; Koval, Vladimir V; Vorobjev, Yury N; Fedorova, Olga S

2012-02-14

Apurinic/apyrimidinic (AP) sites are abundant DNA lesions arising from exposure to UV light, ionizing radiation, alkylating agents, and oxygen radicals. In human cells, AP endonuclease 1 (APE1) recognizes this mutagenic lesion and initiates its repair via a specific incision of the phosphodiester backbone 5' to the AP site. We have investigated a detailed mechanism of APE1 functioning using fluorescently labeled DNA substrates. A fluorescent adenine analogue, 2-aminopurine, was introduced into DNA substrates adjacent to the abasic site to serve as an on-site reporter of conformational transitions in DNA during the catalytic cycle. Application of a pre-steady-state stopped-flow technique allows us to observe changes in the fluorescence intensity corresponding to different stages of the process in real time. We also detected an intrinsic Trp fluorescence of the enzyme during interactions with 2-aPu-containing substrates. Our data have revealed a conformational flexibility of the abasic DNA being processed by APE1. Quantitative analysis of fluorescent traces has yielded a minimal kinetic scheme and appropriate rate constants consisting of four steps. The results obtained from stopped-flow data have shown a substantial influence of the 2-aPu base location on completion of certain reaction steps. Using detailed molecular dynamics simulations of the DNA substrates, we have attributed structural distortions of AP-DNA to realization of specific binding, effective locking, and incision of the damaged DNA. The findings allowed us to accurately discern the step that corresponds to insertion of specific APE1 amino acid residues into the abasic DNA void in the course of stabilization of the precatalytic complex.

Miscoding and mutagenic properties of 8-oxoguanine and abasic sites: Ubiquitous lesions in damaged DNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grollman, A.P.; Takeshita, Masaru

1995-12-31

More than twenty oxidatively-damaged bases, including 8-oxoguanine, have been found to occur in genomic DNA. Some of these lesions block DNA replication and are potentially lethal; others generate mutations which can initiate carcinogenesis and promote cellular aging. In this report, the authors focus attention on the mutagenicity and repair of 8-oxoguanine. Kasai and Nishimura`s discovery that hydroxyl radicals react with guanine residues in DNA to form 8-oxoguanine and the development of sensitive methods for the detection and quantitation of this modified base led to the observation that approximately 1 in 10{sup 5} guanine residues in mammalian DNA are oxidized atmore » the C-8 position. DNA containing 8-oxoguanine and synthetic analogs of the abasic site have been used to investigate the miscoding and mutagenic potential of these ubiquitous lesions. Studies in the laboratory were facilitated by the development of solid state synthetic methods by which these lesions could be introduced at defined positions in DNA. In this paper, the authors review studies in which 8-oxoguanine and abasic sites have been used in model systems to explore various early events in the replication of selectively damaged DNA.« less

Heat shock protein 70 enhanced deoxyribonucleic acid base excision repair in human leukemic cells after ionizing radiation

PubMed Central

Bases, Robert

2006-01-01

Base excision repair (BER) of DNA damage in irradiated THP1 human leukemic cells was stimulated by pretreating the cells with exogenous recombinant Hsp70. The treatment of THP1 cells with recombinant Hsp70 in cell culture promoted repair by reducing the frequency of apurinic, apyrimidinic (AP) sites in DNA before and after 1.3 Gy of radiation. However, by 30 minutes after 2.6 Gy, accelerated repair of abasic sites supervened, which may contribute to the loss of the very-low-dose cell hypersensitivity seen in clonogenic studies of other laboratories. After irradiation with 2.6 Gy, the crucial initial glycosylase step was markedly incomplete when cells had been transfected 24 hours before with a small interfering RNA (siRNA) designed to inhibit synthesis of Hsp70. In confirmation, lysates from irradiated siRNA-treated cells after 2.6 Gy were deficient in uracil glycosylase activity (UDG). Transfection with a scrambled RNA of the same size did not interfere with the glycosylase step, ie, the prompt conversion of damaged pyrimidine sites to abasic sites as well as the subsequent repair of those sites. BER measured by reduction of DNA AP sites before and after low-dose radiation was also deficient in THP1 cells that had been transfected with the siRNA designed to inhibit synthesis of Hsp70. These results implicate BER and the participation of Hsp70 in the repair of DNA in human leukemic cells with the doses of ionizing radiation used in clinical regimens. PMID:17009597

Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1

PubMed Central

Malina, Jaroslav; Scott, Peter; Brabec, Viktor

2015-01-01

Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo–helical ‘flexicate’ complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3]4+ incorporating the common NN–NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo–helical complexes for cancer chemotherapy. PMID:25940617

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PubMed

Elting, L S; Rubenstein, E B; Rolston, K; Cantor, S B; Martin, C G; Kurtin, D; Rodriguez, S; Lam, T; Kanesan, K; Bodey, G

2000-11-01

To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

Heat shock protein 70 stimulation of the deoxyribonucleic acid base excision repair enzyme polymerase β

PubMed Central

Mendez, Frances; Kozin, Elliott; Bases, Robert

2003-01-01

Base excision repair (BER) of damaged deoxyribonucleic acid (DNA) is a multistep process during which potentially lethal abasic sites temporarily exist. Repair of these lesions is greatly stimulated by heat shock protein 70 (Hsp70), which enhances strand incision and removal of the abasic sites by human apurinic-apyrimidinic endonuclease (HAP1). The resulting single-strand gaps must then be filled in. Here, we show that Hsp70 and its 48- and 43-kDa N-terminal domains greatly stimulated filling in the single-strand gaps by DNA polymerase β, a novel finding that extends the role of Hsps in DNA repair. Incorporation of deoxyguanosine monophosphate (dGMP) to fill in single-strand gaps in DNA phagemid pBKS by DNA polymerase β was stimulated by Hsp70. Truncated proteins derived from the C-terminus of Hsp70 as well as unrelated proteins were less effective, but proteins derived from the N-terminus of Hsp70 remained efficient stimulators of DNA polymerase β repair of DNA single-strand gaps. In agreement with these results, repair of a gap in a 30-bp oligonucleotide by polymerase β also was strongly stimulated by Hsp70 although not by a truncated protein from the C-terminus of Hsp70. Sealing of the repaired site in the oligonucleotide by human DNA ligase 1 was not specifically stimulated by Hsp-related proteins. Results presented here now implicate and extend the role of Hsp70 as a partner in the enzymatic repair of damaged DNA. The participation of Hsp70 jointly with base excision enzymes improves repair efficiency by mechanisms that are not yet understood. PMID:14627201

Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA

PubMed Central

Hata, Kuniki; Urushibara, Ayumi; Yamashita, Shinichi; Lin, Mingzhang; Muroya, Yusa; Shikazono, Naoya; Yokoya, Akinari; Fu, Haiying; Katsumura, Yosuke

2015-01-01

Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 108 dm3 mol−1 s−1 and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10–1000 μmol dm−3) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid. PMID:25212600

The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ

PubMed Central

Hirota, Kouji; Yoshikiyo, Kazunori; Guilbaud, Guillaume; Tsurimoto, Toshiki; Murai, Junko; Tsuda, Masataka; Phillips, Lara G.; Narita, Takeo; Nishihara, Kana; Kobayashi, Kaori; Yamada, Kouich; Nakamura, Jun; Pommier, Yves; Lehmann, Alan; Sale, Julian E.; Takeda, Shunichi

2015-01-01

The replicative DNA polymerase Polδ consists of a catalytic subunit POLD1/p125 and three regulatory subunits POLD2/p50, POLD3/p66 and POLD4/p12. The ortholog of POLD3 in Saccharomyces cerevisiae, Pol32, is required for a significant proportion of spontaneous and UV-induced mutagenesis through its additional role in translesion synthesis (TLS) as a subunit of DNA polymerase ζ. Remarkably, chicken DT40 B lymphocytes deficient in POLD3 are viable and able to replicate undamaged genomic DNA with normal kinetics. Like its counterpart in yeast, POLD3 is required for fully effective TLS, its loss resulting in hypersensitivity to a variety of DNA damaging agents, a diminished ability to maintain replication fork progression after UV irradiation and a significant decrease in abasic site-induced mutagenesis in the immunoglobulin loci. However, these defects appear to be largely independent of Polζ, suggesting that POLD3 makes a significant contribution to TLS independently of Polζ in DT40 cells. Indeed, combining polη, polζ and pold3 mutations results in synthetic lethality. Additionally, we show in vitro that POLD3 promotes extension beyond an abasic by the Polδ holoenzyme suggesting that while POLD3 is not required for normal replication, it may help Polδ to complete abasic site bypass independently of canonical TLS polymerases. PMID:25628356

Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1.

PubMed

Malina, Jaroslav; Scott, Peter; Brabec, Viktor

2015-06-23

Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo-helical 'flexicate' complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3](4+) incorporating the common NN-NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo-helical complexes for cancer chemotherapy. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

A commercial PCV2a-based vaccine is effective in protection from experimental challenge of PCV2 mutant with two amino acids elongation in capsid protein.

PubMed

Guo, Long-Jun; Fu, Yu-Jie; Huang, Li-Ping; Wang, Yi-Ping; Wei, Yan-Wu; Wu, Hong-Li; Liu, Chang-Ming

2015-07-17

Current commercial PCV2 vaccines are almost based on PCV2a and have been shown to be effective in reducing PCV2a and PCV2b viremia and PCV2-associated lesions and diseases. The recent emergence of novel mutant PCV2 (mPCV2) strains and linkage of mPCV2 with cases of porcine circovirus associated disease (PCVAD) in pig herds have raised concerns over emergence of vaccine-escape mutants and reduced efficacy of PCV2a-based vaccines. The aim of this study was to determine the ability of a commercial PCV2a-based vaccine developed by our laboratory to protect conventional pigs against experimental challenge with mPCV2 at 9 weeks of age. Twenty 4-week-old pigs free of PCV2 infection were randomly divided into four treatment groups with 5 pigs each. Two groups were unvaccinated as positive and negative controls. Another two groups were vaccinated with the commercial PCV2a-based vaccine (PCV2-LG strain, China) at 4 weeks of age and identical booster immunization was conducted 3 weeks post primary immunization. At 9 weeks of age, all pigs except the negative control were challenged with a mutant PCV2b/YJ (mPCV2b/YJ) with two amino acids elongation in capsid protein. The experiment was terminated 28 days after challenge. Under the conditions of this study, vaccinated pigs were protected against PCV2 viremia and lesions whereas unvaccinated pigs were not. Moreover, mPCV2b/YJ infection was demonstrated in positive control and almost all had macroscopic or microscopic lesions consistent with PCVAD while negative control did not develop PCVAD. This study indicates that mPCV2b/YJ infection alone can trigger PCVAD development and that the commercial vaccine (PCV2-LG) is still effective in protecting conventional pigs against the emerging mPCV2b/YJ strain in China. Copyright © 2015. Published by Elsevier Ltd.

N-terminal domains of human DNA polymerase lambda promote primer realignment during translesion DNA synthesis

PubMed Central

Taggart, David J.; Dayeh, Daniel M.; Fredrickson, Saul W.; Suo, Zucai

2014-01-01

The X-family DNA polymerases λ (Polλ) and β (Polβ) possess similar 5′-2-deoxyribose-5-phosphatelyase (dRPase) and polymerase domains. Besides these domains, Polλ also possesses a BRCA1 C-terminal (BRCT) domain and a proline-rich domain at its N terminus. However, it is unclear how these non-enzymatic domains contribute to the unique biological functions of Polλ. Here, we used primer extension assays and a newly developed high-throughput short oligonucleotide sequencing assay (HT-SOSA) to compare the efficiency of lesion bypass and fidelity of human Polβ, Polλ and two N-terminal deletion constructs of Polλ during the bypass of either an abasic site or a 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) lesion. We demonstrate that the BRCT domain of Polλ enhances the efficiency of abasic site bypass by approximately 1.6-fold. In contrast, deletion of the N-terminal domains of Polλ did not affect the efficiency of 8-oxodG bypass relative to nucleotide incorporations opposite undamaged dG. HT-SOSA analysis demonstrated that Polλ and Polβ preferentially generated −1 or −2 frameshift mutations when bypassing an abasic site and the single or double base deletion frequency was highly sequence dependent. Interestingly, the BRCT and proline-rich domains of Polλ cooperatively promoted the generation of −2 frameshift mutations when the abasic site was situated within a sequence context that was susceptible to homology-driven primer realignment. Furthermore, both N-terminal domains of Polλ increased the generation of −1 frameshift mutations during 8-oxodG bypass and influenced the frequency of substitution mutations produced by Polλ opposite the 8-oxodG lesion. Overall, our data support a model wherein the BRCT and proline-rich domains of Polλ act cooperatively to promote primer/template realignment between DNA strands of limited sequence homology. This function of the N-terminal domains may facilitate the role of Polλ as a gap-filling polymerase within the non-homologous end joining pathway. PMID:25108835

DNA polymerase β variant Ile260Met generates global gene expression changes related to cellular transformation

PubMed Central

Sweasy, Joann B.

2012-01-01

Maintenance of genomic stability is essential for cellular survival. The base excision repair (BER) pathway is critical for resolution of abasic sites and damaged bases, estimated to occur 20,000 times in cells daily. DNA polymerase β (Pol β) participates in BER by filling DNA gaps that result from excision of damaged bases. Approximately 30% of human tumours express Pol β variants, many of which have altered fidelity and activity in vitro and when expressed, induce cellular transformation. The prostate tumour variant Ile260Met transforms cells and is a sequence-context-dependent mutator. To test the hypothesis that mutations induced in vivo by Ile260Met lead to cellular transformation, we characterized the genome-wide expression profile of a clone expressing Ile260Met as compared with its non-induced counterpart. Using a 1.5-fold minimum cut-off with a false discovery rate (FDR) of <0.05, 912 genes exhibit altered expression. Microarray results were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and revealed unique expression profiles in other clones. Gene Ontology (GO) clusters were analyzed using Ingenuity Pathways Analysis to identify altered gene networks and associated nodes. We determined three nodes of interest that exhibited dysfunctional regulation of downstream gene products without themselves having altered expression. One node, peroxisome proliferator-activated protein γ (PPARG), was sequenced and found to contain a coding region mutation in PPARG2 only in transformed cells. Further analysis suggests that this mutation leads to dominant negative activity of PPARG2. PPARG is a transcription factor implicated to have tumour suppressor function. This suggests that the PPARG2 mutant may have played a role in driving cellular transformation. We conclude that PPARG induces cellular transformation by a mutational mechanism. PMID:22914675

Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA.

PubMed

Hata, Kuniki; Urushibara, Ayumi; Yamashita, Shinichi; Lin, Mingzhang; Muroya, Yusa; Shikazono, Naoya; Yokoya, Akinari; Fu, Haiying; Katsumura, Yosuke

2015-01-01

Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 10(8) dm(3) mol(-1) s(-1) and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10-1000 μmol dm(-3)) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Structural insights into abasic site for Fpg specific binding and catalysis: comparative high-resolution crystallographic studies of Fpg bound to various models of abasic site analogues-containing DNA

PubMed Central

de Jésus, Karine Pereira; Serre, Laurence; Zelwer, Charles; Castaing, Bertrand

2005-01-01

Fpg is a DNA glycosylase that recognizes and excises the mutagenic 8-oxoguanine (8-oxoG) and the potentially lethal formamidopyrimidic residues (Fapy). Fpg is also associated with an AP lyase activity which successively cleaves the abasic (AP) site at the 3′ and 5′ sides by βδ-elimination. Here, we present the high-resolution crystal structures of the wild-type and the P1G defective mutant of Fpg from Lactococcus lactis bound to 14mer DNA duplexes containing either a tetrahydrofuran (THF) or 1,3-propanediol (Pr) AP site analogues. Structures show that THF is less extrahelical than Pr and its backbone C5′–C4′–C3′ diverges significantly from those of Pr, rAP, 8-oxodG and FapydG. Clearly, the heterocyclic oxygen of THF is pushed back by the carboxylate of the strictly conserved E2 residue. We can propose that the ring-opened form of the damaged deoxyribose is the structure active form of the sugar for Fpg catalysis process. Both structural and functional data suggest that the first step of catalysis mediated by Fpg involves the expulsion of the O4′ leaving group facilitated by general acid catalysis (involving E2), rather than the immediate cleavage of the N-glycosic bond of the damaged nucleoside. PMID:16243784

Label-free functional nucleic acid sensors for detecting target agents

DOEpatents

Lu, Yi; Xiang, Yu

2015-01-13

A general methodology to design label-free fluorescent functional nucleic acid sensors using a vacant site approach and an abasic site approach is described. In one example, a method for designing label-free fluorescent functional nucleic acid sensors (e.g., those that include a DNAzyme, aptamer or aptazyme) that have a tunable dynamic range through the introduction of an abasic site (e.g., dSpacer) or a vacant site into the functional nucleic acids. Also provided is a general method for designing label-free fluorescent aptamer sensors based on the regulation of malachite green (MG) fluorescence. A general method for designing label-free fluorescent catalytic and molecular beacons (CAMBs) is also provided. The methods demonstrated here can be used to design many other label-free fluorescent sensors to detect a wide range of analytes. Sensors and methods of using the disclosed sensors are also provided.

Adenomatous Polyposis Coli-Mediated Accumulation of Abasic DNA Lesions Lead to Cigarette Smoke Condensate-Induced Neoplastic Transformation of Normal Breast Epithelial Cells1

PubMed Central

Jaiswal, Aruna S; Panda, Harekrushna; Pampo, Christine A; Siemann, Dietmar W; Gairola, C Gary; Hromas, Robert; Narayan, Satya

2013-01-01

Adenomatous polyposis coli (APC) is a multifunctional protein having diverse cellular functions including cell migration, cell-cell adhesion, cell cycle control, chromosomal segregation, and apoptosis. Recently, we found a new role of APC in base excision repair (BER) and showed that it interacts with DNA polymerase β and 5′-flap endonuclease 1 and interferes in BER. Previously, we have also reported that cigarette smoke condensate (CSC) increases expression of APC and enhances the growth of normal human breast epithelial (MCF10A) cells in vitro. In the present study, using APC overexpression and knockdown systems, we have examined the molecular mechanisms by which CSC and its major component, Benzo[α]pyrene, enhances APC-mediated accumulation of abasic DNA lesions, which is cytotoxic and mutagenic in nature, leading to enhanced neoplastic transformation of MCF10A cells in an orthotopic xenograft model. PMID:23555190

Activity-based assay for ricin-like toxins

DOEpatents

Keener, William K.; Ward, Thomas E.

2007-02-06

A method of detecting N-glycosylase activity in a sample involves incubating an oligodeoxyribonucleotide substrate containing a deoxyadenosine or deoxyuridine residue with the sample to be tested such that the N-glycosylase, if present, hydrolyzes the deoxyadenosine or deoxyuridine residue to result in an N-glycosylase product having an abasic site. A primer is annealed to the N-glycosylase product, and the primer is extended with a DNA polymerase, such as Taq DNA polymerase, that pauses at abasic sites. The resulting extension products are melted from the N-glycosylase product, allowed to form hairpins due to self-complementarity, and further extended in the presence of labeled precursors to result in labeled products. Extension products synthesized from undigested substrate as template do not result in labeled products. Thus, detection of labeled products results in detection of N-glycosylase activity. Oligodeoxyribonucleotide substrates, primer, and positive controls and a kit for N-glycosylase assay are also disclosed.

Evidence that a burst of DNA depurination in SENCAR mouse skin induces error-prone repair and forms mutations in the H-ras gene.

PubMed

Chakravarti, D; Mailander, P C; Li, K M; Higginbotham, S; Zhang, H L; Gross, M L; Meza, J L; Cavalieri, E L; Rogan, E G

2001-11-29

Treatment of SENCAR mouse skin with dibenzo[a,l]pyrene results in abundant formation of abasic sites that undergo error-prone excision repair, forming oncogenic H-ras mutations in the early preneoplastic period. To examine whether the abundance of abasic sites causes repair infidelity, we treated SENCAR mouse skin with estradiol-3,4-quinone (E(2)-3,4-Q) and determined adduct levels 1 h after treatment, as well as mutation spectra in the H-ras gene between 6 h and 3 days after treatment. E(2)-3,4-Q formed predominantly (> or =99%) the rapidly-depurinating 4-hydroxy estradiol (4-OHE(2))-1-N3Ade adduct and the slower-depurinating 4-OHE(2)-1-N7Gua adduct. Between 6 h and 3 days, E(2)-3,4-Q induced abundant A to G mutations in H-ras DNA, frequently in the context of a 3'-G residue. Using a T.G-DNA glycosylase (TDG)-PCR assay, we determined that the early A to G mutations (6 and 12 h) were in the form of G.T heteroduplexes, suggesting misrepair at A-specific depurination sites. Since G-specific mutations were infrequent in the spectra, it appears that the slow rate of depurination of the N7Gua adducts during active repair may not generate a threshold level of G-specific abasic sites to affect repair fidelity. These results also suggest that E(2)-3,4-Q, a suspected endogenous carcinogen, is a genotoxic compound and could cause mutations.

Counselor Effectiveness: A Changing Emphasis

ERIC Educational Resources Information Center

Doyle, W. L.; Conklin, R. C.

1970-01-01

It is suggested that emphasis be changed from trait factor personality studies such as tolerance for ambiguity, nurturance, and abasement, to researching the area of cognitive style, flexibility, perception and psychological openness as perhaps being more fruitful in advancing knowledge of the criterion variable. (Author)

Correlation of Thermal Stability and Structural Distortion of DNA Interstrand Cross-Links Produced from Oxidized Abasic Sites with Their Selective Formation and Repair.

PubMed

Ghosh, Souradyuti; Greenberg, Marc M

2015-10-13

C4'-oxidized (C4-AP) and C5'-oxidized abasic sites (DOB) that are produced following abstraction of a hydrogen atom from the DNA backbone reversibly form cross-links selectively with dA opposite a 3'-adjacent nucleotide, despite the comparable proximity of an opposing dA. A previous report on UvrABC incision of DNA substrates containing stabilized analogues of the ICLs derived from C4-AP and DOB also indicated that the latter is repaired more readily by nucleotide excision repair [Ghosh, S., and Greenberg, M. M. (2014) Biochemistry 53, 5958-5965]. The source for selective cross-link formation was probed by comparing the reactivity of ICL analogues of C4-AP and DOB that mimic the preferred and disfavored cross-links with that of reagents that indirectly detect distortion by reacting with the nucleobases. The disfavored C4-AP and DOB analogues were each more reactive than the corresponding preferred cross-link substrates, suggesting that the latter are more stable, which is consistent with selective ICL formation. In addition, the preferred DOB analogue is more reactive than the respective C4-AP ICL, which is consistent with its more efficient incision by UvrABC. The conclusions drawn from the chemical probing experiments are corroborated by UV melting studies. The preferred ICLs exhibit melting temperatures higher than those of the corresponding disfavored isomers. These studies suggest that oxidized abasic sites form reversible interstrand cross-links with dA opposite the 3'-adjacent thymidine because these products are more stable and the thermodynamic preference is reflected in the transition states for their formation.

Risk Factors of Suicidal Ideations and Attempts in Talented, At-Risk Girls

ERIC Educational Resources Information Center

Hull-Blanks, Elva E.; Kerr, Barbara A.; Robinson Kurpius, Sharon E.

2004-01-01

The purpose of the present study was to investigate the relationships among suicidality, substance use, self-esteem, family structure, and eight personality characteristics (harm avoidance, impulsivity, aggression, social recognition, cognitive structure, succorance, abasement, and achievement) with 337 talented, at-risk, adolescent girls. Results…

Induction of Abasic Sites by the Drinking-Water Mutagen MX in Salmonella TA100

EPA Science Inventory

Mutagen X (MX) is a chlorinated furanone that accounts for more of the mutagenic activity of drinking water than any other disinfection by-product. It is one of the most potent base-substitution mutagens in the Salmonella (Ames) mutagenicity assay, producing primarily GC to TA mu...

Oxidized Base Damage and Single-Strand Break Repair in Mammalian Genomes: Role of Disordered Regions and Posttranslational Modifications in Early Enzymes

PubMed Central

Hegde, Muralidhar L.; Izumi, Tadahide; Mitra, Sankar

2012-01-01

Oxidative genome damage induced by reactive oxygen species includes oxidized bases, abasic (AP) sites, and single-strand breaks, all of which are repaired via the evolutionarily conserved base excision repair/single-strand break repair (BER/SSBR) pathway. BER/SSBR in mammalian cells is complex, with preferred and backup sub-pathways, and is linked to genome replication and transcription. The early BER/SSBR enzymes, namely, DNA glycosylases (DGs) and the end-processing proteins such as abasic endonuclease 1 (APE1), form complexes with downstream repair (and other noncanonical) proteins via pairwise interactions. Furthermore, a unique feature of mammalian early BER/ SSBR enzymes is the presence of a disordered terminal extension that is absent in their Escherichia coli prototypes. These nonconserved segments usually contain organelle-targeting signals, common interaction interfaces, and sites of posttranslational modifications that may be involved in regulating their repair function including lesion scanning. Finally, the linkage of BER/SSBR deficiency to cancer, aging, and human neurodegenerative diseases, and therapeutic targeting of BER/SSBR are discussed. PMID:22749145

Detection of DNA Sequences Refractory to PCR Amplification Using a Biophysical SERRS Assay (Surface Enhanced Resonant Raman Spectroscopy)

PubMed Central

Feuillie, Cécile; Merheb, Maxime M.; Gillet, Benjamin; Montagnac, Gilles; Daniel, Isabelle; Hänni, Catherine

2014-01-01

The analysis of ancient or processed DNA samples is often a great challenge, because traditional Polymerase Chain Reaction – based amplification is impeded by DNA damage. Blocking lesions such as abasic sites are known to block the bypass of DNA polymerases, thus stopping primer elongation. In the present work, we applied the SERRS-hybridization assay, a fully non-enzymatic method, to the detection of DNA refractory to PCR amplification. This method combines specific hybridization with detection by Surface Enhanced Resonant Raman Scattering (SERRS). It allows the detection of a series of double-stranded DNA molecules containing a varying number of abasic sites on both strands, when PCR failed to detect the most degraded sequences. Our SERRS approach can quickly detect DNA molecules without any need for DNA repair. This assay could be applied as a pre-requisite analysis prior to enzymatic reparation or amplification. A whole new set of samples, both forensic and archaeological, could then deliver information that was not yet available due to a high degree of DNA damage. PMID:25502338

Detection of DNA sequences refractory to PCR amplification using a biophysical SERRS assay (Surface Enhanced Resonant Raman Spectroscopy).

PubMed

Feuillie, Cécile; Merheb, Maxime M; Gillet, Benjamin; Montagnac, Gilles; Daniel, Isabelle; Hänni, Catherine

2014-01-01

The analysis of ancient or processed DNA samples is often a great challenge, because traditional Polymerase Chain Reaction - based amplification is impeded by DNA damage. Blocking lesions such as abasic sites are known to block the bypass of DNA polymerases, thus stopping primer elongation. In the present work, we applied the SERRS-hybridization assay, a fully non-enzymatic method, to the detection of DNA refractory to PCR amplification. This method combines specific hybridization with detection by Surface Enhanced Resonant Raman Scattering (SERRS). It allows the detection of a series of double-stranded DNA molecules containing a varying number of abasic sites on both strands, when PCR failed to detect the most degraded sequences. Our SERRS approach can quickly detect DNA molecules without any need for DNA repair. This assay could be applied as a pre-requisite analysis prior to enzymatic reparation or amplification. A whole new set of samples, both forensic and archaeological, could then deliver information that was not yet available due to a high degree of DNA damage.

Lesion-induced DNA weak structural changes detected by pulsed EPR spectroscopy combined with site-directed spin labelling.

PubMed

Sicoli, Giuseppe; Mathis, Gérald; Aci-Sèche, Samia; Saint-Pierre, Christine; Boulard, Yves; Gasparutto, Didier; Gambarelli, Serge

2009-06-01

Double electron-electron resonance (DEER) was applied to determine nanometre spin-spin distances on DNA duplexes that contain selected structural alterations. The present approach to evaluate the structural features of DNA damages is thus related to the interspin distance changes, as well as to the flexibility of the overall structure deduced from the distance distribution. A set of site-directed nitroxide-labelled double-stranded DNA fragments containing defined lesions, namely an 8-oxoguanine, an abasic site or abasic site analogues, a nick, a gap and a bulge structure were prepared and then analysed by the DEER spectroscopic technique. New insights into the application of 4-pulse DEER sequence are also provided, in particular with respect to the spin probes' positions and the rigidity of selected systems. The lesion-induced conformational changes observed, which were supported by molecular dynamics studies, confirm the results obtained by other, more conventional, spectroscopic techniques. Thus, the experimental approaches described herein provide an efficient method for probing lesion-induced structural changes of nucleic acids.

Thermodynamic impact of abasic sites on simulated translesion DNA synthesis.

PubMed

Malina, Jaroslav; Brabec, Viktor

2014-06-16

Loss of a base in DNA and the creation of an abasic (apurinic/apyrimidinic, AP) site is a frequent lesion that may occur spontaneously, or as a consequence of the action of DNA-damaging agents. The AP lesion is mutagenic or lethal if not repaired. We report a systematic thermodynamic investigation by differential scanning calorimetry on the evolution, during primer extension, of a model AP site in chemically simulated DNA translesion synthesis. Incorporation of dAMP (deoxyadenosine monophosphate), as well as dTMP (deoxythymidine monophosphate), opposite an AP site is enthalpically unfavorable, although incorporation of dTMP is more enthalpically unfavorable than that of dAMP. This finding is in a good agreement with experimental data showing that AP sites block various DNA polymerases of eukaryotic and prokaryotic origin and that, if bypassed, dAMP is preferentially inserted, whereas insertion of dTMP is less likely. The results emphasize the importance of thermodynamic contributions to the insertion of nucleotides opposite an AP site by DNA polymerases. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of His-83 of yeast apurinic/apyrimidinic endonuclease Apn1 in catalytic incision of abasic sites in DNA.

PubMed

Dyakonova, Elena S; Koval, Vladimir V; Lomzov, Alexander A; Ishchenko, Alexander A; Fedorova, Olga S

2015-06-01

The apurinic/apyrimidinic (AP) endonuclease Apn1 from Saccharomyces cerevisiae is a key enzyme involved in the base excision repair (BER) at the cleavage stage of abasic sites (AP sites) in DNA. The crystal structure of Apn1 from S. cerevisiae is unresolved. Based on its high amino acid homology to Escherichia coli Endo IV, His-83 is believed to coordinate one of three Zn2+ ions in Apn1's active site similar to His-69 in Endo IV. Substituting His-83 with Ala is proposed to decrease the AP endonuclease activity of Apn1 owing to weak coordination of Zn2+ ions involved in enzymatic catalysis. The kinetics of recognition, binding, and incision of DNA substrates with the H83A Apn1 mutant was investigated. The stopped-flow method detecting fluorescence intensity changes of 2-aminopurine (2-aPu) was used to monitor the conformational dynamics of DNA at pre-steady-state conditions. We found substituting His-83 with Ala influenced catalytic complex formation and further incision of the damaged DNA strand. The H83A Apn1 catalysis depends not only on the location of the mismatch relative to the abasic site in DNA, but also on the nature of damage. We consider His-83 properly coordinates the active site Zn2+ ion playing a crucial role in catalytic incision stage. Our data prove suppressed enzymatic activity of H83A Apn1 results from the reduced number of active site Zn2+ ions. Our study provides insights into mechanistic specialty of AP site repair by yeast AP endonuclease Apn1 of Endo IV family, which members are not found in mammals, but are present in many microorganisms. The results will provide useful guidelines for design of new anti-fungal and anti-malarial agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Commercial PCV2a-based vaccines are effective in protecting naturally PCV2b-infected finisher pigs against experimental challenge with a 2012 mutant PCV2.

PubMed

Opriessnig, Tanja; Gerber, Priscilla F; Xiao, Chao-Ting; Halbur, Patrick G; Matzinger, Shannon R; Meng, Xiang-Jin

2014-07-23

Current commercial PCV2 vaccines are all based on PCV2a and have been shown to be effective in reducing PCV2a and PCV2b viremia and PCV2-associated lesions and disease. The recent emergence of novel mutant PCV2 (mPCV2) strains and linkage of mPCV2 with cases of porcine circovirus associated disease (PCVAD) in vaccinated herds have raised concerns over emergence of vaccine-escape mutants and reduced efficacy of PCV2a-based vaccines. The aim of this study was to determine the ability of three commercial PCV2a-based vaccines administered in the presence of an ongoing PCV2b infection and passively-acquired anti-PCV2 antibodies to protect conventional pigs against experimental challenge with mPCV2 at 11 weeks of age. Fifty naturally PCV2b-infected 2-week-old pigs were divided into five treatment groups with 10 pigs each. Pigs were unvaccinated (positive and negative controls) or vaccinated at 3 (VAC-A, VAC-B, VAC-C) and at 5 weeks of age (VAC-C). At 11 weeks of age, all pigs except the negative controls were challenged with a 2012 U.S. strain of mPCV2. The experiment was terminated 21 days after challenge. Under the conditions of this study, vaccinated pigs were protected against PCV2 viremia and lesions whereas non-vaccinated pigs were not. Moreover, concurrent PCV2b and mPCV2 infection was demonstrated in all positive controls and 3/10 had microscopic lesions consistent with PCVAD while negative controls infected with PCV2b alone did not develop PCVAD. The results indicate that concurrent PCV2b/mPCV2 infection can trigger PCVAD development and that commercial vaccines are effective in protecting conventional pigs against emerging mPCV2 strains. Copyright © 2014 Elsevier Ltd. All rights reserved.

77 FR 58058 - Approval and Promulgation of Implementation Plans; Texas; Beaumont/Port Arthur Ozone Maintenance...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-19

.... SUMMARY: EPA is proposing to approve Texas' request to revise its Beaumont/Port Arthur (BPA) 1997 8-hour... (MOVES) 2010a emissions model. The BPA 1997 8-hour ozone maintenance area consists of Hardin, Jefferson... proposing? EPA is proposing to approve new MOVES2010a-based budgets for the Beaumont/Port Arthur (BPA) 1997...

Mutagenicity, Stable DNA Adducts, and Abasic Sites Induced in Salmonella by Phananthro[3,4-b]- and Phenanthro[4,3-b]thiophenes, Sulfur Analogs of Benzo[c]phenanthrene

EPA Science Inventory

Sulfur-containing polycyclic aromatic hydrocarbons (thia-PAHs or thiaarenes) are common constituents of air pollution and cigarette smoke, yet little is known of the biological significance of exposure to these compounds. Some are mutagenic and carcinogenic, but only a few have ...

In vivo evidence for translesion synthesis by the replicative DNA polymerase δ

PubMed Central

Hirota, Kouji; Tsuda, Masataka; Mohiuddin; Tsurimoto, Toshiki; Cohen, Isadora S.; Livneh, Zvi; Kobayashi, Kaori; Narita, Takeo; Nishihara, Kana; Murai, Junko; Iwai, Shigenori; Guilbaud, Guillaume; Sale, Julian E.; Takeda, Shunichi

2016-01-01

The intolerance of DNA polymerase δ (Polδ) to incorrect base pairing contributes to its extremely high accuracy during replication, but is believed to inhibit translesion synthesis (TLS). However, chicken DT40 cells lacking the POLD3 subunit of Polδ are deficient in TLS. Previous genetic and biochemical analysis showed that POLD3 may promote lesion bypass by Polδ itself independently of the translesion polymerase Polζ of which POLD3 is also a subunit. To test this hypothesis, we have inactivated Polδ proofreading in pold3 cells. This significantly restored TLS in pold3 mutants, enhancing dA incorporation opposite abasic sites. Purified proofreading-deficient human Polδ holoenzyme performs TLS of abasic sites in vitro much more efficiently than the wild type enzyme, with over 90% of TLS events resulting in dA incorporation. Furthermore, proofreading deficiency enhances the capability of Polδ to continue DNA synthesis over UV lesions both in vivo and in vitro. These data support Polδ contributing to TLS in vivo and suggest that the mutagenesis resulting from loss of Polδ proofreading activity may in part be explained by enhanced lesion bypass. PMID:27185888

Recognition of DNA abasic site nanocavity by fluorophore-switched probe: Suitable for all sequence environments

NASA Astrophysics Data System (ADS)

Wang, Ying; Hu, Yuehua; Wu, Tao; Zhang, Lihua; Liu, Hua; Zhou, Xiaoshun; Shao, Yong

2016-01-01

Removal of a damaged base in DNA produces an abasic site (AP site) nanocavity. If left un-repaired in vivo by the specific enzyme, this nanocavity will result in nucleotide mutation in the following DNA replication. Therefore, selective recognition of AP site nanocavity by small molecules is important for identification of such DNA damage and development of genetic drugs. In this work, we investigate the fluorescence behavior of isoquinoline alkaloids including palmatine (PAL), berberine (BER), epiberberine (EPI), jatrorrhizine (JAT), coptisine (COP), coralyne (COR), worenine (WOR), berberrubine (BEU), sanguinarine (SAN), chelerythrine (CHE), and nitidine (NIT) upon binding with the AP nanocavity. PAL is screened out as the most efficient fluorophore-switched probe to recognize the AP nanocavity over the fully matched DNA. Its fluorescence enhancement occurs for all of the AP nanocavity sequence environments, which has not been achieved by the previously used probes. The bridged π conjugation effect should partially contribute to the AP nanocavity-specific fluorescence, as opposed to the solvent effect. Due to the strong binding with the AP nanocavity, PAL will find wide applications in the DNA damage recognition and sensor development.

DNA Polymerase λ Inactivation by Oxidized Abasic Sites&

PubMed Central

Stevens, Adam J.; Guan, Lirui; Bebenek, Katarzyna; Kunkel, Thomas A.; Greenberg, Marc M.

2013-01-01

Base excision repair plays a vital role in maintaining genomic integrity in mammalian cells. DNA polymerase λ is believed to play a backup role to DNA polymerase β in base excision repair. Two oxidized abasic lesions that are produced by a variety of DNA damaging agents, including several antitumor antibiotics, the C4′-oxidized abasic site following Ape1 incision (pC4-AP) and 5′-(2-phosphoryl-1,4-dioxobutane) (DOB), irreversibly inactivate Pol β and Pol λ. The interactions of DOB and pC4-AP with Pol λ are examined in detail using DNA substrates containing these lesions at defined sites. Single turnover kinetic experiments show that Pol λ excises DOB almost 13-times more slowly than a 5′-phosphorylated 2-deoxyribose (dRP). pC4-AP is excised approximately twice as fast as DOB. The absolute rate constants are considerably slower than those reported for Pol β at the respective reactions, suggesting that Pol λ may be an inefficient backup in BER. DOB inactivates Pol λ approximately 3-fold less efficiently than it does Pol β and the difference is attributable to a higher KI (33 ± 7 nM). Inactivation of Pol λ’s lyase activity by DOB also prevents the enzyme from carrying out polymerization following preincubation of the protein and DNA. Mass spectral analysis of GluC digested Pol λ inactivated by DOB shows that Lys324 is modified. There is inferential support that Lys312 may also be modified. Both residues are within the Pol λ lyase active site. Protein modification involves reaction with released but-2-ene-1,4-dial. When acting on pC4-AP, Pol λ achieves approximately 4 turnovers on average before being inactivated. Lyase inactivation by pC4-AP is also accompanied by loss of polymerase activity and mass spectrometry indicates that Lys312 and Lys324 are modified by the lesion. The ability of DOB and pC4-AP to inactivate Pol λ provides additional evidence that these lesions are significant sources of the cytotoxicity of DNA damaging agents that produce them. PMID:23330920

New gas phase inorganic ion cluster species and their atmospheric implications

NASA Technical Reports Server (NTRS)

Maerk, T. D.; Peterson, K. I.; Castleman, A. W., Jr.

1980-01-01

Recent experimental laboratory observations, with high-pressure mass spectroscopy, have revealed the existence of previously unreported species involving water clustered to sodium dimer ions, and alkali metal hydroxides clustered to alkali metal ions. The important implications of these results concerning the existence of such species are here discussed, as well as how from a practical aspect they confirm the stability of certain cluster species proposed by Ferguson (1978) to explain masses recently detected at upper altitudes using mass spectrometric techniques.

Spatial Clustering of Aedes aegypti Related to Breeding Container Characteristics in Coastal Ecuador: Implications for Dengue Control

PubMed Central

Schafrick, Nathaniel H.; Milbrath, Meghan O.; Berrocal, Veronica J.; Wilson, Mark L.; Eisenberg, Joseph N. S.

2013-01-01

Mosquito management within households remains central to the control of dengue virus transmission. An important factor in these management decisions is the spatial clustering of Aedes aegypti. We measured spatial clustering of Ae. aegypti in the town of Borbón, Ecuador and assessed what characteristics of breeding containers influenced the clustering. We used logistic regression to assess the spatial extent of that clustering. We found strong evidence for juvenile mosquito clustering within 20 m and for adult mosquito clustering within 10 m, and stronger clustering associations for containers ≥ 40 L than those < 40 L. Aedes aegypti clusters persisted after adjusting for various container characteristics, suggesting that patterns are likely attributable to short dispersal distances rather than shared characteristics of containers in cluster areas. These findings have implications for targeting Ae. aegypti control efforts. PMID:24002483

The Analysis of the Relationship between Well Being and the Levels of Emotional Abuse of the Teacher Candidates Perceive

ERIC Educational Resources Information Center

Sakar, Zuleyha; Akca, Figen; Bozkurt, Aysegul

2017-01-01

Emotional abuse can be defined as a large behavior pattern which the individual is exposed to and can be compiled as, the abasement, violent attitude, exclusion, continuous criticism, unfulfilled need for love and making someone feel worthless. From this point of view the effect on the well being is a key concern about the individuals exposed to…

The Stability and Oxidation Resistance of Iron- and Cobalt-Based Magnetic Nanoparticle Fluids Fabricated by Inert-Gas Condensation

DTIC Science & Technology

2005-01-01

imaging, drug delivery, and hyperthermia treatment for cancer . Ideal magnetic nanoparticle fluids have well-separated, biocompatible nanoparticles with a...Based Magnetic Nanoparticle Fluids Fabricated by Inert-Gas Condensation DISTRIBUTION: Approved for public release, distribution unlimited This paper...Oxidation Resistance of Iron- and Cobalt-Based Magnetic Nanoparticle Fluids Fabricated by Inert-Gas Condensation Nguyen H. Hail, Raymond Lemoine’, Shaina

NDE Research At Nondestructive Measurement Science At NASA Langley

DTIC Science & Technology

1989-06-01

our staff include: ultrasonics, nonlinear acoustics , thermal acoustics and diffusion, magnetics , fiber optics, and x-ray tomography . We have a...based on the simple assumption that acoustic waves interact with the sample and reveal "important" properties . In practice, such assumptions have...between the acoustic wave and the media. The most useful models can generally be inverted to determine the physical properties or geometry of the

Interstrand cross-links arising from strand breaks at true abasic sites in duplex DNA

PubMed Central

Yang, Zhiyu; Price, Nathan E.; Johnson, Kevin M.

2017-01-01

Abstract Interstrand cross-links are exceptionally bioactive DNA lesions. Endogenous generation of interstrand cross-links in genomic DNA may contribute to aging, neurodegeneration, and cancer. Abasic (Ap) sites are common lesions in genomic DNA that readily undergo spontaneous and amine-catalyzed strand cleavage reactions that generate a 2,3-didehydro-2,3-dideoxyribose sugar remnant (3’ddR5p) at the 3’-terminus of the strand break. Interestingly, this strand scission process leaves an electrophilic α,β-unsaturated aldehyde residue embedded within the resulting nicked duplex. Here we present evidence that 3’ddR5p derivatives generated by spermine-catalyzed strand cleavage at Ap sites in duplex DNA can react with adenine residues on the opposing strand to generate a complex lesion consisting of an interstrand cross-link adjacent to a strand break. The cross-link blocks DNA replication by ϕ29 DNA polymerase, a highly processive polymerase enzyme that couples synthesis with strand displacement. This suggests that 3’ddR5p-derived cross-links have the potential to block critical cellular DNA transactions that require strand separation. LC-MS/MS methods developed herein provide powerful tools for studying the occurrence and properties of these cross-links in biochemical and biological systems. PMID:28531327

Selective amyloid β oligomer assay based on abasic site-containing molecular beacon and enzyme-free amplification.

PubMed

Zhu, Linling; Zhang, Junying; Wang, Fengyang; Wang, Ya; Lu, Linlin; Feng, Chongchong; Xu, Zhiai; Zhang, Wen

2016-04-15

Amyloid-beta (Aβ) oligomers are highly toxic species in the process of Aβ aggregation and are regarded as potent therapeutic targets and diagnostic markers for Alzheimer's disease (AD). Herein, a label-free molecular beacon (MB) system integrated with enzyme-free amplification strategy was developed for simple and highly selective assay of Aβ oligomers. The MB system was constructed with abasic site (AP site)-containing stem-loop DNA and a fluorescent ligand 2-amino-5,6,7-trimethyl-1,8-naphyridine (ATMND), of which the fluorescence was quenched upon binding to the AP site in DNA stem. Enzyme-free amplification was realized by target-triggered continuous opening of two delicately designed MBs (MB1 and MB2). Target DNA hybridization with MB1 and then MB2 resulted in the release of two ATMND molecules in one binding event. Subsequent target recycling could greatly amplify the detection sensitivity due to the greatly enhanced turn-on emission of ATMND fluorescence. Combining with Aβ oligomers aptamers, the strategy was applied to analyze Aβ oligomers and the results showed that it could quantify Aβ oligomers with high selectivity and monitor the Aβ aggregation process. This novel method may be conducive to improve the diagnosis and pathogenic study of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Fall 2014 Data-Intensive Systems

DTIC Science & Technology

2014-10-29

Oct 2014 © 2014 Carnegie Mellon University Big Data Systems NoSQL and horizontal scaling are changing architecture principles by creating...University Status LEAP4BD • Ready to pilot QuABase • Prototype is complete – covers 8 NoSQL /NewSQL implementations • Completing validation testing Big...machine learning to automate population of knowledge base • Initial focus on NoSQL /NewSQL technology domain • Extend to create knowledge bases in other

Dosimetric Comparison between Three-Dimensional Magnetic Resonance Imaging-Guided and Conventional Two-Dimensional Point A-Based Intracavitary Brachytherapy Planning for Cervical Cancer

PubMed Central

Ren, Juan; Yuan, Wei; Wang, Ruihua; Wang, Qiuping; Li, Yi; Xue, Chaofan; Yan, Yanli; Ma, Xiaowei; Tan, Li; Liu, Zi

2016-01-01

Objective The purpose of this study was to comprehensively compare the 3-dimensional (3D) magnetic resonance imaging (MRI)-guided and conventional 2-dimensional (2D) point A-based intracavitary brachytherapy (BT) planning for cervical cancer with regard to target dose coverage and dosages to adjacent organs-at risk (OARs). Methods A total of 79 patients with cervical cancer were enrolled to receive 2D point A-based BT planning and then immediately to receive 3D planning between October 2011 and April 2013 at the First Hospital Affiliated to Xi’an Jiao Tong University (Xi’an, China). The dose-volume histogram (DVH) parameters for gross tumor volume (GTV), high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV) and OARs were compared between the 2D and 3D planning. Results In small tumors, there was no significant difference in most of the DVHs between 2D and 3D planning (all p>0.05). While in big tumors, 3D BT planning significantly increased the DVHs for most of the GTV, HR-CTV and IR-CTV, and some OARs compared with 2D planning (all P<0.05). In 3D planning, DVHs for GTV, HR-CTV, IR-CTV and some OARs were significantly higher in big tumors than in small tumors (all p<0.05). In contrast, in 2D planning, DVHs for almost all of the HR-CTV and IR-CTV were significantly lower in big tumors (all p<0.05). In eccentric tumors, 3D planning significantly increased dose coverage but decreased dosages to OARs compared with 2D planning (p<0.05). In tumors invading adjacent tissues, the target dose coverage in 3D planning was generally significantly higher than in 2D planning (P<0.05); the dosages to the adjacent rectum and bladder were significantly higher but those to sigmoid colon were lower in 3D planning (all P<0.05). Conclusions 3D MRI image-guided BT planning exhibits advantages over 2D planning in a complex way, generally showing advantages for the treatment of cervical cancer except small tumors. PMID:27611853

The formation of double-strand breaks at multiply damaged sites is driven by the kinetics of excision/incision at base damage in eukaryotic cells

PubMed Central

Kozmin, Stanislav G.; Sedletska, Yuliya; Reynaud-Angelin, Anne; Gasparutto, Didier; Sage, Evelyne

2009-01-01

It has been stipulated that repair of clustered DNA lesions may be compromised, possibly leading to the formation of double-strand breaks (DSB) and, thus, to deleterious events. Using a variety of model multiply damaged sites (MDS), we investigated parameters that govern the formation of DSB during the processing of MDS. Duplexes carrying MDS were inserted into replicative or integrative vectors, and used to transform yeast Saccharomyces cerevisiae. Formation of DSB was assessed by a relevant plasmid survival assay. Kinetics of excision/incision and DSB formation at MDS was explored using yeast cell extracts. We show that MDS composed of two uracils or abasic sites, were rapidly incised and readily converted into DSB in yeast cells. In marked contrast, none of the MDS carrying opposed oG and hU separated by 3–8 bp gave rise to DSB, despite the fact that some of them contained preexisting single-strand break (a 1-nt gap). Interestingly, the absence of DSB formation in this case correlated with slow excision/incision rates of lesions. We propose that the kinetics of the initial repair steps at MDS is a major parameter that direct towards the conversion of MDS into DSB. Data provides clues to the biological consequences of MDS in eukaryotic cells. PMID:19174565

New ultracool subdwarfs identified in large-scale surveys using Virtual Observatory tools (Corrigendum). I. UKIDSS LAS DR5 vs. SDSS DR7

NASA Astrophysics Data System (ADS)

Lodieu, N.; Espinoza Contreras, M.; Zapatero Osorio, M. R.; Solano, E.; Aberasturi, M.; Martín, E. L.

2017-01-01

Based on observations made with ESO Telescopes at the La Silla Paranal Observatory under programme ID 084.C-0928A.Based on observations made with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias.

Interstrand cross-links arising from strand breaks at true abasic sites in duplex DNA.

PubMed

Yang, Zhiyu; Price, Nathan E; Johnson, Kevin M; Wang, Yinsheng; Gates, Kent S

2017-06-20

Interstrand cross-links are exceptionally bioactive DNA lesions. Endogenous generation of interstrand cross-links in genomic DNA may contribute to aging, neurodegeneration, and cancer. Abasic (Ap) sites are common lesions in genomic DNA that readily undergo spontaneous and amine-catalyzed strand cleavage reactions that generate a 2,3-didehydro-2,3-dideoxyribose sugar remnant (3'ddR5p) at the 3'-terminus of the strand break. Interestingly, this strand scission process leaves an electrophilic α,β-unsaturated aldehyde residue embedded within the resulting nicked duplex. Here we present evidence that 3'ddR5p derivatives generated by spermine-catalyzed strand cleavage at Ap sites in duplex DNA can react with adenine residues on the opposing strand to generate a complex lesion consisting of an interstrand cross-link adjacent to a strand break. The cross-link blocks DNA replication by ϕ29 DNA polymerase, a highly processive polymerase enzyme that couples synthesis with strand displacement. This suggests that 3'ddR5p-derived cross-links have the potential to block critical cellular DNA transactions that require strand separation. LC-MS/MS methods developed herein provide powerful tools for studying the occurrence and properties of these cross-links in biochemical and biological systems. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

The Human DNA glycosylases NEIL1 and NEIL3 Excise Psoralen-Induced DNA-DNA Cross-Links in a Four-Stranded DNA Structure.

PubMed

Martin, Peter R; Couvé, Sophie; Zutterling, Caroline; Albelazi, Mustafa S; Groisman, Regina; Matkarimov, Bakhyt T; Parsons, Jason L; Elder, Rhoderick H; Saparbaev, Murat K

2017-12-12

Interstrand cross-links (ICLs) are highly cytotoxic DNA lesions that block DNA replication and transcription by preventing strand separation. Previously, we demonstrated that the bacterial and human DNA glycosylases Nei and NEIL1 excise unhooked psoralen-derived ICLs in three-stranded DNA via hydrolysis of the glycosidic bond between the crosslinked base and deoxyribose sugar. Furthermore, NEIL3 from Xenopus laevis has been shown to cleave psoralen- and abasic site-induced ICLs in Xenopus egg extracts. Here we report that human NEIL3 cleaves psoralen-induced DNA-DNA cross-links in three-stranded and four-stranded DNA substrates to generate unhooked DNA fragments containing either an abasic site or a psoralen-thymine monoadduct. Furthermore, while Nei and NEIL1 also cleave a psoralen-induced four-stranded DNA substrate to generate two unhooked DNA duplexes with a nick, NEIL3 targets both DNA strands in the ICL without generating single-strand breaks. The DNA substrate specificities of these Nei-like enzymes imply the occurrence of long uninterrupted three- and four-stranded crosslinked DNA-DNA structures that may originate in vivo from DNA replication fork bypass of an ICL. In conclusion, the Nei-like DNA glycosylases unhook psoralen-derived ICLs in various DNA structures via a genuine repair mechanism in which complex DNA lesions can be removed without generation of highly toxic double-strand breaks.

Combining H/D exchange mass spectroscopy and computational docking reveals extended DNA-binding surface on uracil-DNA glycosylase

PubMed Central

Roberts, Victoria A.; Pique, Michael E.; Hsu, Simon; Li, Sheng; Slupphaug, Geir; Rambo, Robert P.; Jamison, Jonathan W.; Liu, Tong; Lee, Jun H.; Tainer, John A.; Ten Eyck, Lynn F.; Woods, Virgil L.

2012-01-01

X-ray crystallography provides excellent structural data on protein–DNA interfaces, but crystallographic complexes typically contain only small fragments of large DNA molecules. We present a new approach that can use longer DNA substrates and reveal new protein–DNA interactions even in extensively studied systems. Our approach combines rigid-body computational docking with hydrogen/deuterium exchange mass spectrometry (DXMS). DXMS identifies solvent-exposed protein surfaces; docking is used to create a 3-dimensional model of the protein–DNA interaction. We investigated the enzyme uracil-DNA glycosylase (UNG), which detects and cleaves uracil from DNA. UNG was incubated with a 30 bp DNA fragment containing a single uracil, giving the complex with the abasic DNA product. Compared with free UNG, the UNG–DNA complex showed increased solvent protection at the UNG active site and at two regions outside the active site: residues 210–220 and 251–264. Computational docking also identified these two DNA-binding surfaces, but neither shows DNA contact in UNG–DNA crystallographic structures. Our results can be explained by separation of the two DNA strands on one side of the active site. These non-sequence-specific DNA-binding surfaces may aid local uracil search, contribute to binding the abasic DNA product and help present the DNA product to APE-1, the next enzyme on the DNA-repair pathway. PMID:22492624

APE1 incision activity at abasic sites in tandem repeat sequences.

PubMed

Li, Mengxia; Völker, Jens; Breslauer, Kenneth J; Wilson, David M

2014-05-29

Repetitive DNA sequences, such as those present in microsatellites and minisatellites, telomeres, and trinucleotide repeats (linked to fragile X syndrome, Huntington disease, etc.), account for nearly 30% of the human genome. These domains exhibit enhanced susceptibility to oxidative attack to yield base modifications, strand breaks, and abasic sites; have a propensity to adopt non-canonical DNA forms modulated by the positions of the lesions; and, when not properly processed, can contribute to genome instability that underlies aging and disease development. Knowledge on the repair efficiencies of DNA damage within such repetitive sequences is therefore crucial for understanding the impact of such domains on genomic integrity. In the present study, using strategically designed oligonucleotide substrates, we determined the ability of human apurinic/apyrimidinic endonuclease 1 (APE1) to cleave at apurinic/apyrimidinic (AP) sites in a collection of tandem DNA repeat landscapes involving telomeric and CAG/CTG repeat sequences. Our studies reveal the differential influence of domain sequence, conformation, and AP site location/relative positioning on the efficiency of APE1 binding and strand incision. Intriguingly, our data demonstrate that APE1 endonuclease efficiency correlates with the thermodynamic stability of the DNA substrate. We discuss how these results have both predictive and mechanistic consequences for understanding the success and failure of repair protein activity associated with such oxidatively sensitive, conformationally plastic/dynamic repetitive DNA domains. Published by Elsevier Ltd.

Apurinic/Apyrimidinic Endonuclease 1 Is the Essential Nuclease during Immunoglobulin Class Switch Recombination

PubMed Central

Masani, Shahnaz; Han, Li

2013-01-01

Immunoglobulin (Ig) class switch recombination (CSR) is initiated by activation-induced cytidine deaminase (AID) that catalyzes numerous DNA cytosine deaminations within switch regions. The resulting uracils are processed by uracil base excision and/or mismatch repair enzymes that ultimately generate switch region DNA double-strand breaks (DSBs). Uracil glycosylase 2 (UNG2) is required for CSR, most likely by removing uracils to generate abasic sites. Although it is presumed that the apurinic/apyrimidinic endonuclease 1 (APE1) generates DNA strand incisions (a prerequisite for CSR) at these abasic sites, a direct test of the requirement for APE1 in CSR has been difficult because of the embryonic lethality of APE1 ablation in mice. Here, we report the successful deletion of the APE1 gene in a mouse B cell line (CH12F3) capable of robust CSR in vitro. In contrast to the general assumption that APE1 is essential for cellular viability, deletion of APE1 in CH12F3 cells has no apparent effect on cell viability or growth. Moreover, CSR in APE1-null CH12F3 cells is drastically reduced, providing direct evidence for an essential role for APE1 in switch region cleavage and CSR. Finally, deletion of AP endonuclease 2 (APE2) has no effect on CSR in either APE1-proficient or -deficient cells. PMID:23382073

Analysis of Structural Flexibility of Damaged DNA Using Thiol-Tethered Oligonucleotide Duplexes

PubMed Central

Fujita, Masashi; Watanabe, Shun; Yoshizawa, Mariko; Yamamoto, Junpei; Iwai, Shigenori

2015-01-01

Bent structures are formed in DNA by the binding of small molecules or proteins. We developed a chemical method to detect bent DNA structures. Oligonucleotide duplexes in which two mercaptoalkyl groups were attached to the positions facing each other across the major groove were prepared. When the duplex contained the cisplatin adduct, which was proved to induce static helix bending, interstrand disulfide bond formation under an oxygen atmosphere was detected by HPLC analyses, but not in the non-adducted duplex, when the two thiol-tethered nucleosides were separated by six base pairs. When the insert was five and seven base pairs, the disulfide bond was formed and was not formed, respectively, regardless of the cisplatin adduct formation. The same reaction was observed in the duplexes containing an abasic site analog and the (6–4) photoproduct. Compared with the cisplatin case, the disulfide bond formation was slower in these duplexes, but the reaction rate was nearly independent of the linker length. These results indicate that dynamic structural changes of the abasic site- and (6–4) photoproduct-containing duplexes could be detected by our method. It is strongly suggested that the UV-damaged DNA-binding protein, which specifically binds these duplexes and functions at the first step of global-genome nucleotide excision repair, recognizes the easily bendable nature of damaged DNA. PMID:25679955

In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.

PubMed

Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom

2013-11-26

Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.

DNA abasic site-directed formation of fluorescent silver nanoclusters for selective nucleobase recognition

NASA Astrophysics Data System (ADS)

Ma, Kun; Cui, Qinghua; Liu, Guiying; Wu, Fei; Xu, Shujuan; Shao, Yong

2011-07-01

DNA single-nucleotide polymorphism (SNP) detection has attracted much attention due to mutation related diseases. Various methods for SNP detection have been proposed and many are already in use. Here, we find that the abasic site (AP site) in the DNA duplex can be developed as a capping scaffold for the generation of fluorescent silver nanoclusters (Ag NCs). As a proof of concept, the DNA sequences from fragments near codon 177 of cancer supression gene p53 were used as a model for SNP detection by in situ formed Ag NCs. The formation of fluorescent Ag NCs in the AP site-containing DNA duplex is highly selective for cytosine facing the AP site and guanines flanking the site and can be employed in situ as readout for SNP detection. The fluorescent signal-on sensing for SNP based on this inorganic fluorophore is substantially advantageous over the previously reported signal-off responses using low-molecular-weight organic ligands. The strong dependence of fluorescent Ag NC formation on the sequences surrounding the AP site was successfully used to identify mutations in codon 177 of cancer supression gene p53. We anticipate that this approach will be employed to develop a practical SNP detection method by locating an AP site toward the midway cytosine in a target strand containing more than three consecutive cytosines.

Roles of Rev1, Pol ζ, Pol32 and Pol η in the bypass of chromosomal abasic sites in Saccharomyces cerevisiae

PubMed Central

Auerbach, Paul A.; Demple, Bruce

2010-01-01

Translesion synthesis (TLS) on DNA is a process by which potentially cytotoxic replication-blocking lesions are bypassed, but at the risk of increased mutagenesis. The exact in vivo role of the individual TLS enzymes in Saccharomyces cerevisiae has been difficult to determine from previous studies due to differing results from the variety of systems used. We have generated a series of S.cerevisiae strains in which each of the TLS-related genes REV1, REV3, REV7, RAD30 and POL32 was deleted, and in which chromosomal apyrimidinic sites were generated during normal cell growth by the activity of altered forms of human uracil-DNA glycosylase that remove undamaged cytosines or thymines. Deletion of REV1, REV3 or REV7 resulted in slower growth dependent on (rev3Δ and rev7Δ) or enhanced by (rev1Δ) expression of the mutator glycosylases and a nearly complete abolition of glycosylase-induced mutagenesis. Deletion of POL32 resulted in cell death when the mutator glycosylases were expressed and, in their absence, diminished spontaneous mutagenesis. RAD30 appeared to be unnecessary for mutagenesis in response to abasic sites, as deleting this gene caused no significant change in either the mutation rates or the mutational spectra due to glycosylase expression. PMID:19901007

Seizure clusters: characteristics and treatment.

PubMed

Haut, Sheryl R

2015-04-01

Many patients with epilepsy experience 'clusters' or flurries of seizures, also termed acute repetitive seizures (ARS). Seizure clustering has a significant impact on health and quality of life. This review summarizes recent advances in the definition and neurophysiologic understanding of clustering, the epidemiology and risk factors for clustering and both inpatient and outpatient clinical implications. New treatments for seizure clustering/ARS are perhaps the area of greatest recent progress. Efforts have focused on creating a uniform definition of a seizure cluster. In neurophysiologic studies of refractory epilepsy, seizures within a cluster appear to be self-triggering. Clinical progress has been achieved towards a more precise prevalence of clustering, and consensus guidelines for epilepsy monitoring unit safety. The greatest recent advances are in the study of nonintravenous route of benzodiazepines as rescue medications for seizure clusters/ARS. Rectal benzodiazepines have been very effective but barriers to use exist. New data on buccal, intramuscular and intranasal preparations are anticipated to lead to a greater number of approved treatments. Progesterone may be effective for women who experience catamenial clusters. Seizure clustering is common, particularly in the setting of medically refractory epilepsy. Clustering worsens health and quality of life, and the field requires greater focus on clarifying of definition and clinical implications. Progress towards the development of nonintravenous routes of benzodiazepines has the potential to improve care in this area.

Effect of Coupling Point Selection on Distortion in Internet-distributed Hardware-in-the-Loop Simulation (PREPRINT)

DTIC Science & Technology

2011-04-01

USA, with a hybrid-powertrain-system simulator in Santa Clara, CA, USA ( Compere et al. 2006; Goodell et al. 2006; Brudnak et al. 2007) and, as a...based ( Compere et al. 2006; Goodell et al. 2006; Brudnak et al. 2007) frameworks, to address stability and distortion issues under a delayed coupling...loop simulation." Mechatronics 19(7): 1041-1042. Brudnak, M., M. Pozolo, V. Paul, S. Mohammad, W. Smith, M. Compere , J. Goodell, D. Holtz, T

Unusual interaction of human apurinic/apyrimidinic endonuclease 1 (APE1) with abasic sites via the Schiff-base-dependent mechanism.

PubMed

Ilina, Ekaterina S; Khodyreva, Svetlana N; Lavrik, Olga I

2018-05-03

Clustered apurinic/apyrimidinic (AP) sites are more cytotoxic than isolated AP lesions because double strand breaks (DSB) can be formed during repair of closely positioned bistranded AP sites. Formation of DSB due to simultaneous cleavage of bistranded AP sites may be regulated by proteins specifically interacting with this complex lesion. A set of AP DNA duplexes containing AP sites in both strands in different mutual orientation (BS-AP DNAs) was used for search in the extracts of human cells proteins specifically recognizing clustered AP sites. A protein, which formed the Schiff-base-dependent covalent products having an apparent molecular mass of 50 kDa with the subset of BS-AP DNAs, was identified by mass spectrometry as apurinic/apyrimidinic endonuclease 1 (APE1). The identity of trapped protein was confirmed by Western blot analysis with anti-APE1 antibodies. Purified recombinant human APE1 is also capable of forming the 50 kDa-adducts with efficiency of BS-AP DNAs cross-linking to APE1 being dependent on the mutual orientation of AP sites. In spite of formation of the Schiff-base-dependent intermediate, which is prerequisite for the β-elimination mechanism, APE1 is unable to cleave AP sites. APE1 lacking the first 34 amino acids at the N-terminus, unlike wild type enzyme, is unable to form cross-links with BS-AP DNAs that testifies to the involvement of disordered N-terminal extension, which is enriched in lysine residues, in the interaction with AP sites. The yield of APE1-AP DNA cross-links was found to correlate with the enzyme amount in the extracts estimated by the immunochemical approach; therefore the BS-AP DNA-probes can be useful for comparative analysis of APE1 content in cell extracts. Copyright © 2018. Published by Elsevier B.V.

MicroRNA-34a: A Versatile Regulator of Myriads of Targets in Different Cancers.

PubMed

Farooqi, Ammad Ahmad; Tabassum, Sobia; Ahmad, Aamir

2017-10-02

MicroRNA-34a (miR-34a) is a tumor suppressor that has attracted considerable attention in recent years. It modulates cancer cell invasion, metastasis, and drug resistance, and has also been evaluated as a diagnostic and/or prognostic biomarker. A number of targets of miR-34a have been identified, including some other non-coding RNAs, and it is believed that the modulation of these myriads of targets underlines the versatile role of miR-34a in cancer progression and pathogenesis. Seemingly appealing results from preclinical studies have advocated the testing of miR-34a in clinical trials. However, the results obtained are not very encouraging and there is a need to re-interpret how miR-34a behaves in a context dependent manner in different cancers. In this review, we have attempted to summarize the most recent evidence related to the regulation of different genes and non-coding RNAs by miR-34a and the advances in the field of nanotechnology for the targeted delivery of miR-34a-based therapeutics and mimics. With the emergence of data that contradicts miR-34a's tumor suppressive function, it is important to understand miR-34a's precise functioning, with the aim to establish its role in personalized medicine and to apply this knowledge for the identification of individual patients that are likely to benefit from miR-34a-based therapy.

Temperature and electrolyte optimization of the α-hemolysin latch sensing zone for detection of base modification in double-stranded DNA.

PubMed

Johnson, Robert P; Fleming, Aaron M; Jin, Qian; Burrows, Cynthia J; White, Henry S

2014-08-19

The latch region of the wild-type protein pore α-hemolysin (α-HL) constitutes a sensing zone for individual abasic sites (and furan analogs) in double-stranded DNA (dsDNA). The presence of an abasic site or furan within a DNA duplex, electrophoretically captured in the α-HL vestibule and positioned at the latch region, can be detected based on the current blockage prior to duplex unzipping. We investigated variations in blockage current as a function of temperature (12-35°C) and KCl concentration (0.15-1.0 M) to understand the origin of the current signature and to optimize conditions for identifying the base modification. In 1 M KCl solution, substitution of a furan for a cytosine base in the latch region results in an ∼ 8 kJ mol(-1) decrease in the activation energy for ion transport through the protein pore. This corresponds to a readily measured ∼ 2 pA increase in current at room temperature. Optimal resolution for detecting the presence of a furan in the latch region is achieved at lower KCl concentrations, where the noise in the measured blockage current is significantly lower. The noise associated with the blockage current also depends on the stability of the duplex (as measured from the melting temperature), where a greater noise in the measured blockage current is observed for less stable duplexes. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Mechanisms by which herpes simplex virus DNA polymerase limits translesion synthesis through abasic sites.

PubMed

Zhu, Yali; Song, Liping; Stroud, Jason; Parris, Deborah S

2008-01-01

Results suggest a high probability that abasic (AP) sites occur at least once per herpes simplex virus type 1 (HSV-1) genome. The parameters that control the ability of HSV-1 DNA polymerase (pol) to engage in AP translesion synthesis (TLS) were examined because AP lesions could influence the completion and fidelity of viral DNA synthesis. Pre-steady-state kinetic experiments demonstrated that wildtype (WT) and exonuclease-deficient (exo-) pol could incorporate opposite an AP lesion, but full TLS required absence of exo function. Virtually all of the WT pol was bound at the exo site to AP-containing primer-templates (P/Ts) at equilibrium, and the pre-steady-state rate of excision by WT pol was higher on AP-containing than on matched DNA. However, several factors influencing polymerization work synergistically with exo activity to prevent HSV-1 pol from engaging in TLS. Although the pre-steady-state catalytic rate constant for insertion of dATP opposite a T or AP site was similar, ground-state-binding affinity of dATP for insertion opposite an AP site was reduced 3-9-fold. Single-turnover running-start experiments demonstrated a reduced proportion of P/Ts extended to the AP site compared to the preceding site during processive synthesis by WT or exo- pol. Only the exo- pol engaged in TLS, though inefficiently and without burst kinetics, suggesting a much slower rate-limiting step for extension beyond the AP site.

MicroRNA-34a: A Versatile Regulator of Myriads of Targets in Different Cancers

PubMed Central

Farooqi, Ammad Ahmad; Tabassum, Sobia

2017-01-01

MicroRNA-34a (miR-34a) is a tumor suppressor that has attracted considerable attention in recent years. It modulates cancer cell invasion, metastasis, and drug resistance, and has also been evaluated as a diagnostic and/or prognostic biomarker. A number of targets of miR-34a have been identified, including some other non-coding RNAs, and it is believed that the modulation of these myriads of targets underlines the versatile role of miR-34a in cancer progression and pathogenesis. Seemingly appealing results from preclinical studies have advocated the testing of miR-34a in clinical trials. However, the results obtained are not very encouraging and there is a need to re-interpret how miR-34a behaves in a context dependent manner in different cancers. In this review, we have attempted to summarize the most recent evidence related to the regulation of different genes and non-coding RNAs by miR-34a and the advances in the field of nanotechnology for the targeted delivery of miR-34a-based therapeutics and mimics. With the emergence of data that contradicts miR-34a’s tumor suppressive function, it is important to understand miR-34a’s precise functioning, with the aim to establish its role in personalized medicine and to apply this knowledge for the identification of individual patients that are likely to benefit from miR-34a-based therapy. PMID:29036883

Ethical implications of excessive cluster sizes in cluster randomised trials.

PubMed

Hemming, Karla; Taljaard, Monica; Forbes, Gordon; Eldridge, Sandra M; Weijer, Charles

2018-02-20

The cluster randomised trial (CRT) is commonly used in healthcare research. It is the gold-standard study design for evaluating healthcare policy interventions. A key characteristic of this design is that as more participants are included, in a fixed number of clusters, the increase in achievable power will level off. CRTs with cluster sizes that exceed the point of levelling-off will have excessive numbers of participants, even if they do not achieve nominal levels of power. Excessively large cluster sizes may have ethical implications due to exposing trial participants unnecessarily to the burdens of both participating in the trial and the potential risks of harm associated with the intervention. We explore these issues through the use of two case studies. Where data are routinely collected, available at minimum cost and the intervention poses low risk, the ethical implications of excessively large cluster sizes are likely to be low (case study 1). However, to maximise the social benefit of the study, identification of excessive cluster sizes can allow for prespecified and fully powered secondary analyses. In the second case study, while there is no burden through trial participation (because the outcome data are routinely collected and non-identifiable), the intervention might be considered to pose some indirect risk to patients and risks to the healthcare workers. In this case study it is therefore important that the inclusion of excessively large cluster sizes is justifiable on other grounds (perhaps to show sustainability). In any randomised controlled trial, including evaluations of health policy interventions, it is important to minimise the burdens and risks to participants. Funders, researchers and research ethics committees should be aware of the ethical issues of excessively large cluster sizes in cluster trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The X-ray structure of a galaxy cluster at z = 0.54 - Implications for cluster evolution and cosmology

NASA Technical Reports Server (NTRS)

White, S. D. M.; Silk, J.; Henry, J. P.

1981-01-01

High-resolution X-ray observations of the rich cluster 0016+16 at a redshift of 0.541 are presented. The emitting gas in this cluster is hot and extremely luminous, and its structure resembles that seen in the brightest nearby cluster sources. In most of its properties, 0016+16 resembles a richer version of the Coma cluster, and it offers little support to the hypothesis that clusters at z greater than 0.5 differ fundamentally from nearer objects.

United States-Vietnam Relations 1945-1967, Study Prepared by the Department of Defense, Book 10 of 12

DTIC Science & Technology

1971-01-01

may be the only sound solution ." Collins . . * • (Saigon) 2250 to Dulles, 13 December 195^ 8l1 -226. The Defense Department reviews the...continued support of Diem in spite of a "Bao Dai solution ." The fear that $300 million plus our national prestige would be lost in a gamble" is a...basic disagreement. ’ The French conclude:. "Diem is a bad choice...without him some solution might be possible but with him there is none...What

Somalia and Vietnam. Deja Vu All Over Again

DTIC Science & Technology

1994-04-01

Rev. 2-89) Pre•cribed by ANSI Std. Z39-18 298-102 AIR WAR COLLEGE AIR LUNIVRITY SOMALIA AND VIETNAM " DEJA VU ALL OVER AGAIN" by James M. Comgan A...BASE., ALABAMA APRIL 1994 II II 3 AIR WAR COLLEGE AIR UNIVERITY *! SOMALIA AND VIETNAM S1 " DEJA VU ALL OVER AGAIN" I 3 by James M. Corrigan A RESEARCH...Vietnam: " Deja Vu All Over Again" AUTHOR. James M. Corrigan, Lieutenant Colonel During the recet involvemen in Somalia, U.S. leadership likely

Seizure clustering.

PubMed

Haut, Sheryl R

2006-02-01

Seizure clusters, also known as repetitive or serial seizures, occur commonly in epilepsy. Clustering implies that the occurrence of one seizure may influence the probability of a subsequent seizure; thus, the investigation of the clustering phenomenon yields insights into both specific mechanisms of seizure clustering and more general concepts of seizure occurrence. Seizure clustering has been defined clinically as a number of seizures per unit time and, statistically, as a deviation from a random distribution, or interseizure interval dependence. This review explores the pathophysiology, epidemiology, and clinical implications of clustering, as well as other periodic patterns of seizure occurrence. Risk factors for experiencing clusters and potential precipitants of clustering are also addressed.

ASCA Temperature Maps for Several Interesting Clusters and Their Interpretations

NASA Technical Reports Server (NTRS)

Markevitch, M.; Sarazin, C.; Forman, W.; Vikhlinin, A.

1998-01-01

We present ASCA temperature maps for several galaxy clusters with strong mergers, as well as for several relaxed clusters selected for X-ray mass determination. From the merger temperature maps, we estimate velocities of the colliding subunits and discuss several implications of these estimates. For the relaxed clusters, we derive unprecedentedly accurate mass and gas fraction profiles out to radii of overdensity approximately 500.

Differences Between Ward's and UPGMA Methods of Cluster Analysis: Implications for School Psychology.

ERIC Educational Resources Information Center

Hale, Robert L.; Dougherty, Donna

1988-01-01

Compared the efficacy of two methods of cluster analysis, the unweighted pair-groups method using arithmetic averages (UPGMA) and Ward's method, for students grouped on intelligence, achievement, and social adjustment by both clustering methods. Found UPGMA more efficacious based on output, on cophenetic correlation coefficients generated by each…

The replicative DNA polymerase of herpes simplex virus 1 exhibits apurinic/apyrimidinic and 5′-deoxyribose phosphate lyase activities

PubMed Central

Bogani, Federica; Boehmer, Paul E.

2008-01-01

Base excision repair (BER) is essential for maintaining genome stability both to counter the accumulation of unusual bases and to protect from base loss in the DNA. Herpes simplex virus 1 (HSV-1) is a large dsDNA virus that encodes its own DNA replication machinery, including enzymes involved in nucleotide metabolism. We report on a replicative family B and a herpesvirus-encoded DNA Pol that possesses DNA lyase activity. We have discovered that the catalytic subunit of the HSV-1 DNA polymerase (Pol) (UL30) exhibits apurinic/apyrimidinic (AP) and 5′-deoxyribose phosphate (dRP) lyase activities. These activities are integral to BER and lead to DNA cleavage on the 3′ side of abasic sites and 5′-dRP residues that remain after cleavage by 5′-AP endonuclease. The UL30-catalyzed reaction occurs independently of divalent cation and proceeds via a Schiff base intermediate, indicating that it occurs via a lyase mechanism. Partial proteolysis of the Schiff base shows that the DNA lyase activity resides in the Pol domain of UL30. These observations together with the presence of a virus-encoded uracil DNA glycosylase indicates that HSV-1 has the capacity to perform critical steps in BER. These findings have implications on the role of BER in viral genome maintenance during lytic replication and reactivation from latency. PMID:18695225

Downregulation of hPMC2 imparts chemotherapeutic sensitivity to alkylating agents in breast cancer cells.

PubMed

Krishnamurthy, Nirmala; Liu, Lili; Xiong, Xiahui; Zhang, Junran; Montano, Monica M

2015-01-01

Triple negative breast cancer cell lines have been reported to be resistant to the cyotoxic effects of temozolomide (TMZ). We have shown previously that a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2) has a role in the repair of estrogen-induced abasic sites. Our present study provides evidence that downregulation of hPMC2 in MDA-MB-231 and MDA-MB-468 breast cancer cells treated with temozolomide (TMZ) decreases cell survival. This increased sensitivity to TMZ is associated with an increase in number of apurinic/apyrimidinic (AP) sites in the DNA. We also show that treatment with another alkylating agent, BCNU, results in an increase in AP sites and decrease in cell survival. Quantification of western blot analyses and immunofluorescence experiments reveal that treatment of hPMC2 downregulated cells with TMZ results in an increase in γ-H2AX levels, suggesting an increase in double strand DNA breaks. The enhancement of DNA double strand breaks in TMZ treated cells upon downregulation of hPCM2 is also revealed by the comet assay. Overall, we provide evidence that downregulation of hPMC2 in breast cancer cells increases cytotoxicity of alkylating agents, representing a novel mechanism of treatment for breast cancer. Our data thus has important clinical implications in the management of breast cancer and brings forth potentially new therapeutic strategies.

Pathways of Metabolite-related Damage to A Synthetic p53 Gene Exon 7 Oligonucleotide using Magnetic Enzyme Bioreactor Beads and LC-MS/MS Sequencing.

PubMed

Malla, Spundana; Kadimisetty, Karteek; Jiang, Di; Choudhary, Dharamainder; Rusling, James F

2018-05-11

Reactive metabolites of environmental chemicals and drugs can cause site-specific damage to p53 tumor suppressor gene in a major pathway for genotoxicity. We report here a high throughput, cell-free, 96-well plate magnetic bead-enzyme system interfaced with LC-MS/MS sequencing to bioactivate test chemicals and identify resulting adduction sites on genes. Bioactivated aflatoxin B1 was reacted with a 32 bp exon 7 fragment of the p53 gene using 8 microsomal cyt P450 enzymes from different organs coated on magnetic beads. All cyt P450s converted aflatoxin B1 to aflatoxin B1-8,9-epoxide that adducts guanine (G) in codon 249, with subsequent depurination to give abasic sites, then strand breaks. This is the first demonstration in a cell-free medium that aflatoxin B1 metabolite selectively causes abasic site formation and strand breaks at codon 249 of the p53 probe, corresponding to the chemical pathway and mutations of p53 in human liver cells and tumors. Molecular modeling supports the view that binding of aflatoxin B1-8,9-epoxide to G in codon 249 precedes the SN2 adduction reaction. Among a range of metabolic enzymes characteristic of different organs, human liver microsomes and cyt P450 3A5 supersomes showed the highest bioactivation rate for p53 exon 7 damage. This method to identify metabolite-related gene damage sites may facilitate predictions of organ-specific cancers for test chemicals via correlations with mutation sites.

A Common Function of Basal Ganglia-Cortical Circuits Subserving Speed in Both Motor and Cognitive Domains

PubMed Central

2017-01-01

Abstract Distinct regions of the frontal cortex connect with their basal ganglia and thalamic counterparts, constituting largely segregated basal ganglia-thalamo-cortical (BTC) circuits. However, any common role of the BTC circuits in different behavioral domains remains unclear. Indeed, whether dysfunctional motor and cognitive BTC circuits are responsible for motor slowing and cognitive slowing, respectively, in Parkinson’s disease (PD) is a matter of debate. Here, we used an effortful behavioral paradigm in which the effects of task rate on accuracy were tested in movement, imagery, and calculation tasks in humans. Using nonlinear fitting, we separated baseline accuracy (Abase) and “agility” (ability to function quickly) components of performance in healthy participants and then confirmed reduced agility and preserved Abase for the three tasks in PD. Using functional magnetic resonance imaging (fMRI) and diffusion tractography, we explored the neural substrates underlying speeded performance of the three tasks in healthy participants, suggesting the involvement of distinct BTC circuits in cognitive and motor agility. Language and motor BTC circuits were specifically active during speeded performance of the calculation and movement tasks, respectively, whereas premotor BTC circuits revealed activity for speeded performance of all tasks. Finally, PD showed reduced task rate-correlated activity in the language BTC circuits for speeded calculation, in the premotor BTC circuit for speeded imagery, and in the motor BTC circuits for speeded movement, as compared with controls. The present study casts light on the anatomo-functional organization of the BTC circuits and their parallel roles in invigorating movement and cognition through a function of dopamine. PMID:29379873

Core-halo age gradients and star formation in the Orion Nebula and NGS 2024 young stellar clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Getman, Konstantin V.; Feigelson, Eric D.; Kuhn, Michael A.

2014-06-01

We analyze age distributions of two nearby rich stellar clusters, the NGC 2024 (Flame Nebula) and Orion Nebula cluster (ONC) in the Orion molecular cloud complex. Our analysis is based on samples from the MYStIX survey and a new estimator of pre-main sequence (PMS) stellar ages, Age{sub JX} , derived from X-ray and near-infrared photometric data. To overcome the problem of uncertain individual ages and large spreads of age distributions for entire clusters, we compute median ages and their confidence intervals of stellar samples within annular subregions of the clusters. We find core-halo age gradients in both the NGC 2024more » cluster and ONC: PMS stars in cluster cores appear younger and thus were formed later than PMS stars in cluster peripheries. These findings are further supported by the spatial gradients in the disk fraction and K-band excess frequency. Our age analysis is based on Age{sub JX} estimates for PMS stars and is independent of any consideration of OB stars. The result has important implications for the formation of young stellar clusters. One basic implication is that clusters form slowly and the apparent age spreads in young stellar clusters, which are often controversial, are (at least in part) real. The result further implies that simple models where clusters form inside-out are incorrect and more complex models are needed. We provide several star formation scenarios that alone or in combination may lead to the observed core-halo age gradients.« less

Geographic Clustering of Cardiometabolic Risk Factors in Metropolitan Centres in France and Australia

PubMed Central

Paquet, Catherine; Chaix, Basile; Howard, Natasha J.; Coffee, Neil T.; Adams, Robert J.; Taylor, Anne W.; Thomas, Frédérique; Daniel, Mark

2016-01-01

Understanding how health outcomes are spatially distributed represents a first step in investigating the scale and nature of environmental influences on health and has important implications for statistical power and analytic efficiency. Using Australian and French cohort data, this study aimed to describe and compare the extent of geographic variation, and the implications for analytic efficiency, across geographic units, countries and a range of cardiometabolic parameters (Body Mass Index (BMI) waist circumference, blood pressure, resting heart rate, triglycerides, cholesterol, glucose, HbA1c). Geographic clustering was assessed using Intra-Class Correlation (ICC) coefficients in biomedical cohorts from Adelaide (Australia, n = 3893) and Paris (France, n = 6430) for eight geographic administrative units. The median ICC was 0.01 suggesting 1% of risk factor variance attributable to variation between geographic units. Clustering differed by cardiometabolic parameters, administrative units and countries and was greatest for BMI and resting heart rate in the French sample, HbA1c in the Australian sample, and for smaller geographic units. Analytic inefficiency due to clustering was greatest for geographic units in which participants were nested in fewer, larger geographic units. Differences observed in geographic clustering across risk factors have implications for choice of geographic unit in sampling and analysis, and highlight potential cross-country differences in the distribution, or role, of environmental features related to cardiometabolic health. PMID:27213423

Nursing home care quality: a cluster analysis.

PubMed

Grøndahl, Vigdis Abrahamsen; Fagerli, Liv Berit

2017-02-13

Purpose The purpose of this paper is to explore potential differences in how nursing home residents rate care quality and to explore cluster characteristics. Design/methodology/approach A cross-sectional design was used, with one questionnaire including questions from quality from patients' perspective and Big Five personality traits, together with questions related to socio-demographic aspects and health condition. Residents ( n=103) from four Norwegian nursing homes participated (74.1 per cent response rate). Hierarchical cluster analysis identified clusters with respect to care quality perceptions. χ 2 tests and one-way between-groups ANOVA were performed to characterise the clusters ( p<0.05). Findings Two clusters were identified; Cluster 1 residents (28.2 per cent) had the best care quality perceptions and Cluster 2 (67.0 per cent) had the worst perceptions. The clusters were statistically significant and characterised by personal-related conditions: gender, psychological well-being, preferences, admission, satisfaction with staying in the nursing home, emotional stability and agreeableness, and by external objective care conditions: healthcare personnel and registered nurses. Research limitations/implications Residents assessed as having no cognitive impairments were included, thus excluding the largest group. By choosing questionnaire design and structured interviews, the number able to participate may increase. Practical implications Findings may provide healthcare personnel and managers with increased knowledge on which to develop strategies to improve specific care quality perceptions. Originality/value Cluster analysis can be an effective tool for differentiating between nursing homes residents' care quality perceptions.

Energy spectra of X-ray clusters of galaxies

NASA Technical Reports Server (NTRS)

Avni, Y.

1976-01-01

A procedure for estimating the ranges of parameters that describe the spectra of X-rays from clusters of galaxies is presented. The applicability of the method is proved by statistical simulations of cluster spectra; such a proof is necessary because of the nonlinearity of the spectral functions. Implications for the spectra of the Perseus, Coma, and Virgo clusters are discussed. The procedure can be applied in more general problems of parameter estimation.

Interpreting sperm DNA damage in a diverse range of mammalian sperm by means of the two-tailed comet assay

PubMed Central

Cortés-Gutiérrez, Elva I.; López-Fernández, Carmen; Fernández, José Luis; Dávila-Rodríguez, Martha I.; Johnston, Stephen D.; Gosálvez, Jaime

2014-01-01

Key Concepts The two-dimensional Two-Tailed Comet assay (TT-comet) protocol is a valuable technique to differentiate between single-stranded (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell.Protein lysis inherent with the TT-comet protocol accounts for differences in sperm protamine composition at a species-specific level to produce reliable visualization of sperm DNA damage.Alkaline treatment may break the sugar–phosphate backbone in abasic sites or at sites with deoxyribose damage, transforming these lesions into DNA breaks that are also converted into ssDNA. These lesions are known as Alkali Labile Sites “ALSs.”DBD–FISH permits the in situ visualization of DNA breaks, abasic sites or alkaline-sensitive DNA regions.The alkaline comet single assay reveals that all mammalian species display constitutive ALS related with the requirement of the sperm to undergo transient changes in DNA structure linked with chromatin packing.Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome.The TT is a valuable tool for identifying SSBs or DSBs in sperm cells with DNA fragmentation and can be therefore used for the purposes of fertility assessment. Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome. A series of methodologies to assess DNA damage in spermatozoa have been developed but most are unable to differentiate between single-stranded DNA breaks (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell. The two-dimensional Two-Tailed Comet assay (TT-comet) protocol highlighted in this review overcomes this limitation and emphasizes the importance in accounting for the difference in sperm protamine composition at a species-specific level for the appropriate preparation of the assay. The TT-comet is a modification of the original comet assay that uses a two dimensional electrophoresis to allow for the simultaneous evaluation of DSBs and SSBs in mammalian spermatozoa. Here we have compiled a retrospective overview of how the TT-comet assay has been used to investigate the structure and function of sperm DNA across a diverse range of mammalian species (eutheria, metatheria, and prototheria). When conducted as part of the TT-comet assay, we illustrate (a) how the alkaline comet single assay has been used to help understand the constitutive and transient changes in DNA structure associated with chromatin packing, (b) the capacity of the TT-comet to differentiate between the presence of SSBs and DSBs (c) and the possible implications of SSBs or DSBs for the assessment of infertility. PMID:25505901

Initial conditions of formation of starburst clusters: constraints from stellar dynamics

NASA Astrophysics Data System (ADS)

Banerjee, Sambaran

2017-03-01

How starburst clusters form out of molecular clouds is still an open question. In this article, I highlight some of the key constraints in this regard, that one can get from the dynamical evolutionary properties of dense stellar systems. I particularly focus on secular expansion of massive star clusters and hierarchical merging of sub-clusters, and discuss their implications vis-á-vis the observed properties of young massive clusters. The analysis suggests that residual gas expulsion is necessary for shaping these clusters as we see them today, irrespective of their monolithic or hierarchical mode of formation.

Mammalian Fe-S cluster biogenesis and its implication in disease.

PubMed

Beilschmidt, Lena K; Puccio, Hélène M

2014-05-01

Iron-sulfur (Fe-S) clusters are inorganic cofactors that are ubiquitous and essential. Due to their chemical versatility, Fe-S clusters are implicated in a wide range of protein functions including mitochondrial respiration and DNA repair. Composed of iron and sulfur, they are sensible to oxygen and their biogenesis requires a highly conserved protein machinery that facilitates assembly of the cluster as well as its insertion into apoproteins. Mitochondria are the central cellular compartment for Fe-S cluster biogenesis in eukaryotic cells and the importance of proper function of this biogenesis for life is highlighted by a constantly increasing number of human genetic diseases that are associated with dysfunction of this Fe-S cluster biogenesis pathway. Although these disorders are rare and appear dissimilar, common aspects are found among them. This review will give an overview on what is known on mammalian Fe-S cluster biogenesis today, by putting it into the context of what is known from studies from lower model organisms, and focuses on the associated diseases, by drawing attention to the respective mutations. Finally, it outlines the importance of adequate cellular and murine models to uncover not only each protein function, but to resolve their role and requirement throughout the mammalian organism. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Biological and Nano-Technological Applications of Artificial DNAs Made Exclusively of Nonnatural C-Nucleosides with Four Types of Nonnatural Bases

DTIC Science & Technology

2011-08-19

A) CD, (B) UV, (C) Tm, and (D) titration experiments of d(iG*)8/d(C)8. d(T/A*/T)n WC WC
 d(T/A/T)n Watson – Crick (WC)
 Hoogsteen
 Symmetrical A...base Figure 7. Triplex formation of the natural T/A/T which has one Watson - Crick (WC)-type and one Hoogsteen-type hydrogen-bondings, and the...Final Report for AOARD Grant FA2386-10-1-4033 “Biological and Nano-technological Applications of Artificial DNAs Made Exclusively of Nonnatutal C

Memristor emulator causes dissimilarity on a coupled memristive systems

NASA Astrophysics Data System (ADS)

Sabarathinam, S.; Prasad, Awadhesh

2018-04-01

The memristor is known as abasic fourth passive solid state circuit element. Itgaining increasing attention to create the next generation electronic devices commonly used as fundamental chaotic circuit although often arbitrary (typically piecewise linear or cubic) fluxcharge characteristics. In thispresent work, the causes of the memristor emulator studied in a coupled memristive chaoticoscillator for the first time. We confirm that the emulator that allows synchronization between theoscillators and cause the dissimilarity between the systems when increasing the couplingstrength, and co-efficient of the memristor emulator. The detailed statistical analysis was performed to confirm such phenomenon.

The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto Rican Health Study

USDA-ARS?s Scientific Manuscript database

The APOA1/C3/A4/A5 cluster encodes key regulators of plasma lipids. Interactions between dietary factors and single nucleotide polymorphisms (SNPs) in the cluster have been reported. Allostatic load, or physiological dysregulation in response to stress, has been implicated in shaping health disparit...

Neutrino masses, neutrino oscillations, and cosmological implications

NASA Technical Reports Server (NTRS)

Stecker, F. W.

1982-01-01

Theoretical concepts and motivations for considering neutrinos having finite masses are discussed and the experimental situation on searches for neutrino masses and oscillations is summarized. The solar neutrino problem, reactor, deep mine and accelerator data, tri decay experiments and double beta-decay data are considered and cosmological implications and astrophysical data relating to neutrino masses are reviewed. The neutrino oscillation solution to the solar neutrino problem, the missing mass problem in galaxy halos and galaxy cluster galaxy formation and clustering, and radiative neutrino decay and the cosmic ultraviolet background radiation are examined.

Dark matter and the equivalence principle

NASA Technical Reports Server (NTRS)

Frieman, Joshua A.; Gradwohl, Ben-Ami

1991-01-01

If the dark matter in galaxies and clusters is nonbaryonic, it can interact with additional long-range fields that are invisible to experimental tests of the equivalence principle. The astrophysical and cosmological implications of a long-range force coupled only to the dark matter are discussed and rather tight constraints on its strength are found. If the force is repulsive (attractive), the masses of galaxy groups and clusters (and the mean density of the universe inferred from them) have been systematically underestimated (overestimated). Such an interaction also has unusual implications for the growth of large-scale structure.

Implications of a possible clustering of highest-energy cosmic rays

PubMed Central

Sigl, Günter; Schramm, David N.; Lee, Sangjin; Hill, Christopher T.

1997-01-01

Recently, a possible clustering of a subset of observed ultra-high energy cosmic rays above ≃40 EeV (4 × 1019 eV) in pairs near the supergalactic plane was reported. We show that a confirmation of this effect would provide information on the origin and nature of these events and, in case of charged primaries, imply interesting constraints on the extragalactic magnetic field. Possible implications for the most common models of ultra-high energy cosmic ray production in the literature are discussed. PMID:11038576

Are Large Core Radius Clusters Merging Systems?

NASA Technical Reports Server (NTRS)

Forman, William R.

1997-01-01

We have analyzed observations for two lensing clusters of galaxies, A1689 and A2218. Our investigations have explored the implications of their X-ray properties for mass determinations both in X-rays and through both weak and strong gravitational lensing. The work on these two clusters is summarized below and copies of the two papers submitted to the Astrophysical Journal and accepted for publication are attached.

A Taxonomic Approach to the Gestalt Theory of Perls

ERIC Educational Resources Information Center

Raming, Henry E.; Frey, David H.

1974-01-01

This study applied content analysis and cluster analysis to the ideas of Fritz Perls to develop a taxonomy of Gestalt processes and goals. Summaries of the typal groups or clusters were written and the implications of taxonomic research in counseling discussed. (Author)

Active Galactic Nucleus Feedback with the Square Kilometre Array and Implications for Cluster Physics and Cosmology

NASA Astrophysics Data System (ADS)

Iqbal, Asif; Kale, Ruta; Majumdar, Subhabrata; Nath, Biman B.; Pandge, Mahadev; Sharma, Prateek; Malik, Manzoor A.; Raychaudhury, Somak

2017-12-01

Active Galactic Nuclei (AGN) feedback is regarded as an important non-gravitational process in galaxy clusters, providing useful constraints on large-scale structure formation. It modifies the structure and energetics of the intra-cluster medium (ICM) and hence its understanding is crucially needed in order to use clusters as high precision cosmological probes. In this context, particularly keeping in mind the upcoming high quality radio data expected from radio surveys like Square Kilometre Array (SKA) with its higher sensitivity, high spatial and spectral resolutions, we review our current understanding of AGN feedback, its cosmological implications and the impact that SKA can have in revolutionizing our understanding of AGN feedback in large-scale structures. Recent developments regarding the AGN outbursts and its possible contribution to excess entropy in the hot atmospheres of groups and clusters, its correlation with the feedback energy in ICM, quenching of cooling flows and the possible connection between cool core clusters and radio mini-halos, are discussed. We describe current major issues regarding modeling of AGN feedback and its impact on the surrounding medium. With regard to the future of AGN feedback studies, we examine the possible breakthroughs that can be expected from SKA observations. In the context of cluster cosmology, for example, we point out the importance of SKA observations for cluster mass calibration by noting that most of z>1 clusters discovered by eROSITA X-ray mission can be expected to be followed up through a 1000 hour SKA1-mid programme. Moreover, approximately 1000 radio mini halos and ˜ 2500 radio halos at z<0.6 can be potentially detected by SKA1 and SKA2 and used as tracers of galaxy clusters and determination of cluster selection function.

Carbinolamine Formation and Dehydration in a DNA Repair Enzyme Active Site

PubMed Central

Dodson, M. L.; Walker, Ross C.; Lloyd, R. Stephen

2012-01-01

In order to suggest detailed mechanistic hypotheses for the formation and dehydration of a key carbinolamine intermediate in the T4 pyrimidine dimer glycosylase (T4PDG) reaction, we have investigated these reactions using steered molecular dynamics with a coupled quantum mechanics–molecular mechanics potential (QM/MM). We carried out simulations of DNA abasic site carbinolamine formation with and without a water molecule restrained to remain within the active site quantum region. We recovered potentials of mean force (PMF) from thirty replicate reaction trajectories using Jarzynski averaging. We demonstrated feasible pathways involving water, as well as those independent of water participation. The water–independent enzyme–catalyzed reaction had a bias–corrected Jarzynski–average barrier height of approximately for the carbinolamine formation reaction and ) for the reverse reaction at this level of representation. When the proton transfer was facilitated with an intrinsic quantum water, the barrier height was approximately in the forward (formation) reaction and for the reverse. In addition, two modes of unsteered (free dynamics) carbinolamine dehydration were observed: in one, the quantum water participated as an intermediate proton transfer species, and in the other, the active site protonated glutamate hydrogen was directly transferred to the carbinolamine oxygen. Water–independent unforced proton transfer from the protonated active site glutamate carboxyl to the unprotonated N–terminal amine was also observed. In summary, complex proton transfer events, some involving water intermediates, were studied in QM/MM simulations of T4PDG bound to a DNA abasic site. Imine carbinolamine formation was characterized using steered QM/MM molecular dynamics. Dehydration of the carbinolamine intermediate to form the final imine product was observed in free, unsteered, QM/MM dynamics simulations, as was unforced acid-base transfer between the active site carboxylate and the N–terminal amine. PMID:22384015

Abasic Phosphorothioate Oligomers Inhibit HIV-1 Reverse Transcription and Block Virus Transmission across Polarized Ectocervical Organ Cultures

PubMed Central

Fraietta, Joseph A.; Mueller, Yvonne M.; Lozenski, Karissa L.; Ratner, Deena; Boesteanu, Alina C.; Hancock, Aidan S.; Lackman-Smith, Carol; Zentner, Isaac J.; Chaiken, Irwin M.; Chung, Suhman; LeGrice, Stuart F. J.; Snyder, Beth A.; Mankowski, Marie K.; Jones, Natalie M.; Hope, Jennifer L.; Gupta, Phalguni; Anderson, Sharon H.; Wigdahl, Brian

2014-01-01

In the absence of universally available antiretroviral (ARV) drugs or a vaccine against HIV-1, microbicides may offer the most immediate hope for controlling the AIDS pandemic. The most advanced and clinically effective microbicides are based on ARV agents that interfere with the earliest stages of HIV-1 replication. Our objective was to identify and characterize novel ARV-like inhibitors, as well as demonstrate their efficacy at blocking HIV-1 transmission. Abasic phosphorothioate 2′ deoxyribose backbone (PDB) oligomers were evaluated in a variety of mechanistic assays and for their ability to inhibit HIV-1 infection and virus transmission through primary human cervical mucosa. Cellular and biochemical assays were used to elucidate the antiviral mechanisms of action of PDB oligomers against both lab-adapted and primary CCR5- and CXCR4-utilizing HIV-1 strains, including a multidrug-resistant isolate. A polarized cervical organ culture was used to test the ability of PDB compounds to block HIV-1 transmission to primary immune cell populations across ectocervical tissue. The antiviral activity and mechanisms of action of PDB-based compounds were dependent on oligomer size, with smaller molecules preventing reverse transcription and larger oligomers blocking viral entry. Importantly, irrespective of molecular size, PDBs potently inhibited virus infection and transmission within genital tissue samples. Furthermore, the PDB inhibitors exhibited excellent toxicity and stability profiles and were found to be safe for vaginal application in vivo. These results, coupled with the previously reported intrinsic anti-inflammatory properties of PDBs, support further investigations in the development of PDB-based topical microbicides for preventing the global spread of HIV-1. PMID:25224013

Pharmaceutical analysis of synthetic lipid A-based vaccine adjuvants in poly (D,L-lactic-co-glycolic acid) nanoparticle formulations.

PubMed

Hamdy, Samar; Haddadi, Azita; Somayaji, Vishwa; Ruan, David; Samuel, John

2007-08-15

The present study had two main objectives. First, was to compare the immune stimulatory effect of two synthetic lipid A analogues (7-acyl lipid A and pentaerythritol-based lipid A (PET lipid A)) on maturation/stimulation of bone marrow derived dendritic cells (DCs). Our second objective was to develop a liquid chromatography/mass spectrometry (LC-MS) method for the quantitative analysis of lipid A-based vaccine adjuvants. Treatment of immature DCs with 7-acyl lipid A and PET lipid A up regulated the surface expression of CD86 and CD40 molecules, and also induced similar profile of pro-inflammatory cytokine secretion. LC-MS analyses were performed using a Waters Micromass ZQ 4000 spectrometer, coupled to a Waters 2795 separations module with an autosampler. Calibration curves with R(2)>0.999 were constructed over the concentration range of 1.25-20 microg/ml for the solution of 7-acyl lipid A and PET lipid A. The method was tested in a 3 day validation protocol. The accuracy of the assay at different concentrations tested ranged from 89 to 108% and from 92 to 107% for 7-acyl lipid A and PET lipid A, respectively. The limit of quantification for both 7-acyl lipid A and PET lipid A was 1.25 microg/ml (signal/noise (S/N)) ratio >15:1. The sensitivity of the method (the limit of detection) was 0.35 and 0.15 ng for 7-acyl lipid A and PET lipid A, respectively (S/N ratio between 4:1 or 3:1). As a preliminary application, this method has been successfully applied to the determination of 7-acyl lipid A and PET lipid A content in poly (D,L-lactic-co-glycolic acid) nanoparticles (PLGA-NP).

Chemical repair of base lesions, AP-sites, and strand breaks on plasmid DNA in dilute aqueous solution by ascorbic acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hata, Kuniki; Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakatashirane, Tokai-mura, Naka-gun, Ibaraki 319-1195; Urushibara, Ayumi

Highlights: •We report a novel mechanism of radiation protection of DNA by chemical activity of ascorbic acid. •The “chemical repair” of DNA damage was revealed using biochemical assay and chemical kinetics analysis. •We found that ascorbic acid significantly repairs precursors of nucleobase lesions and abasic sites. •However, ascorbic acid seldom repairs precursors of DNA-strand breaks. -- Abstract: We quantified the damage yields produced in plasmid DNA by γ-irradiation in the presence of low concentrations (10–100 μM) of ascorbic acid, which is a major antioxidant in living systems, to clarify whether it chemically repairs radiation damage in DNA. The yield ofmore » DNA single strand breaks induced by irradiation was analyzed with agarose gel electrophoresis as conformational changes in closed circular plasmids. Base lesions and abasic sites were also observed as additional conformational changes by treating irradiated samples with glycosylase proteins. By comparing the suppression efficiencies to the induction of each DNA lesion, in addition to scavenging of the OH radicals derived from water radiolysis, it was found that ascorbic acid promotes the chemical repair of precursors of AP-sites and base lesions more effectively than those of single strand breaks. We estimated the efficiency of the chemical repair of each lesion using a kinetic model. Approximately 50–60% of base lesions and AP-sites were repaired by 10 μM ascorbic acid, although strand breaks were largely unrepaired by ascorbic acid at low concentrations. The methods in this study will provide a route to understanding the mechanistic aspects of antioxidant activity in living systems.« less

Kinetic mechanism and fidelity of nick sealing by Escherichia coli NAD+-dependent DNA ligase (LigA)

PubMed Central

Chauleau, Mathieu; Shuman, Stewart

2016-01-01

Escherichia coli DNA ligase (EcoLigA) repairs 3′-OH/5′-PO4 nicks in duplex DNA via reaction of LigA with NAD+ to form a covalent LigA-(lysyl-Nζ)–AMP intermediate (step 1); transfer of AMP to the nick 5′-PO4 to form an AppDNA intermediate (step 2); and attack of the nick 3′-OH on AppDNA to form a 3′-5′ phosphodiester (step 3). A distinctive feature of EcoLigA is its stimulation by ammonium ion. Here we used rapid mix-quench methods to analyze the kinetic mechanism of single-turnover nick sealing by EcoLigA–AMP. For substrates with correctly base-paired 3′-OH/5′-PO4 nicks, kstep2 was fast (6.8–27 s−1) and similar to kstep3 (8.3–42 s−1). Absent ammonium, kstep2 and kstep3 were 48-fold and 16-fold slower, respectively. EcoLigA was exquisitely sensitive to 3′-OH base mispairs and 3′ N:abasic lesions, which elicited 1000- to >20000-fold decrements in kstep2. The exception was the non-canonical 3′ A:oxoG configuration, which EcoLigA accepted as correctly paired for rapid sealing. These results underscore: (i) how EcoLigA requires proper positioning of the nick 3′ nucleoside for catalysis of 5′ adenylylation; and (ii) EcoLigA's potential to embed mutations during the repair of oxidative damage. EcoLigA was relatively tolerant of 5′-phosphate base mispairs and 5′ N:abasic lesions. PMID:26857547

Structural and thermodynamic analysis of modified nucleosides in self-assembled DNA cross-tiles.

PubMed

Hakker, Lauren; Marchi, Alexandria N; Harris, Kimberly A; LaBean, Thomas H; Agris, Paul F

2014-01-01

DNA Holliday junctions are important natural strand-exchange structures that form during homologous recombination. Immobile four-arm junctions, analogs to Holliday junctions, have been designed to self-assemble into cross-tile structures by maximizing Watson-Crick base pairing and fixed crossover points. The cross-tiles, self-assembled from base pair recognition between designed single-stranded DNAs, form higher order lattice structures through cohesion of self-associating sticky ends. These cross-tiles have 16 unpaired nucleosides in the central loop at the junction of the four duplex stems. The importance of the centralized unpaired nucleosides to the structure's thermodynamic stability and self-assembly is unknown. Cross-tile DNA nanostructures were designed and constructed from nine single-stranded DNAs with four shell strands, four arms, and a central loop containing 16 unpaired bases. The 16 unpaired bases were either 2'-deoxyribothymidines, 2'-O-methylribouridines, or abasic 1',2'-dideoxyribonucleosides. Thermodynamic profiles and structural base-stacking contributions were assessed using UV absorption spectroscopy during thermal denaturation and circular dichroism spectroscopy, respectively, and the resulting structures were observed by atomic force microscopy. There were surprisingly significant changes in the thermodynamic and structural properties of lattice formation as a result of altering only the 16 unpaired, centralized nucleosides. The 16 unpaired 2'-O-methyluridines were stabilizing and produced uniform tubular structures. In contrast, the abasic nucleosides were destabilizing producing a mixture of structures. These results strongly indicate the importance of a small number of centrally located unpaired nucleosides within the structures. Since minor modifications lead to palpable changes in lattice formation, DNA cross-tiles present an easily manipulated structure convenient for applications in biomedical and biosensing devices.

Embedded Clusters

NASA Astrophysics Data System (ADS)

Ascenso, Joana

The past decade has seen an increase of star formation studies made at the molecular cloud scale, motivated mostly by the deployment of a wealth of sensitive infrared telescopes and instruments. Embedded clusters, long recognised as the basic units of coherent star formation in molecular clouds, are now seen to inhabit preferentially cluster complexes tens of parsecs across. This chapter gives an overview of some important properties of the embedded clusters in these complexes and of the complexes themselves, along with the implications of viewing star formation as a molecular-cloud scale process rather than an isolated process at the scale of clusters.

Segmenting Student Markets with a Student Satisfaction and Priorities Survey.

ERIC Educational Resources Information Center

Borden, Victor M. H.

1995-01-01

A market segmentation analysis of 872 university students compared 2 hierarchical clustering procedures for deriving market segments: 1 using matching-type measures and an agglomerative clustering algorithm, and 1 using the chi-square based automatic interaction detection. Results and implications for planning, evaluating, and improving academic…

The Implications of "Contamination" for Experimental Design in Education

ERIC Educational Resources Information Center

Rhoads, Christopher H.

2011-01-01

Experimental designs that randomly assign entire clusters of individuals (e.g., schools and classrooms) to treatments are frequently advocated as a way of guarding against contamination of the estimated average causal effect of treatment. However, in the absence of contamination, experimental designs that randomly assign intact clusters to…

Multimorbidity and health-related quality of life (HRQoL) in a nationally representative population sample: implications of count versus cluster method for defining multimorbidity on HRQoL.

PubMed

Wang, Lili; Palmer, Andrew J; Cocker, Fiona; Sanderson, Kristy

2017-01-09

No universally accepted definition of multimorbidity (MM) exists, and implications of different definitions have not been explored. This study examined the performance of the count and cluster definitions of multimorbidity on the sociodemographic profile and health-related quality of life (HRQoL) in a general population. Data were derived from the nationally representative 2007 Australian National Survey of Mental Health and Wellbeing (n = 8841). The HRQoL scores were measured using the Assessment of Quality of Life (AQoL-4D) instrument. The simple count (2+ & 3+ conditions) and hierarchical cluster methods were used to define/identify clusters of multimorbidity. Linear regression was used to assess the associations between HRQoL and multimorbidity as defined by the different methods. The assessment of multimorbidity, which was defined using the count method, resulting in the prevalence of 26% (MM2+) and 10.1% (MM3+). Statistically significant clusters identified through hierarchical cluster analysis included heart or circulatory conditions (CVD)/arthritis (cluster-1, 9%) and major depressive disorder (MDD)/anxiety (cluster-2, 4%). A sensitivity analysis suggested that the stability of the clusters resulted from hierarchical clustering. The sociodemographic profiles were similar between MM2+, MM3+ and cluster-1, but were different from cluster-2. HRQoL was negatively associated with MM2+ (β: -0.18, SE: -0.01, p < 0.001), MM3+ (β: -0.23, SE: -0.02, p < 0.001), cluster-1 (β: -0.10, SE: 0.01, p < 0.001) and cluster-2 (β: -0.36, SE: 0.01, p < 0.001). Our findings confirm the existence of an inverse relationship between multimorbidity and HRQoL in the Australian population and indicate that the hierarchical clustering approach is validated when the outcome of interest is HRQoL from this head-to-head comparison. Moreover, a simple count fails to identify if there are specific conditions of interest that are driving poorer HRQoL. Researchers should exercise caution when selecting a definition of multimorbidity because it may significantly influence the study outcomes.

Making Sense of Cluster Analysis: Revelations from Pakistani Science Classes

ERIC Educational Resources Information Center

Pell, Tony; Hargreaves, Linda

2011-01-01

Cluster analysis has been applied to quantitative data in educational research over several decades and has been a feature of the Maurice Galton's research in primary and secondary classrooms. It has offered potentially useful insights for teaching yet its implications for practice are rarely implemented. It has been subject also to negative…

Sleep, Dietary, and Exercise Behavioral Clusters among Truck Drivers with Obesity: Implications for Interventions

PubMed Central

Olson, Ryan; Thompson, Sharon V.; Wipfli, Brad; Hanson, Ginger; Elliot, Diane L.; Anger, W. Kent; Bodner, Todd; Hammer, Leslie B.; Hohn, Elliot; Perrin, Nancy A.

2015-01-01

Objective Our objectives were to describe a sample of truck drivers, identify clusters of drivers with similar patterns in behaviors affecting energy balance (sleep, diet, and exercise), and test for cluster differences in health and psychosocial factors. Methods Participants’ (n=452, BMI M=37.2, 86.4% male) self-reported behaviors were dichotomized prior to hierarchical cluster analysis, which identified groups with similar behavior co-variation. Cluster differences were tested with generalized estimating equations. Results Five behavioral clusters were identified that differed significantly in age, smoking status, diabetes prevalence, lost work days, stress, and social support, but not in BMI. Cluster 2, characterized by the best sleep quality, had significantly lower lost workdays and stress than other clusters. Conclusions Weight management interventions for drivers should explicitly address sleep, and may be maximally effective after establishing socially supportive work environments that reduce stress exposures. PMID:26949883

Kinetics of carbon clustering in detonation of high explosives: Does theory match experiment?

NASA Astrophysics Data System (ADS)

Velizhanin, Kirill; Watkins, Erik; Dattelbaum, Dana; Gustavsen, Richard; Aslam, Tariq; Podlesak, David; Firestone, Millicent; Huber, Rachel; Ringstrand, Bryan; Willey, Trevor; Bagge-Hansen, Michael; Hodgin, Ralph; Lauderbach, Lisa; van Buuren, Tony; Sinclair, Nicholas; Rigg, Paulo; Seifert, Soenke; Gog, Thomas

2017-06-01

Chemical reactions in detonation of carbon-rich high explosives yield carbon clusters as major constituents of the products. Efforts to model carbon clustering as a diffusion-limited irreversible coagulation of carbon clusters go back to the seminal paper by Shaw and Johnson. However, first direct experimental observations of the kinetics of clustering yielded cluster growth one to two orders of magnitude slower than theoretical predictions. Multiple efforts were undertaken to test and revise the basic assumptions of the model in order to achieve better agreement with experiment. We discuss our very recent direct experimental observations of carbon clustering dynamics and demonstrate that these new results are in much better agreement with the modified Shaw-Johnson model. The implications of this much better agreement on our present understanding of detonation carbon clustering processes and possible ways to increase the agreement between theory and experiment even further are discussed.

Sleep, Dietary, and Exercise Behavioral Clusters Among Truck Drivers With Obesity: Implications for Interventions.

PubMed

Olson, Ryan; Thompson, Sharon V; Wipfli, Brad; Hanson, Ginger; Elliot, Diane L; Anger, W Kent; Bodner, Todd; Hammer, Leslie B; Hohn, Elliot; Perrin, Nancy A

2016-03-01

The objectives of the study were to describe a sample of truck drivers, identify clusters of drivers with similar patterns in behaviors affecting energy balance (sleep, diet, and exercise), and test for cluster differences in health safety, and psychosocial factors. Participants' (n = 452, body mass index M = 37.2, 86.4% male) self-reported behaviors were dichotomized prior to hierarchical cluster analysis, which identified groups with similar behavior covariation. Cluster differences were tested with generalized estimating equations. Five behavioral clusters were identified that differed significantly in age, smoking status, diabetes prevalence, lost work days, stress, and social support, but not in body mass index. Cluster 2, characterized by the best sleep quality, had significantly lower lost workdays and stress than other clusters. Weight management interventions for drivers should explicitly address sleep, and may be maximally effective after establishing socially supportive work environments that reduce stress exposures.

Clustering cancer gene expression data by projective clustering ensemble

PubMed Central

Yu, Xianxue; Yu, Guoxian

2017-01-01

Gene expression data analysis has paramount implications for gene treatments, cancer diagnosis and other domains. Clustering is an important and promising tool to analyze gene expression data. Gene expression data is often characterized by a large amount of genes but with limited samples, thus various projective clustering techniques and ensemble techniques have been suggested to combat with these challenges. However, it is rather challenging to synergy these two kinds of techniques together to avoid the curse of dimensionality problem and to boost the performance of gene expression data clustering. In this paper, we employ a projective clustering ensemble (PCE) to integrate the advantages of projective clustering and ensemble clustering, and to avoid the dilemma of combining multiple projective clusterings. Our experimental results on publicly available cancer gene expression data show PCE can improve the quality of clustering gene expression data by at least 4.5% (on average) than other related techniques, including dimensionality reduction based single clustering and ensemble approaches. The empirical study demonstrates that, to further boost the performance of clustering cancer gene expression data, it is necessary and promising to synergy projective clustering with ensemble clustering. PCE can serve as an effective alternative technique for clustering gene expression data. PMID:28234920

Role of Hydrophobic Clusters and Long-Range Contact Networks in the Folding of (α/β)8 Barrel Proteins

PubMed Central

Selvaraj, S.; Gromiha, M. Michael

2003-01-01

Analysis on the three dimensional structures of (α/β)8 barrel proteins provides ample light to understand the factors that are responsible for directing and maintaining their common fold. In this work, the hydrophobically enriched clusters are identified in 92% of the considered (α/β)8 barrel proteins. The residue segments with hydrophobic clusters have high thermal stability. Further, these clusters are formed and stabilized through long-range interactions. Specifically, a network of long-range contacts connects adjacent β-strands of the (α/β)8 barrel domain and the hydrophobic clusters. The implications of hydrophobic clusters and long-range networks in providing a feasible common mechanism for the folding of (α/β)8 barrel proteins are proposed. PMID:12609894

Implications of Pearl, Gold, Silver (PGS) craft industrial cluster towards settlements region in Karang Pule Village, Sekarbela District Of Mataram City

NASA Astrophysics Data System (ADS)

Sushanti, I. R.; Fitri, I. S.

2017-06-01

The existence of industry clusters in Mataram City gave effect to the surrounding residential areas [1]. In accordance Spatial Plan of Mataram City in 2011-2031 PGS industry cluster in the village of Karang Pule, Sekarbela district established as shopping tourism area. Distribution of industrial locations were in four of seven environments in Karang Pule. Distribution of PGS industry is divided into three (3) groups: craftsmen, craftsmen who is also a seller, and the seller (merchant). The location of the craftsmen, craftsmen who are also businessmen and entrepreneurs are also used as a dwelling house or workshop and store. So most of the people living in settlements around clusters of industry that there is a link between industry cluster and settlements. This study aims to determine the implications or the impact of the presence of PGS industry clusters the surrounding residential areas. The method used in this research is descriptive qualitative with the collection of primary data through direct observation and questionnaires. Based on direct observation on the shopping tourism area there are inequality between the conditions of industry clusters and settlements area by the presence of slums. The results showed that the PGS industry cluster impact on social, economic and environment near settlements area. Impacts that occur are: 1) the social aspect, there is a significant change in the level of education, social welfare and social disparities but less significant to the formation of institutions, particularly in community participation, 2) the economic aspect of the change status of community work, and increased revenue and 3) the environmental aspects of the change to the condition of the building, the quality of public housing, the presence of slums, changes in infrastructure and the environmental pollution.

MicroRNA-17-92 cluster promotes the proliferation and the chemokine production of keratinocytes: implication for the pathogenesis of psoriasis.

PubMed

Zhang, Weigang; Yi, Xiuli; An, Yawen; Guo, Sen; Li, Shuli; Song, Pu; Chang, Yuqian; Zhang, Shaolong; Gao, Tianwen; Wang, Gang; Li, Chunying

2018-05-11

Keratinocytes are the main epidermal cell type that constitutes the skin barrier against environmental damages, which emphasizes the balance between the growth and the death of keratinocytes in maintaining skin homeostasis. Aberrant proliferation of keratinocytes and the secretion of inflammatory factors from keratinocytes are related to the formation of chronic inflammatory skin diseases like psoriasis. MicroRNA-17-92 (miRNA-17-92 or miR-17-92) is a miRNA cluster that regulates cell growth and immunity, but the role of miR-17-92 cluster in keratinocytes and its relation to skin diseases have not been well investigated. In the present study, we initially found that miR-17-92 cluster promoted the proliferation and the cell-cycle progression of keratinocytes via suppressing cyclin-dependent kinase inhibitor 2B (CDKN2B). Furthermore, miR-17-92 cluster facilitated the secretion of C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10) from keratinocytes by inhibiting suppressor of cytokine signaling 1 (SOCS1), which enhanced the chemotaxis for T lymphocytes formed by keratinocytes. In addition, we detected increased expression of miR-17-92 cluster in psoriatic lesions and the level of lesional miR-17-92 cluster was positively correlated with the disease severity in psoriasis patients. At last, miR-17-92 cluster was increased in keratinocytes by cytokines through the activation of signal transducers and activators of transcription 1 (STAT1) signaling pathway. Our findings demonstrate that cytokine-induced overexpression of miR-17-92 cluster can promote the proliferation and the immune function of keratinocytes, and thus may contribute to the development of inflammatory skin diseases like psoriasis, which implicates miR-17-92 cluster as a potential therapeutic target for psoriasis and other skin diseases with similar inflammatory pathogenesis.

Sonority and Cross-Linguistic Acquisition of Initial S-Clusters

ERIC Educational Resources Information Center

Yavas, Mehmet; Ben-David, Avivit; Gerrits, Ellen; Kristoffersen, Kristian E.; Simonsen, Hanne G.

2008-01-01

This paper examines the findings and implications of the cross-linguistic acquisition of #sC clusters in relation to sonority patterns. Data from individual studies on English, Dutch, Norwegian, and Hebrew are compared for accuracy of production as well as the reductions with respect to potential differences across subtypes of #sC groups. In all…

[Time for cluster C personality disorders: state of the art].

PubMed

Hutsebaut, J; Willemsen, E M C; Van, H L

Compared to cluster B personality disorders, the assessment and treatment of people with obsessive-compulsive, dependent, and avoidant personality disorders (cluster C) is given little attention in the field of research and clinical practice. Presenting the current state of affairs in regard to cluster C personality disorders. A systematic literature search was conducted using the main data bases. Cluster C personality disorders are present in approximately 3-9% of the general population. In about half of the cases of mood, anxiety, and eating disorders, there is co-morbid cluster C pathology. This has a major influence on the progression of symptoms, treatment effectiveness and potential relapse. There are barely any well conducted randomized studies on the treatment of cluster-C in existence. Open cohort studies, however, show strong, lasting treatment effects. Given the frequent occurrence of cluster C personality disorders, the burden of disease, associated societal costs and the prognostic implications in case of a co-morbid cluster C personality disorder, early detection and treatment of these disorders is warranted.

Photo-induced transformation process at gold clusters-semiconductor interface: Implications for the complexity of gold clusters-based photocatalysis

NASA Astrophysics Data System (ADS)

Liu, Siqi; Xu, Yi-Jun

2016-03-01

The recent thrust in utilizing atomically precise organic ligands protected gold clusters (Au clusters) as photosensitizer coupled with semiconductors for nano-catalysts has led to the claims of improved efficiency in photocatalysis. Nonetheless, the influence of photo-stability of organic ligands protected-Au clusters at the Au/semiconductor interface on the photocatalytic properties remains rather elusive. Taking Au clusters-TiO2 composites as a prototype, we for the first time demonstrate the photo-induced transformation of small molecular-like Au clusters to larger metallic Au nanoparticles under different illumination conditions, which leads to the diverse photocatalytic reaction mechanism. This transformation process undergoes a diffusion/aggregation mechanism accompanied with the onslaught of Au clusters by active oxygen species and holes resulting from photo-excited TiO2 and Au clusters. However, such Au clusters aggregation can be efficiently inhibited by tuning reaction conditions. This work would trigger rational structural design and fine condition control of organic ligands protected-metal clusters-semiconductor composites for diverse photocatalytic applications with long-term photo-stability.

DISCOVERY OF A DISSOCIATIVE GALAXY CLUSTER MERGER WITH LARGE PHYSICAL SEPARATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dawson, William A.; Wittman, David; Jee, M. James

2012-03-10

We present DLSCL J0916.2+2951 (z = 0.53), a newly discovered major cluster merger in which the collisional cluster gas has become dissociated from the collisionless galaxies and dark matter (DM). We identified the cluster using optical and weak-lensing observations as part of the Deep Lens Survey. Our follow-up observations with Keck, Subaru, Hubble Space Telescope, and Chandra show that the cluster is a dissociative merger and constrain the DM self-interaction cross-section {sigma}{sub DM} m{sup -1}{sub DM} {approx}< 7 cm{sup 2} g{sup -1}. The system is observed at least 0.7 {+-} 0.2 Gyr since first pass-through, thus providing a picture ofmore » cluster mergers 2-5 times further progressed than similar systems observed to date. This improved temporal leverage has implications for our understanding of merging clusters and their impact on galaxy evolution.« less

Towards Effective Clustering Techniques for the Analysis of Electric Power Grids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hogan, Emilie A.; Cotilla Sanchez, Jose E.; Halappanavar, Mahantesh

2013-11-30

Clustering is an important data analysis technique with numerous applications in the analysis of electric power grids. Standard clustering techniques are oblivious to the rich structural and dynamic information available for power grids. Therefore, by exploiting the inherent topological and electrical structure in the power grid data, we propose new methods for clustering with applications to model reduction, locational marginal pricing, phasor measurement unit (PMU or synchrophasor) placement, and power system protection. We focus our attention on model reduction for analysis based on time-series information from synchrophasor measurement devices, and spectral techniques for clustering. By comparing different clustering techniques onmore » two instances of realistic power grids we show that the solutions are related and therefore one could leverage that relationship for a computational advantage. Thus, by contrasting different clustering techniques we make a case for exploiting structure inherent in the data with implications for several domains including power systems.« less

Profiles of behavioral problems in children who witness domestic violence.

PubMed

Spilsbury, James C; Kahana, Shoshana; Drotar, Dennis; Creeden, Rosemary; Flannery, Daniel J; Friedman, Steve

2008-01-01

Unlike previous investigations of shelter-based samples, our study examined whether profiles of adjustment problems occurred in a community-program-based sample of 175 school-aged children exposed to domestic violence. Cluster analysis revealed three stable profiles/clusters. The largest cluster (69%) consisted of children below clinical thresholds for any internalizing or externalizing problem. Children in the next largest cluster (18%) were characterized as having externalizing problems with or without internalizing problems. The smallest cluster (13%) consisted of children with internalizing problems only. Comparison across demographic and violence characteristics revealed that the profiles differed by child gender, mother's education, child's lifetime exposure to violence, and aspects of the event precipitating contact with the community program. Clinical and future research implications of study findings are discussed.

ASCA Temperature Maps for Merging and Relaxed Clusters and Physics of the Cluster Gas

NASA Technical Reports Server (NTRS)

Markevitch, M.; Sarazin, C.; Nevalainen, J.; Vikhlinin, A.; Forman, W.

1999-01-01

ASCA temperature maps for several galaxy clusters undergoing strong mergers will be presented. From these maps, it is possible to estimate velocities of the colliding subclusters. I will discuss several interesting implications of these estimates for the physics of the cluster gas and the shape of the gravitational potential. I will also present temperature maps and profiles for several relaxed clusters selected for X-ray mass determination, and present the mass values derived without the assumption of isothermality. The accurate mass-temperature and luminosity-temperature relations will be discussed. This talk will review how AXAF will revolutionize X-ray astronomy through its radically better imaging and spectroscopic resolution. Examples from many fields of astrophysics will be given.

The Student-Teacher Relationship Quality of Abused Children

PubMed Central

Haskett, Mary E.; Hawkins, Amy L.

2016-01-01

Considering the association between children’s quality of relationships with teachers and their academic adjustment, information pertaining to how abused children are functioning in their relationships with teachers could be useful in promoting their academic success— yet there has been limited research in this area. The purpose of this study was to use cluster analyses to explore within-group differences in relational schemas and quality of student-teacher relationships for 70 abused children. Two clusters of abused children emerged, and as hypothesized, there were significant differences in student-teacher relationships for the two clusters. The cluster with more positive relational schemas had less conflict and less dependency reported by their teachers compared to the cluster with negative relational schemas. However, there were no differences between the clusters in terms of closeness with teachers. Implications for practice in schools is discussed. PMID:28713179

Photo-induced transformation process at gold clusters-semiconductor interface: Implications for the complexity of gold clusters-based photocatalysis

PubMed Central

Liu, Siqi; Xu, Yi-Jun

2016-01-01

The recent thrust in utilizing atomically precise organic ligands protected gold clusters (Au clusters) as photosensitizer coupled with semiconductors for nano-catalysts has led to the claims of improved efficiency in photocatalysis. Nonetheless, the influence of photo-stability of organic ligands protected-Au clusters at the Au/semiconductor interface on the photocatalytic properties remains rather elusive. Taking Au clusters–TiO2 composites as a prototype, we for the first time demonstrate the photo-induced transformation of small molecular-like Au clusters to larger metallic Au nanoparticles under different illumination conditions, which leads to the diverse photocatalytic reaction mechanism. This transformation process undergoes a diffusion/aggregation mechanism accompanied with the onslaught of Au clusters by active oxygen species and holes resulting from photo-excited TiO2 and Au clusters. However, such Au clusters aggregation can be efficiently inhibited by tuning reaction conditions. This work would trigger rational structural design and fine condition control of organic ligands protected-metal clusters-semiconductor composites for diverse photocatalytic applications with long-term photo-stability. PMID:26947754

Peroxynitrite modified DNA presents better epitopes for anti-DNA autoantibodies in diabetes type 1 patients.

PubMed

Tripathi, Prashant; Moinuddin; Dixit, Kiran; Mir, Abdul Rouf; Habib, Safia; Alam, Khursheed; Ali, Asif

2014-07-01

Peroxynitrite (ONOO(-)), formed by the reaction between nitric oxide (NO) and superoxide (O2(-)), has been implicated in the etiology of numerous disease processes. Peroxynitrite interacts with DNA via direct oxidative reactions or via indirect radical-mediated mechanism. It can inflict both oxidative and nitrosative damages on DNA bases, generating abasic sites, resulting in the single strand breaks. Plasmid pUC 18 isolated from Escherichiacoli was modified with peroxynitrite, generated by quenched flow process. Modifications incurred in plasmid DNA were characterized by ultraviolet and fluorescence spectroscopy, circular dichroism, HPLC and melting temperature studies. Binding characteristics and specificity of antibodies from diabetes patients were analyzed by direct binding and inhibition ELISA. Peroxynitrite modification of pUC 18 plasmid resulted in the formation of strand breaks and base modification. The major compound formed when peroxynitrite reacted with DNA was 8-nitroguanine, a specific marker for peroxynitrite induced DNA damage in inflamed tissues. The concentration of 8-nitroguanine was found to be 3.8 μM. Sera from diabetes type 1 patients from different age groups were studied for their binding to native and peroxynitrite modified plasmid. Direct binding and competitive-inhibition ELISA results showed higher recognition of peroxynitrite modified plasmid, as compared to the native form, by auto-antibodies present in diabetes patients. The preferential recognition of modified plasmid by diabetes autoantibodies was further reiterated by gel shift assay. Experimentally induced anti-peroxynitrite-modified plasmid IgG was used as a probe to detect nitrosative lesions in the DNA isolated from diabetes patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Large stability and high catalytic activities of sub-nm metal (0) clusters: implications into the nucleation and growth theory.

PubMed

Piñeiro, Yolanda; Buceta, David; Calvo, Javier; Huseyinova, Shahana; Cuerva, Miguel; Pérez, Ángel; Domínguez, Blanca; López-Quintela, M Arturo

2015-07-01

Clusters are stable catalytic species, which are produced during the synthesis of nanoparticles (NPs). Their existence contradicts the thermodynamic principles used to explain the formation of NPs by the classical nucleation and growth theories (NGTs). Using chemical and electrochemical methods we will show that depending on the experimental conditions one can produce either Ag clusters or Ag NPs. Moreover, using already prepared Ag clusters one can observe the disappearance of the usual induction period observed for the kinetics of NP formation, indicating that clusters catalyze the formation of NPs. Taking these data together with some previous examples of cluster-catalyzed anisotropic growth, we derived a qualitative approach to include the catalytic activities of clusters into the formation of NPs, which is incorporated into the NGT. Some qualitative conclusions about the main experimental parameters, which affect the formation of clusters versus NPs, as well as the catalytic mechanism versus the non-catalytic one, are also described. Copyright © 2015 Elsevier Inc. All rights reserved.

Simultaneous fluorescence light-up and selective multicolor nucleobase recognition based on sequence-dependent strong binding of berberine to DNA abasic site.

PubMed

Wu, Fei; Shao, Yong; Ma, Kun; Cui, Qinghua; Liu, Guiying; Xu, Shujuan

2012-04-28

Label-free DNA nucleobase recognition by fluorescent small molecules has received much attention due to its simplicity in mutation identification and drug screening. However, sequence-dependent fluorescence light-up nucleobase recognition and multicolor emission with individual emission energy for individual nucleobases have been seldom realized. Herein, an abasic site (AP site) in a DNA duplex was employed as a binding field for berberine, one of isoquinoline alkaloids. Unlike weak binding of berberine to the fully matched DNAs without the AP site, strong binding of berberine to the AP site occurs and the berberine's fluorescence light-up behaviors are highly dependent on the target nucleobases opposite the AP site in which the targets thymine and cytosine produce dual emission bands, while the targets guanine and adenine only give a single emission band. Furthermore, more intense emissions are observed for the target pyrimidines than purines. The flanking bases of the AP site also produce some modifications of the berberine's emission behavior. The binding selectivity of berberine at the AP site is also confirmed by measurements of fluorescence resonance energy transfer, excited-state lifetime, DNA melting and fluorescence quenching by ferrocyanide and sodium chloride. It is expected that the target pyrimidines cause berberine to be stacked well within DNA base pairs near the AP site, which results in a strong resonance coupling of the electronic transitions to the particular vibration mode to produce the dual emissions. The fluorescent signal-on and emission energy-modulated sensing for nucleobases based on this fluorophore is substantially advantageous over the previously used fluorophores. We expect that this approach will be developed as a practical device for differentiating pyrimidines from purines by positioning an AP site toward a target that is available for readout by this alkaloid probe. This journal is © The Royal Society of Chemistry 2012

On the Formation and Properties of Interstrand DNA-DNA Cross-links Forged by Reaction of an Abasic Site With the Opposing Guanine Residue of 5′-CAp Sequences in Duplex DNA

PubMed Central

Johnson, Kevin M.; Price, Nathan E.; Wang, Jin; Fekry, Mostafa I.; Dutta, Sanjay; Seiner, Derrick R.; Wang, Yinsheng; Gates, Kent S.

2014-01-01

We recently reported that the aldehyde residue of an abasic (Ap) site in duplex DNA can generate an interstrand cross-link via reaction with a guanine residue on the opposing strand. This finding is intriguing because the highly deleterious nature of interstrand cross-links suggests that even small amounts of Ap-derived cross-links could make a significant contribution to the biological consequences stemming from the generation of Ap sites in cellular DNA. Incubation of 21-bp duplexes containing a central 5′-CAp sequence under conditions of reductive amination (NaCNBH3, pH 5.2) generated much higher yields of cross-linked DNA than reported previously. At pH 7, in the absence of reducing agents, these Ap-containing duplexes also produced cross-linked duplexes that were readily detected on denaturing polyacrylamide gels. Cross-link formation was not highly sensitive to reaction conditions and, once formed, the cross-link was stable to a variety of work-up conditions. Results of multiple experiments including MALDI-TOF mass spectrometry, gel mobility, methoxyamine capping of the Ap aldehyde, inosine-for-guanine replacement, hydroxyl radical footprinting, and LCMS/MS were consistent with a cross-linking mechanism involving reversible reaction of the Ap aldehyde residue with the N2-amino group of the opposing guanine residue in 5′-CAp sequences to generate hemiaminal, imine, or cyclic hemiaminal cross-links (7-10) that were irreversibly converted under conditions of reductive amination (NaCNBH3/pH 5.2) to a stable amine linkage. Further support for the importance of the exocyclic N2-amino group in this reaction was provided by an experiment showing that installation of a 2-aminopurine-thymine base pair at the cross-linking site produced high yields (15-30%) of a cross-linked duplex at neutral pH, in the absence of NaCNBH3. PMID:23215239

The exonuclease activity of hPMC2 is required for transcriptional regulation of the QR gene and repair of estrogen-induced abasic sites.

PubMed

Krishnamurthy, N; Ngam, C R; Berdis, A J; Montano, M M

2011-11-24

We have previously reported that the expression of antioxidative stress enzymes is upregulated by trans-hydroxytamoxifen (TOT) in breast epithelial cell lines providing protection against estrogen-induced DNA damage. This regulation involves Estrogen Receptor β (ERβ) recruitment to the Electrophile Response Element (EpRE) and a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2). We have also demonstrated that ERβ and hPMC2 are required for TOT-dependent recruitment of poly (ADP-ribose) polymerase 1 (PARP-1) and Topoisomerase IIβ (Topo IIβ) to the EpRE. Sequence analysis reveals that the C-terminus of hPMC2 encodes a putative exonuclease domain. Using in vitro kinetic assays, we found that hPMC2 is a 3'-5' non-processive exonuclease that degrades both single-stranded and double-stranded substrates. Mutation of two conserved carboxylate residues drastically reduced the exonuclease activity of hPMC2, indicating the relative importance of the catalytic residues. Western blot analysis of breast cancer cell lines for Quinone Reductase (QR) levels revealed that the intrinsic exonuclease activity of hPMC2 was required for TOT-induced QR upregulation. Chromatin immunoprecipitation (ChIP) assays also indicated that hPMC2 was involved in the formation of strand breaks observed with TOT treatment and is specific for the EpRE-containing region of the QR gene. We also determined that the transcription factor NF-E2-related factor-2 (Nrf2) is involved in the specificity of hPMC2 for the EpRE. In addition, we determined that the catalytic activity of hPMC2 is required for repair of abasic sites that result from estrogen-induced DNA damage. Thus, our study provides a mechanistic basis for transcriptional regulation by hPMC2 and provides novel insights into its role in cancer prevention.

The exonuclease activity of hPMC2 is required for transcriptional regulation of the QR gene and repair of estrogen-induced abasic sites

PubMed Central

Krishnamurthy, Nirmala; Ngam, Caitlyn R.; Berdis, Anthony J.; Montano, Monica M.

2011-01-01

We have previously reported that the expression of antioxidative stress enzymes are upregulated by trans-hydroxytamoxifen (TOT) in breast epithelial cell lines providing protection against estrogen-induced DNA damage. This regulation involves Estrogen Receptor beta (ERβ) recruitment to the Electrophile Response Element (EpRE) and a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2). We have also demonstrated that ERβ and hPMC2 are required for TOT-dependent recruitment of poly (ADP-ribose) polymerase 1 (PARP-1) and Topoisomerase IIβ (Topo IIβ) to the EpRE. Sequence analysis reveals that the C-terminus of hPMC2 encodes a putative exonuclease domain. Using in vitro kinetic assays, we found that hPMC2 is a 3'–5' non-processive exonuclease that degrades both single stranded and double stranded substrates. Mutation of two conserved carboxylate residues drastically reduced the exonuclease activity of hPMC2 indicating the relative importance of the catalytic residues. Western blot analysis of breast cancer cell lines for Quinone Reductase (QR) levels revealed that the intrinsic exonuclease activity of hPMC2 was required for TOT-induced QR upregulation. Chromatin immunoprecipitation assays (ChIP) also indicated that hPMC2 was involved in the formation of strand breaks observed with TOT-treatment and is specific for the EpRE-containing region of the QR gene. We also determined that the transcription factor NF-E2-related factor-2 (Nrf2) is involved in the specificity of hPMC2 for the EpRE. In addition, we determined that the catalytic activity of hPMC2 is required for repair of abasic sites that result from estrogen-induced DNA damage. Thus our study provides a mechanistic basis for transcriptional regulation by hPMC2 and provides novel insights into its role in cancer prevention. PMID:21602889

The relationship between negative expressivity, anger, and PTSD symptom clusters.

PubMed

Claycomb, Meredith; Roley, Michelle E; Contractor, Ateka A; Armour, Cherie; Dranger, Paula; Wang, Li; Elhai, Jon D

2016-09-30

More investigation is needed to understand how specific posttraumatic stress disorder (PTSD) symptom clusters relate to the internal experience of anger and overt negative behaviors in response to anger (negative expressivity). We investigated whether anger mediated relations between PTSD symptom clusters and negative expressivity. Multiple regression revealed lower PTSD intrusion symptoms associated with higher levels of negative expressivity. Anger mediated this relationship. Higher avoidance symptoms related to higher negative expressivity. Clinical implications, limitations, and strengths are discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

X-radiation from clusters of galaxies: Spectral evidence for a hot evolved gas

NASA Technical Reports Server (NTRS)

Serlemitsos, P. J.; Smith, B. W.; Boldt, E. A.; Holt, S. S.; Swank, J. H.

1976-01-01

OSO-8 observations of the X-ray flux in the range 2-60 keV from the Virgo, Perseus, and Coma Clusters provide strong evidence for the thermal origin of the radiation, including iron line emission. The data are adequately described by emission from an isothermal plasma with an iron abundance in near agreement with cosmic levels. A power law description is generally less acceptable and is ruled out in the case of Perseus. Implications on the origin of the cluster gas are discussed.

Exploratory Cluster Analysis to Identify Patterns of Chronic Kidney Disease in the 500 Cities Project.

PubMed

Liu, Shelley H; Li, Yan; Liu, Bian

2018-05-17

Chronic kidney disease is a leading cause of death in the United States. We used cluster analysis to explore patterns of chronic kidney disease in 500 of the largest US cities. After adjusting for socio-demographic characteristics, we found that unhealthy behaviors, prevention measures, and health outcomes related to chronic kidney disease differ between cities in Utah and those in the rest of the United States. Cluster analysis can be useful for identifying geographic regions that may have important policy implications for preventing chronic kidney disease.

Cosmological Implications of the Effects of X-Ray Clusters on the Cosmic Microwave Background

NASA Technical Reports Server (NTRS)

Forman, William R.

1996-01-01

We have been carrying forward a program to confront X-ray observations of clusters and their evolution as derived from X-ray observatories with observations of the cosmic microwave background radiation (CMBR). In addition to the material covered in our previous reports (including three published papers), most recently we have explored the effects of a cosmological constant on the predicted Sunyaev-Zel'dovich effect from the ensemble of clusters. In this report we summarize that work from which a paper will be prepared.

Lithium in a short-period tidally locked binary of M67: Implications for stellar evolution, Galactic Lithium evolution, and cosmology

NASA Technical Reports Server (NTRS)

Deliyannis, Constantine P.; King, Jeremy R.; Boesgaard, Ann M.; Ryan, Sean G.

1994-01-01

In open clusters, late-F stars exhibit a Li maximum (the Li 'peak' region) at lower abundance with age, which could be due either to stellar depletion or Galactic Li enrichment (or some other cause). We have observed a short-period tidally locked binary (SPTLB) on the Li peak region in the old cluster M67 to distinguish between alternatives. SPTLBs which synchronized in the early pre-main sequence would avoid the rotational mixing which, according to Yale models, may be responsible for depleting Li with age in open cluster dwarfs. We find that both components of the M67 SPTLB have a Li abundance lying about a factor of 2 or more above any other M67 single star and about a factor of 3 or more above the mean Li peak region abundance in M67. Our results suggest that the initial Li abundance in M67 is at least as high as approximately 3.0 = 12 + log (N(sub Li)/N(sub H)). Our high M67 SPTLB Li abundance and those in other clusters support the combination of Zahn's tidal circularization and the Yale rotational mixing theories and may indicate that the halo Li plateau (analogous to the cluster Li peak region) abundance has been depleted from a higher primordial value. Implications are discussed.

Spatial distribution of end-stage renal disease (ESRD) and social inequalities in mixed urban and rural areas: a study in the Bretagne administrative region of France.

PubMed

Kihal-Talantikite, Wahida; Deguen, Séverine; Padilla, Cindy; Siebert, Muriel; Couchoud, Cécile; Vigneau, Cécile; Bayat, Sahar

2015-02-01

Several studies have investigated the implication of biological and environmental factors on geographic variations of end-stage renal disease (ESRD) incidence at large area scales, but none of them assessed the implication of neighbourhood characteristics (healthcare supply, socio-economic level and urbanization degree) on spatial repartition of ESRD. We evaluated the spatial implications of adjustment for neighbourhood characteristics on the spatial distribution of ESRD incidence at the smallest geographic unit in France. All adult patients living in Bretagne and beginning renal replacement therapy during the 2004-09 period were included. Their residential address was geocoded at the census block level. Each census block was characterized by socio-economic deprivation index, healthcare supply and rural/urban typology. Using a spatial scan statistic, we examined whether there were significant clusters of high risk of ESRD incidence. The ESRD incidence was non-randomly spatially distributed, with a cluster of high risk in the western Bretagne region (relative risk, RR = 1.28, P-value = 0.0003). Adjustment for sex, age and neighbourhood characteristics induced cluster shifts. After these adjustments, a significant cluster (P = 0.013) persisted. Our spatial analysis of ESRD incidence at a fine scale, across a mixed rural/urban area, indicated that, beyond age and sex, neighbourhood characteristics explained a great part of spatial distribution of ESRD incidence. However, to better understand spatial variation of ESRD incidence, it would be necessary to research and adjust for other determinants of ESRD.

Interactions of small platinum clusters with the TiC(001) surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao, Jianjun; Li, Shasha; Chu, Xingli

2015-11-14

Density functional theory calculations are used to elucidate the interactions of small platinum clusters (Pt{sub n}, n = 1–5) with the TiC(001) surface. The results are analyzed in terms of geometric, energetic, and electronic properties. It is found that a single Pt atom prefers to be adsorbed at the C-top site, while a Pt{sub 2} cluster prefers dimerization and a Pt{sub 3} cluster forms a linear structure on the TiC(001). As for the Pt{sub 4} cluster, the three-dimensional distorted tetrahedral structure and the two-dimensional square structure almost have equal stability. In contrast with the two-dimensional isolated Pt{sub 5} cluster, the adsorbed Pt{submore » 5} cluster prefers a three-dimensional structure on TiC(001). Substantial charge transfer takes place from TiC(001) surface to the adsorbed Pt{sub n} clusters, resulting in the negatively charged Pt{sub n} clusters. At last, the d-band centers of the absorbed Pt atoms and their implications in the catalytic activity are discussed.« less

Studies in the X-Ray Emission of Clusters of Galaxies and Other Topics

NASA Technical Reports Server (NTRS)

Vrtilek, Jan; Thronson, Harley (Technical Monitor)

2001-01-01

The paper discusses the following: (1) X-ray study of groups of galaxies with Chandra and XMM. (2) X-ray properties of point sources in Chandra deep fields. (3) Study of cluster substructure using wavelet techniques. (4) Combined study of galaxy clusters with X-ray and the S-Z effect. Groups of galaxies are the fundamental building blocks of large scale structure in the Universe. X-ray study of the intragroup medium offers a powerful approach to addressing some of the major questions that still remain about almost all aspects of groups: their ages, origins, importance of composition of various galaxy types, relations to clusters, and origin and enrichment of the intragroup gas. Long exposures with Chandra have opened new opportunities for the study of X-ray background. The presence of substructure within clusters of galaxies has substantial implications for our understanding of cluster evolution as well as fundamental questions in cosmology.

Very Broad [O III] λλ4959, 5007 Emission from the NGC 4472 Globular Cluster RZ 2109 and Implications for the Mass of Its Black Hole X-Ray Source

NASA Astrophysics Data System (ADS)

Zepf, Stephen E.; Stern, Daniel; Maccarone, Thomas J.; Kundu, Arunav; Kamionkowski, Marc; Rhode, Katherine L.; Salzer, John J.; Ciardullo, Robin; Gronwall, Caryl

2008-08-01

We present Keck LRIS spectroscopy of the black hole-hosting globular cluster RZ 2109 in the Virgo elliptical galaxy NGC 4472. We find that this object has extraordinarily broad [O III] λ5007 and [O III] λ4959 emission lines, with velocity widths of approximately 2000 km s-1. This result has significant implications for the nature of this accreting black hole system and the mass of the globular cluster black hole. We show that the broad [O III] λ5007 emission must arise from material driven at high velocity from the black hole system. This is because the volume available near the black hole is too small by many orders of magnitude to have enough [O III]-emitting atoms to account for the observed L([O III] λ5007) at high velocities, even if this volume is filled with oxygen at the critical density for [O III] λ5007. The Balmer emission is also weak, indicating the observed [O III] is not due to shocks. We therefore conclude that the [O III] λλ4959, 5007 is produced by photoionization of material driven across the cluster. The only known way to drive significant material at high velocity is for a system accreting mass near or above its Eddington limit, which indicates a stellar-mass black hole. Since it is dynamically implausible to form an accreting stellar-mass black hole system in a globular cluster with an intermediate-mass black hole (IMBH), it appears this massive globular cluster does not have an IMBH. We discuss further tests of this conclusion, and its implications for the MBH - Mstellar and MBH - σ relations. Based on observations made at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

The Psychology of Yoga Practitioners: A Cluster Analysis.

PubMed

Genovese, Jeremy E C; Fondran, Kristine M

2017-11-01

Yoga practitioners (N = 261) completed the revised Expression of Spirituality Inventory (ESI) and the Multidimensional Body-Self Relations Questionnaire. Cluster analysis revealed three clusters: Cluster A scored high on all four spiritual constructs. They had high positive evaluations of their appearance, but a lower orientation towards their appearance. They tended to have a high evaluation of their fitness and health, and higher body satisfaction. Cluster B showed lower scores on the spiritual constructs. Like Cluster A, members of Cluster B tended to show high positive evaluations of appearance and fitness. They also had higher body satisfaction. Members of Cluster B had a higher fitness orientation and a higher appearance orientation than members of Cluster A. Members of Cluster C had low scores for all spiritual constructs. They had a low evaluation of, and unhappiness with, their appearance. They were unhappy with the size and appearance of their bodies. They tended to see themselves as overweight. There was a significant difference in years of practice between the three groups (Kruskall -Wallis, p = .0041). Members of Cluster A have the most years of yoga experience and members of Cluster B have more yoga experience than members of Cluster C. These results suggest the possible existence of a developmental trajectory for yoga practitioners. Such a developmental sequence may have important implications for yoga practice and instruction.

The Psychology of Yoga Practitioners: A Cluster Analysis.

PubMed

Genovese, Jeremy E C; Fondran, Kristine M

2017-03-30

Yoga practitioners (N = 261) completed the revised Expression of Spirituality Inventory (ESI) and the Multidimensional Body-Self Relations Questionnaire. Cluster analysis revealed three clusters: Cluster A scored high on all four spiritual constructs. They had high positive evaluations of their appearance, but a lower orientation towards their appearance. They tended to have a high evaluation of their fitness and health, and higher body satisfaction. Cluster B showed lower scores on the spiritual constructs. Like Cluster A, members of Cluster B tended to show high positive evaluations of appearance and fitness. They also had higher body satisfaction. Members of Cluster B had a higher fitness orientation and a higher appearance orientation than members of Cluster A. Members of Cluster C had low scores for all spiritual constructs. They had a low evaluation of, and unhappiness with, their appearance. They were unhappy with the size and appearance of their bodies. They tended to see themselves as overweight. There was a significant difference in years of practice between the three groups (Kruskall-Wallis, p = .0041). Members of Cluster A have the most years of yoga experience and members of Cluster B have more yoga experience than members of Cluster C. These results suggest the possible existence of a developmental trajectory for yoga practitioners. Such a developmental sequence may have important implications for yoga practice and instruction.

Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling

PubMed Central

Mattila, Pieta K.; Batista, Facundo D.

2016-01-01

Recent evidence implicates the actin cytoskeleton in the control of receptor signaling. This may be of particular importance in the context of immune receptors, such as the B cell receptor, where dysregulated signaling can result in autoimmunity and malignancy. Here, we discuss the role of the actin cytoskeleton in controlling receptor compartmentalization, dynamics, and clustering as a means to regulate receptor signaling through controlling the interactions with protein partners. We propose that the actin cytoskeleton is a point of integration for receptor cross talk through modulation of protein dynamics and clustering. We discuss the implication of this cross talk via the cytoskeleton for both ligand-induced and low-level constitutive (tonic) signaling necessary for immune cell survival. PMID:26833785

Cyclic nocturnal awakening: a warning sign of a cluster bout.

PubMed

Martins, Isabel Pavão

2015-04-01

Cluster headache is an excruciating unilateral headache with autonomic symptoms whose periodic nocturnal activity, which interrupts sleep, has been attributed to a hypothalamic generator. We describe a patient with a longstanding episodic cluster headache who experienced, on two occasions, a period of nocturnal awakenings without pain or autonomic symptoms, lasting one week before the onset of a cluster bout. Awakenings occurred twice/night at the same hours of impending cluster attacks and had no apparent trigger, being unusual for this patient who had no previous sleep disturbances. Neurological examination and brain imaging were normal. This case documents two new aspects of cluster headache. It suggests that repeated nocturnal awakenings can be a warning sign of an impending cluster period, a finding that may have therapeutic implications, and also that hypothalamic activation may begin several days before trigemino-autonomic symptoms, thus behaving as a true bout generator. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release.

PubMed

Pesce, Luca; Calandrini, Vania; Marjault, Henri-Baptiste; Lipper, Colin H; Rossetti, Gulia; Mittler, Ron; Jennings, Patricia A; Bauer, Andreas; Nechushtai, Rachel; Carloni, Paolo

2017-11-30

The NEET proteins are a novel family of iron-sulfur proteins characterized by an unusual three cysteine and one histidine coordinated [2Fe-2S] cluster. Aberrant cluster release, facilitated by the breakage of the Fe-N bond, is implicated in a variety of human diseases, including cancer. Here, the molecular dynamics in the multi-microsecond timescale, along with quantum chemical calculations, on two representative members of the family (the human NAF-1 and mitoNEET proteins), show that the loss of the cluster is associated with a dramatic decrease in secondary and tertiary structure. In addition, the calculations provide a mechanism for cluster release and clarify, for the first time, crucial differences existing between the two proteins, which are reflected in the experimentally observed difference in the pH-dependent cluster reactivity. The reliability of our conclusions is established by an extensive comparison with the NMR data of the solution proteins, in part measured in this work.

Sensing Size through Clustering in Non-Equilibrium Membranes and the Control of Membrane-Bound Enzymatic Reactions

PubMed Central

Vagne, Quentin; Turner, Matthew S.; Sens, Pierre

2015-01-01

The formation of dynamical clusters of proteins is ubiquitous in cellular membranes and is in part regulated by the recycling of membrane components. We show, using stochastic simulations and analytic modeling, that the out-of-equilibrium cluster size distribution of membrane components undergoing continuous recycling is strongly influenced by lateral confinement. This result has significant implications for the clustering of plasma membrane proteins whose mobility is hindered by cytoskeletal “corrals” and for protein clustering in cellular organelles of limited size that generically support material fluxes. We show how the confinement size can be sensed through its effect on the size distribution of clusters of membrane heterogeneities and propose that this could be regulated to control the efficiency of membrane-bound reactions. To illustrate this, we study a chain of enzymatic reactions sensitive to membrane protein clustering. The reaction efficiency is found to be a non-monotonic function of the system size, and can be optimal for sizes comparable to those of cellular organelles. PMID:26656912

MASGOMAS PROJECT, New automatic-tool for cluster search on IR photometric surveys

NASA Astrophysics Data System (ADS)

Rübke, K.; Herrero, A.; Borissova, J.; Ramirez-Alegria, S.; García, M.; Marin-Franch, A.

2015-05-01

The Milky Way is expected to contain a large number of young massive (few x 1000 solar masses) stellar clusters, borne in dense cores of gas and dust. Yet, their known number remains small. We have started a programme to search for such clusters, MASGOMAS (MAssive Stars in Galactic Obscured MAssive clusterS). Initially, we selected promising candidates by means of visual inspection of infrared images. In a second phase of the project we have presented a semi-automatic method to search for obscured massive clusters that resulted in the identification of new massive clusters, like MASGOMAS-1 (with more than 10,000 solar masses) and MASGOMAS-4 (a double-cored association of about 3,000 solar masses). We have now developped a new automatic tool for MASGOMAS that allows the identification of a large number of massive cluster candidates from the 2MASS and VVV catalogues. Cluster candidates fulfilling criteria appropriated for massive OB stars are thus selected in an efficient and objective way. We present the results from this tool and the observations of the first selected cluster, and discuss the implications for the Milky Way structure.

A new giant luminous arc gravitational lens associated with a z = 0.62 galaxy cluster, and the environments of distant radio galaxies

NASA Technical Reports Server (NTRS)

Dickinson, Mark

1993-01-01

In the course of a survey investigating the cluster environments of distant 3CR radio galaxies, I have identified a previously unknown 'giant luminous arc' gravitational lens. The lensing cluster is associated with the radio galaxy 3C 220.1 at z = 0.62 and is the most distant cluster now known to produce such arcs. I present imaging and spectroscopic observations of the cluster and the arc, and discuss the implications for the cluster mass. At z greater than 0.6 the cluster velocity dispersions implied by such giant arcs may provide an interesting constraint on theories of large scale structure formation. The parent investigation in which this arc was identified concerns galaxy clusters and radio galaxy environments at 0.35 less than z less than 0.8. At the present epoch, powerful FR 2 radio galaxies tend to be found in environments of poor or average galaxy density. In contrast, at the higher redshifts investigated here, richer group and cluster environments are common. I present additional data on other clusters from this survey, and discuss its extension to z greater than 1 through a program of near-infrared and optical imaging.

Adherens Junctions Revisualized: Organizing Cadherins as Nanoassemblies.

PubMed

Yap, Alpha S; Gomez, Guillermo A; Parton, Robert G

2015-10-12

This Perspective considers how classical cadherin cell-cell adhesion receptors are organized at the nanoscale to generate lateral clusters. Recent advances in optical microscopy reveal that clustering constitutes a general feature of cadherin organization, but one that takes diverse forms. Here we consider the molecular mechanisms responsible for cadherin clustering and their functional implications. We frame our discussion in light of what is known about how nanoscale organization is conferred upon the plasma membrane, through protein-protein interactions, regulation of the cortical actin cytoskeleton, and the lipid environment of the membrane. Copyright © 2015 Elsevier Inc. All rights reserved.

Hard X-ray emission from accretion shocks around galaxy clusters

NASA Astrophysics Data System (ADS)

Kushnir, Doron; Waxman, Eli

2010-02-01

We show that the hard X-ray (HXR) emission observed from several galaxy clusters is consistent with a simple model, in which the nonthermal emission is produced by inverse Compton scattering of cosmic microwave background photons by electrons accelerated in cluster accretion shocks: The dependence of HXR surface brightness on cluster temperature is consistent with that predicted by the model, and the observed HXR luminosity is consistent with the fraction of shock thermal energy deposited in relativistic electrons being lesssim0.1. Alternative models, where the HXR emission is predicted to be correlated with the cluster thermal emission, are disfavored by the data. The implications of our predictions to future HXR observations (e.g. by NuStar, Simbol-X) and to (space/ground based) γ-ray observations (e.g. by Fermi, HESS, MAGIC, VERITAS) are discussed.

Binary Black Hole Mergers from Globular Clusters: Implications for Advanced LIGO.

PubMed

Rodriguez, Carl L; Morscher, Meagan; Pattabiraman, Bharath; Chatterjee, Sourav; Haster, Carl-Johan; Rasio, Frederic A

2015-07-31

The predicted rate of binary black hole mergers from galactic fields can vary over several orders of magnitude and is extremely sensitive to the assumptions of stellar evolution. But in dense stellar environments such as globular clusters, binary black holes form by well-understood gravitational interactions. In this Letter, we study the formation of black hole binaries in an extensive collection of realistic globular cluster models. By comparing these models to observed Milky Way and extragalactic globular clusters, we find that the mergers of dynamically formed binaries could be detected at a rate of ∼100 per year, potentially dominating the binary black hole merger rate. We also find that a majority of cluster-formed binaries are more massive than their field-formed counterparts, suggesting that Advanced LIGO could identify certain binaries as originating from dense stellar environments.

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

PubMed

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.

Waiting-time distributions of magnetic discontinuities: clustering or Poisson process?

PubMed

Greco, A; Matthaeus, W H; Servidio, S; Dmitruk, P

2009-10-01

Using solar wind data from the Advanced Composition Explorer spacecraft, with the support of Hall magnetohydrodynamic simulations, the waiting-time distributions of magnetic discontinuities have been analyzed. A possible phenomenon of clusterization of these discontinuities is studied in detail. We perform a local Poisson's analysis in order to establish if these intermittent events are randomly distributed or not. Possible implications about the nature of solar wind discontinuities are discussed.

Language Acquisition and Machine Learning.

DTIC Science & Technology

1986-02-01

machine learning and examine its implications for computational models of language acquisition. As a framework for understanding this research, the authors propose four component tasks involved in learning from experience-aggregation, clustering, characterization, and storage. They then consider four common problems studied by machine learning researchers-learning from examples, heuristics learning, conceptual clustering, and learning macro-operators-describing each in terms of our framework. After this, they turn to the problem of grammar

Waiting-time distributions of magnetic discontinuities: Clustering or Poisson process?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greco, A.; Matthaeus, W. H.; Servidio, S.

2009-10-15

Using solar wind data from the Advanced Composition Explorer spacecraft, with the support of Hall magnetohydrodynamic simulations, the waiting-time distributions of magnetic discontinuities have been analyzed. A possible phenomenon of clusterization of these discontinuities is studied in detail. We perform a local Poisson's analysis in order to establish if these intermittent events are randomly distributed or not. Possible implications about the nature of solar wind discontinuities are discussed.

MULTI-K: accurate classification of microarray subtypes using ensemble k-means clustering

PubMed Central

Kim, Eun-Youn; Kim, Seon-Young; Ashlock, Daniel; Nam, Dougu

2009-01-01

Background Uncovering subtypes of disease from microarray samples has important clinical implications such as survival time and sensitivity of individual patients to specific therapies. Unsupervised clustering methods have been used to classify this type of data. However, most existing methods focus on clusters with compact shapes and do not reflect the geometric complexity of the high dimensional microarray clusters, which limits their performance. Results We present a cluster-number-based ensemble clustering algorithm, called MULTI-K, for microarray sample classification, which demonstrates remarkable accuracy. The method amalgamates multiple k-means runs by varying the number of clusters and identifies clusters that manifest the most robust co-memberships of elements. In addition to the original algorithm, we newly devised the entropy-plot to control the separation of singletons or small clusters. MULTI-K, unlike the simple k-means or other widely used methods, was able to capture clusters with complex and high-dimensional structures accurately. MULTI-K outperformed other methods including a recently developed ensemble clustering algorithm in tests with five simulated and eight real gene-expression data sets. Conclusion The geometric complexity of clusters should be taken into account for accurate classification of microarray data, and ensemble clustering applied to the number of clusters tackles the problem very well. The C++ code and the data sets tested are available from the authors. PMID:19698124

Interstitial telomeric sequences in human chromosomes cluster with common fragile sites, mutagen sensitive sites, viral integration sites, cancer breakpoints, proto-oncogenes and breakpoints involved in primate evolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adekunle, S.S.A.; Wyandt, H.; Mark, H.F.L.

1994-09-01

Recently we mapped the telomeric repeat sequences to 111 interstitial sites in the human genome and to sites of gaps and breaks induced by aphidicolin and sister chromatid exchange sites detected by BrdU. Many of these sites correspond to conserved fragile sites in man, gorilla and chimpazee, to sites of conserved sister chromatid exchange in the mammalian X chromosome, to mutagenic sensitive sites, mapped locations of proto-oncogenes, breakpoints implicated in primate evolution and to breakpoints indicated as the sole anomaly in neoplasia. This observation prompted us to investigate if the interstitial telomeric sites cluster with these sites. An extensive literaturemore » search was carried out to find all the available published sites mentioned above. For comparison, we also carried out a statistical analysis of the clustering of the sites of the telomeric repeats with the gene locations where only nucleotide mutations have been observed as the only chromosomal abnormality. Our results indicate that the telomeric repeats cluster most with fragile sites, mutagenic sensitive sites and breakpoints implicated in primate evolution and least with cancer breakpoints, mapped locations of proto-oncogenes and other genes with nucleotide mutations.« less

HEAO-A2 observations of the X-ray spectra of the Centaurus and A1060 clusters of galaxies

NASA Technical Reports Server (NTRS)

Mitchell, R.; Mushotzky, R.

1979-01-01

The X-ray spectral observations of two low luminosity clusters of galaxies, Centaurus and A1060, are presented. An emission feature of the Centaurus cluster at 7.9 keV is detected at about one third of the strength of the 6.7 keV line. This higher energy line represents K sub beta emission from highly ionized iron. An isothermal model with an Fe emission line is discussed and it is shown that the model cannot fit the data of the Centaurus or the A1060 clusters. The implications of the two component nature of the continuum on the Fe abundance and the X-ray surface brightness distribution are discussed.

Motivational and emotional profiles in university undergraduates: a self-determination theory perspective.

PubMed

González, Antonio; Paoloni, Verónica; Donolo, Danilo; Rinaudo, Cristina

2012-11-01

Previous research has focused on specific forms of self-determined motivation or discrete class-related emotions, but few studies have simultaneously examined both constructs. The aim of this study on 472 undergraduates was twofold: to perform cluster analysis to identify homogeneous groups of motivation in the sample; and to determine the profile of each cluster for emotions and academic achievement. Cluster analysis configured four groups in terms of motivation: controlled, autonomous, both high, and both low. Each cluster revealed a distinct emotional profile, autonomous motivation being the most adaptable with high scores for academic achievement and pleasant emotions and low values for unpleasant emotions. The results are discussed in the light of their implications for academic adjustment.

Multiscale mutation clustering algorithm identifies pan-cancer mutational clusters associated with pathway-level changes in gene expression

PubMed Central

Poole, William; Leinonen, Kalle; Shmulevich, Ilya

2017-01-01

Cancer researchers have long recognized that somatic mutations are not uniformly distributed within genes. However, most approaches for identifying cancer mutations focus on either the entire-gene or single amino-acid level. We have bridged these two methodologies with a multiscale mutation clustering algorithm that identifies variable length mutation clusters in cancer genes. We ran our algorithm on 539 genes using the combined mutation data in 23 cancer types from The Cancer Genome Atlas (TCGA) and identified 1295 mutation clusters. The resulting mutation clusters cover a wide range of scales and often overlap with many kinds of protein features including structured domains, phosphorylation sites, and known single nucleotide variants. We statistically associated these multiscale clusters with gene expression and drug response data to illuminate the functional and clinical consequences of mutations in our clusters. Interestingly, we find multiple clusters within individual genes that have differential functional associations: these include PTEN, FUBP1, and CDH1. This methodology has potential implications in identifying protein regions for drug targets, understanding the biological underpinnings of cancer, and personalizing cancer treatments. Toward this end, we have made the mutation clusters and the clustering algorithm available to the public. Clusters and pathway associations can be interactively browsed at m2c.systemsbiology.net. The multiscale mutation clustering algorithm is available at https://github.com/IlyaLab/M2C. PMID:28170390

Multiscale mutation clustering algorithm identifies pan-cancer mutational clusters associated with pathway-level changes in gene expression.

PubMed

Poole, William; Leinonen, Kalle; Shmulevich, Ilya; Knijnenburg, Theo A; Bernard, Brady

2017-02-01

Cancer researchers have long recognized that somatic mutations are not uniformly distributed within genes. However, most approaches for identifying cancer mutations focus on either the entire-gene or single amino-acid level. We have bridged these two methodologies with a multiscale mutation clustering algorithm that identifies variable length mutation clusters in cancer genes. We ran our algorithm on 539 genes using the combined mutation data in 23 cancer types from The Cancer Genome Atlas (TCGA) and identified 1295 mutation clusters. The resulting mutation clusters cover a wide range of scales and often overlap with many kinds of protein features including structured domains, phosphorylation sites, and known single nucleotide variants. We statistically associated these multiscale clusters with gene expression and drug response data to illuminate the functional and clinical consequences of mutations in our clusters. Interestingly, we find multiple clusters within individual genes that have differential functional associations: these include PTEN, FUBP1, and CDH1. This methodology has potential implications in identifying protein regions for drug targets, understanding the biological underpinnings of cancer, and personalizing cancer treatments. Toward this end, we have made the mutation clusters and the clustering algorithm available to the public. Clusters and pathway associations can be interactively browsed at m2c.systemsbiology.net. The multiscale mutation clustering algorithm is available at https://github.com/IlyaLab/M2C.

Hunting for origins of migraine pain: cluster analysis of spontaneous and capsaicin-induced firing in meningeal trigeminal nerve fibers

PubMed Central

Zakharov, A.; Vitale, C.; Kilinc, E.; Koroleva, K.; Fayuk, D.; Shelukhina, I.; Naumenko, N.; Skorinkin, A.; Khazipov, R.; Giniatullin, R.

2015-01-01

Trigeminal nerves in meninges are implicated in generation of nociceptive firing underlying migraine pain. However, the neurochemical mechanisms of nociceptive firing in meningeal trigeminal nerves are little understood. In this study, using suction electrode recordings from peripheral branches of the trigeminal nerve in isolated rat meninges, we analyzed spontaneous and capsaicin-induced orthodromic spiking activity. In control, biphasic single spikes with variable amplitude and shapes were observed. Application of the transient receptor potential vanilloid 1 (TRPV1) agonist capsaicin to meninges dramatically increased firing whereas the amplitudes and shapes of spikes remained essentially unchanged. This effect was antagonized by the specific TRPV1 antagonist capsazepine. Using the clustering approach, several groups of uniform spikes (clusters) were identified. The clustering approach combined with capsaicin application allowed us to detect and to distinguish “responder” (65%) from “non-responder” clusters (35%). Notably, responders fired spikes at frequencies exceeding 10 Hz, high enough to provide postsynaptic temporal summation of excitation at brainstem and spinal cord level. Almost all spikes were suppressed by tetrodotoxin (TTX) suggesting an involvement of the TTX-sensitive sodium channels in nociceptive signaling at the peripheral branches of trigeminal neurons. Our analysis also identified transient (desensitizing) and long-lasting (slowly desensitizing) responses to the continuous application of capsaicin. Thus, the persistent activation of nociceptors in capsaicin-sensitive nerve fibers shown here may be involved in trigeminal pain signaling and plasticity along with the release of migraine-related neuropeptides from TRPV1 positive neurons. Furthermore, cluster analysis could be widely used to characterize the temporal and neurochemical profiles of other pain transducers likely implicated in migraine. PMID:26283923

Regulation of the ATPase activity of ABCE1 from Pyrococcus abyssi by Fe-S cluster status and Mg²⁺: implication for ribosomal function.

PubMed

Sims, Lynn M; Igarashi, Robert Y

2012-08-15

Ribosomal function is dependent on multiple proteins. The ABCE1 ATPase, a unique ABC superfamily member that bears two Fe₄S₄ clusters, is crucial for ribosomal biogenesis and recycling. Here, the ATPase activity of the Pyrococcus abyssi ABCE1 (PabABCE1) was studied using both apo- (without reconstituted Fe-S clusters) and holo- (with full complement of Fe-S clusters reconstituted post-purification) forms, and is shown to be jointly regulated by the status of Fe-S clusters and Mg²⁺. Typically ATPases require Mg²⁺, as is true for PabABCE1, but Mg²⁺ also acts as a negative allosteric effector that modulates ATP affinity of PabABCE1. Physiological [Mg²⁺] inhibits the PabABCE1 ATPase (K(i) of ∼1 μM) for both apo- and holo-PabABCE1. Comparative kinetic analysis of Mg²⁺ inhibition shows differences in degree of allosteric regulation between the apo- and holo-PabABCE1 where the apparent ATP K(m) of apo-PabABCE1 increases >30-fold from ∼30 μM to over 1 mM with M²⁺. This effect would significantly convert the ATPase activity of PabABCE1 from being independent of cellular energy charge (φ) to being dependent on φ with cellular [Mg²⁺]. These findings uncover intricate overlapping effects by both [Mg²⁺] and the status of Fe-S clusters that regulate ABCE1's ATPase activity with implications to ribosomal function. Copyright © 2012 Elsevier Inc. All rights reserved.

Megacity analysis: a clustering approach to classification

DTIC Science & Technology

2017-06-01

kinetic or non -kinetic urban operations. We develop and implement a methodology to classify megacities into groups. Using 33 variables, we construct a...is interested in these megacity networks and their implications for potential urban operations. We develop a methodology to group like megacities...is interested in these megacity networks and their implications for potential urban operations. We develop a methodology to group like megacities

A Model-Based Cluster Analysis of Maternal Emotion Regulation and Relations to Parenting Behavior.

PubMed

Shaffer, Anne; Whitehead, Monica; Davis, Molly; Morelen, Diana; Suveg, Cynthia

2017-10-15

In a diverse community sample of mothers (N = 108) and their preschool-aged children (M age  = 3.50 years), this study conducted person-oriented analyses of maternal emotion regulation (ER) based on a multimethod assessment incorporating physiological, observational, and self-report indicators. A model-based cluster analysis was applied to five indicators of maternal ER: maternal self-report, observed negative affect in a parent-child interaction, baseline respiratory sinus arrhythmia (RSA), and RSA suppression across two laboratory tasks. Model-based cluster analyses revealed four maternal ER profiles, including a group of mothers with average ER functioning, characterized by socioeconomic advantage and more positive parenting behavior. A dysregulated cluster demonstrated the greatest challenges with parenting and dyadic interactions. Two clusters of intermediate dysregulation were also identified. Implications for assessment and applications to parenting interventions are discussed. © 2017 Family Process Institute.

A Massive Galaxy Cluster At z=1.45 From The XMM Cluster Survey: Discovery, Confirmation And Implications For The L-T Relation And Cosmology

NASA Astrophysics Data System (ADS)

Sabirli, Kivanc; Romer, A. K.; Davidson, M.; Stanford, S. A.; Viana, P. T.; Hilton, M.; Collins, C. A.; Kay, S. T.; Liddle, A. R.; Mann, R. G.; Miller, C. J.; Nichol, R. C.; West, M. J.; Conselice, C. J.; Spinrad, H.; Stern, D.; XCS Collaboration

2006-06-01

We report the discovery of the hottest cluster known at z > 1. It was identified as an extended X-ray source in the XMM Cluster Survey (XCS, Romer et al., 2001) and optical spectroscopy shows that 6 galaxies within a 60 arcsec diameter region lie at z = 1.45 ± 0.01. Hence its redshift is the highest currently known for a spectroscopically-confirmed cluster. Analysis of the X-ray spectra yields kT = 7.9+2.8-1.8 keV (90% confidence) and suggests that it is relatively massive for such a high redshift cluster.We acknowledge financial support from NASA grant NAG-11634 (AKR, RCN, KS, MD, PTPV), The Royal Astronomical Society's Hosie Request (MD, KS), PPARC (ARL, STK, RGM), the NASA XMM program (KS), the Institute of Astronomy at the University of Edinburgh (MD), Liverpool John Moores University (MH), Carnegie Mellon University (KS, AKR), and NSF grant AST-0205960 (MJW).

Down-to-earth studies of carbon clusters

NASA Technical Reports Server (NTRS)

Smalley, R. E.

1990-01-01

Recent advances in supersonic beam experiments with laser-vaporization sources of clusters have provided some interesting new insights into the nature of the small clusters of carbon, and the processes through which carbon condenses. One cluster in particular, C(sub 60), appears to play a central role. It is argued that this cluster takes the shape of a soccerball: a hollow sphere composed of a shell of 60 carbon atoms connected by a lattice of hexagonal and pentagonal rings, in a pattern of overall icosahedral symmetry. Although C(sub 60) appears to be uniquely stable due to its perfect symmetry, all other even-numbered carbon clusters in the 32 to 100+ atom size range seem to favor similar closed spheroidal forms. These species are interpreted as relatively unreactive side products in condensation reactions of carbon vapor involving spiraling graphitic sheets. The prevalence of C(sub 60) in laser-vaporized carbon vapors and sooting flames suggests that it may be formed readily whenever carbon condenses. Such ready formation and extraordinary stability may have substantial astrophysical implications.

Down-to-earth studies of carbon clusters

NASA Astrophysics Data System (ADS)

Smalley, R. E.

1990-04-01

Recent advances in supersonic beam experiments with laser-vaporization sources of clusters have provided some interesting new insights into the nature of the small clusters of carbon, and the processes through which carbon condenses. One cluster in particular, C60, appears to play a central role. It is argued that this cluster takes the shape of a soccer ball: a hollow sphere composed of a shell of 60 carbon atoms connected by a lattice of hexagonal and pentagonal rings, in a pattern of overall icosahedral symmetry. Although C60 appears to be uniquely stable due to its perfect symmetry, all other even-numbered carbon clusters in the 32 to 100+ atom size range seem to favor similar closed spheroidal forms. These species are interpreted as relatively unreactive side products in condensation reactions of carbon vapor involving spiraling graphitic sheets. The prevalence of C60 in laser-vaporized carbon vapors and sooting flames suggests that it may be formed readily whenever carbon condenses. Such ready formation and extraordinary stability may have substantial astrophysical implications.

A comparison of IQ and memory cluster solutions in moderate and severe pediatric traumatic brain injury.

PubMed

Thaler, Nicholas S; Terranova, Jennifer; Turner, Alisa; Mayfield, Joan; Allen, Daniel N

2015-01-01

Recent studies have examined heterogeneous neuropsychological outcomes in childhood traumatic brain injury (TBI) using cluster analysis. These studies have identified homogeneous subgroups based on tests of IQ, memory, and other cognitive abilities that show some degree of association with specific cognitive, emotional, and behavioral outcomes, and have demonstrated that the clusters derived for children with TBI are different from those observed in normal populations. However, the extent to which these subgroups are stable across abilities has not been examined, and this has significant implications for the generalizability and clinical utility of TBI clusters. The current study addressed this by comparing IQ and memory profiles of 137 children who sustained moderate-to-severe TBI. Cluster analysis of IQ and memory scores indicated that a four-cluster solution was optimal for the IQ scores and a five-cluster solution was optimal for the memory scores. Three clusters on each battery differed primarily by level of performance, while the others had pattern variations. Cross-plotting the clusters across respective IQ and memory test scores indicated that clusters defined by level were generally stable, while clusters defined by pattern differed. Notably, children with slower processing speed exhibited low-average to below-average performance on memory indexes. These results provide some support for the stability of previously identified memory and IQ clusters and provide information about the relationship between IQ and memory in children with TBI.

Clustering mechanism of oxocarboxylic acids involving hydration reaction: Implications for the atmospheric models

NASA Astrophysics Data System (ADS)

Liu, Ling; Kupiainen-Määttä, Oona; Zhang, Haijie; Li, Hao; Zhong, Jie; Kurtén, Theo; Vehkamäki, Hanna; Zhang, Shaowen; Zhang, Yunhong; Ge, Maofa; Zhang, Xiuhui; Li, Zesheng

2018-06-01

The formation of atmospheric aerosol particles from condensable gases is a dominant source of particulate matter in the boundary layer, but the mechanism is still ambiguous. During the clustering process, precursors with different reactivities can induce various chemical reactions in addition to the formation of hydrogen bonds. However, the clustering mechanism involving chemical reactions is rarely considered in most of the nucleation process models. Oxocarboxylic acids are common compositions of secondary organic aerosol, but the role of oxocarboxylic acids in secondary organic aerosol formation is still not fully understood. In this paper, glyoxylic acid, the simplest and the most abundant atmospheric oxocarboxylic acid, has been selected as a representative example of oxocarboxylic acids in order to study the clustering mechanism involving hydration reactions using density functional theory combined with the Atmospheric Clusters Dynamic Code. The hydration reaction of glyoxylic acid can occur either in the gas phase or during the clustering process. Under atmospheric conditions, the total conversion ratio of glyoxylic acid to its hydration reaction product (2,2-dihydroxyacetic acid) in both gas phase and clusters can be up to 85%, and the product can further participate in the clustering process. The differences in cluster structures and properties induced by the hydration reaction lead to significant differences in cluster formation rates and pathways at relatively low temperatures.

Assessment of Multiple Types of DNA Damage in Human Placentas from Smoking and Non-smoking Women in the Czech Republic

PubMed Central

Margaret Pratt, M.; King, Leon C.; Adams, Linda D.; John, Kaarthik; Sirajuddin, Paul; Olivero, Ofelia A.; Manchester, David K.; Sram, Radim J.; DeMarini, David M.; Poirier, Miriam C.

2010-01-01

Three classes of DNA damage were assessed in human placentas collected (in 2000-4) from 51 women living in the Teplice region of the Czech Republic, a mining area considered to have some of the worst environmental pollution in Europe in the 1980s. Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were localized and semiquantified using immunohistochemistry (IHC) and the Automated Cellular Imaging System (ACIS). More generalized DNA damage was measured both by 32P-postlabeling and by abasic (AB) site analysis. Placenta stained with antiserum elicited against DNA modified with r7, t8-dihydroxy-t-9, 10-oxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE) revealed PAH-DNA adduct localization in nuclei of the cytotrophoblast (CT) cells and syncytiotrophoblast (ST) knots lining the chorionic villi. The highest levels of DNA damage, 49–312 PAH-DNA adducts/108 nucleotides, were found by IHC/ACIS in 14 immediately-fixed placenta samples. An additional 37 placenta samples were stored frozen before fixation and embedding, and because PAH-DNA adducts were largely undetectable in these samples, freezing was implicated in the loss of IHC signal. The same placentas (n = 37) contained 1.7 – 8.6 stable/bulky DNA adducts/108 nucleotides and 0.6 – 47.2 AB sites/105 nucleotides. For all methods there was no correlation among types of DNA damage and no difference in extent of DNA damage between smokers and non-smokers. Therefore, the data show that DNA from placentas obtained in Teplice contained multiple types of DNA damage, which likely arose from various environmental exposures. In addition, PAH-DNA adducts were present at high concentrations in the CT cells and ST knots of the chorionic villi. PMID:20839217

Assessment of multiple types of DNA damage in human placentas from smoking and nonsmoking women in the Czech Republic.

PubMed

Pratt, M Margaret; King, Leon C; Adams, Linda D; John, Kaarthik; Sirajuddin, Paul; Olivero, Ofelia A; Manchester, David K; Sram, Radim J; DeMarini, David M; Poirier, Miriam C

2011-01-01

Three classes of DNA damage were assessed in human placentas collected (2000-2004) from 51 women living in the Teplice region of the Czech Republic, a mining area considered to have some of the worst environmental pollution in Europe in the 1980s. Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were localized and semiquantified using immunohistochemistry (IHC) and the Automated Cellular Imaging System (ACIS). More generalized DNA damage was measured both by (32)P-postlabeling and by abasic (AB) site analysis. Placenta stained with antiserum elicited against DNA modified with 7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE) revealed PAH-DNA adduct localization in nuclei of the cytotrophoblast (CT) cells and syncytiotrophoblast (ST) knots lining the chorionic villi. The highest levels of DNA damage, 49-312 PAH-DNA adducts/10(8) nucleotides, were found by IHC/ACIS in 14 immediately fixed placenta samples. An additional 37 placenta samples were stored frozen before fixation and embedding, and because PAH-DNA adducts were largely undetectable in these samples, freezing was implicated in the loss of IHC signal. The same placentas (n = 37) contained 1.7-8.6 stable/bulky DNA adducts/10(8) nucleotides and 0.6-47.2 AB sites/10(5) nucleotides. For all methods, there was no correlation among types of DNA damage and no difference in extent of DNA damage between smokers and nonsmokers. Therefore, the data show that DNA from placentas obtained in Teplice contained multiple types of DNA damage, which likely arose from various environmental exposures. In addition, PAH-DNA adducts were present at high concentrations in the CT cells and ST knots of the chorionic villi. Copyright © 2010 Wiley-Liss, Inc.

Mechanism of Adenomatous Polyposis Coli (APC)-mediated Blockage of Longpatch Base Excision Repair†

PubMed Central

Jaiswal, Aruna S.; Balusu, Ramesh; Armas, Melissa L.; Kundu, Chanakya N.; Narayan, Satya

2008-01-01

Recently, we found an interaction between adenomatous polyposis coli (APC) and DNA polymerase β (pol-β) and showed that APC blocks strand-displacement synthesis of long-patch base excision repair (LP-BER) however, the mechanism is not clear. Using an in vivo LP-BER assay system, we now show that the LP-BER is higher in APC−/− cells than in APC+/+ cells. In addition to pol-β, the pull-down experiments showed that the full-length APC also interacted with flap endonuclease 1 (Fen-1). To further characterize the interaction of APC with pol-β and Fen-1, we performed a domain-mapping of APC and found that both pol-β and Fen-1 interact with a 138-amino acids peptide from the APC at the DRI-domain. Our functional assays showed that APC blocks pol-β-mediated 1-nucleotide (1-nt) as well as strand-displacement synthesis of reduced abasic, nicked-, or 1-nt gapped-DNA substrates. Our further studies demonstrated that APC blocks 5′-flap endonuclease as well as 5′-3′ exonuclease activity of Fen-1 resulting in the blockage of LP-BER. From these results we concluded that APC can have three different effects in the LP-BER pathway. First, APC can block pol-β-mediated 1-nt incorporation and strand-displacement synthesis. Second, APC can block LP-BER by blocking coordinated formation and removal of the strand-displaced flap. Third, APC can block LP-BER by blocking “Hit and Run” synthesis. These studies will have important implications of APC in DNA damage-induced carcinogenesis and chemoprevention. PMID:17176113

Modulation of the conformational state of the SV2A protein by an allosteric mechanism as evidenced by ligand binding assays

PubMed Central

Daniels, V; Wood, M; Leclercq, K; Kaminski, R M; Gillard, M

2013-01-01

Background and Purpose Synaptic vesicle protein 2A (SV2A) is the specific binding site of the anti-epileptic drug levetiracetam (LEV) and its higher affinity analogue UCB30889. Moreover, the protein has been well validated as a target for anticonvulsant therapy. Here, we report the identification of UCB1244283 acting as a SV2A positive allosteric modulator of UCB30889. Experimental Approach UCB1244283 was characterized in vitro using radioligand binding assays with [3H]UCB30889 on recombinant SV2A expressed in HEK cells and on rat cortex. In vivo, the compound was tested in sound-sensitive mice. Key Results Saturation binding experiments in the presence of UCB1244283 demonstrated a fivefold increase in the affinity of [3H]UCB30889 for human recombinant SV2A, combined with a twofold increase of the total number of binding sites. Similar results were obtained on rat cortex. In competition binding experiments, UCB1244283 potentiated the affinity of UCB30889 while the affinity of LEV remained unchanged. UCB1244283 significantly slowed down both the association and dissociation kinetics of [3H]UCB30889. Following i.c.v. administration in sound-sensitive mice, UCB1244283 showed a clear protective effect against both tonic and clonic convulsions. Conclusions and Implications These results indicate that UCB1244283 can modulate the conformation of SV2A, thereby inducing a higher affinity state for UCB30889. Our results also suggest that the conformation of SV2A per se might be an important determinant of its functioning, especially during epileptic seizures. Therefore, agents that act on the conformation of SV2A might hold great potential in the search for new SV2A-based anticonvulsant therapies. PMID:23530581

Hierarchical Velocity Structure in the Core of Abell 2597

NASA Technical Reports Server (NTRS)

Still, Martin; Mushotzky, Richard

2004-01-01

We present XMM-Newton RGS and EPIC data of the putative cooling flow cluster Abell 2597. Velocities of the low-ionization emission lines in the spectrum are blue shifted with respect to the high-ionization lines by 1320 (sup +660) (sub -210) kilometers per second, which is consistent with the difference in the two peaks of the galaxy velocity distribution and may be the signature of bulk turbulence, infall, rotation or damped oscillation in the cluster. A hierarchical velocity structure such as this could be the direct result of galaxy mergers in the cluster core, or the injection of power into the cluster gas from a central engine. The uniform X-ray morphology of the cluster, the absence of fine scale temperature structure and the random distribution of the the galaxy positions, independent of velocity, suggests that our line of sight is close to the direction of motion. These results have strong implications for cooling flow models of the cluster Abell 2597. They give impetus to those models which account for the observed temperature structure of some clusters using mergers instead of cooling flows.

X-ray and IR Surveys of the Orion Molecular Clouds and the Cepheus OB3b Cluster

NASA Astrophysics Data System (ADS)

Megeath, S. Thomas; Wolk, Scott J.; Pillitteri, Ignazio; Allen, Tom

2014-08-01

X-ray and IR surveys of molecular clouds between 400 and 700 pc provide complementary means to map the spatial distribution of young low mass stars associated with the clouds. We overview an XMM survey of the Orion Molecular Clouds, at a distance of 400 pc. By using the fraction of X-ray sources with disks as a proxy for age, this survey has revealed three older clusters rich in diskless X-ray sources. Two are smaller clusters found at the northern and southern edges of the Orion A molecular cloud. The third cluster surrounds the O-star Iota Ori (the point of Orion's sword) and is in the foreground to the Orion molecular cloud. In addition, we present a Chandra and Spitzer survey of the Cep OB3b cluster at 700 pc. These data show a spatially variable disk fraction indicative of age variations within the cluster. We discuss the implication of these results for understanding the spread of ages in young clusters and the star formation histories of molecular clouds.

Population changes in residential clusters in Japan.

PubMed

Sekiguchi, Takuya; Tamura, Kohei; Masuda, Naoki

2018-01-01

Population dynamics in urban and rural areas are different. Understanding factors that contribute to local population changes has various socioeconomic and political implications. In the present study, we use population census data in Japan to examine contributors to the population growth of residential clusters between years 2005 and 2010. The data set covers the entirety of Japan and has a high spatial resolution of 500 × 500 m2, enabling us to examine population dynamics in various parts of the country (urban and rural) using statistical analysis. We found that, in addition to the area, population density, and age, the shape of the cluster and the spatial distribution of inhabitants within the cluster are significantly related to the population growth rate of a residential cluster. Specifically, the population tends to grow if the cluster is "round" shaped (given the area) and the population is concentrated near the center rather than periphery of the cluster. Combination of the present results and analysis framework with other factors that have been omitted in the present study, such as migration, terrain, and transportation infrastructure, will be fruitful.

Unexpectedly high bacteriochlorophyll a concentrations in neotropical tank bromeliads.

PubMed

Lehours, Anne-Catherine; Jeune, Anne-Hélène Le; Aguer, Jean-Pierre; Céréghino, Régis; Corbara, Bruno; Kéraval, Benoit; Leroy, Céline; Perrière, Fanny; Jeanthon, Christian; Carrias, Jean-François

2016-06-06

The contribution of bacteriochlorophyll a (BChl a) to photosynthetically driven electron transport is generally low in aquatic and terrestrial systems. Here, we provide evidence that anoxygenic bacterial phototrophy is widespread and substantial in water retained by tank bromeliads of a primary rainforest in French Guiana. An analysis of the water extracted from 104 randomly selected tank bromeliads using infrared fluorimetry suggested the overall presence of abundant anoxygenic phototrophic bacterial populations. We found that purple bacteria dominated these populations responsible for unusually high BChl a/chlorophyll a ratios (>50%). Our data suggest that BChl a-based phototrophy in tank bromeliads can have significant effects on the ecology of tank-bromeliad ecosystems and on the carbon and energy fluxes in Neotropical forests. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Clustering of worry appraisals among college students.

PubMed

Schwab, Nicholas G; Cullum, Jerry C; Harton, Helen C

2016-01-01

The present study investigated the potential clustering of worry appraisals within college social networks. Participants living in campus residence buildings responded to online surveys across the course of several months. Worry appraisals were measured 10 weeks into the fall semester and again approximately 6 months later. Analysis of sociometric data suggests that the majority of participants' social interactions occurred within their respective residence building floors, indicating that proximity strongly influenced the development of social network ties and sources of social influence. Further, significant clustering of worry appraisals occurred across time, and more importantly, within residence building floors. The present findings compliment previous work suggesting that several physical and psychological states appear to spread and cluster within social networks. Implications for the study of emotional appraisals and future research are discussed.

A cluster analysis investigation of workaholism as a syndrome.

PubMed

Aziz, Shahnaz; Zickar, Michael J

2006-01-01

Workaholism has been conceptualized as a syndrome although there have been few tests that explicitly consider its syndrome status. The authors analyzed a three-dimensional scale of workaholism developed by Spence and Robbins (1992) using cluster analysis. The authors identified three clusters of individuals, one of which corresponded to Spence and Robbins's profile of the workaholic (high work involvement, high drive to work, low work enjoyment). Consistent with previously conjectured relations with workaholism, individuals in the workaholic cluster were more likely to label themselves as workaholics, more likely to have acquaintances label them as workaholics, and more likely to have lower life satisfaction and higher work-life imbalance. The importance of considering workaholism as a syndrome and the implications for effective interventions are discussed. Copyright 2006 APA.

Constraints on cold dark matter theories from observations of massive x-ray-luminous clusters of galaxies at high redshift

NASA Technical Reports Server (NTRS)

Luppino, G. A.; Gioia, I. M.

1995-01-01

During the course of a gravitational lensing survey of distant, X-ray selected Einstein Observatory Extended Medium Sensitivity Survey (EMSS) clusters of galaxies, we have studied six X-ray-luminous (L(sub x) greater than 5 x 10(exp 44)(h(sub 50)(exp -2))ergs/sec) clusters at redshifts exceeding z = 0.5. All of these clusters are apparently massive. In addition to their high X-ray luminosity, two of the clusters at z approximately 0.6 exhibit gravitationally lensed arcs. Furthermore, the highest redshift cluster in our sample, MS 1054-0321 at z = 0.826, is both extremely X-ray luminous (L(sub 0.3-3.5keV)=9.3 x 10(exp 44)(h(sub 50)(exp -2))ergs/sec) and exceedingly rich with an optical richness comparable to an Abell Richness Class 4 cluster. In this Letter, we discuss the cosmological implications of the very existence of these clusters for hierarchical structure formation theories such as standard Omega = 1 CDM (cold dark matter), hybrid Omega = 1 C + HDM (hot dark matter), and flat, low-density Lambda + CDM models.

Observation of small cluster formation in concentrated monoclonal antibody solutions and its implications to solution viscosity.

PubMed

Yearley, Eric J; Godfrin, Paul D; Perevozchikova, Tatiana; Zhang, Hailiang; Falus, Peter; Porcar, Lionel; Nagao, Michihiro; Curtis, Joseph E; Gawande, Pradad; Taing, Rosalynn; Zarraga, Isidro E; Wagner, Norman J; Liu, Yun

2014-04-15

Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable mAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Life history factors, personality and the social clustering of sexual experience in adolescents.

PubMed

van Leeuwen, Abram J; Mace, Ruth

2016-10-01

Adolescent sexual behaviour may show clustering in neighbourhoods, schools and friendship networks. This study aims to assess how experience with sexual intercourse clusters across the social world of adolescents and whether predictors implicated by life history theory or personality traits can account for its between-individual variation and social patterning. Using data on 2877 adolescents from the Avon Longitudinal Study of Parents and Children, we ran logistic multiple classification models to assess the clustering of sexual experience by approximately 17.5 years in schools, neighbourhoods and friendship networks. We examined how much clustering at particular levels could be accounted for by life history predictors and Big Five personality factors. Sexual experience exhibited substantial clustering in friendship networks, while clustering at the level of schools and neighbourhoods was minimal, suggesting a limited role for socio-ecological influences at those levels. While life history predictors did account for some variation in sexual experience, they did not explain clustering in friendship networks. Personality, especially extraversion, explained about a quarter of friends' similarity. After accounting for life history factors and personality, substantial unexplained similarity among friends remained, which may reflect a tendency to associate with similar individuals or the social transmission of behavioural norms.

Life history factors, personality and the social clustering of sexual experience in adolescents

PubMed Central

2016-01-01

Adolescent sexual behaviour may show clustering in neighbourhoods, schools and friendship networks. This study aims to assess how experience with sexual intercourse clusters across the social world of adolescents and whether predictors implicated by life history theory or personality traits can account for its between-individual variation and social patterning. Using data on 2877 adolescents from the Avon Longitudinal Study of Parents and Children, we ran logistic multiple classification models to assess the clustering of sexual experience by approximately 17.5 years in schools, neighbourhoods and friendship networks. We examined how much clustering at particular levels could be accounted for by life history predictors and Big Five personality factors. Sexual experience exhibited substantial clustering in friendship networks, while clustering at the level of schools and neighbourhoods was minimal, suggesting a limited role for socio-ecological influences at those levels. While life history predictors did account for some variation in sexual experience, they did not explain clustering in friendship networks. Personality, especially extraversion, explained about a quarter of friends' similarity. After accounting for life history factors and personality, substantial unexplained similarity among friends remained, which may reflect a tendency to associate with similar individuals or the social transmission of behavioural norms. PMID:27853543

Implications of a localized zone of seismic activity near the Inner Piedmont-Blue Ridge boundary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Douglas, S.; Powell, C.

1994-03-01

A small but distinct cluster of earthquake activity is located in Henderson County, NC, near the boundary of the Inner Piedmont and Blue Ridge physiographic provinces. Over twenty events have occurred within the cluster since 1776 and four had body-wave magnitudes exceeding 3.0. Average focal depth for instrumentally recorded events is 7.7 km. Epicenters plot within the Inner Piedmont, roughly 13 km from the surface expression of the Brevard fault zone. The reason for sustained earthquake activity in Henderson County is not known but the close spatial association of the events with the Brevard fault suggests a causal relationship. Themore » Brevard zone dips steeply to the SE and the events could be associated with the fault at depth. An even more intriguing possibility is that the events are associated with the intersection of the Brevard zone and the decollemont; this possibility is compatible with available information concerning the depth to the decollemont and the dip on the Brevard zone. An association of seismic activity with the Brevard zone at depth is supported by the presence of another small cluster of activity located in Rutherford County, NC. This cluster is located in the Inner Piedmont, roughly 30 km NE of the Henderson cluster and 16 km from the Brevard fault zone. Association of seismic activity with known faults is very rare in the eastern US and has implications for tectonic models and hazard evaluation. Additional research must be conducted to determine the feasibility that activity is associated with the Brevard zone.« less

INTER- AND INTRA-CLUSTER AGE GRADIENTS IN MASSIVE STAR FORMING REGIONS AND INDIVIDUAL NEARBY STELLAR CLUSTERS REVEALED BY MYStIX

NASA Astrophysics Data System (ADS)

Getman, Konstantin V.; Feigelson, Eric; Kuhn, Michael A.; Broos, Patrick S; Townsley, Leisa K.; Naylor, Tim; Povich, Matthew S.; Luhman, Kevin; Garmire, Gordon

2014-08-01

The MYStIX (Massive Young Star-Forming Complex Study in Infrared and X-ray) project seeks to characterize 20 OB-dominated young star forming regions (SFRs) at distances <4 kpc using photometric catalogs from the Chandra X-ray Observatory, Spitzer Space Telescope, UKIRT and 2MASS surveys. As part of the MYStIX project, we developed a new stellar chronometer that employs near-infrared and X-ray photometry data, AgeJX. Computing AgeJX averaged over MYStIX (sub)clusters reveals previously unknown age gradients across most of the MYStIX regions as well as within some individual rich clusters. Within the SFRs, the inferred AgeJX ages are youngest in obscured locations in molecular clouds, intermediate in revealed stellar clusters, and oldest in distributed stellar populations. Noticeable intra-cluster gradients are seen in the NGC 2024 (Flame Nebula) star cluster and the Orion Nebula Cluster (ONC): stars in cluster cores appear younger and thus were formed later than stars in cluster halos. The latter result has two important implications for the formation of young stellar clusters. Clusters likely form slowly: they do not arise from a single nearly-instantaneous burst of star formation. The simple models where clusters form inside-out are likely incorrect, and more complex models are needed. We provide several star formation scenarios that alone or in combination may lead to the observed core-halo age gradients.

From hormones to secondary metabolism: the emergence of metabolic gene clusters in plants.

PubMed

Chu, Hoi Yee; Wegel, Eva; Osbourn, Anne

2011-04-01

Gene clusters for the synthesis of secondary metabolites are a common feature of microbial genomes. Well-known examples include clusters for the synthesis of antibiotics in actinomycetes, and also for the synthesis of antibiotics and toxins in filamentous fungi. Until recently it was thought that genes for plant metabolic pathways were not clustered, and this is certainly true in many cases; however, five plant secondary metabolic gene clusters have now been discovered, all of them implicated in synthesis of defence compounds. An obvious assumption might be that these eukaryotic gene clusters have arisen by horizontal gene transfer from microbes, but there is compelling evidence to indicate that this is not the case. This raises intriguing questions about how widespread such clusters are, what the significance of clustering is, why genes for some metabolic pathways are clustered and those for others are not, and how these clusters form. In answering these questions we may hope to learn more about mechanisms of genome plasticity and adaptive evolution in plants. It is noteworthy that for the five plant secondary metabolic gene clusters reported so far, the enzymes for the first committed steps all appear to have been recruited directly or indirectly from primary metabolic pathways involved in hormone synthesis. This may or may not turn out to be a common feature of plant secondary metabolic gene clusters as new clusters emerge. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

Weighing galaxy clusters with gas. II. On the origin of hydrostatic mass bias in ΛCDM galaxy clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, Kaylea; Nagai, Daisuke; Yu, Liang

2014-02-20

The use of galaxy clusters as cosmological probes hinges on our ability to measure their masses accurately and with high precision. Hydrostatic mass is one of the most common methods for estimating the masses of individual galaxy clusters, which suffer from biases due to departures from hydrostatic equilibrium. Using a large, mass-limited sample of massive galaxy clusters from a high-resolution hydrodynamical cosmological simulation, in this work we show that in addition to turbulent and bulk gas velocities, acceleration of gas introduces biases in the hydrostatic mass estimate of galaxy clusters. In unrelaxed clusters, the acceleration bias is comparable to themore » bias due to non-thermal pressure associated with merger-induced turbulent and bulk gas motions. In relaxed clusters, the mean mass bias due to acceleration is small (≲ 3%), but the scatter in the mass bias can be reduced by accounting for gas acceleration. Additionally, this acceleration bias is greater in the outskirts of higher redshift clusters where mergers are more frequent and clusters are accreting more rapidly. Since gas acceleration cannot be observed directly, it introduces an irreducible bias for hydrostatic mass estimates. This acceleration bias places limits on how well we can recover cluster masses from future X-ray and microwave observations. We discuss implications for cluster mass estimates based on X-ray, Sunyaev-Zel'dovich effect, and gravitational lensing observations and their impact on cluster cosmology.« less

Weighing Galaxy Clusters with Gas. II. On the Origin of Hydrostatic Mass Bias in ΛCDM Galaxy Clusters

NASA Astrophysics Data System (ADS)

Nelson, Kaylea; Lau, Erwin T.; Nagai, Daisuke; Rudd, Douglas H.; Yu, Liang

2014-02-01

The use of galaxy clusters as cosmological probes hinges on our ability to measure their masses accurately and with high precision. Hydrostatic mass is one of the most common methods for estimating the masses of individual galaxy clusters, which suffer from biases due to departures from hydrostatic equilibrium. Using a large, mass-limited sample of massive galaxy clusters from a high-resolution hydrodynamical cosmological simulation, in this work we show that in addition to turbulent and bulk gas velocities, acceleration of gas introduces biases in the hydrostatic mass estimate of galaxy clusters. In unrelaxed clusters, the acceleration bias is comparable to the bias due to non-thermal pressure associated with merger-induced turbulent and bulk gas motions. In relaxed clusters, the mean mass bias due to acceleration is small (lsim 3%), but the scatter in the mass bias can be reduced by accounting for gas acceleration. Additionally, this acceleration bias is greater in the outskirts of higher redshift clusters where mergers are more frequent and clusters are accreting more rapidly. Since gas acceleration cannot be observed directly, it introduces an irreducible bias for hydrostatic mass estimates. This acceleration bias places limits on how well we can recover cluster masses from future X-ray and microwave observations. We discuss implications for cluster mass estimates based on X-ray, Sunyaev-Zel'dovich effect, and gravitational lensing observations and their impact on cluster cosmology.

Semiempirical limits on the thermal conductivity of intracluster gas

NASA Technical Reports Server (NTRS)

David, Laurence P.; Hughes, John P.; Tucker, Wallace H.

1992-01-01

A semiempirical method for establishing lower limits on the thermal conductivity of hot gas in clusters of galaxies is described. The method is based on the observation that the X-ray imaging data (e.g., Einstein IPC) for clusters are well described by the hydrostatic-isothermal beta model, even for cooling flow clusters beyond about one core radius. In addition, there are strong indications that noncooling flow clusters (like the Coma Cluster) have a large central region (up to several core radii) of nearly constant gas temperature. This suggests that thermal conduction is an effective means of transporting and redistributing the thermal energy of the gas. This in turn has implications for the extent to which magnetic fields in the cluster are effective in reducing the thermal conductivity of the gas. Time-dependent hydrodynamic simulations for the gas in the Coma Cluster under two separate evolutionary scenarios are presented. One scenario assumes that the cluster potential is static and that the gas has an initial adiabatic distribution. The second scenario uses an evolving cluster potential. These models along with analytic results show that the thermal conductivity of the gas in the Coma Cluster cannot be less than 0.1 of full Spitzer conductivity. These models also show that high gas conductivity assists rather than hinders the development of radiative cooling in the central regions of clusters.

Bounds on graviton mass using weak lensing and SZ effect in galaxy clusters

NASA Astrophysics Data System (ADS)

Rana, Akshay; Jain, Deepak; Mahajan, Shobhit; Mukherjee, Amitabha

2018-06-01

In General Relativity (GR), the graviton is massless. However, a common feature in several theoretical alternatives of GR is a non-zero mass for the graviton. These theories can be described as massive gravity theories. Despite many theoretical complexities in these theories, on phenomenological grounds the implications of massive gravity have been widely used to put bounds on graviton mass. One of the generic implications of giving a mass to the graviton is that the gravitational potential will follow a Yukawa-like fall off. We use this feature of massive gravity theories to probe the mass of graviton by using the largest gravitationally bound objects, namely galaxy clusters. In this work, we use the mass estimates of galaxy clusters measured at various cosmologically defined radial distances measured via weak lensing (WL) and Sunyaev-Zel'dovich (SZ) effect. We also use the model independent values of Hubble parameter H (z) smoothed by a non-parametric method, Gaussian process. Within 1σ confidence region, we obtain the mass of graviton mg < 5.9 ×10-30 eV with the corresponding Compton length scale λg > 6.82 Mpc from weak lensing and mg < 8.31 ×10-30 eV with λg > 5.012 Mpc from SZ effect. This analysis improves the upper bound on graviton mass obtained earlier from galaxy clusters.

Nuclear pasta in hot dense matter and its implications for neutrino scattering

NASA Astrophysics Data System (ADS)

Roggero, Alessandro; Margueron, Jérôme; Roberts, Luke F.; Reddy, Sanjay

2018-04-01

The abundance of large clusters of nucleons in neutron-rich matter at subnuclear density is found to be greatly reduced by finite-temperature effects when matter is close to β equilibrium, compared to the case where the electron fraction is fixed at Ye>0.1 , as often considered in the literature. Large nuclei and exotic nonspherical nuclear configurations called pasta, favored in the vicinity of the transition to uniform matter at T =0 , dissolve at a relatively low temperature Tu as protons leak out of nuclei and pasta. For matter at β equilibrium with a negligible neutrino chemical potential we find that Tuβ≃4 ±1 MeV for realistic equations of state. This is lower than the maximum temperature Tmaxβ≃9 ±1 MeV at which nuclei can coexist with a gas of nucleons and can be explained by a change in the nature of the transition to uniform matter called retrograde condensation. An important new finding is that coherent neutrino scattering from nuclei and pasta makes a modest contribution to the opacity under the conditions encountered in supernovas and neutron star mergers. This is because large nuclear clusters dissolve at most relevant temperatures, and at lower temperatures, when clusters are present, Coulomb correlations between them suppress coherent neutrino scattering off individual clusters. Implications for neutrino signals from galactic supernovas are briefly discussed.

Distantly related lipocalins share two conserved clusters of hydrophobic residues: use in homology modeling

PubMed Central

Adam, Benoit; Charloteaux, Benoit; Beaufays, Jerome; Vanhamme, Luc; Godfroid, Edmond; Brasseur, Robert; Lins, Laurence

2008-01-01

Background Lipocalins are widely distributed in nature and are found in bacteria, plants, arthropoda and vertebra. In hematophagous arthropods, they are implicated in the successful accomplishment of the blood meal, interfering with platelet aggregation, blood coagulation and inflammation and in the transmission of disease parasites such as Trypanosoma cruzi and Borrelia burgdorferi. The pairwise sequence identity is low among this family, often below 30%, despite a well conserved tertiary structure. Under the 30% identity threshold, alignment methods do not correctly assign and align proteins. The only safe way to assign a sequence to that family is by experimental determination. However, these procedures are long and costly and cannot always be applied. A way to circumvent the experimental approach is sequence and structure analyze. To further help in that task, the residues implicated in the stabilisation of the lipocalin fold were determined. This was done by analyzing the conserved interactions for ten lipocalins having a maximum pairwise identity of 28% and various functions. Results It was determined that two hydrophobic clusters of residues are conserved by analysing the ten lipocalin structures and sequences. One cluster is internal to the barrel, involving all strands and the 310 helix. The other is external, involving four strands and the helix lying parallel to the barrel surface. These clusters are also present in RaHBP2, a unusual "outlier" lipocalin from tick Rhipicephalus appendiculatus. This information was used to assess assignment of LIR2 a protein from Ixodes ricinus and to build a 3D model that helps to predict function. FTIR data support the lipocalin fold for this protein. Conclusion By sequence and structural analyzes, two conserved clusters of hydrophobic residues in interactions have been identified in lipocalins. Since the residues implicated are not conserved for function, they should provide the minimal subset necessary to confer the lipocalin fold. This information has been used to assign LIR2 to lipocalins and to investigate its structure/function relationship. This study could be applied to other protein families with low pairwise similarity, such as the structurally related fatty acid binding proteins or avidins. PMID:18190694

Differential regulation of ParaHox genes by retinoic acid in the invertebrate chordate amphioxus (Branchiostoma floridae).

PubMed

Osborne, Peter W; Benoit, Gérard; Laudet, Vincent; Schubert, Michael; Ferrier, David E K

2009-03-01

The ParaHox cluster is the evolutionary sister to the Hox cluster. Like the Hox cluster, the ParaHox cluster displays spatial and temporal regulation of the component genes along the anterior/posterior axis in a manner that correlates with the gene positions within the cluster (a feature called collinearity). The ParaHox cluster is however a simpler system to study because it is composed of only three genes. We provide a detailed analysis of the amphioxus ParaHox cluster and, for the first time in a single species, examine the regulation of the cluster in response to a single developmental signalling molecule, retinoic acid (RA). Embryos treated with either RA or RA antagonist display altered ParaHox gene expression: AmphiGsx expression shifts in the neural tube, and the endodermal boundary between AmphiXlox and AmphiCdx shifts its anterior/posterior position. We identified several putative retinoic acid response elements and in vitro assays suggest some may participate in RA regulation of the ParaHox genes. By comparison to vertebrate ParaHox gene regulation we explore the evolutionary implications. This work highlights how insights into the regulation and evolution of more complex vertebrate arrangements can be obtained through studies of a simpler, unduplicated amphioxus gene cluster.

Structural and functional characterization of two unusual endonuclease III enzymes from Deinococcus radiodurans.

PubMed

Sarre, Aili; Ökvist, Mats; Klar, Tobias; Hall, David R; Smalås, Arne O; McSweeney, Sean; Timmins, Joanna; Moe, Elin

2015-08-01

While most bacteria possess a single gene encoding the bifunctional DNA glycosylase Endonuclease III (EndoIII) in their genomes, Deinococcus radiodurans possesses three: DR2438 (DrEndoIII1), DR0289 (DrEndoIII2) and DR0982 (DrEndoIII3). Here we have determined the crystal structures of DrEndoIII1 and an N-terminally truncated form of DrEndoIII3 (DrEndoIII3Δ76). We have also generated a homology model of DrEndoIII2 and measured activity of the three enzymes. All three structures consist of two all α-helical domains, one of which exhibits a [4Fe-4S] cluster and the other a HhH-motif, separated by a DNA binding cleft, similar to previously determined structures of endonuclease III from Escherichia coli and Geobacillus stearothermophilus. However, both DrEndoIII1 and DrEndoIII3 possess an extended HhH motif with extra helical features and an altered electrostatic surface potential. In addition, the DNA binding cleft of DrEndoIII3 seems to be less accessible for DNA interactions, while in DrEndoIII1 it seems to be more open. Analysis of the enzyme activities shows that DrEndoIII2 is most similar to the previously studied enzymes, while DrEndoIII1 seems to be more distant with a weaker activity towards substrate DNA containing either thymine glycol or an abasic site. DrEndoIII3 is the most distantly related enzyme and displays no detectable activity towards these substrates even though the suggested catalytic residues are conserved. Based on a comparative structural analysis, we suggest that the altered surface potential, shape of the substrate-binding pockets and specific amino acid substitutions close to the active site and in the DNA interacting loops may underlie the unexpected differences in activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Association between mutation spectra and stable and unstable DNA adduct profiles in Salmonella for benzo[a]pyrene and dibenzo[a,l]pyrene.

PubMed

DeMarini, David M; Hanley, Nancy M; Warren, Sarah H; Adams, Linda D; King, Leon C

2011-09-01

Benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) are two polycyclic aromatic hydrocarbons (PAHs) that exhibit distinctly different mutagenicity and carcinogenicity profiles. Although some studies show that these PAHs produce unstable DNA adducts, conflicting data and arguments have been presented regarding the relative roles of these unstable adducts versus stable adducts, as well as oxidative damage, in the mutagenesis and tumor-mutation spectra of these PAHs. However, no study has determined the mutation spectra along with the stable and unstable DNA adducts in the same system with both PAHs. Thus, we determined the mutagenic potencies and mutation spectra of BP and DBP in strains TA98, TA100 and TA104 of Salmonella, and we also measured the levels of abasic sites (aldehydic-site assay) and characterized the stable DNA adducts ((32)P-postlabeling/HPLC) induced by these PAHs in TA104. Our results for the mutation spectra and site specificity of stable adducts were consistent with those from other systems, showing that DBP was more mutagenic than BP in TA98 and TA100. The mutation spectra of DBP and BP were significantly different in TA98 and TA104, with 24% of the mutations induced by BP in TA98 being complex frameshifts, whereas DBP produced hardly any of these mutations. In TA104, BP produced primarily GC to TA transversions, whereas DBP produced primarily AT to TA transversions. The majority (96%) of stable adducts induced by BP were at guanine, whereas the majority (80%) induced by DBP were at adenine. Although BP induced abasic sites, DBP did not. Most importantly, the proportion of mutations induced by DBP at adenine and guanine paralleled the proportion of stable DNA adducts induced by DBP at adenine and guanine; however, this was not the case for BP. Our results leave open a possible role for unstable DNA adducts in the mutational specificity of BP but not for DBP. Published by Elsevier B.V.

Incision of trivalent chromium [Cr(III)]-induced DNA damage by Bacillus caldotenax UvrABC endonuclease.

PubMed

O'Brien, Travis J; Jiang, Guohui; Chun, Gina; Mandel, H George; Westphal, Craig S; Kahen, Kaveh; Montaser, Akbar; States, J Christopher; Patierno, Steven R

2006-11-07

Some hexavalent chromium [Cr(VI)]-containing compounds are lung carcinogens. Once within cells, Cr(VI) is reduced to trivalent chromium [Cr(III)] which displays an affinity for both DNA bases and the phosphate backbone. A diverse array of genetic lesions is produced by Cr including Cr-DNA monoadducts, DNA interstrand crosslinks (ICLs), DNA-Cr-protein crosslinks (DPCs), abasic sites, DNA strand breaks and oxidized bases. Despite the large amount of information available on the genotoxicity of Cr, little is known regarding the molecular mechanisms involved in the removal of these lesions from damaged DNA. Recent work indicates that nucleotide excision repair (NER) is involved in the processing of Cr-DNA adducts in human and rodent cells. In order to better understand this process at the molecular level and begin to identify the Cr-DNA adducts processed by NER, the incision of CrCl(3) [Cr(III)]-damaged plasmid DNA was studied using a thermal-resistant UvrABC NER endonuclease from Bacillus caldotenax (Bca). Treatment of plasmid DNA with Cr(III) (as CrCl(3)) increased DNA binding as a function of dose. For example, at a Cr(III) concentration of 1 microM we observed approximately 2 Cr(III)-DNA adducts per plasmid. At this same concentration of Cr(III) we found that approximately 17% of the plasmid DNA contained ICLs ( approximately 0.2 ICLs/plasmid). When plasmid DNA treated with Cr(III) (1 microM) was incubated with Bca UvrABC we observed approximately 0.8 incisions/plasmid. The formation of endonuclease IV-sensitive abasic lesions or Fpg-sensitive oxidized DNA bases was not detected suggesting that the incision of Cr(III)-damaged plasmid DNA by UvrABC was not related to the generation of oxidized DNA damage. Taken together, our data suggest that a sub-fraction of Cr(III)-DNA adducts is recognized and processed by the prokaryotic NER machinery and that ICLs are not necessarily the sole lesions generated by Cr(III) that are substrates for NER.

A PCV2 vaccine based on genotype 2b is more effective than a 2a-based vaccine to protect against PCV2b or combined PCV2a/2b viremia in pigs with concurrent PCV2, PRRSV and PPV infection.

PubMed

Opriessnig, Tanja; O'Neill, Kevin; Gerber, Priscilla F; de Castro, Alessandra M M G; Gimenéz-Lirola, Luis G; Beach, Nathan M; Zhou, Lei; Meng, Xiang-Jin; Wang, Chong; Halbur, Patrick G

2013-01-07

The predominant genotype of porcine circovirus (PCV) in the pig population today is PCV2b yet PCV2a-based commercial vaccines are considered effective in protecting against porcine circovirus associated disease. The objective of this study was to compare the ability of PCV2a- and PCV2b-based vaccines to control PCV2b viremia in a challenge model that mimics the U.S. field situation. Sixty-three pigs were randomly assigned to one of eight groups. Sixteen pigs were vaccinated with an experimental live-attenuated chimeric PCV1-2a vaccine based on genotype 2a and another 16 pigs with a chimeric PCV1-2b vaccine based on genotype 2b. Challenge was done 28 days post vaccination (dpv) using PCV2b (or a combination of PCV2a and PCV2b), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine parvovirus (PPV) to mimic what commonly occurs in the field. The experiment was terminated 21 days post challenge (dpc) or 49dpv. Pigs vaccinated with the chimeric PCV1-2b vaccine had significantly higher levels of PCV1-2b viremia and shedding of the PCV1-2b vaccine virus in feces and nasal secretions but also a more robust humoral immune response as evidenced by significantly higher ELISA S/P ratios compared to the PCV1-2a vaccination. Regardless of challenge, the PCV1-2b vaccination significantly reduced the prevalence and amount of PCV2 viremia compared to the PCV1-2a vaccination. Interestingly, in the non-vaccinated pigs concurrent PCV2a infection resulted in clinical disease and increased macroscopic lung lesions compared to pigs challenged with PCV2b alone, further supporting the idea that concurrent PCV2a/PCV2b infection is necessary for optimal PCV2 replication. Copyright © 2012 Elsevier Ltd. All rights reserved.

Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications.

PubMed

Howrylak, Judie A; Fuhlbrigge, Anne L; Strunk, Robert C; Zeiger, Robert S; Weiss, Scott T; Raby, Benjamin A

2014-05-01

Although recent studies have identified the presence of phenotypic clusters in asthmatic patients, the clinical significance and temporal stability of these clusters have not been explored. Our aim was to examine the clinical relevance and temporal stability of phenotypic clusters in children with asthma. We applied spectral clustering to clinical data from 1041 children with asthma participating in the Childhood Asthma Management Program. Posttreatment randomization follow-up data collected over 48 months were used to determine the effect of these clusters on pulmonary function and treatment response to inhaled anti-inflammatory medication. We found 5 reproducible patient clusters that could be differentiated on the basis of 3 groups of features: atopic burden, degree of airway obstruction, and history of exacerbation. Cluster grouping predicted long-term asthma control, as measured by the need for oral prednisone (P < .0001) or additional controller medications (P = .001), as well as longitudinal differences in pulmonary function (P < .0001). We also found that the 2 clusters with the highest rates of exacerbation had different responses to inhaled corticosteroids when compared with the other clusters. One cluster demonstrated a positive response to both budesonide (P = .02) and nedocromil (P = .01) compared with placebo, whereas the other cluster demonstrated minimal responses to both budesonide (P = .12) and nedocromil (P = .56) compared with placebo. Phenotypic clustering can be used to identify longitudinally consistent and clinically relevant patient subgroups, with implications for targeted therapeutic strategies and clinical trials design.

Formation of Very Young Massive Clusters and Implications for Globular Clusters

NASA Astrophysics Data System (ADS)

Banerjee, Sambaran; Kroupa, Pavel

How Very Young Massive star Clusters (VYMCs; also known as "starburst" clusters), which typically are of ≳ 104 M ⊙ and are a few Myr old, form out of Giant Molecular Clouds is still largely an open question. Increasingly detailed observations of young star clusters and star-forming molecular clouds and computational studies provide clues about their formation scenarios and the underlying physical processes involved. This chapter is focused on reviewing the decade-long studies that attempt to computationally reproduce the well-observed nearby VYMCs, such as the Orion Nebula Cluster, R136 and NGC 3603 young cluster, thereby shedding light on birth conditions of massive star clusters, in general. On this regard, focus is given on direct N-body modelling of real-sized massive star clusters, with a monolithic structure and undergoing residual gas expulsion, which have consistently reproduced the observed characteristics of several VYMCs and also of young star clusters, in general. The connection of these relatively simplified model calculations with the structural richness of dense molecular clouds and the complexity of hydrodynamic calculations of star cluster formation is presented in detail. Furthermore, the connections of such VYMCs with globular clusters, which are nearly as old as our Universe, is discussed. The chapter is concluded by addressing long-term deeply gas-embedded (at least apparently) and substructured systems like W3 Main. While most of the results are quoted from existing and up-to-date literature, in an integrated fashion, several new insights and discussions are provided.

Beverage consumption patterns of Canadian adults aged 19 to 65 years.

PubMed

Nikpartow, Nooshin; Danyliw, Adrienne D; Whiting, Susan J; Lim, Hyun J; Vatanparast, Hassanali

2012-12-01

To investigate the beverage intake patterns of Canadian adults and explore characteristics of participants in different beverage clusters. Analyses of nationally representative data with cross-sectional complex stratified design. Canadian Community Health Survey, Cycle 2.2 (2004). A total of 14 277 participants aged 19-65 years, in whom dietary intake was assessed using a single 24 h recall, were included in the study. After determining total intake and the contribution of beverages to total energy intake among age/sex groups, cluster analysis (K-means method) was used to classify males and females into distinct clusters based on the dominant pattern of beverage intakes. To test differences across clusters, χ2 tests and 95 % confidence intervals of the mean intakes were used. Six beverage clusters in women and seven beverage clusters in men were identified. 'Sugar-sweetened' beverage clusters - regular soft drinks and fruit drinks - as well as a 'beer' cluster, appeared for both men and women. No 'milk' cluster appeared among women. The mean consumption of the dominant beverage in each cluster was higher among men than women. The 'soft drink' cluster in men had the lowest proportion of the higher levels of education, and in women the highest proportion of inactivity, compared with other beverage clusters. Patterns of beverage intake in Canadian women indicate high consumption of sugar-sweetened beverages particularly fruit drinks, low intake of milk and high intake of beer. These patterns in women have implications for poor bone health, risk of obesity and other morbidities.

Symptom clustering and quality of life in patients with ovarian cancer undergoing chemotherapy.

PubMed

Nho, Ju-Hee; Reul Kim, Sung; Nam, Joo-Hyun

2017-10-01

The symptom clusters in patients with ovarian cancer undergoing chemotherapy have not been well evaluated. We investigated the symptom clusters and effects of symptom clusters on the quality of life of patients with ovarian cancer. We recruited 210 ovarian cancer patients being treated with chemotherapy and used a descriptive cross-sectional study design to collect information on their symptoms. To determine inter-relationships among symptoms, a principal component analysis with varimax rotation was performed based on the patient's symptoms (fatigue, pain, sleep disturbance, chemotherapy-induced peripheral neuropathy, anxiety, depression, and sexual dysfunction). All patients had experienced at least two domains of concurrent symptoms, and there were two types of symptom clusters. The first symptom cluster consisted of anxiety, depression, fatigue, and sleep disturbance symptoms, while the second symptom cluster consisted of pain and chemotherapy-induced peripheral neuropathy symptoms. Our subgroup cluster analysis showed that ovarian cancer patients with higher-scoring symptoms had significantly poorer quality of life in both symptom cluster 1 and 2 subgroups, with subgroup-specific patterns. The symptom clusters were different depending on age, age at disease onset, disease duration, recurrence, and performance status of patients with ovarian cancer. In addition, ovarian cancer patients experienced different symptom clusters according to cancer stage. The current study demonstrated that there is a specific pattern of symptom clusters, and symptom clusters negatively influence the quality of life in patients with ovarian cancer. Identifying symptom clusters of ovarian cancer patients may have clinical implications in improving symptom management. Copyright © 2017 Elsevier Ltd. All rights reserved.

Personality Patterns Among Correctional Officer Applicants

ERIC Educational Resources Information Center

Holland, Terrill R.; And Others

1976-01-01

The MMPI profiles of 359 correctional officer applicants were cluster analyzed, which resulted in the identification of five relatively homogeneous subgroups. The implications of the findings for occupationally adaptive and maladaptive correctional officer behavior were discussed. (Editor)

Interpersonal Pathoplasticity in Individuals with Generalized Anxiety Disorder

PubMed Central

Przeworski, Amy; Newman, Michelle G.; Pincus, Aaron L.; Kasoff, Michele B.; Yamasaki, Alissa S.; Castonguay, Louis G.; Berlin, Kristoffer S.

2011-01-01

Recent theories of Generalized Anxiety Disorder (GAD) have emphasized interpersonal and personality functioning as important aspects of the disorder. The current paper examines heterogeneity in interpersonal problems in two studies of individuals with GAD (n = 47 and n = 83). Interpersonal subtypes were assessed using the Inventory of Interpersonal Problems (IIP-C; Alden, Wiggins, & Pincus, 1990). Across both studies, individuals with GAD exhibited heterogeneous interpersonal problems, and cluster analyses of these patients' interpersonal characteristics yielded four replicable clusters identified as intrusive, exploitable, cold, and nonassertive subtypes. Consistent with our pathoplasticity hypotheses, clusters did not differ in GAD severity, anxiety severity, depression severity. Clusters in study two differed on rates of personality disorders, including avoidant personality disorder, further providing support for the validity of interpersonal subtypes. The presence of interpersonal subtypes in GAD may have important implications for treatment planning and efficacy. PMID:21553942

HEAO A-2 observations of the X-ray spectra of the Centaurus and A1060 clusters of galaxies

NASA Technical Reports Server (NTRS)

Mitchell, R.; Mushotzky, R.

1980-01-01

X-ray spectral observations of two nearby low-luminosity clusters of galaxies are presented. For the Centaurus cluster an emission feature at 7.9 keV is detected at about one-third of the strength of the 6.7 keV line. This higher energy line represents K-beta emission from highly ionized iron. In addition, it is demonstrated that for neither the Centaurus nor the A1060 cluster can an isothermal model with an Fe emission line adequately fit the data. Instead, the simplest models which provide acceptable fits include a second, harder component which may be either a second exponential or a power law. The implications of the two-component nature of the continuum on the Fe abundance and the X-ray surface-brightness distribution are discussed.

Clustering of health-related behaviors among early and mid-adolescents in Tuscany: results from a representative cross-sectional study

PubMed Central

Lazzeri, Giacomo; Panatto, Donatella; Domnich, Alexander; Arata, Lucia; Pammolli, Andrea; Simi, Rita; Giacchi, Mariano Vincenzo; Amicizia, Daniela; Gasparini, Roberto

2018-01-01

Abstract Background A huge amount of literature suggests that adolescents’ health-related behaviors tend to occur in clusters, and the understanding of such behavioral clustering may have direct implications for the effective tailoring of health-promotion interventions. Despite the usefulness of analyzing clustering, Italian data on this topic are scant. This study aimed to evaluate the clustering patterns of health-related behaviors. Methods The present study is based on data from the Health Behaviors in School-aged Children (HBSC) study conducted in Tuscany in 2010, which involved 3291 11-, 13- and 15-year olds. To aggregate students’ data on 22 health-related behaviors, factor analysis and subsequent cluster analysis were performed. Results Factor analysis revealed eight factors, which were dubbed in accordance with their main traits: ‘Alcohol drinking’, ‘Smoking’, ‘Physical activity’, ‘Screen time’, ‘Signs & symptoms’, ‘Healthy eating’, ‘Violence’ and ‘Sweet tooth’. These factors explained 67% of variance and underwent cluster analysis. A six-cluster κ-means solution was established with a 93.8% level of classification validity. The between-cluster differences in both mean age and gender distribution were highly statistically significant. Conclusions Health-compromising behaviors are common among Tuscan teens and occur in distinct clusters. These results may be used by schools, health-promotion authorities and other stakeholders to design and implement tailored preventive interventions in Tuscany. PMID:27908972

Clustering of health-related behaviors among early and mid-adolescents in Tuscany: results from a representative cross-sectional study.

PubMed

Lazzeri, Giacomo; Panatto, Donatella; Domnich, Alexander; Arata, Lucia; Pammolli, Andrea; Simi, Rita; Giacchi, Mariano Vincenzo; Amicizia, Daniela; Gasparini, Roberto

2018-03-01

A huge amount of literature suggests that adolescents' health-related behaviors tend to occur in clusters, and the understanding of such behavioral clustering may have direct implications for the effective tailoring of health-promotion interventions. Despite the usefulness of analyzing clustering, Italian data on this topic are scant. This study aimed to evaluate the clustering patterns of health-related behaviors. The present study is based on data from the Health Behaviors in School-aged Children (HBSC) study conducted in Tuscany in 2010, which involved 3291 11-, 13- and 15-year olds. To aggregate students' data on 22 health-related behaviors, factor analysis and subsequent cluster analysis were performed. Factor analysis revealed eight factors, which were dubbed in accordance with their main traits: 'Alcohol drinking', 'Smoking', 'Physical activity', 'Screen time', 'Signs & symptoms', 'Healthy eating', 'Violence' and 'Sweet tooth'. These factors explained 67% of variance and underwent cluster analysis. A six-cluster κ-means solution was established with a 93.8% level of classification validity. The between-cluster differences in both mean age and gender distribution were highly statistically significant. Health-compromising behaviors are common among Tuscan teens and occur in distinct clusters. These results may be used by schools, health-promotion authorities and other stakeholders to design and implement tailored preventive interventions in Tuscany.

THE HUBBLE SPACE TELESCOPE UV LEGACY SURVEY OF GALACTIC GLOBULAR CLUSTERS. VII. IMPLICATIONS FROM THE NEARLY UNIVERSAL NATURE OF HORIZONTAL BRANCH DISCONTINUITIES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, T. M.; Bellini, A.; Anderson, J.

2016-05-01

The UV-initiative Hubble Space Telescope Treasury survey of Galactic globular clusters provides a new window into the phenomena that shape the morphological features of the horizontal branch (HB). Using this large and homogeneous catalog of UV and blue photometry, we demonstrate that the HB exhibits discontinuities that are remarkably consistent in color (effective temperature). This consistency is apparent even among some of the most massive clusters hosting multiple distinct sub-populations (such as NGC 2808, ω Cen, and NGC 6715), demonstrating that these phenomena are primarily driven by atmospheric physics that is independent of the underlying population properties. However, inconsistencies arisemore » in the metal-rich clusters NGC 6388 and NGC 6441, where the discontinuity within the blue HB (BHB) distribution shifts ∼1000–2000 K hotter. We demonstrate that this shift is likely due to a large helium enhancement in the BHB stars of these clusters, which in turn affects the surface convection and evolution of such stars. Our survey also increases the number of Galactic globular clusters known to host blue-hook stars (also known as late hot flashers) from 6 to 23 clusters. These clusters are biased toward the bright end of the globular cluster luminosity function, confirming that blue-hook stars tend to form in the most massive clusters with significant self-enrichment.« less

REMOVING COOL CORES AND CENTRAL METALLICITY PEAKS IN GALAXY CLUSTERS WITH POWERFUL ACTIVE GALACTIC NUCLEUS OUTBURSTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo Fulai; Mathews, William G., E-mail: fulai@ucolick.or

2010-07-10

Recent X-ray observations of galaxy clusters suggest that cluster populations are bimodally distributed according to central gas entropy and are separated into two distinct classes: cool core (CC) and non-cool core (NCC) clusters. While it is widely accepted that active galactic nucleus (AGN) feedback plays a key role in offsetting radiative losses and maintaining many clusters in the CC state, the origin of NCC clusters is much less clear. At the same time, a handful of extremely powerful AGN outbursts have recently been detected in clusters, with a total energy {approx}10{sup 61}-10{sup 62} erg. Using two-dimensional hydrodynamic simulations, we showmore » that if a large fraction of this energy is deposited near the centers of CC clusters, which is likely common due to dense cores, these AGN outbursts can completely remove CCs, transforming them to NCC clusters. Our model also has interesting implications for cluster abundance profiles, which usually show a central peak in CC systems. Our calculations indicate that during the CC to NCC transformation, AGN outbursts efficiently mix metals in cluster central regions and may even remove central abundance peaks if they are not broad enough. For CC clusters with broad central abundance peaks, AGN outbursts decrease peak abundances, but cannot effectively destroy the peaks. Our model may simultaneously explain the contradictory (possibly bimodal) results of abundance profiles in NCC clusters, some of which are nearly flat, while others have strong central peaks similar to those in CC clusters. A statistical analysis of the sizes of central abundance peaks and their redshift evolution may shed interesting insights on the origin of both types of NCC clusters and the evolution history of thermodynamics and AGN activity in clusters.« less

The Nature and Origin of UCDs in the Coma Cluster

NASA Astrophysics Data System (ADS)

Chiboucas, Kristin; Tully, R. Brent; Madrid, Juan; Phillipps, Steven; Carter, David; Peng, Eric

2018-01-01

UCDs are super massive star clusters found largely in dense regions but have also been found around individual galaxies and in smaller groups. Their origin is still under debate but currently favored scenarios include formation as giant star clusters, either as the brightest globular clusters or through mergers of super star clusters, themselves formed during major galaxy mergers, or as remnant nuclei from tidal stripping of nucleated dwarf ellipticals. Establishing the nature of these enigmatic objects has important implications for our understanding of star formation, star cluster formation, the missing satellite problem, and galaxy evolution. We are attempting to disentangle these competing formation scenarios with a large survey of UCDs in the Coma cluster. Using ACS two-passband imaging from the HST/ACS Coma Cluster Treasury Survey, we are using colors and sizes to identify the UCD cluster members. With a large size limited sample of the UCD population within the core region of the Coma cluster, we are investigating the population size, properties, and spatial distribution, and comparing that with the Coma globular cluster and nuclear star cluster populations to discriminate between the threshing and globular cluster scenarios. In previous work, we had found a possible correlation of UCD colors with host galaxy and a possible excess of UCDs around a non-central giant galaxy with an unusually large globular cluster population, both suggestive of a globular cluster origin. With a larger sample size and additional imaging fields that encompass the regions around these giant galaxies, we have found that the color correlation with host persists and the giant galaxy with unusually large globular cluster population does appear to host a large UCD population as well. We present the current status of the survey.

[Trigeminal autonomic cephalgias: diagnostic and therapeutic implications].

PubMed

Rosenberg-Nordmann, Mirjam; Tölle, Thomas R; Sprenger, Till

2007-09-06

Trigeminal autonomic cephalgias (TACs) are primary headache syndromes characterized by severe short-lasting headaches accompanied by ipsilateral facial autonomic symptoms. The group includes cluster headache (CH), paroxysmal hemicrania (PH), and short-lasting neuralgiform headache with conjunctival injection and tearing (SUNCT). By far, Cluster headache is the most frequent of these syndromes. Similar hypothalamic and trigeminovascular mechanisms have been discussed as pathophysiologic mechanisms for all TACs. The therapeutic strategies, however, differ considerably. Although unusual, structural lesions in TACs have been described, affecting the therapeutic management.

General purpose molecular dynamics simulations fully implemented on graphics processing units

NASA Astrophysics Data System (ADS)

Anderson, Joshua A.; Lorenz, Chris D.; Travesset, A.

2008-05-01

Graphics processing units (GPUs), originally developed for rendering real-time effects in computer games, now provide unprecedented computational power for scientific applications. In this paper, we develop a general purpose molecular dynamics code that runs entirely on a single GPU. It is shown that our GPU implementation provides a performance equivalent to that of fast 30 processor core distributed memory cluster. Our results show that GPUs already provide an inexpensive alternative to such clusters and discuss implications for the future.

Discovery of 4ms and 7 MS Pulsars in M15 (F & H)

NASA Astrophysics Data System (ADS)

Middleditch, J.

1992-12-01

Observations of M15 taken during Oct. 23-Nov. 1 1991 with the Arecibo 305-m telescope at 430 MHz, which were analyzed using 2-billion point Fourier transforms on supercomputers at Los Alamos National Laboratory, reveal two new ms pulsars in the globular cluster, M15. The sixth and fastest yet discovered in this cluster, M15F, has a spin rate of 248.3 Hz, while the eighth and latest to be discovered in this cluster has a spin rate of 148.3 Hz, the only one known so far in the frequency interval of 100-200 Hz. Further details and implications of these discoveries will be discussed.

Superposition-free comparison and clustering of antibody binding sites: implications for the prediction of the nature of their antigen

PubMed Central

Di Rienzo, Lorenzo; Milanetti, Edoardo; Lepore, Rosalba; Olimpieri, Pier Paolo; Tramontano, Anna

2017-01-01

We describe here a superposition free method for comparing the surfaces of antibody binding sites based on the Zernike moments and show that they can be used to quickly compare and cluster sets of antibodies. The clusters provide information about the nature of the bound antigen that, when combined with a method for predicting the number of direct antibody antigen contacts, allows the discrimination between protein and non-protein binding antibodies with an accuracy of 76%. This is of relevance in several aspects of antibody science, for example to select the framework to be used for a combinatorial antibody library. PMID:28338016

Cluster sizes in a classical Lennard-Jones chain

NASA Astrophysics Data System (ADS)

Lee-Dadswell, G. R.; Barrett, Nicholas; Power, Michael

2017-09-01

The definitions of breaks and clusters in a one-dimensional chain in equilibrium are discussed. Analytical expressions are obtained for the expected cluster length, 〈K 〉 , as a function of temperature and pressure in a one-dimensional Lennard-Jones chain. These expressions are compared with results from molecular dynamics simulations. It is found that 〈K 〉 increases exponentially with β =1 /kBT and with pressure, P in agreement with previous results in the literature. A method is illustrated for using 〈K 〉(β ,P ) to generate a "phase diagram" for the Lennard-Jones chain. Some implications for the study of heat transport in Lennard-Jones chains are discussed.

Gender-specific behavioral health and community release patterns among New Jersey prison inmates: implications for treatment and community reentry.

PubMed

Blitz, Cynthia L; Wolff, Nancy; Pan, Ko-Yu; Pogorzelski, Wendy

2005-10-01

We describe behavioral health diagnoses and community release patterns among adult male and female inmates in New Jersey prisons and assess their implications for correctional health care and community reentry. We used clinical and classification data on a census of "special needs" inmates (those with behavioral health disorders) in New Jersey (n=3189) and a census of all special needs inmates released to New Jersey communities over a 12-month period (n=974). Virtually all adult inmates with special needs had at least 1 Axis I mental disorder, and 68% of these had at least 1 additional Axis I mental disorder, a personality disorder, or addiction problem (67% of all male and 75% of all female special needs inmates). Of those special needs inmates released, 25% returned to the most disadvantaged counties in New Jersey (27% of all male and 18% of all female special needs inmates). Two types of clustering were found: gender-specific clustering of disorders among inmates and spatial clustering of ex-offenders in impoverished communities. These findings suggest a need for gendered treatment strategies within correctional settings and need for successful reentry strategies.

More than one way to be happy: a typology of marital happiness.

PubMed

Rauer, Amy; Volling, Brenda

2013-09-01

This study utilized observational and self-report data from 57 happily married couples to explore assumptions regarding marital happiness. Suggesting that happily married couples are not a homogeneous group, cluster analyses revealed the existence of three types of couples based on their observed behaviors in a problem-solving task: (1) mutually engaged couples (characterized by both spouses' higher negative and positive problem-solving); (2) mutually supportive couples (characterized by both spouses' higher positivity and support); and (3) wife compensation couples (characterized by high wife positivity). Although couples in all three clusters were equally happy with and committed to their marriages, these clusters were differentially associated with spouses' evaluations of their marriage. Spouses in the mutually supportive cluster reported greater intimacy and maintenance and less conflict and ambivalence, although this was more consistently the case in comparison to the wife compensation cluster, as opposed to the mutually engaged cluster. The implications of these typologies are discussed as they pertain to efforts on the part of both practitioners to promote marital happiness and repair marital relations when couples are faced with difficulties. © FPI, Inc.

Ambiguity and judgments of obese individuals: no news could be bad news.

PubMed

Ross, Kathryn M; Shivy, Victoria A; Mazzeo, Suzanne E

2009-08-01

Stigmatization towards obese individuals has not decreased despite the increasing prevalence of obesity. Nonetheless, stigmatization remains difficult to study, given concerns about social desirability. To address this issue, this study used paired comparisons and cluster analysis to examine how undergraduates (n=189) categorized scenarios describing the health-related behaviors of obese individuals. The cluster analysis found that the scenarios were categorized into two distinct clusters. The first cluster included all scenarios with health behaviors indicating high responsibility for body weight. These individuals were perceived as unattractive, lazy, less likeable, less disciplined, and more deserving of their condition compared to individuals in the second cluster, which included all scenarios with health behaviors indicating low responsibility for body weight. Four scenarios depicted obese individuals with ambiguous information regarding health behaviors; three out of these four individuals were categorized in the high-responsibility cluster. These findings suggested that participants viewed these individuals as negatively as those who were responsible for their condition. These results have practical implications for reducing obesity bias, as the etiology of obesity is typically not known in real-life situations.

Dietary patterns and sarcopenia in an urban African American and White population in the United States.

PubMed

Fanelli Kuczmarski, Marie; Mason, Marc A; Beydoun, May A; Allegro, Deanne; Zonderman, Alan B; Evans, Michele K

2013-01-01

The primary objective of this cross-sectional study was to characterize dietary patterns of African Americans and Whites, 30 to 64 years, examined in the Healthy Aging in Neighborhoods of Diversity across the Life Span study. Other objectives of the study were to evaluate micronutrient adequacy of each pattern and to determine the association of diet with sarcopenia. Cluster analysis was used to determine patterns and mean adequacy ratio (MAR) to determine adequacy of 15 micronutrients. Ten clusters were identified: sandwich, sweet drink, pizza, poultry, frozen meal, dessert, alcoholic drink, bread, starchy vegetables, and pasta/rice dish. MAR ranged from 69 for the sweet drink cluster to 82 for the pasta/rice dish cluster. Sarcopenia was present in 6.4% of the sample, ranging from 1.5% in the poultry cluster to 14.1% in the alcoholic drink cluster. This study is the first to report an association between diet and sarcopenia in people younger than 65 years. The identification of presarcopenia has important implications for dietary interventions that might delay age-associated loss of lean mass.

Mixing and Matching Siderophore Clusters: Structure and Biosynthesis of Serratiochelins from Serratia sp. V4

PubMed Central

2012-01-01

Interrogation of the evolutionary history underlying the remarkable structures and biological activities of natural products has been complicated by not knowing the functions they have evolved to fulfill. Siderophores—soluble, low molecular weight compounds—have an easily understood and measured function: acquiring iron from the environment. Bacteria engage in a fierce competition to acquire iron, which rewards the production of siderophores that bind iron tightly and cannot be used or pirated by competitors. The structures and biosyntheses of “odd” siderophores can reveal the evolutionary strategy that led to their creation. We report a new Serratia strain that produces serratiochelin and an analog of serratiochelin. A genetic approach located the serratiochelin gene cluster, and targeted mutations in several genes implicated in serratiochelin biosynthesis were generated. Bioinformatic analyses and mutagenesis results demonstrate that genes from two well-known siderophore clusters, the Escherichia coli enterobactin cluster and the Vibrio cholera vibriobactin cluster, were shuffled to produce a new siderophore biosynthetic pathway. These results highlight how modular siderophore gene clusters can be mixed and matched during evolution to generate structural diversity in siderophores. PMID:22830960

Mixing and matching siderophore clusters: structure and biosynthesis of serratiochelins from Serratia sp. V4.

PubMed

Seyedsayamdost, Mohammad R; Cleto, Sara; Carr, Gavin; Vlamakis, Hera; João Vieira, Maria; Kolter, Roberto; Clardy, Jon

2012-08-22

Interrogation of the evolutionary history underlying the remarkable structures and biological activities of natural products has been complicated by not knowing the functions they have evolved to fulfill. Siderophores-soluble, low molecular weight compounds-have an easily understood and measured function: acquiring iron from the environment. Bacteria engage in a fierce competition to acquire iron, which rewards the production of siderophores that bind iron tightly and cannot be used or pirated by competitors. The structures and biosyntheses of "odd" siderophores can reveal the evolutionary strategy that led to their creation. We report a new Serratia strain that produces serratiochelin and an analog of serratiochelin. A genetic approach located the serratiochelin gene cluster, and targeted mutations in several genes implicated in serratiochelin biosynthesis were generated. Bioinformatic analyses and mutagenesis results demonstrate that genes from two well-known siderophore clusters, the Escherichia coli enterobactin cluster and the Vibrio cholera vibriobactin cluster, were shuffled to produce a new siderophore biosynthetic pathway. These results highlight how modular siderophore gene clusters can be mixed and matched during evolution to generate structural diversity in siderophores.

Two Cepheid variables in the Fornax dwarf galaxy

NASA Technical Reports Server (NTRS)

Light, R. M.; Armandroff, T. E.; Zinn, R.

1986-01-01

Two fields surrounding globular clusters 2 and 3 in the Fornax dwarf spheroidal galaxy have been searched for short-period variable stars that are brighter than the horizontal branch. This survey confirmed as variable the two suspected suprahorizontal-branch variables discovered by Buonanno et al. (1985) in their photometry of the clusters. The observations show that the star in cluster 2 is a W Virginis variable of 14.4 day period. It is the first W Vir variable to be found in a dwarf spheroidal galaxy, and its proximity to the center of cluster 2 suggests that it is a cluster member. The other star appears to be an anomalous Cephpeid of 0.78 day period. It lies outside or very near the boundary of cluster 3, and is therefore probably a member of the field population of Fornax. Although no other suprahorizontal-branch variables were discovered in the survey, it did confirm as variable two of the RR Lyrae candidates of Buonanno et al., which appeared at the survey limit. The implications of these observations for the understanding of the stellar content at Fornax are discussed.

Links between patterns of racial socialization and discrimination experiences and psychological adjustment: a cluster analysis.

PubMed

Ajayi, Alex A; Syed, Moin

2014-10-01

This study used a person-oriented analytic approach to identify meaningful patterns of barriers-focused racial socialization and perceived racial discrimination experiences in a sample of 295 late adolescents. Using cluster analysis, three distinct groups were identified: Low Barrier Socialization-Low Discrimination, High Barrier Socialization-Low Discrimination, and High Barrier Socialization-High Discrimination clusters. These groups were substantively unique in terms of the frequency of racial socialization messages about bias preparation and out-group mistrust its members received and their actual perceived discrimination experiences. Further, individuals in the High Barrier Socialization-High Discrimination cluster reported significantly higher depressive symptoms than those in the Low Barrier Socialization-Low Discrimination and High Barrier Socialization-Low Discrimination clusters. However, no differences in adjustment were observed between the Low Barrier Socialization-Low Discrimination and High Barrier Socialization-Low Discrimination clusters. Overall, the findings highlight important individual differences in how young people of color experience their race and how these differences have significant implications on psychological adjustment. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Clustering of four major lifestyle risk factors among Korean adults with metabolic syndrome.

PubMed

Ha, Shin; Choi, Hui Ran; Lee, Yo Han

2017-01-01

The purpose of this study was to investigate the clustering pattern of four major lifestyle risk factors-smoking, heavy drinking, poor diet, and physical inactivity-among people with metabolic syndrome in South Korea. There were 2,469 adults with metabolic syndrome aged 30 years or older available with the 5th Korean National Health and Nutrition Examination Survey dataset. We calculated the ratio of the observed to expected (O/E) prevalence for the 16 different combinations and the prevalence odds ratios (POR) of four lifestyle risk factors. The four lifestyle risk factors tended to cluster in specific multiple combinations. Smoking and heavy drinking was clustered (POR: 1.86 for male, 4.46 for female), heavy drinking and poor diet were clustered (POR: 1.38 for male, 1.74 for female), and smoking and physical inactivity were also clustered (POR: 1.48 for male). Those who were male, younger, low-educated and living alone were much more likely to have a higher number of lifestyle risk factors. Some helpful implications can be drawn from the knowledge on clustering pattern of lifestyle risk factors for more effective intervention program targeting metabolic syndrome.

A near ambient pressure XPS study of subnanometer silver clusters on Al 2O 3 and TiO 2 ultrathin film supports

DOE PAGES

Mao, Bao -Hua; Chang, Rui; Shi, Lei; ...

2014-10-29

Here, we have investigated model systems of silver clusters with different sizes (3 and 15 atoms) deposited on alumina and titania supports using ambient pressure X-ray photoelectron spectroscopy. The electronic structures of silver clusters and support materials are studied upon exposure to various atmospheres (ultrahigh vacuum, O 2 and CO) at different temperatures. Compared to bulk silver, the binding energies of silver clusters are about 0.55 eV higher on TiO 2 and 0.95 eV higher on Al 2O 3 due to the final state effect and the interaction with supports. No clear size effect of the silver XPS peak ismore » observed on different silver clusters among these samples. Silver clusters on titania show better stability against sintering. Al 2p and Ti 2p core level peak positions of the alumina and titania support surfaces change upon exposure to oxygen while the Ag 3d core level position remains unchanged. We discuss the origin of these core level shifts and their implications for catalytic properties of Ag clusters.« less

The very massive star content of the nuclear star clusters in NGC 5253

NASA Astrophysics Data System (ADS)

Smith, Linda J.; Crowther, Paul A.; Calzetti, Daniela

2017-11-01

The blue compact dwarf galaxy NGC 5253 hosts a very young starburst containing twin nuclear star clusters. Calzetti et al. (2015) find that the two clusters have an age of 1 Myr, in contradiction to the age of 3-5 Myr inferred from the presence of Wolf-Rayet (W-R) spectral features. We use Hubble Space Telescope (HST) far-ultraviolet (FUV) and ground-based optical spectra to show that the cluster stellar features arise from very massive stars (VMS), with masses greater than 100 M⊙, at an age of 1-2 Myr. We discuss the implications of this and show that the very high ionizing flux can only be explained by VMS. We further discuss our findings in the context of VMS contributing to He ii λ1640 emission in high redshift galaxies, and emphasize that population synthesis models with upper mass cut-offs greater than 100 M⊙ are crucial for future studies of young massive clusters.

Emerging critical roles of Fe-S clusters in DNA replication and repair

PubMed Central

Fuss, Jill O.; Tsai, Chi-Lin; Ishida, Justin P.; Tainer, John A.

2015-01-01

Fe-S clusters are partners in the origin of life that predate cells, acetyl-CoA metabolism, DNA, and the RNA world. The double helix solved the mystery of DNA replication by base pairing for accurate copying. Yet, for genome stability necessary to life, the double helix has equally important implications for damage repair. Here we examine striking advances that uncover Fe-S cluster roles both in copying the genetic sequence by DNA polymerases and in crucial repair processes for genome maintenance, as mutational defects cause cancer and degenerative disease. Moreover, we examine an exciting, controversial role for Fe-S clusters in a third element required for life – the long-range coordination and regulation of replication and repair events. By their ability to delocalize electrons over both Fe and S centers, Fe-S clusters have unbeatable features for protein conformational control and charge transfer via double-stranded DNA that may fundamentally transform our understanding of life, replication, and repair. PMID:25655665

Photometric Calibrations of Gemini Images of NGC 6253

NASA Astrophysics Data System (ADS)

Pearce, Sean; Jeffery, Elizabeth

2017-01-01

We present preliminary results of our analysis of the metal-rich open cluster NGC 6253 using imaging data from GMOS on the Gemini-South Observatory. These data are part of a larger project to observe the effects of high metallicity on white dwarf cooling processes, especially the white dwarf cooling age, which have important implications on the processes of stellar evolution. To standardize the Gemini photometry, we have also secured imaging data of both the cluster and standard star fields using the 0.6-m SARA Observatory at CTIO. By analyzing and comparing the standard star fields of both the SARA data and the published Gemini zero-points of the standard star fields, we will calibrate the data obtained for the cluster. These calibrations are an important part of the project to obtain a standardized deep color-magnitude diagram to analyze the cluster. We present the process of verifying our standardization process. With a standardized CMD, we also present an analysis of the cluster's main sequence turn off age.

MASS ACCRETION AND ITS EFFECTS ON THE SELF-SIMILARITY OF GAS PROFILES IN THE OUTSKIRTS OF GALAXY CLUSTERS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lau, Erwin T.; Nagai, Daisuke; Avestruz, Camille

2015-06-10

Galaxy clusters exhibit remarkable self-similar behavior which allows us to establish simple scaling relationships between observable quantities and cluster masses, making galaxy clusters useful cosmological probes. Recent X-ray observations suggested that self-similarity may be broken in the outskirts of galaxy clusters. In this work, we analyze a mass-limited sample of massive galaxy clusters from the Omega500 cosmological hydrodynamic simulation to investigate the self-similarity of the diffuse X-ray emitting intracluster medium (ICM) in the outskirts of galaxy clusters. We find that the self-similarity of the outer ICM profiles is better preserved if they are normalized with respect to the mean densitymore » of the universe, while the inner profiles are more self-similar when normalized using the critical density. However, the outer ICM profiles as well as the location of accretion shock around clusters are sensitive to their mass accretion rate, which causes the apparent breaking of self-similarity in cluster outskirts. We also find that the collisional gas does not follow the distribution of collisionless dark matter (DM) perfectly in the infall regions of galaxy clusters, leading to 10% departures in the gas-to-DM density ratio from the cosmic mean value. Our results have a number implications for interpreting observations of galaxy clusters in X-ray and through the Sunyaev–Zel’dovich effect, and their applications to cosmology.« less

Transcriptome Analysis of Aspergillus flavus Reveals veA-Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster

PubMed Central

Cary, J. W.; Han, Z.; Yin, Y.; Lohmar, J. M.; Shantappa, S.; Harris-Coward, P. Y.; Mack, B.; Ehrlich, K. C.; Wei, Q.; Arroyo-Manzanares, N.; Uka, V.; Vanhaecke, L.; Bhatnagar, D.; Yu, J.; Nierman, W. C.; Johns, M. A.; Sorensen, D.; Shen, H.; De Saeger, S.; Diana Di Mavungu, J.

2015-01-01

The global regulatory veA gene governs development and secondary metabolism in numerous fungal species, including Aspergillus flavus. This is especially relevant since A. flavus infects crops of agricultural importance worldwide, contaminating them with potent mycotoxins. The most well-known are aflatoxins, which are cytotoxic and carcinogenic polyketide compounds. The production of aflatoxins and the expression of genes implicated in the production of these mycotoxins are veA dependent. The genes responsible for the synthesis of aflatoxins are clustered, a signature common for genes involved in fungal secondary metabolism. Studies of the A. flavus genome revealed many gene clusters possibly connected to the synthesis of secondary metabolites. Many of these metabolites are still unknown, or the association between a known metabolite and a particular gene cluster has not yet been established. In the present transcriptome study, we show that veA is necessary for the expression of a large number of genes. Twenty-eight out of the predicted 56 secondary metabolite gene clusters include at least one gene that is differentially expressed depending on presence or absence of veA. One of the clusters under the influence of veA is cluster 39. The absence of veA results in a downregulation of the five genes found within this cluster. Interestingly, our results indicate that the cluster is expressed mainly in sclerotia. Chemical analysis of sclerotial extracts revealed that cluster 39 is responsible for the production of aflavarin. PMID:26209694

Biased phylodynamic inferences from analysing clusters of viral sequences

PubMed Central

Xiang, Fei; Frost, Simon D. W.

2017-01-01

Abstract Phylogenetic methods are being increasingly used to help understand the transmission dynamics of measurably evolving viruses, including HIV. Clusters of highly similar sequences are often observed, which appear to follow a ‘power law’ behaviour, with a small number of very large clusters. These clusters may help to identify subpopulations in an epidemic, and inform where intervention strategies should be implemented. However, clustering of samples does not necessarily imply the presence of a subpopulation with high transmission rates, as groups of closely related viruses can also occur due to non-epidemiological effects such as over-sampling. It is important to ensure that observed phylogenetic clustering reflects true heterogeneity in the transmitting population, and is not being driven by non-epidemiological effects. We qualify the effect of using a falsely identified ‘transmission cluster’ of sequences to estimate phylodynamic parameters including the effective population size and exponential growth rate under several demographic scenarios. Our simulation studies show that taking the maximum size cluster to re-estimate parameters from trees simulated under a randomly mixing, constant population size coalescent process systematically underestimates the overall effective population size. In addition, the transmission cluster wrongly resembles an exponential or logistic growth model 99% of the time. We also illustrate the consequences of false clusters in exponentially growing coalescent and birth-death trees, where again, the growth rate is skewed upwards. This has clear implications for identifying clusters in large viral databases, where a false cluster could result in wasted intervention resources. PMID:28852573

Teenage suicide cluster formation and contagion: implications for primary care

PubMed Central

Johansson, Lars; Lindqvist, Per; Eriksson, Anders

2006-01-01

Background We have previously studied unintentional as well as intentional injury deaths among teenagers living in the four northernmost counties, forming approximately 55% of Sweden with 908,000 inhabitants in 1991. During this work, we found what we suspected to be a suicide cluster among teenagers and we also suspected contagion since there were links between these cases. In this present study, we investigate the occurrence of suicide clustering among teenagers, analyze cluster definitions, and suggest preventive measures. Methods A retrospective study of teenager suicides autopsied at the Department of Forensic Medicine in Umeå, Sweden, during 1981 through 2000. Police reports, autopsy protocols, and medical records were studied in all cases, and the police officers that conducted the investigation at the scene were interviewed in all cluster cases. Parents of the suicide victims of the first cluster were also interviewed. Two aggregations of teenager suicides were detected and evaluated as possible suicide clusters using the US Centers for Disease Control definition of a suicide cluster. Results Two clusters including six teenagers were confirmed, and contagion was established within each cluster. Conclusion The general practitioner is identified as a key person in the aftermath of a teenage suicide since the general practitioner often meet the family, friends of the deceased, and other acquaintances early in the process after a suicide. This makes the general practitioner suitable to initiate contacts with others involved in the well-being of the young, in order to prevent suicide cluster formation and para-suicidal activities. PMID:16707009

Fatality rate of pedestrians and fatal crash involvement rate of drivers in pedestrian crashes: a case study of Iran.

PubMed

Kashani, Ali Tavakoli; Besharati, Mohammad Mehdi

2017-06-01

The aim of this study was to uncover patterns of pedestrian crashes. In the first stage, 34,178 pedestrian-involved crashes occurred in Iran during a four-year period were grouped into homogeneous clusters using a clustering analysis. Next, some in-cluster and inter-cluster crash patterns were analysed. The clustering analysis yielded six pedestrian crash groups. Car/van/pickup crashes on rural roads as well as heavy vehicle crashes were found to be less frequent but more likely to be fatal compared to other crash clusters. In addition, after controlling for crash frequency in each cluster, it was found that the fatality rate of each pedestrian age group as well as the fatal crash involvement rate of each driver age group varies across the six clusters. Results of present study has some policy implications including, promoting pedestrian safety training sessions for heavy vehicle drivers, imposing limitations over elderly heavy vehicle drivers, reinforcing penalties toward under 19 drivers and motorcyclists. In addition, road safety campaigns in rural areas may be promoted to inform people about the higher fatality rate of pedestrians on rural roads. The crash patterns uncovered in this study might also be useful for prioritizing future pedestrian safety research areas.

The ergot alkaloid gene cluster: functional analyses and evolutionary aspects.

PubMed

Lorenz, Nicole; Haarmann, Thomas; Pazoutová, Sylvie; Jung, Manfred; Tudzynski, Paul

2009-01-01

Ergot alkaloids and their derivatives have been traditionally used as therapeutic agents in migraine, blood pressure regulation and help in childbirth and abortion. Their production in submerse culture is a long established biotechnological process. Ergot alkaloids are produced mainly by members of the genus Claviceps, with Claviceps purpurea as best investigated species concerning the biochemistry of ergot alkaloid synthesis (EAS). Genes encoding enzymes involved in EAS have been shown to be clustered; functional analyses of EAS cluster genes have allowed to assign specific functions to several gene products. Various Claviceps species differ with respect to their host specificity and their alkaloid content; comparison of the ergot alkaloid clusters in these species (and of clavine alkaloid clusters in other genera) yields interesting insights into the evolution of cluster structure. This review focuses on recently published and also yet unpublished data on the structure and evolution of the EAS gene cluster and on the function and regulation of cluster genes. These analyses have also significant biotechnological implications: the characterization of non-ribosomal peptide synthetases (NRPS) involved in the synthesis of the peptide moiety of ergopeptines opened interesting perspectives for the synthesis of ergot alkaloids; on the other hand, defined mutants could be generated producing interesting intermediates or only single peptide alkaloids (instead of the alkaloid mixtures usually produced by industrial strains).

Rayleigh Scattering Density Measurements, Cluster Theory, and Nucleation Calculations at Mach 10

NASA Technical Reports Server (NTRS)

Balla, R. Jeffrey; Everhart, Joel L.

2012-01-01

In an exploratory investigation, quantitative unclustered laser Rayleigh scattering measurements of density were performed in the air in the NASA Langley Research Center's 31 in. Mach 10 wind tunnel. A review of 20 previous years of data in supersonic and Mach 6 hypersonic flows is presented where clustered signals typically overwhelmed molecular signals. A review of nucleation theory and accompanying nucleation calculations are also provided to interpret the current observed lack of clustering. Data were acquired at a fixed stagnation temperature near 990Kat five stagnation pressures spanning 2.41 to 10.0 MPa (350 to 1454 psi) using a pulsed argon fluoride excimer laser and double-intensified charge-coupled device camera. Data averaged over 371 images and 210 pixels along a 36.7mmline measured freestream densities that agree with computed isentropic-expansion densities to less than 2% and less than 6% at the highest and lowest densities, respectively. Cluster-free Mach 10 results are compared with previous clustered Mach 6 and condensation-free Mach 14 results. Evidence is presented indicating vibrationally excited oxygen and nitrogen molecules are absorbed as the clusters form, release their excess energy, and inhibit or possibly reverse the clustering process. Implications for delaying clustering and condensation onset in hypersonic and hypervelocity facilities are discussed.

The clustering of galaxies in the completed SDSS-III Baryon Oscillation Spectroscopic Survey: Cosmological implications of the Fourier space wedges of the final sample

NASA Astrophysics Data System (ADS)

Grieb, Jan Niklas; Sánchez, Ariel G.; Salazar-Albornoz, Salvador; Scoccimarro, Román; Crocce, Martín; Dalla Vecchia, Claudio; Montesano, Francesco; Gil-Marín, Héctor; Ross, Ashley J.; Beutler, Florian; Rodríguez-Torres, Sergio; Chuang, Chia-Hsun; Prada, Francisco; Kitaura, Francisco-Shu; Cuesta, Antonio J.; Eisenstein, Daniel J.; Percival, Will J.; Vargas-Magaña, Mariana; Tinker, Jeremy L.; Tojeiro, Rita; Brownstein, Joel R.; Maraston, Claudia; Nichol, Robert C.; Olmstead, Matthew D.; Samushia, Lado; Seo, Hee-Jong; Streblyanska, Alina; Zhao, Gong-bo

2017-05-01

We extract cosmological information from the anisotropic power-spectrum measurements from the recently completed Baryon Oscillation Spectroscopic Survey (BOSS), extending the concept of clustering wedges to Fourier space. Making use of new fast-Fourier-transform-based estimators, we measure the power-spectrum clustering wedges of the BOSS sample by filtering out the information of Legendre multipoles ℓ > 4. Our modelling of these measurements is based on novel approaches to describe non-linear evolution, bias and redshift-space distortions, which we test using synthetic catalogues based on large-volume N-body simulations. We are able to include smaller scales than in previous analyses, resulting in tighter cosmological constraints. Using three overlapping redshift bins, we measure the angular-diameter distance, the Hubble parameter and the cosmic growth rate, and explore the cosmological implications of our full-shape clustering measurements in combination with cosmic microwave background and Type Ia supernova data. Assuming a Λ cold dark matter (ΛCDM) cosmology, we constrain the matter density to Ω M= 0.311_{-0.010}^{+0.009} and the Hubble parameter to H_0 = 67.6_{-0.6}^{+0.7} km s^{-1 Mpc^{-1}}, at a confidence level of 68 per cent. We also allow for non-standard dark energy models and modifications of the growth rate, finding good agreement with the ΛCDM paradigm. For example, we constrain the equation-of-state parameter to w = -1.019_{-0.039}^{+0.048}. This paper is part of a set that analyses the final galaxy-clustering data set from BOSS. The measurements and likelihoods presented here are combined with others in Alam et al. to produce the final cosmological constraints from BOSS.

Robust Production, Crystallization, Structure Determination, and Analysis of [Fe-S] Proteins: Uncovering Control of Electron Shuttling and Gating in the Respiratory Metabolism of Molybdopterin Guanine Dinucleotide Enzymes.

PubMed

Tsai, Chi-Lin; Tainer, John A

2018-01-01

[Fe-S] clusters are essential cofactors in all domains of life. They play many biological roles due to their unique abilities for electron transfer and conformational control. Yet, producing and analyzing Fe-S proteins can be difficult and even misleading if not done anaerobically. Due to unique redox properties of [Fe-S] clusters and their oxygen sensitivity, they pose multiple challenges and can lose enzymatic activity or cause their component proteins to be structurally disordered due to [Fe-S] cluster oxidation and loss in air. Here we highlight tested protocols and strategies enabling efficient and stable [Fe-S] protein production, purification, crystallization, X-ray diffraction data collection, and structure determination. From multiple high-resolution anaerobic crystal structures, we furthermore analyze exemplary data defining [Fe-S] clusters, substrate entry, and product exit for the functional oxidation states of type II molybdo-bis(molybdopterin guanine dinucleotide) (Mo-bisMGD) enzymes. Notably, these enzymes perform electron shuttling between quinone pools and specific substrates to catalyze respiratory metabolism. The identified structure-activity relationships for this enzyme class have broad implications germane to perchlorate environments on Earth and Mars extending to an alternative mechanism underlying metabolic origins for the evolution of the oxygen atmosphere. Integrated structural analyses of type II Mo-bisMGD enzymes unveil novel distinctive shared molecular mechanisms for dynamic control of substrate entry and product release gated by hydrophobic residues. Collective findings support a prototypic model for type II Mo-bisMGD enzymes including insights for a fundamental molecular mechanistic understanding of selectivity and regulation by a conformationally gated channel with general implications for [Fe-S] cluster respiratory enzymes. © 2018 Elsevier Inc. All rights reserved.

Nuclear pasta in hot dense matter and its implications for neutrino scattering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roggero, Alessandro; Margueron, Jerome; Roberts, Luke F.

The abundance of large clusters of nucleons in neutron-rich matter at subnuclear density is found to be greatly reduced by finite-temperature effects when matter is close to β equilibrium, compared to the case where the electron fraction is fixed at Y e > 0.1 , as often considered in the literature. Large nuclei and exotic nonspherical nuclear configurations called pasta, favored in the vicinity of the transition to uniform matter at T = 0 , dissolve at a relatively low temperature T u as protons leak out of nuclei and pasta. For matter at β-equilibrium with a negligible neutrino chemical potential we find that Tmore » $$β\\atop{u}$$ ≃ 4 ± 1 MeV for realistic equations of state. This is lower than the maximum temperature T$$β\\atop{max}$$ ≃ 9 ± 1 MeV at which nuclei can coexist with a gas of nucleons and can be explained by a change in the nature of the transition to uniform matter called retrograde condensation. An important new finding is that coherent neutrino scattering from nuclei and pasta makes a modest contribution to the opacity under the conditions encountered in supernovas and neutron star mergers. This is because large nuclear clusters dissolve at most relevant temperatures, and at lower temperatures, when clusters are present, Coulomb correlations between them suppress coherent neutrino scattering off individual clusters. Lastly, implications for neutrino signals from galactic supernovas are briefly discussed.« less

Nuclear pasta in hot dense matter and its implications for neutrino scattering

DOE PAGES

Roggero, Alessandro; Margueron, Jerome; Roberts, Luke F.; ...

2018-04-16

The abundance of large clusters of nucleons in neutron-rich matter at subnuclear density is found to be greatly reduced by finite-temperature effects when matter is close to β equilibrium, compared to the case where the electron fraction is fixed at Y e > 0.1 , as often considered in the literature. Large nuclei and exotic nonspherical nuclear configurations called pasta, favored in the vicinity of the transition to uniform matter at T = 0 , dissolve at a relatively low temperature T u as protons leak out of nuclei and pasta. For matter at β-equilibrium with a negligible neutrino chemical potential we find that Tmore » $$β\\atop{u}$$ ≃ 4 ± 1 MeV for realistic equations of state. This is lower than the maximum temperature T$$β\\atop{max}$$ ≃ 9 ± 1 MeV at which nuclei can coexist with a gas of nucleons and can be explained by a change in the nature of the transition to uniform matter called retrograde condensation. An important new finding is that coherent neutrino scattering from nuclei and pasta makes a modest contribution to the opacity under the conditions encountered in supernovas and neutron star mergers. This is because large nuclear clusters dissolve at most relevant temperatures, and at lower temperatures, when clusters are present, Coulomb correlations between them suppress coherent neutrino scattering off individual clusters. Lastly, implications for neutrino signals from galactic supernovas are briefly discussed.« less

Characterization of the Amicetin Biosynthesis Gene Cluster from Streptomyces vinaceusdrappus NRRL 2363 Implicates Two Alternative Strategies for Amide Bond Formation

PubMed Central

Zhang, Gaiyun; Zhang, Haibo; Li, Sumei; Xiao, Ji; Zhang, Guangtao; Zhu, Yiguang; Niu, Siwen; Ju, Jianhua

2012-01-01

Amicetin, an antibacterial and antiviral agent, belongs to a group of disaccharide nucleoside antibiotics featuring an α-(1→4)-glycoside bond in the disaccharide moiety. In this study, the amicetin biosynthesis gene cluster was cloned from Streptomyces vinaceusdrappus NRRL 2363 and localized on a 37-kb contiguous DNA region. Heterologous expression of the amicetin biosynthesis gene cluster in Streptomyces lividans TK64 resulted in the production of amicetin and its analogues, thereby confirming the identity of the ami gene cluster. In silico sequence analysis revealed that 21 genes were putatively involved in amicetin biosynthesis, including 3 for regulation and transportation, 10 for disaccharide biosynthesis, and 8 for the formation of the amicetin skeleton by the linkage of cytosine, p-aminobenzoic acid (PABA), and the terminal (+)-α-methylserine moieties. The inactivation of the benzoate coenzyme A (benzoate-CoA) ligase gene amiL and the N-acetyltransferase gene amiF led to two mutants that accumulated the same two compounds, cytosamine and 4-acetamido-3-hydroxybenzoic acid. These data indicated that AmiF functioned as an amide synthethase to link cytosine and PABA. The inactivation of amiR, encoding an acyl-CoA-acyl carrier protein transacylase, resulted in the production of plicacetin and norplicacetin, indicating AmiR to be responsible for attachment of the terminal methylserine moiety to form another amide bond. These findings implicated two alternative strategies for amide bond formation in amicetin biosynthesis. PMID:22267658

Stellar Wind Retention and Expulsion in Massive Star Clusters

NASA Astrophysics Data System (ADS)

Naiman, J. P.; Ramirez-Ruiz, E.; Lin, D. N. C.

2018-05-01

Mass and energy injection throughout the lifetime of a star cluster contributes to the gas reservoir available for subsequent episodes of star formation and the feedback energy budget responsible for ejecting material from the cluster. In addition, mass processed in stellar interiors and ejected as winds has the potential to augment the abundance ratios of currently forming stars, or stars which form at a later time from a retained gas reservoir. Here we present hydrodynamical simulations that explore a wide range of cluster masses, compactnesses, metallicities and stellar population age combinations in order to determine the range of parameter space conducive to stellar wind retention or wind powered gas expulsion in star clusters. We discuss the effects of the stellar wind prescription on retention and expulsion effectiveness, using MESA stellar evolutionary models as a test bed for exploring how the amounts of wind retention/expulsion depend upon the amount of mixing between the winds from stars of different masses and ages. We conclude by summarizing some implications for gas retention and expulsion in a variety of compact (σv ≳ 20 kms-1) star clusters including young massive star clusters (105 ≲ M/M⊙ ≲ 107, age ≲ 500 Myrs), intermediate age clusters (105 ≲ M/M⊙ ≲ 107, age ≈ 1 - 4 Gyrs), and globular clusters (105 ≲ M/M⊙ ≲ 107, age ≳ 10 Gyrs).

Distinct phenotype clusters in childhood inflammatory brain diseases: implications for diagnostic evaluation.

PubMed

Cellucci, Tania; Tyrrell, Pascal N; Twilt, Marinka; Sheikh, Shehla; Benseler, Susanne M

2014-03-01

To identify distinct clusters of children with inflammatory brain diseases based on clinical, laboratory, and imaging features at presentation, to assess which features contribute strongly to the development of clusters, and to compare additional features between the identified clusters. A single-center cohort study was performed with children who had been diagnosed as having an inflammatory brain disease between June 1, 1989 and December 31, 2010. Demographic, clinical, laboratory, neuroimaging, and histologic data at diagnosis were collected. K-means cluster analysis was performed to identify clusters of patients based on their presenting features. Associations between the clusters and patient variables, such as diagnoses, were determined. A total of 147 children (50% female; median age 8.8 years) were identified: 105 with primary central nervous system (CNS) vasculitis, 11 with secondary CNS vasculitis, 8 with neuronal antibody syndromes, 6 with postinfectious syndromes, and 17 with other inflammatory brain diseases. Three distinct clusters were identified. Paresis and speech deficits were the most common presenting features in cluster 1. Children in cluster 2 were likely to present with behavior changes, cognitive dysfunction, and seizures, while those in cluster 3 experienced ataxia, vision abnormalities, and seizures. Lesions seen on T2/fluid-attenuated inversion recovery sequences of magnetic resonance imaging were common in all clusters, but unilateral ischemic lesions were more prominent in cluster 1. The clusters were associated with specific diagnoses and diagnostic test results. Children with inflammatory brain diseases presented with distinct phenotypical patterns that are associated with specific diagnoses. This information may inform the development of a diagnostic classification of childhood inflammatory brain diseases and suggest that specific pathways of diagnostic evaluation are warranted. Copyright © 2014 by the American College of Rheumatology.

Cosmological Simulations of Galaxy Clusters

NASA Astrophysics Data System (ADS)

Borgani, Stefano; Kravtsov, Andrey

2011-02-01

We review recent progress in the description of the formation and evolution of galaxy clusters in a cosmological context by using state-of-art numerical simulations. We focus our presentation on the comparison between simulated and observed X-ray properties, while we will also discuss numerical predictions on properties of the galaxy population in clusters, as observed in the optical band. Many of the salient observed properties of clusters, such as scaling relations between X-ray observables and total mass, radial profiles of entropy and density of the intracluster gas, and radial distribution of galaxies are reproduced quite well. In particular, the outer regions of cluster at radii beyond about 10 per cent of the virial radius are quite regular and exhibit scaling with mass remarkably close to that expected in the simplest case in which only the action of gravity determines the evolution of the intra-cluster gas. However, simulations generally fail at reproducing the observed "cool core" structure of clusters: simulated clusters generally exhibit a significant excess of gas cooling in their central regions, which causes both an overestimate of the star formation in the cluster centers and incorrect temperature and entropy profiles. The total baryon fraction in clusters is below the mean universal value, by an amount which depends on the cluster-centric distance and the physics included in the simulations, with interesting tensions between observed stellar and gas fractions in clusters and predictions of simulations. Besides their important implications for the cosmological application of clusters, these puzzles also point towards the important role played by additional physical processes, beyond those already included in the simulations. We review the role played by these processes, along with the difficulty for their implementation, and discuss the outlook for the future progress in numerical modeling of clusters.

Assessing environmental quality: the implications for social justice

EPA Science Inventory

Individuals experience simultaneous exposure to pollutants and social factors, which cluster to affect human health outcomes. The optimal approach to combining these factors is unknown, therefore we developed a method to model simultaneous exposure using criteria air pollutants, ...

Implications for gravitational lensing and the dark matter content in clusters of galaxies from spatially resolved x-ray spectra

NASA Technical Reports Server (NTRS)

Loewenstein, M.

1994-01-01

A simple method for deriving well-behaved temperature solutions to the equation of hydrostatic equilibrium for intracluster media with X-ray imaging observations is presented and applied to a series of generalized models as well as to observations of the Perseus cluster and Abell 2256. In these applications the allowed range in the ratio of nonbaryons to baryons as a function of radius is derived, taking into account the uncertainties and crude spatial resolution of the X-ray spectra and considering a range of physically reasonable mass models with various scale heights. Particular attention is paid to the central regions of the cluster, and it is found that the dark matter can be sufficiently concentrated to be consistent with the high central mass surface densities for moderate-redshift clusters from their gravitational lensing properties.

Mutation Clusters from Cancer Exome.

PubMed

Kakushadze, Zura; Yu, Willie

2017-08-15

We apply our statistically deterministic machine learning/clustering algorithm *K-means (recently developed in https://ssrn.com/abstract=2908286) to 10,656 published exome samples for 32 cancer types. A majority of cancer types exhibit a mutation clustering structure. Our results are in-sample stable. They are also out-of-sample stable when applied to 1389 published genome samples across 14 cancer types. In contrast, we find in- and out-of-sample instabilities in cancer signatures extracted from exome samples via nonnegative matrix factorization (NMF), a computationally-costly and non-deterministic method. Extracting stable mutation structures from exome data could have important implications for speed and cost, which are critical for early-stage cancer diagnostics, such as novel blood-test methods currently in development.

Mutation Clusters from Cancer Exome

PubMed Central

Kakushadze, Zura; Yu, Willie

2017-01-01

We apply our statistically deterministic machine learning/clustering algorithm *K-means (recently developed in https://ssrn.com/abstract=2908286) to 10,656 published exome samples for 32 cancer types. A majority of cancer types exhibit a mutation clustering structure. Our results are in-sample stable. They are also out-of-sample stable when applied to 1389 published genome samples across 14 cancer types. In contrast, we find in- and out-of-sample instabilities in cancer signatures extracted from exome samples via nonnegative matrix factorization (NMF), a computationally-costly and non-deterministic method. Extracting stable mutation structures from exome data could have important implications for speed and cost, which are critical for early-stage cancer diagnostics, such as novel blood-test methods currently in development. PMID:28809811

Intertumoral Heterogeneity within Medulloblastoma Subgroups.

PubMed

Cavalli, Florence M G; Remke, Marc; Rampasek, Ladislav; Peacock, John; Shih, David J H; Luu, Betty; Garzia, Livia; Torchia, Jonathon; Nor, Carolina; Morrissy, A Sorana; Agnihotri, Sameer; Thompson, Yuan Yao; Kuzan-Fischer, Claudia M; Farooq, Hamza; Isaev, Keren; Daniels, Craig; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Lee, Ji Yeoun; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Vasiljevic, Alexandre; Faure-Conter, Cecile; Jouvet, Anne; Giannini, Caterina; Nageswara Rao, Amulya A; Li, Kay Ka Wai; Ng, Ho-Keung; Eberhart, Charles G; Pollack, Ian F; Hamilton, Ronald L; Gillespie, G Yancey; Olson, James M; Leary, Sarah; Weiss, William A; Lach, Boleslaw; Chambless, Lola B; Thompson, Reid C; Cooper, Michael K; Vibhakar, Rajeev; Hauser, Peter; van Veelen, Marie-Lise C; Kros, Johan M; French, Pim J; Ra, Young Shin; Kumabe, Toshihiro; López-Aguilar, Enrique; Zitterbart, Karel; Sterba, Jaroslav; Finocchiaro, Gaetano; Massimino, Maura; Van Meir, Erwin G; Osuka, Satoru; Shofuda, Tomoko; Klekner, Almos; Zollo, Massimo; Leonard, Jeffrey R; Rubin, Joshua B; Jabado, Nada; Albrecht, Steffen; Mora, Jaume; Van Meter, Timothy E; Jung, Shin; Moore, Andrew S; Hallahan, Andrew R; Chan, Jennifer A; Tirapelli, Daniela P C; Carlotti, Carlos G; Fouladi, Maryam; Pimentel, José; Faria, Claudia C; Saad, Ali G; Massimi, Luca; Liau, Linda M; Wheeler, Helen; Nakamura, Hideo; Elbabaa, Samer K; Perezpeña-Diazconti, Mario; Chico Ponce de León, Fernando; Robinson, Shenandoah; Zapotocky, Michal; Lassaletta, Alvaro; Huang, Annie; Hawkins, Cynthia E; Tabori, Uri; Bouffet, Eric; Bartels, Ute; Dirks, Peter B; Rutka, James T; Bader, Gary D; Reimand, Jüri; Goldenberg, Anna; Ramaswamy, Vijay; Taylor, Michael D

2017-06-12

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials. Copyright © 2017 Elsevier Inc. All rights reserved.

The relationship between sleep-wake cycle and cognitive functioning in young people with affective disorders.

PubMed

Carpenter, Joanne S; Robillard, Rébecca; Lee, Rico S C; Hermens, Daniel F; Naismith, Sharon L; White, Django; Whitwell, Bradley; Scott, Elizabeth M; Hickie, Ian B

2015-01-01

Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16-30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18-30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a 'long sleep' cluster, a 'disrupted sleep' cluster, and a 'delayed and disrupted sleep' cluster. Circadian clusters included a 'strong circadian' cluster, a 'weak circadian' cluster, and a 'delayed circadian' cluster. Medication use differed between clusters. The 'long sleep' cluster displayed significantly worse visual memory performance compared to the 'disrupted sleep' cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement of functioning in young adults early in the course of affective illness.

Clinical Implications of Cluster Analysis-Based Classification of Acute Decompensated Heart Failure and Correlation with Bedside Hemodynamic Profiles.

PubMed

Ahmad, Tariq; Desai, Nihar; Wilson, Francis; Schulte, Phillip; Dunning, Allison; Jacoby, Daniel; Allen, Larry; Fiuzat, Mona; Rogers, Joseph; Felker, G Michael; O'Connor, Christopher; Patel, Chetan B

2016-01-01

Classification of acute decompensated heart failure (ADHF) is based on subjective criteria that crudely capture disease heterogeneity. Improved phenotyping of the syndrome may help improve therapeutic strategies. To derive cluster analysis-based groupings for patients hospitalized with ADHF, and compare their prognostic performance to hemodynamic classifications derived at the bedside. We performed a cluster analysis on baseline clinical variables and PAC measurements of 172 ADHF patients from the ESCAPE trial. Employing regression techniques, we examined associations between clusters and clinically determined hemodynamic profiles (warm/cold/wet/dry). We assessed association with clinical outcomes using Cox proportional hazards models. Likelihood ratio tests were used to compare the prognostic value of cluster data to that of hemodynamic data. We identified four advanced HF clusters: 1) male Caucasians with ischemic cardiomyopathy, multiple comorbidities, lowest B-type natriuretic peptide (BNP) levels; 2) females with non-ischemic cardiomyopathy, few comorbidities, most favorable hemodynamics; 3) young African American males with non-ischemic cardiomyopathy, most adverse hemodynamics, advanced disease; and 4) older Caucasians with ischemic cardiomyopathy, concomitant renal insufficiency, highest BNP levels. There was no association between clusters and bedside-derived hemodynamic profiles (p = 0.70). For all adverse clinical outcomes, Cluster 4 had the highest risk, and Cluster 2, the lowest. Compared to Cluster 4, Clusters 1-3 had 45-70% lower risk of all-cause mortality. Clusters were significantly associated with clinical outcomes, whereas hemodynamic profiles were not. By clustering patients with similar objective variables, we identified four clinically relevant phenotypes of ADHF patients, with no discernable relationship to hemodynamic profiles, but distinct associations with adverse outcomes. Our analysis suggests that ADHF classification using simultaneous considerations of etiology, comorbid conditions, and biomarker levels, may be superior to bedside classifications.

Early stages of carbonate mineralization revealed from molecular simulations: Implications for biomineral formation

NASA Astrophysics Data System (ADS)

Wallace, A. F.; DeYoreo, J.; Banfield, J. F.

2011-12-01

The carbonate mineral constituents of many biomineralized products, formed both in and ex vivo, grow by a multi-stage crystallization process that involves the nucleation and structural reorganization of transient amorphous phases. The existence of transient phases and cluster species has significant implications for carbonate nucleation and growth in natural and engineered environments, both modern and ancient. The structure of these intermediate phases remains elusive, as does the nature of the disorder to order transition, however, these process details may strongly influence the interpretation of elemental and isotopic climate proxy data obtained from authigenic and biogenic carbonates. While molecular simulations have been applied to certain aspects of crystal growth, studies of metal carbonate nucleation are strongly inhibited by the presence of kinetic traps that prevent adequate sampling of the potential landscape upon which the growing clusters reside within timescales accessible by simulation. This research addresses this challenge by marrying the recent Kawska-Zahn (KZ) approach to simulation of crystal nucleation and growth from solution with replica-exchange molecular dynamics (REMD) techniques. REMD has been used previously to enhance sampling of protein conformations that occupy energy wells that are separated by sizable thermodynamic and kinetic barriers, and is used here to probe the initial formation and onset of order within hydrated calcium and iron carbonate cluster species during nucleation. Results to date suggest that growing clusters initiate as short linear ion chains that evolve into two- and three-dimensional structures with continued growth. The planar structures exhibit an obvious 2d lattice, while establishment of a 3d lattice is hindered by incomplete ion desolvation. The formation of a dehydrated core consisting of a single carbonate ion is observed when the clusters are ~0.75 nm. At the same size a distorted, but discernible calcite-type lattice is also apparent. Continued growth results in expansion of the dehydrated core, however, complete desolvation and incorporation of cations into the growing carbonate phase is not achieved until the cluster grows to ~1.2 nm. Exploration of the system free energy along the crystallization path reveals "special" cluster sizes that correlate with ion desolvation milestones. The formation of these species comprise critical bottlenecks on the energy landscape and for the establishment of order within the growing clusters.

Two genetic markers closely linked to adult polycystic kidney disease on chromosome 16.

PubMed Central

Reeders, S T; Breuning, M H; Corney, G; Jeremiah, S J; Meera Khan, P; Davies, K E; Hopkinson, D A; Pearson, P L; Weatherall, D J

1986-01-01

The genetic locus for autosomal dominant adult polycystic kidney disease was recently assigned to chromosome 16 by the finding of genetic linkage to the alpha globin gene cluster. Further study showed that the phosphoglycolate phosphatase locus is also closely linked to both the locus for adult polycystic kidney disease and the alpha globin gene cluster. These findings have important implications for the prenatal and presymptomatic diagnosis of adult polycystic kidney disease and for a better understanding of its pathogenesis. Images FIG 1 PMID:3008903

Spatial clustering of childhood leukaemia in Switzerland: A nationwide study.

PubMed

Konstantinoudis, Garyfallos; Kreis, Christian; Ammann, Roland A; Niggli, Felix; Kuehni, Claudia E; Spycher, Ben D

2017-10-01

The aetiology of childhood leukaemia remains largely unknown. Several hypotheses involve environmental exposures that could implicate spatial clustering of cases. The evidence from previous clustering studies is inconclusive. Most of them used areal data and thus had limited spatial resolution. We investigated whether childhood leukaemia tends to cluster in space using exact geocodes of place of residence both at the time of birth or diagnosis. We included 1,871 leukaemia cases diagnosed between 1985 and 2015 at age 0-15 years from the Swiss Childhood Cancer Registry. For each case, we randomly sampled 10 age and sex matched controls from national censuses closest in time. We used the difference of k-functions, Cuzick-Edwards' test and Tango's index for point data to assess spatial clustering and Kulldorff's circular scan to detect clusters. We separately investigated acute lymphoid leukaemia (ALL), acute myeloid leukaemia (AML), different age groups at diagnosis (0-4, 5-15 years) and adjusted for multiple testing. After adjusting for multiple testing, we found no evidence of spatial clustering of childhood leukaemia neither around time of birth (p = 0.52) nor diagnosis (p = 0.51). Individual tests indicated spatial clustering for leukaemia diagnosed at age 5-15 years, p k-functions = 0.05 and p Cuzick-Edwards' = 0.04 and a cluster of ALL cases diagnosed at age 0-4 years in a small rural area (p = 0.05). This study provides little evidence of spatial clustering of childhood leukaemia in Switzerland and highlights the importance of accounting for multiple testing in clustering studies. © 2017 UICC.

Size-selective reactivity of subnanometer Ag 4 and Ag 16 clusters on a TiO 2 surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Po-Tuan; Tyo, Eric C.; Hayashi, Michitoshi

Size-selected Ag 4 and Ag 16 clusters on a titania surface have been studied for their potential in CO oxidation using theoretical calculations and X-ray absorption near edge spectroscopy. The first peak at the measured Ag K-edge of Ag 16@TiO 2 is more prominent in air than in carbon monoxide environment, but no variation was found between the spectra of Ag 4@TiO 2 in air and in carbon monoxide environments. Density functional theory calculations show a preference for molecular oxygen adsorption for Ag 4@TiO 2 and that for a dissociative one on Ag 16@TiO 2, while carbon monoxide reactions withmore » adsorbed oxygen reduced the Ag 16@TiO 2 cluster. The dissociated oxygen atoms increased the oxidation state of Ag 16 cluster and resulted in the prominent first peak in Ag K-edge spectrum in quasi-particle theory calculations, with the subsequent carbon monoxide oxidation reversing the character of Ag K-edge spectrum associated with the reduction of the cluster. Finally, the results provide insight into the size selectivity of supported subnanometer silver clusters in their interactions with oxygen and carbon monoxide, with implications on the cluster catalytic properties in oxidative reactions.« less

Size-selective reactivity of subnanometer Ag 4 and Ag 16 clusters on a TiO 2 surface

DOE PAGES

Chen, Po-Tuan; Tyo, Eric C.; Hayashi, Michitoshi; ...

2017-03-08

Size-selected Ag 4 and Ag 16 clusters on a titania surface have been studied for their potential in CO oxidation using theoretical calculations and X-ray absorption near edge spectroscopy. The first peak at the measured Ag K-edge of Ag 16@TiO 2 is more prominent in air than in carbon monoxide environment, but no variation was found between the spectra of Ag 4@TiO 2 in air and in carbon monoxide environments. Density functional theory calculations show a preference for molecular oxygen adsorption for Ag 4@TiO 2 and that for a dissociative one on Ag 16@TiO 2, while carbon monoxide reactions withmore » adsorbed oxygen reduced the Ag 16@TiO 2 cluster. The dissociated oxygen atoms increased the oxidation state of Ag 16 cluster and resulted in the prominent first peak in Ag K-edge spectrum in quasi-particle theory calculations, with the subsequent carbon monoxide oxidation reversing the character of Ag K-edge spectrum associated with the reduction of the cluster. Finally, the results provide insight into the size selectivity of supported subnanometer silver clusters in their interactions with oxygen and carbon monoxide, with implications on the cluster catalytic properties in oxidative reactions.« less

Chill, Be Cool Man: African American Men, Identity, Coping, and Aggressive Ideation

PubMed Central

Thomas, Alvin; Hammond, Wizdom Powell; Kohn-Wood, Laura P.

2016-01-01

Aggression is an important correlate of violence, depression, coping, and suicide among emerging young African American males. Yet most researchers treat aggression deterministically, fail to address cultural factors, or consider the potential for individual characteristics to exert an intersectional influence on this psychosocial outcome. Addressing this gap, we consider the moderating effect of coping on the relationship between masculine and racial identity and aggressive ideation among African American males (N = 128) drawn from 2 large Midwestern universities. Using the phenomenological variant of ecological systems theory and person-centered methodology as a guide, hierarchical cluster analysis grouped participants into profile groups based on their responses to both a measure of racial identity and a measure of masculine identity. Results from the cluster analysis revealed 3 distinct identity clusters: Identity Ambivalent, Identity Appraising, and Identity Consolidated. Although these cluster groups did not differ with regard to coping, significant differences were observed between cluster groups in relation to aggressive ideation. Further, a full model with identity profile clusters, coping, and aggressive ideation indicates that cluster membership significantly moderates the relationship between coping and aggressive ideation. The implications of these data for intersecting identities of African American men, and the association of identity and outcomes related to risk for mental health and violence, are discussed. PMID:25090145

Chill, be cool man: African American men, identity, coping, and aggressive ideation.

PubMed

Thomas, Alvin; Hammond, Wizdom Powell; Kohn-Wood, Laura P

2015-07-01

Aggression is an important correlate of violence, depression, coping, and suicide among emerging young African American males. Yet most researchers treat aggression deterministically, fail to address cultural factors, or consider the potential for individual characteristics to exert an intersectional influence on this psychosocial outcome. Addressing this gap, we consider the moderating effect of coping on the relationship between masculine and racial identity and aggressive ideation among African American males (N = 128) drawn from 2 large Midwestern universities. Using the phenomenological variant of ecological systems theory and person-centered methodology as a guide, hierarchical cluster analysis grouped participants into profile groups based on their responses to both a measure of racial identity and a measure of masculine identity. Results from the cluster analysis revealed 3 distinct identity clusters: Identity Ambivalent, Identity Appraising, and Identity Consolidated. Although these cluster groups did not differ with regard to coping, significant differences were observed between cluster groups in relation to aggressive ideation. Further, a full model with identity profile clusters, coping, and aggressive ideation indicates that cluster membership significantly moderates the relationship between coping and aggressive ideation. The implications of these data for intersecting identities of African American men, and the association of identity and outcomes related to risk for mental health and violence, are discussed. (c) 2015 APA, all rights reserved).

Calibrating First-Order Strong Lensing Mass Estimates in Clusters of Galaxies

NASA Astrophysics Data System (ADS)

Reed, Brendan; Remolian, Juan; Sharon, Keren; Li, Nan; SPT Clusters Cooperation

2018-01-01

We investigate methods to reduce the statistical and systematic errors inherent to using the Einstein Radius as a first-order mass estimate in strong lensing galaxy clusters. By finding an empirical universal calibration function, we aim to enable a first-order mass estimate of large cluster data sets in a fraction of the time and effort of full-scale strong lensing mass modeling. We use 74 simulated cluster data from the Argonne National Laboratory in a lens redshift slice of [0.159, 0.667] with various source redshifts in the range of [1.23, 2.69]. From the simulated density maps, we calculate the exact mass enclosed within the Einstein Radius. We find that the mass inferred from the Einstein Radius alone produces an error width of ~39% with respect to the true mass. We explore an array of polynomial and exponential correction functions with dependence on cluster redshift and projected radii of the lensed images, aiming to reduce the statistical and systematic uncertainty. We find that the error on the the mass inferred from the Einstein Radius can be reduced significantly by using a universal correction function. Our study has implications for current and future large galaxy cluster surveys aiming to measure cluster mass, and the mass-concentration relation.

Perceptual prothesis in native Spanish speakers

NASA Astrophysics Data System (ADS)

Theodore, Rachel M.; Schmidt, Anna M.

2003-04-01

Previous research suggests a perceptual bias exists for native phonotactics [D. Massaro and M. Cohen, Percept. Psychophys. 34, 338-348 (1983)] such that listeners report nonexistent segments when listening to stimuli that violate native phonotactics [E. Dupoux, K. Kakehi, Y. Hirose, C. Pallier, and J. Mehler, J. Exp. Psychol.: Human Percept. Perform. 25, 1568-1578 (1999)]. This study investigated how native-language experience affects second language processing, focusing on how native Spanish speakers perceive the English clusters /st/, /sp/, and /sk/, which represent phonotactically illegal forms in Spanish. To preserve native phonotactics, Spanish speakers often produce prothetic vowels before English words beginning with /s/ clusters. Is the influence of native phonotactics also present in the perception of illegal clusters? A stimuli continuum ranging from no vowel (e.g., ``sku'') to a full vowel (e.g., ``esku'') before the cluster was used. Four final vowel contexts were used for each cluster, resulting in 12 sCV and 12 VsCV nonword endpoints. English and Spanish listeners were asked to discriminate between pairs differing in vowel duration and to identify the presence or absence of a vowel before the cluster. Results will be discussed in terms of implications for theories of second language speech perception.

A model of the evaporation of binary-fuel clusters of drops

NASA Technical Reports Server (NTRS)

Harstad, K.; Bellan, J.

1991-01-01

A formulation has been developed to describe the evaporation of dense or dilute clusters of binary-fuel drops. The binary fuel is assumed to be made of a solute and a solvent whose volatility is much lower than that of the solute. Convective flow effects, inducing a circulatory motion inside the drops, are taken into account, as well as turbulence external to the cluster volume. Results obtained with this model show that, similar to the conclusions for single isolated drops, the evaporation of the volatile is controlled by liquid mass diffusion when the cluster is dilute. In contrast, when the cluster is dense, the evaporation of the volatile is controlled by surface layer stripping, that is, by the regression rate of the drop, which is in fact controlled by the evaporation rate of the solvent. These conclusions are in agreement with existing experimental observations. Parametric studies show that these conclusions remain valid with changes in ambient temperature, initial slip velocity between drops and gas, initial drop size, initial cluster size, initial liquid mass fraction of the solute, and various combinations of solvent and solute. The implications of these results for computationally intensive combustor calculations are discussed.

Cancer Detection in Microarray Data Using a Modified Cat Swarm Optimization Clustering Approach

PubMed

M, Pandi; R, Balamurugan; N, Sadhasivam

2017-12-29

Objective: A better understanding of functional genomics can be obtained by extracting patterns hidden in gene expression data. This could have paramount implications for cancer diagnosis, gene treatments and other domains. Clustering may reveal natural structures and identify interesting patterns in underlying data. The main objective of this research was to derive a heuristic approach to detection of highly co-expressed genes related to cancer from gene expression data with minimum Mean Squared Error (MSE). Methods: A modified CSO algorithm using Harmony Search (MCSO-HS) for clustering cancer gene expression data was applied. Experiment results are analyzed using two cancer gene expression benchmark datasets, namely for leukaemia and for breast cancer. Result: The results indicated MCSO-HS to be better than HS and CSO, 13% and 9% with the leukaemia dataset. For breast cancer dataset improvement was by 22% and 17%, respectively, in terms of MSE. Conclusion: The results showed MCSO-HS to outperform HS and CSO with both benchmark datasets. To validate the clustering results, this work was tested with internal and external cluster validation indices. Also this work points to biological validation of clusters with gene ontology in terms of function, process and component. Creative Commons Attribution License

Deformation band clusters on Mars and implications for subsurface fluid flow

USGS Publications Warehouse

Okubo, C.H.; Schultz, R.A.; Chan, M.A.; Komatsu, G.

2009-01-01

High-resolution imagery reveals unprecedented lines of evidence for the presence of deformation band clusters in layered sedimentary deposits in the equatorial region of Mars. Deformation bands are a class of geologic structural discontinuity that is a precursor to faults in clastic rocks and soils. Clusters of deformation bands, consisting of many hundreds of individual subparallel bands, can act as important structural controls on subsurface fluid flow in terrestrial reservoirs, and evidence of diagenetic processes is often preserved along them. Deformation band clusters are identified on Mars based on characteristic meter-scale architectures and geologic context as observed in data from the High-Resolution Imaging Science Experiment (HiRISE) camera. The identification of deformation band clusters on Mars is a key to investigating the migration of fluids between surface and subsurface reservoirs in the planet's vast sedimentary deposits. Similar to terrestrial examples, evidence of diagenesis in the form of light- and dark-toned discoloration and wall-rock induration is recorded along many of the deformation band clusters on Mars. Therefore, these structures are important sites for future exploration and investigations into the geologic history of water and water-related processes on Mars. ?? 2008 Geological Society of America.

Human frataxin is an allosteric switch that activates the Fe-S cluster biosynthetic complex.

PubMed

Tsai, Chi-Lin; Barondeau, David P

2010-11-02

Cellular depletion of the human protein frataxin is correlated with the neurodegenerative disease Friedreich's ataxia and results in the inactivation of Fe-S cluster proteins. Most researchers agree that frataxin functions in the biogenesis of Fe-S clusters, but its precise role in this process is unclear. Here we provide in vitro evidence that human frataxin binds to a Nfs1, Isd11, and Isu2 complex to generate the four-component core machinery for Fe-S cluster biosynthesis. Frataxin binding dramatically changes the K(M) for cysteine from 0.59 to 0.011 mM and the catalytic efficiency (k(cat)/K(M)) of the cysteine desulfurase from 25 to 7900 M⁻¹s⁻¹. Oxidizing conditions diminish the levels of both complex formation and frataxin-based activation, whereas ferrous iron further stimulates cysteine desulfurase activity. Together, these results indicate human frataxin functions with Fe(2+) as an allosteric activator that triggers sulfur delivery and Fe-S cluster assembly. We propose a model in which cellular frataxin levels regulate human Fe-S cluster biosynthesis that has implications for mitochondrial dysfunction, oxidative stress response, and both neurodegenerative and cardiovascular disease.

Identification and validation of asthma phenotypes in Chinese population using cluster analysis.

PubMed

Wang, Lei; Liang, Rui; Zhou, Ting; Zheng, Jing; Liang, Bing Miao; Zhang, Hong Ping; Luo, Feng Ming; Gibson, Peter G; Wang, Gang

2017-10-01

Asthma is a heterogeneous airway disease, so it is crucial to clearly identify clinical phenotypes to achieve better asthma management. To identify and prospectively validate asthma clusters in a Chinese population. Two hundred eighty-four patients were consecutively recruited and 18 sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis. Then, a prospective 12-month cohort study was used to validate the identified clusters. Five clusters were successfully identified. Clusters 1 (n = 71) and 3 (n = 81) were mild asthma phenotypes with slight airway obstruction and low exacerbation risk, but with a sex differential. Cluster 2 (n = 65) described an "allergic" phenotype, cluster 4 (n = 33) featured a "fixed airflow limitation" phenotype with smoking, and cluster 5 (n = 34) was a "low socioeconomic status" phenotype. Patients in clusters 2, 4, and 5 had distinctly lower socioeconomic status and more psychological symptoms. Cluster 2 had a significantly increased risk of exacerbations (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03-1.25), unplanned visits for asthma (RR 1.98, 95% CI 1.07-3.66), and emergency visits for asthma (RR 7.17, 95% CI 1.26-40.80). Cluster 4 had an increased risk of unplanned visits (RR 2.22, 95% CI 1.02-4.81), and cluster 5 had increased emergency visits (RR 12.72, 95% CI 1.95-69.78). Kaplan-Meier analysis confirmed that cluster grouping was predictive of time to the first asthma exacerbation, unplanned visit, emergency visit, and hospital admission (P < .0001 for all comparisons). We identified 3 clinical clusters as "allergic asthma," "fixed airflow limitation," and "low socioeconomic status" phenotypes that are at high risk of severe asthma exacerbations and that have management implications for clinical practice in developing countries. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Inference from clustering with application to gene-expression microarrays.

PubMed

Dougherty, Edward R; Barrera, Junior; Brun, Marcel; Kim, Seungchan; Cesar, Roberto M; Chen, Yidong; Bittner, Michael; Trent, Jeffrey M

2002-01-01

There are many algorithms to cluster sample data points based on nearness or a similarity measure. Often the implication is that points in different clusters come from different underlying classes, whereas those in the same cluster come from the same class. Stochastically, the underlying classes represent different random processes. The inference is that clusters represent a partition of the sample points according to which process they belong. This paper discusses a model-based clustering toolbox that evaluates cluster accuracy. Each random process is modeled as its mean plus independent noise, sample points are generated, the points are clustered, and the clustering error is the number of points clustered incorrectly according to the generating random processes. Various clustering algorithms are evaluated based on process variance and the key issue of the rate at which algorithmic performance improves with increasing numbers of experimental replications. The model means can be selected by hand to test the separability of expected types of biological expression patterns. Alternatively, the model can be seeded by real data to test the expected precision of that output or the extent of improvement in precision that replication could provide. In the latter case, a clustering algorithm is used to form clusters, and the model is seeded with the means and variances of these clusters. Other algorithms are then tested relative to the seeding algorithm. Results are averaged over various seeds. Output includes error tables and graphs, confusion matrices, principal-component plots, and validation measures. Five algorithms are studied in detail: K-means, fuzzy C-means, self-organizing maps, hierarchical Euclidean-distance-based and correlation-based clustering. The toolbox is applied to gene-expression clustering based on cDNA microarrays using real data. Expression profile graphics are generated and error analysis is displayed within the context of these profile graphics. A large amount of generated output is available over the web.

Network approach to the symptom-level association between alcohol use disorder and posttraumatic stress disorder.

PubMed

Afzali, Mohammad H; Sunderland, Matthew; Batterham, Philip J; Carragher, Natacha; Calear, Alison; Slade, Tim

2017-03-01

The high prevalence of alcohol use disorder among individuals with a history of trauma and posttraumatic stress disorder is well documented. The current study applied network analysis to map the structure of symptom associations between these disorders. Data come from a community sample of 449 Australian adults with a history of trauma and alcohol consumption during the last 12 months. Data analysis consisted of the construction of the comorbidity network of PTSD/AUD symptoms, identification of the bridging symptoms, computation of the centrality measures, and evaluation of the robustness of the results. Results highlighted two main symptom clusters, corresponding to two disorders, and that only nine edges connected the two clusters. Bridging symptoms connecting the two clusters were: alcohol use in dangerous situations, physical or mental health problems as a result of alcohol use, loss of interest or reduced social activities, and reckless/self-destructive behaviour. Identification of both central symptoms, because of their key role in the constellation and strong associations with majority of symptoms, and bridge symptoms, because of their mediating role between two disorders, has some implications in terms of self-medication and risk-taking/self-regulation theories of comorbidity and provides a number of clinical implications, which warrants further exploration within clinical samples.

Distinct differences in striatal dysmorphology between attention deficit hyperactivity disorder boys with and without a comorbid reading disability.

PubMed

Goradia, Dhruman D; Vogel, Sherry; Mohl, Brianne; Khatib, Dalal; Zajac-Benitez, Caroline; Rajan, Usha; Robin, Arthur; Rosenberg, David R; Stanley, Jeffrey A

2016-12-30

There is evidence of greater cognitive deficits in attention deficit hyperactivity disorder with a comorbid reading disability (ADHD/+RD) compared to ADHD alone (ADHD/-RD). Additionally, the striatum has been consistently implicated in ADHD. However, the extent of morphological alterations in the striatum of ADHD/+RD is poorly understood, which is the main purpose of this study. Based on structural MRI images, the surface deformation of the caudate and putamen was assessed in 59 boys matching in age and IQ [19 ADHD/-RD, 15 ADHD/+RD and 25 typically developing controls (TDC)]. A vertex based analysis with multiple comparison correction was conducted to compare ADHD/-RD and ADHD/+RD to TDC. Compared to TDC, ADHD/+RD showed multiple bilateral significant clusters of surface compression. In contrast, ADHD/-RD showed fewer significant clusters of surface compression and restricted to the left side. Regarding the putamen, only ADHD/-RD showed significant clusters of surface compression. Results demonstrate for the first time a greater extent of morphological alterations in the caudate of ADHD/+RD than ADHD/-RD compared to TDC, which may suggest greater implicated cortical areas projecting to the caudate that are associated with the greater neuropsychological impairments observed in ADHD/+RD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cancer-Related NEET Proteins Transfer 2Fe-2S Clusters to Anamorsin, a Protein Required for Cytosolic Iron-Sulfur Cluster Biogenesis.

PubMed

Lipper, Colin H; Paddock, Mark L; Onuchic, José N; Mittler, Ron; Nechushtai, Rachel; Jennings, Patricia A

2015-01-01

Iron-sulfur cluster biogenesis is executed by distinct protein assembly systems. Mammals have two systems, the mitochondrial Fe-S cluster assembly system (ISC) and the cytosolic assembly system (CIA), that are connected by an unknown mechanism. The human members of the NEET family of 2Fe-2S proteins, nutrient-deprivation autophagy factor-1 (NAF-1) and mitoNEET (mNT), are located at the interface between the mitochondria and the cytosol. These proteins have been implicated in cancer cell proliferation, and they can transfer their 2Fe-2S clusters to a standard apo-acceptor protein. Here we report the first physiological 2Fe-2S cluster acceptor for both NEET proteins as human Anamorsin (also known as cytokine induced apoptosis inhibitor-1; CIAPIN-1). Anamorsin is an electron transfer protein containing two iron-sulfur cluster-binding sites that is required for cytosolic Fe-S cluster assembly. We show, using UV-Vis spectroscopy, that both NAF-1 and mNT can transfer their 2Fe-2S clusters to apo-Anamorsin with second order rate constants similar to those of other known human 2Fe-2S transfer proteins. A direct protein-protein interaction of the NEET proteins with apo-Anamorsin was detected using biolayer interferometry. Furthermore, electrospray mass spectrometry of holo-Anamorsin prepared by cluster transfer shows that it receives both of its 2Fe-2S clusters from the NEETs. We propose that mNT and NAF-1 can provide parallel routes connecting the mitochondrial ISC system and the CIA. 2Fe-2S clusters assembled in the mitochondria are received by NEET proteins and when needed transferred to Anamorsin, activating the CIA.

Nature's polyoxometalate chemistry: X-ray structure of the Mo storage protein loaded with discrete polynuclear Mo-O clusters.

PubMed

Kowalewski, Björn; Poppe, Juliane; Demmer, Ulrike; Warkentin, Eberhard; Dierks, Thomas; Ermler, Ulrich; Schneider, Klaus

2012-06-13

Some N(2)-fixing bacteria prolong the functionality of nitrogenase in molybdenum starvation by a special Mo storage protein (MoSto) that can store more than 100 Mo atoms. The presented 1.6 Å X-ray structure of MoSto from Azotobacter vinelandii reveals various discrete polyoxomolybdate clusters, three covalently and three noncovalently bound Mo(8), three Mo(5-7), and one Mo(3) clusters, and several low occupied, so far undefinable clusters, which are embedded in specific pockets inside a locked cage-shaped (αβ)(3) protein complex. The structurally identical Mo(8) clusters (three layers of two, four, and two MoO(n) octahedra) are distinguishable from the [Mo(8)O(26)](4-) cluster formed in acidic solutions by two displaced MoO(n) octahedra implicating three kinetically labile terminal ligands. Stabilization in the covalent Mo(8) cluster is achieved by Mo bonding to Hisα156-N(ε2) and Gluα129-O(ε1). The absence of covalent protein interactions in the noncovalent Mo(8) cluster is compensated by a more extended hydrogen-bond network involving three pronounced histidines. One displaced MoO(n) octahedron might serve as nucleation site for an inhomogeneous Mo(5-7) cluster largely surrounded by bulk solvent. In the Mo(3) cluster located on the 3-fold axis, the three accurately positioned His140-N(ε2) atoms of the α subunits coordinate to the Mo atoms. The formed polyoxomolybdate clusters of MoSto, not detectable in bulk solvent, are the result of an interplay between self- and protein-driven assembly processes that unite inorganic supramolecular and protein chemistry in a host-guest system. Template, nucleation/protection, and catalyst functions of the polypeptide as well as perspectives for designing new clusters are discussed.

Analysis of RXTE data on Clusters of Galaxies

NASA Technical Reports Server (NTRS)

Petrosian, Vahe

2004-01-01

This grant provided support for the reduction, analysis and interpretation of of hard X-ray (HXR, for short) observations of the cluster of galaxies RXJO658--5557 scheduled for the week of August 23, 2002 under the RXTE Cycle 7 program (PI Vahe Petrosian, Obs. ID 70165). The goal of the observation was to search for and characterize the shape of the HXR component beyond the well established thermal soft X-ray (SXR) component. Such hard components have been detected in several nearby clusters. distant cluster would provide information on the characteristics of this radiation at a different epoch in the evolution of the imiverse and shed light on its origin. We (Petrosian, 2001) have argued that thermal bremsstrahlung, as proposed earlier, cannot be the mechanism for the production of the HXRs and that the most likely mechanism is Compton upscattering of the cosmic microwave radiation by relativistic electrons which are known to be present in the clusters and be responsible for the observed radio emission. Based on this picture we estimated that this cluster, in spite of its relatively large distance, will have HXR signal comparable to the other nearby ones. The planned observation of a relatively The proposed RXTE observations were carried out and the data have been analyzed. We detect a hard X-ray tail in the spectrum of this cluster with a flux very nearly equal to our predicted value. This has strengthen the case for the Compton scattering model. We intend the data obtained via this observation to be a part of a larger data set. We have identified other clusters of galaxies (in archival RXTE and other instrument data sets) with sufficiently high quality data where we can search for and measure (or at least put meaningful limits) on the strength of the hard component. With these studies we expect to clarify the mechanism for acceleration of particles in the intercluster medium and provide guidance for future observations of this intriguing phenomenon by instrument on GLAST. The details of the nonthermal particle population has important implications for the theories of cluster formation, mergers and evolution. The results of this work were first presented at the High Energy Division meeting of the American astronomical Society at Mt. Tremblene, Canada (Petrosian et al. 2003). and in an invited review talk at the General Assembly of the International Astronomical Union at Sydney, Australia (Petrosian, 2003). A paper describe the observations, the data analysis and its implication is being prepared for publication in the Astrophysical Journal.

The Case for a Hierarchical Cosmology

ERIC Educational Resources Information Center

Vaucouleurs, G. de

1970-01-01

The development of modern theoretical cosmology is presented and some questionable assumptions of orthodox cosmology are pointed out. Suggests that recent observations indicate that hierarchical clustering is a basic factor in cosmology. The implications of hierarchical models of the universe are considered. Bibliography. (LC)

Genome-Wide Prediction of Metabolic Enzymes, Pathways, and Gene Clusters in Plants

DOE PAGES

Schläpfer, Pascal; Zhang, Peifen; Wang, Chuan; ...

2017-04-01

Plant metabolism underpins many traits of ecological and agronomic importance. Plants produce numerous compounds to cope with their environments but the biosynthetic pathways for most of these compounds have not yet been elucidated. To engineer and improve metabolic traits, we will need comprehensive and accurate knowledge of the organization and regulation of plant metabolism at the genome scale. Here, we present a computational pipeline to identify metabolic enzymes, pathways, and gene clusters from a sequenced genome. Using this pipeline, we generated metabolic pathway databases for 22 species and identified metabolic gene clusters from 18 species. This unified resource can bemore » used to conduct a wide array of comparative studies of plant metabolism. Using the resource, we discovered a widespread occurrence of metabolic gene clusters in plants: 11,969 clusters from 18 species. The prevalence of metabolic gene clusters offers an intriguing possibility of an untapped source for uncovering new metabolite biosynthesis pathways. For example, more than 1,700 clusters contain enzymes that could generate a specialized metabolite scaffold (signature enzymes) and enzymes that modify the scaffold (tailoring enzymes). In four species with sufficient gene expression data, we identified 43 highly coexpressed clusters that contain signature and tailoring enzymes, of which eight were characterized previously to be functional pathways. Finally, we identified patterns of genome organization that implicate local gene duplication and, to a lesser extent, single gene transposition as having played roles in the evolution of plant metabolic gene clusters.« less

The gamma-ray pulsar population of globular clusters: implications for the GeV excess

NASA Astrophysics Data System (ADS)

Hooper, Dan; Linden, Tim

2016-08-01

It has been suggested that the GeV excess, observed from the region surrounding the Galactic Center, might originate from a population of millisecond pulsars that formed in globular clusters. With this in mind, we employ the publicly available Fermi data to study the gamma-ray emission from 157 globular clusters, identifying a statistically significant signal from 25 of these sources (ten of which are not found in existing gamma-ray catalogs). We combine these observations with the predicted pulsar formation rate based on the stellar encounter rate of each globular cluster to constrain the gamma-ray luminosity function of millisecond pulsars in the Milky Way's globular cluster system. We find that this pulsar population exhibits a luminosity function that is quite similar to those millisecond pulsars observed in the field of the Milky Way (i.e. the thick disk). After pulsars are expelled from a globular cluster, however, they continue to lose rotational kinetic energy and become less luminous, causing their luminosity function to depart from the steady-state distribution. Using this luminosity function and a model for the globular cluster disruption rate, we show that millisecond pulsars born in globular clusters can account for only a few percent or less of the observed GeV excess. Among other challenges, scenarios in which the entire GeV excess is generated from such pulsars are in conflict with the observed mass of the Milky Way's Central Stellar Cluster.

Genome-Wide Prediction of Metabolic Enzymes, Pathways, and Gene Clusters in Plants1[OPEN

PubMed Central

Zhang, Peifen; Kim, Taehyong; Banf, Michael; Chavali, Arvind K.; Nilo-Poyanco, Ricardo; Bernard, Thomas

2017-01-01

Plant metabolism underpins many traits of ecological and agronomic importance. Plants produce numerous compounds to cope with their environments but the biosynthetic pathways for most of these compounds have not yet been elucidated. To engineer and improve metabolic traits, we need comprehensive and accurate knowledge of the organization and regulation of plant metabolism at the genome scale. Here, we present a computational pipeline to identify metabolic enzymes, pathways, and gene clusters from a sequenced genome. Using this pipeline, we generated metabolic pathway databases for 22 species and identified metabolic gene clusters from 18 species. This unified resource can be used to conduct a wide array of comparative studies of plant metabolism. Using the resource, we discovered a widespread occurrence of metabolic gene clusters in plants: 11,969 clusters from 18 species. The prevalence of metabolic gene clusters offers an intriguing possibility of an untapped source for uncovering new metabolite biosynthesis pathways. For example, more than 1,700 clusters contain enzymes that could generate a specialized metabolite scaffold (signature enzymes) and enzymes that modify the scaffold (tailoring enzymes). In four species with sufficient gene expression data, we identified 43 highly coexpressed clusters that contain signature and tailoring enzymes, of which eight were characterized previously to be functional pathways. Finally, we identified patterns of genome organization that implicate local gene duplication and, to a lesser extent, single gene transposition as having played roles in the evolution of plant metabolic gene clusters. PMID:28228535

The gamma-ray pulsar population of globular clusters: implications for the GeV excess

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hooper, Dan; Linden, Tim, E-mail: dhooper@fnal.gov, E-mail: linden.70@osu.edu

It has been suggested that the GeV excess, observed from the region surrounding the Galactic Center, might originate from a population of millisecond pulsars that formed in globular clusters. With this in mind, we employ the publicly available Fermi data to study the gamma-ray emission from 157 globular clusters, identifying a statistically significant signal from 25 of these sources (ten of which are not found in existing gamma-ray catalogs). We combine these observations with the predicted pulsar formation rate based on the stellar encounter rate of each globular cluster to constrain the gamma-ray luminosity function of millisecond pulsars in themore » Milky Way's globular cluster system. We find that this pulsar population exhibits a luminosity function that is quite similar to those millisecond pulsars observed in the field of the Milky Way (i.e. the thick disk). After pulsars are expelled from a globular cluster, however, they continue to lose rotational kinetic energy and become less luminous, causing their luminosity function to depart from the steady-state distribution. Using this luminosity function and a model for the globular cluster disruption rate, we show that millisecond pulsars born in globular clusters can account for only a few percent or less of the observed GeV excess. Among other challenges, scenarios in which the entire GeV excess is generated from such pulsars are in conflict with the observed mass of the Milky Way's Central Stellar Cluster.« less

The gamma-ray pulsar population of globular clusters: Implications for the GeV excess

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hooper, Dan; Linden, Tim

In this study, it has been suggested that the GeV excess, observed from the region surrounding the Galactic Center, might originate from a population of millisecond pulsars that formed in globular clusters. With this in mind, we employ the publicly available Fermi data to study the gamma-ray emission from 157 globular clusters, identifying a statistically significant signal from 25 of these sources (ten of which are not found in existing gamma-ray catalogs). We combine these observations with the predicted pulsar formation rate based on the stellar encounter rate of each globular cluster to constrain the gamma-ray luminosity function of millisecondmore » pulsars in the Milky Way's globular cluster system. We find that this pulsar population exhibits a luminosity function that is quite similar to those millisecond pulsars observed in the field of the Milky Way (i.e. the thick disk). After pulsars are expelled from a globular cluster, however, they continue to lose rotational kinetic energy and become less luminous, causing their luminosity function to depart from the steady-state distribution. Using this luminosity function and a model for the globular cluster disruption rate, we show that millisecond pulsars born in globular clusters can account for only a few percent or less of the observed GeV excess. Among other challenges, scenarios in which the entire GeV excess is generated from such pulsars are in conflict with the observed mass of the Milky Way's Central Stellar Cluster.« less

Genome-Wide Prediction of Metabolic Enzymes, Pathways, and Gene Clusters in Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schläpfer, Pascal; Zhang, Peifen; Wang, Chuan

Plant metabolism underpins many traits of ecological and agronomic importance. Plants produce numerous compounds to cope with their environments but the biosynthetic pathways for most of these compounds have not yet been elucidated. To engineer and improve metabolic traits, we will need comprehensive and accurate knowledge of the organization and regulation of plant metabolism at the genome scale. Here, we present a computational pipeline to identify metabolic enzymes, pathways, and gene clusters from a sequenced genome. Using this pipeline, we generated metabolic pathway databases for 22 species and identified metabolic gene clusters from 18 species. This unified resource can bemore » used to conduct a wide array of comparative studies of plant metabolism. Using the resource, we discovered a widespread occurrence of metabolic gene clusters in plants: 11,969 clusters from 18 species. The prevalence of metabolic gene clusters offers an intriguing possibility of an untapped source for uncovering new metabolite biosynthesis pathways. For example, more than 1,700 clusters contain enzymes that could generate a specialized metabolite scaffold (signature enzymes) and enzymes that modify the scaffold (tailoring enzymes). In four species with sufficient gene expression data, we identified 43 highly coexpressed clusters that contain signature and tailoring enzymes, of which eight were characterized previously to be functional pathways. Finally, we identified patterns of genome organization that implicate local gene duplication and, to a lesser extent, single gene transposition as having played roles in the evolution of plant metabolic gene clusters.« less

The gamma-ray pulsar population of globular clusters: Implications for the GeV excess

DOE PAGES

Hooper, Dan; Linden, Tim

2016-08-09

In this study, it has been suggested that the GeV excess, observed from the region surrounding the Galactic Center, might originate from a population of millisecond pulsars that formed in globular clusters. With this in mind, we employ the publicly available Fermi data to study the gamma-ray emission from 157 globular clusters, identifying a statistically significant signal from 25 of these sources (ten of which are not found in existing gamma-ray catalogs). We combine these observations with the predicted pulsar formation rate based on the stellar encounter rate of each globular cluster to constrain the gamma-ray luminosity function of millisecondmore » pulsars in the Milky Way's globular cluster system. We find that this pulsar population exhibits a luminosity function that is quite similar to those millisecond pulsars observed in the field of the Milky Way (i.e. the thick disk). After pulsars are expelled from a globular cluster, however, they continue to lose rotational kinetic energy and become less luminous, causing their luminosity function to depart from the steady-state distribution. Using this luminosity function and a model for the globular cluster disruption rate, we show that millisecond pulsars born in globular clusters can account for only a few percent or less of the observed GeV excess. Among other challenges, scenarios in which the entire GeV excess is generated from such pulsars are in conflict with the observed mass of the Milky Way's Central Stellar Cluster.« less

Genome-Wide Prediction of Metabolic Enzymes, Pathways, and Gene Clusters in Plants.

PubMed

Schläpfer, Pascal; Zhang, Peifen; Wang, Chuan; Kim, Taehyong; Banf, Michael; Chae, Lee; Dreher, Kate; Chavali, Arvind K; Nilo-Poyanco, Ricardo; Bernard, Thomas; Kahn, Daniel; Rhee, Seung Y

2017-04-01

Plant metabolism underpins many traits of ecological and agronomic importance. Plants produce numerous compounds to cope with their environments but the biosynthetic pathways for most of these compounds have not yet been elucidated. To engineer and improve metabolic traits, we need comprehensive and accurate knowledge of the organization and regulation of plant metabolism at the genome scale. Here, we present a computational pipeline to identify metabolic enzymes, pathways, and gene clusters from a sequenced genome. Using this pipeline, we generated metabolic pathway databases for 22 species and identified metabolic gene clusters from 18 species. This unified resource can be used to conduct a wide array of comparative studies of plant metabolism. Using the resource, we discovered a widespread occurrence of metabolic gene clusters in plants: 11,969 clusters from 18 species. The prevalence of metabolic gene clusters offers an intriguing possibility of an untapped source for uncovering new metabolite biosynthesis pathways. For example, more than 1,700 clusters contain enzymes that could generate a specialized metabolite scaffold (signature enzymes) and enzymes that modify the scaffold (tailoring enzymes). In four species with sufficient gene expression data, we identified 43 highly coexpressed clusters that contain signature and tailoring enzymes, of which eight were characterized previously to be functional pathways. Finally, we identified patterns of genome organization that implicate local gene duplication and, to a lesser extent, single gene transposition as having played roles in the evolution of plant metabolic gene clusters. © 2017 American Society of Plant Biologists. All Rights Reserved.

Interaction of Gas Phase Oxalic Acid with Ammonia and its Atmospheric Implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, Xiu-Qiu; Liu, Yi-Rong; Huang, Teng

Oxalic acid is believed to play an important role in the formation and growth of atmospheric organic aerosols. However, as a common organic acid, the understanding of the larger clusters formed by gas phase oxalic acid with multiple ammonia molecules is incomplete. In this work, the structural characteristics and thermodynamics of oxalic acid clusters with up to six ammonia molecules have been investigated at the PW91PW91/6-311++G(3df,3pd) level of theory. We found that oxalic acid forms relatively stable clusters with ammonia molecules, and that ionization events play a key role. The analyses of the thermodynamics and atmospheric relevance indicate that themore » heterodimer (H2C2O4)(NH3) shows an obvious relative concentration in the atmosphere, and thus likely participates in new particle formation. However, with increasing number of ammonia molecules, the concentration of clusters decreases gradually. Additionally, clusters of oxalic acid with ammonia molecules are predicted to form favorably in low temperature conditions and show high Rayleigh scattering intensities.« less

Exome sequencing identifies NFS1 deficiency in a novel Fe-S cluster disease, infantile mitochondrial complex II/III deficiency.

PubMed

Farhan, Sali M K; Wang, Jian; Robinson, John F; Lahiry, Piya; Siu, Victoria M; Prasad, Chitra; Kronick, Jonathan B; Ramsay, David A; Rupar, C Anthony; Hegele, Robert A

2014-01-01

Iron-sulfur (Fe-S) clusters are a class of highly conserved and ubiquitous prosthetic groups with unique chemical properties that allow the proteins that contain them, Fe-S proteins, to assist in various key biochemical pathways. Mutations in Fe-S proteins often disrupt Fe-S cluster assembly leading to a spectrum of severe disorders such as Friedreich's ataxia or iron-sulfur cluster assembly enzyme (ISCU) myopathy. Herein, we describe infantile mitochondrial complex II/III deficiency, a novel autosomal recessive mitochondrial disease characterized by lactic acidemia, hypotonia, respiratory chain complex II and III deficiency, multisystem organ failure and abnormal mitochondria. Through autozygosity mapping, exome sequencing, in silico analyses, population studies and functional tests, we identified c.215G>A, p.Arg72Gln in NFS1 as the likely causative mutation. We describe the first disease in man likely caused by deficiency in NFS1, a cysteine desulfurase that is implicated in respiratory chain function and iron maintenance by initiating Fe-S cluster biosynthesis. Our results further demonstrate the importance of sufficient NFS1 expression in human physiology.

Race, deprivation, and immigrant isolation: The spatial demography of air-toxic clusters in the continental United States.

PubMed

Liévanos, Raoul S

2015-11-01

This article contributes to environmental inequality outcomes research on the spatial and demographic factors associated with cumulative air-toxic health risks at multiple geographic scales across the United States. It employs a rigorous spatial cluster analysis of census tract-level 2005 estimated lifetime cancer risk (LCR) of ambient air-toxic emissions from stationary (e.g., facility) and mobile (e.g., vehicular) sources to locate spatial clusters of air-toxic LCR risk in the continental United States. It then tests intersectional environmental inequality hypotheses on the predictors of tract presence in air-toxic LCR clusters with tract-level principal component factor measures of economic deprivation by race and immigrant status. Logistic regression analyses show that net of controls, isolated Latino immigrant-economic deprivation is the strongest positive demographic predictor of tract presence in air-toxic LCR clusters, followed by black-economic deprivation and isolated Asian/Pacific Islander immigrant-economic deprivation. Findings suggest scholarly and practical implications for future research, advocacy, and policy. Copyright © 2015 Elsevier Inc. All rights reserved.

Two cases of occupational allergic contact dermatitis from a cycloaliphatic epoxy resin in a neat oil: Case Report

PubMed Central

Jensen, Charlotte D; Andersen, Klaus E

2003-01-01

Background Metal-working fluids contain complex mixtures of chemicals and metal workers constitute a potential risk group for the development of allergic contact dermatitis. Case presentation Two metal workers developed allergic contact dermatitis on the hands and lower arms from exposure to a neat oil used in metal processing. Patch testing revealed that the relevant contact allergen was a cycloaliphatic epoxy resin, 1,2-cyclohexanedicarboxylic acid, bis(oxiranylmethyl) ester, added to the oil as a stabilizer. None of the patients had positive reactions to the bisphenol A-based epoxy resin in the standard series. Conclusions These cases emphasize that well-known contact allergens may show up from unexpected sources of exposure. Further, it can be a long-lasting, laborious process to detect an occupational contact allergen and cooperation from the patient and the manufacturer of the sensitizing product is essential. PMID:12685935

Emergency sacrificial sealing method in filters, equipment, or systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Erik P.

A system seals a filter or equipment component to abase and will continue to seal the filter or equipment component to the base in the event of hot air or fire. The system includes a first sealing material between the filter or equipment component and the base; and a second sealing material between the filter or equipment component and the base and proximate the first sealing material. The first sealing material and the second seal material are positioned relative to each other and relative to the filter or equipment component and the base to seal the filter or equipment componentmore » to the base and upon the event of fire the second sealing material will be activated and expand to continue to seal the filter or equipment component to the base in the event of hot air or fire.« less

Base Excision Repair

PubMed Central

Krokan, Hans E.; Bjørås, Magnar

2013-01-01

Base excision repair (BER) corrects DNA damage from oxidation, deamination and alkylation. Such base lesions cause little distortion to the DNA helix structure. BER is initiated by a DNA glycosylase that recognizes and removes the damaged base, leaving an abasic site that is further processed by short-patch repair or long-patch repair that largely uses different proteins to complete BER. At least 11 distinct mammalian DNA glycosylases are known, each recognizing a few related lesions, frequently with some overlap in specificities. Impressively, the damaged bases are rapidly identified in a vast excess of normal bases, without a supply of energy. BER protects against cancer, aging, and neurodegeneration and takes place both in nuclei and mitochondria. More recently, an important role of uracil-DNA glycosylase UNG2 in adaptive immunity was revealed. Furthermore, other DNA glycosylases may have important roles in epigenetics, thus expanding the repertoire of BER proteins. PMID:23545420

Robust synthesis of epoxy resin-filled microcapsules for application to self-healing materials.

PubMed

Bolimowski, Patryk A; Bond, Ian P; Wass, Duncan F

2016-02-28

Mechanically and thermally robust microcapsules containing diglycidyl ether bisphenol A-based epoxy resin and a high-boiling-point organic solvent were synthesized in high yield using in situ polymerization of urea and formaldehyde in an oil-in-water emulsion. Microcapsules were characterized in terms of their size and size distribution, shell surface morphology and thermal resistance to the curing cycles of commercially used epoxy polymers. The size distribution of the capsules and characteristics such as shell thickness can be controlled by the specific parameters of microencapsulation, including concentrations of reagents, stirrer speed and sonication. Selected microcapsules, and separated core and shell materials, were analysed using thermogravimetric analysis and differential scanning calorimetry. It is demonstrated that capsules lose minimal 2.5 wt% at temperatures no higher than 120°C. These microcapsules can be applied to self-healing carbon fibre composite structural materials, with preliminary results showing promising performance. © 2016 The Author(s).

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zahn, Karl E.; Averill, April M.; Aller, Pierre

DNA polymerase θ protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks. Polymerase θ is overexpressed in breast, lung and oral cancers, and reduction of its activity in mammalian cells increases sensitivity to double-strand break–inducing agents, including ionizing radiation. Reported in this paper are crystal structures of the C-terminal polymerase domain from human polymerase θ, illustrating two potential modes of dimerization. One structure depicts insertion of ddATP opposite an abasic-site analog during translesion DNA synthesis. The second structure describes a cognate ddGTP complex. Polymerase θ uses a specialized thumb subdomain to establish unique upstream contactsmore » to the primer DNA strand, including an interaction with the 3'-terminal phosphate from one of five distinctive insertion loops. Finally, these observations demonstrate how polymerase θ grasps the primer to bypass DNA lesions or extend poorly annealed DNA termini to mediate end-joining.« less

From the Superatom Model to a Diverse Array of Super-Elements: A Systematic Study of Dopant Influence on the Electronic Structure of Thiolate-Protected Gold Clusters.

PubMed

Schacht, Julia; Gaston, Nicola

2016-10-18

The electronic properties of doped thiolate-protected gold clusters are often referred to as tunable, but their study to date, conducted at different levels of theory, does not allow a systematic evaluation of this claim. Here, using density functional theory, the applicability of the superatomic model to these clusters is critically evaluated, and related to the degree of structural distortion and electronic inhomogeneity in the differently doped clusters, with dopant atoms Pd, Pt, Cu, and Ag. The effect of electron number is systematically evaluated by varying the charge on the overall cluster, and the nominal number of delocalized electrons, employed in the superatomic model, is compared to the numbers obtained from Bader analysis of individual atomic charges. We find that the superatomic model is highly applicable to all of these clusters, and is able to predict and explain the changing electronic structure as a function of charge. However, significant perturbations of the model arise due to doping, due to distortions of the core structure of the Au 13 [RS(AuSR) 2 ] 6 - cluster. In addition, analysis of the electronic structure indicates that the superatomic character is distributed further across the ligand shell in the case of the doped clusters, which may have implications for the self-assembly of these clusters into materials. The prediction of appropriate clusters for such superatomic solids relies critically on such quantitative analysis of the tunability of the electronic structure. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

[3Fe-4S] to [4Fe-4S] cluster conversion in Desulfovibrio fructosovorans [NiFe] hydrogenase by site-directed mutagenesis.

PubMed

Rousset, M; Montet, Y; Guigliarelli, B; Forget, N; Asso, M; Bertrand, P; Fontecilla-Camps, J C; Hatchikian, E C

1998-09-29

The role of the high potential [3Fe-4S]1+,0 cluster of [NiFe] hydrogenase from Desulfovibrio species located halfway between the proximal and distal low potential [4Fe-4S]2+,1+ clusters has been investigated by using site-directed mutagenesis. Proline 238 of Desulfovibrio fructosovorans [NiFe] hydrogenase, which occupies the position of a potential ligand of the lacking fourth Fe-site of the [3Fe-4S] cluster, was replaced by a cysteine residue. The properties of the mutant enzyme were investigated in terms of enzymatic activity, EPR, and redox properties of the iron-sulfur centers and crystallographic structure. We have shown on the basis of both spectroscopic and x-ray crystallographic studies that the [3Fe-4S] cluster of D. fructosovorans hydrogenase was converted into a [4Fe-4S] center in the P238 mutant. The [3Fe-4S] to [4Fe-4S] cluster conversion resulted in a lowering of approximately 300 mV of the midpoint potential of the modified cluster, whereas no significant alteration of the spectroscopic and redox properties of the two native [4Fe-4S] clusters and the NiFe center occurred. The significant decrease of the midpoint potential of the intermediate Fe-S cluster had only a slight effect on the catalytic activity of the P238C mutant as compared with the wild-type enzyme. The implications of the results for the role of the high-potential [3Fe-4S] cluster in the intramolecular electron transfer pathway are discussed.

Line-of-sight structure toward strong lensing galaxy clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bayliss, Matthew B.; Johnson, Traci; Sharon, Keren

2014-03-01

We present an analysis of the line-of-sight structure toward a sample of 10 strong lensing cluster cores. Structure is traced by groups that are identified spectroscopically in the redshift range, 0.1 ≤ z ≤ 0.9, and we measure the projected angular and comoving separations between each group and the primary strong lensing clusters in each corresponding line of sight. From these data we measure the distribution of projected angular separations between the primary strong lensing clusters and uncorrelated large-scale structure as traced by groups. We then compare the observed distribution of angular separations for our strong lensing selected lines ofmore » sight against the distribution of groups that is predicted for clusters lying along random lines of sight. There is clear evidence for an excess of structure along the line of sight at small angular separations (θ ≤ 6') along the strong lensing selected lines of sight, indicating that uncorrelated structure is a significant systematic that contributes to producing galaxy clusters with large cross sections for strong lensing. The prevalence of line-of-sight structure is one of several biases in strong lensing clusters that can potentially be folded into cosmological measurements using galaxy cluster samples. These results also have implications for current and future studies—such as the Hubble Space Telescope Frontier Fields—that make use of massive galaxy cluster lenses as precision cosmological telescopes; it is essential that the contribution of line-of-sight structure be carefully accounted for in the strong lens modeling of the cluster lenses.« less

Spitzer Imaging of Planck-Herschel Dusty Proto-Clusters at z=2-3

NASA Astrophysics Data System (ADS)

Cooray, Asantha; Ma, Jingzhe; Greenslade, Joshua; Kubo, Mariko; Nayyeri, Hooshang; Clements, David; Cheng, Tai-An

2018-05-01

We have recently introduced a new proto-cluster selection technique by combing Herschel/SPIRE imaging data and Planck/HFIk all-sky survey point source catalog. These sources are identified as Planck point sources with clumps of Herschel source over-densities with far-IR colors comparable to z=0 ULIRGS redshifted to z=2 to 3. The selection is sensitive to dusty starbursts and obscured QSOs and we have recovered couple of the known proto-clusters and close to 30 new proto-clusters. The candidate proto-clusters selected from this technique have far-IR flux densities several times higher than those that are optically selected, such as using LBG selection, implying that the member galaxies are in a special phase of heightened dusty starburst and dusty QSO activity. This far-IR luminous phase may be short but likely to be necessary piece to understand the whole stellar mass assembly history of clusters. Moreover, our photo-clusters are missed in optical selections, suggesting that optically selected proto-clusters alone do not provide adequate statistics and a comparison of the far-IR and optical selected clusters may reveal the importance of the dusty stellar mass assembly. Here, we propose IRAC observations of six of the highest priority new proto-clusters, to establish the validity of the technique and to determine the total stellar mass through SED models. For a modest observing time the science program will have a substantial impact on an upcoming science topic in cosmology with implications for observations with JWST and WFIRST to understand the mass assembly in the universe.

Do obesity-promoting food environments cluster around socially disadvantaged schools in Glasgow, Scotland?

PubMed

Ellaway, Anne; Macdonald, Laura; Lamb, Karen; Thornton, Lukar; Day, Peter; Pearce, Jamie

2012-11-01

Increase in the consumption of food and drinks outside the home by adolescents and young people and associations with rising levels of obesity is a significant concern worldwide and it has been suggested that the food environment around schools may be a contributory factor. As few studies have explored this issue in a UK setting, we examined whether different types of food outlets are clustered around public secondary schools in Glasgow, and whether this pattern differed by social disadvantage. We found evidence of clustering of food outlets around schools but a more complex picture in relation to deprivation was observed. Across all schools there were numerous opportunities for pupils to purchase energy dense foods locally and the implications for policy are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synaptic clustering within dendrites: an emerging theory of memory formation

PubMed Central

Kastellakis, George; Cai, Denise J.; Mednick, Sara C.; Silva, Alcino J.; Poirazi, Panayiota

2015-01-01

It is generally accepted that complex memories are stored in distributed representations throughout the brain, however the mechanisms underlying these representations are not understood. Here, we review recent findings regarding the subcellular mechanisms implicated in memory formation, which provide evidence for a dendrite-centered theory of memory. Plasticity-related phenomena which affect synaptic properties, such as synaptic tagging and capture, synaptic clustering, branch strength potentiation and spinogenesis provide the foundation for a model of memory storage that relies heavily on processes operating at the dendrite level. The emerging picture suggests that clusters of functionally related synapses may serve as key computational and memory storage units in the brain. We discuss both experimental evidence and theoretical models that support this hypothesis and explore its advantages for neuronal function. PMID:25576663

Exercise Recommendations for the Management of Symptoms Clusters Resulting from Cancer and Cancer Treatments

PubMed Central

Mustian, Karen M.; Cole, Calvin L.; Lin, Po Ju; Asare, Matt; Fung, Chunkit; Janelsins, Michelle C.; Kamen, Charles S.; Peppone, Luke J.; Magnuson, Allison

2017-01-01

Objective To review existing exercise guidelines for cancer patients and survivors for the management of symptom clusters. Data source Review of Pubmed literature and published exercise guidelines. Conclusion Cancer and its treatments are responsible for a copious number of incapacitating symptoms that markedly impair quality of life (QOL). The exercise oncology literature provides consistent support for the safety and efficacy of exercise interventions in managing cancer- and treatment-related symptoms as well as improving quality of life in cancer patients and survivors. Implications for Nursing Practice Effective management of symptoms enhances recovery, resumption of normal life activities and QOL for patients and survivors. Exercise is a safe, appropriate and effective therapeutic option before, during, and after the completion of treatment for alleviating symptoms and symptom clusters. PMID:27776835

The properties of clusters in the gas phase. IV - Complexes of H2O and HNOx clustering on NOx/-/

NASA Technical Reports Server (NTRS)

Lee, N.; Castleman, A. W., Jr.; Keesee, R. G.

1980-01-01

Thermodynamic quantities for the gas-phase clustering equilibria of NO2(-) and NO3(-) were determined with high-pressure mass spectrometry. A comparison of values of the free energy of hydration derived from the data shows good agreement with formerly reported values at 296 K. New data for larger NO2(-) and NO3(-) hydrates as well as NO2(-)(HNO2)n were obtained in this study. To aid in understanding the bonding and stability of the hydrates of nitrite and nitrate ions, CNDO/2 calculations were performed, and the results are discussed. A correlation between the aqueous-phase total hydration enthalpy of a single ion and its gas-phase hydration enthalpy was obtained. Atmospheric implications of the data are also briefly discussed.

Binaries at Birth: Stellar multiplicity in embedded clusters from radial velocity variations in the IN-SYNC survey

NASA Astrophysics Data System (ADS)

Oskar Jaehnig, Karl; Stassun, Keivan; Tan, Jonathan C.; Covey, Kevin R.; Da Rio, Nicola

2016-01-01

We study the nature of stellar multiplicity in young stellar systems using the INfrared Spectroscopy of Young Nebulous Clusters (IN-SYNC) survey, carried out in SDSS III with the APOGEE spectrograph. Multi-epoch observations of thousands of low-mass stars in Orion A, NGC2264, NGC1333 and IC348 have been carried out, yielding H-band spectra with R=22,500 for sources with H<12 mag. Radial velocity sensitivities ~0.3 km/s can be achieved, depending on the spectral type of the star. We search the IN-SYNC radial velocity catalog to identify sources with radial velocity variations indicative of spectroscopically undetected companions, analyze their spectral properties and discuss the implications for the overall multiplicity of stellar populations in young, embedded star clusters.

Clustering of diet, physical activity and smoking and a general willingness to change.

PubMed

de Vries, Hein; Kremers, Stef; Smeets, Tamara; Reubsaet, Astrid

2008-01-01

Addressing multiple health behaviours are important in preventing disease and mortality. The present study investigated the clustering of health behaviours, cognitive determinants and stages of change in 2827 adults for the lifestyle factors of physical activity, fruit, vegetable and fat consumption and smoking. The results showed that only 3% of the total population met recommended guidelines for all of the five behaviours. Behaviours were found to be weakly associated. Behaviour-specific cognitions and stages of change for the behaviours clustered more strongly, however. With respect to diet and physical activity, respondents in the preparation stage for one behaviour were likely also to be preparing to change another behaviour. Possible mechanisms for the apparent general willingness to change multiple behaviours are discussed, as well as potential implications for health promotion practice.

From Luminous Hot Stars to Starburst Galaxies

NASA Astrophysics Data System (ADS)

Conti, Peter S.; Crowther, Paul A.; Leitherer, Claus

2012-10-01

1. Introduction; 2. Observed properties; 3. Stellar atmospheres; 4. Stellar winds; 5. Evolution of single stars; 6. Binaries; 7. Birth of massive stars and star clusters; 8. The interstellar environment; 9. From giant HII regions to HII galaxies; 10. Starburst phenomena; 11. Cosmological implications; References; Index.

Adoption: Misunderstood, Mythologized, Marginalized

ERIC Educational Resources Information Center

Friedlander, Myrna L.

2003-01-01

Implications are discussed in response to the Major Contribution in this issue reviewing the history, controversies, and theoretical and research literature related to adoption. Practice recommendations for therapists working with adopted children and their families are clustered around three prominent themes in the reviews by Lee, O'Brien and…

Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma.

PubMed

Schatz, Michael; Hsu, Jin-Wen Y; Zeiger, Robert S; Chen, Wansu; Dorenbaum, Alejandro; Chipps, Bradley E; Haselkorn, Tmirah

2014-06-01

Asthma phenotyping can facilitate understanding of disease pathogenesis and potential targeted therapies. To further characterize the distinguishing features of phenotypic groups in difficult-to-treat asthma. Children ages 6-11 years (n = 518) and adolescents and adults ages ≥12 years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were evaluated in this post hoc cluster analysis. Analyzed variables included sex, race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the hierarchical clustering algorithm with the Ward minimum variance method. The results were compared among clusters by χ(2) analysis; variables with significant (P < .05) differences among clusters were considered as distinguishing feature candidates. Associations among clusters and asthma-related health outcomes were assessed in multivariable analyses by adjusting for socioeconomic status, environmental exposures, and intensity of therapy. Five clusters were identified in each age stratum. Sex, atopic status, and nonwhite race were distinguishing variables in both strata; passive smoke exposure was distinguishing in children and aspirin sensitivity in adolescents and adults. Clusters were not related to outcomes in children, but 2 adult and adolescent clusters distinguished by nonwhite race and aspirin sensitivity manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster experienced more frequent asthma exacerbations (P < .0001). Distinct phenotypes appear to exist in patients with severe or difficult-to-treat asthma, which is related to outcomes in adolescents and adults but not in children. The study of the therapeutic implications of these phenotypes is warranted. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Clustering by neurocognition for fine-mapping of the schizophrenia susceptibility loci on chromosome 6p

PubMed Central

Lin, Sheng-Hsiang; Liu, Chih-Min; Liu, Yu-Li; Fann, Cathy Shen-Jang; Hsiao, Po-Chang; Wu, Jer-Yuarn; Hung, Shuen-Iu; Chen, Chun-Houh; Wu, Han-Ming; Jou, Yuh-Shan; Liu, Shi K.; Hwang, Tzung J.; Hsieh, Ming H.; Chang, Chien-Ching; Yang, Wei-Chih; Lin, Jin-Jia; Chou, Frank Huang-Chih; Faraone, Stephen V.; Tsuang, Ming T.; Hwu, Hai-Gwo; Chen, Wei J.

2009-01-01

Chromosome 6p is one of the most commonly implicated regions in the genome-wide linkage scans of schizophrenia, whereas further association studies for markers in this region were inconsistent likely due to heterogeneity. This study aimed to identify more homogeneous subgroups of families for fine mapping on regions around markers D6S296 and D6S309 (both in 6p24.3) as well as D6S274 (in 6p22.3) by means of similarity in neurocognitive functioning. A total of 160 families of patients with schizophrenia comprising at least two affected siblings who had data for 8 neurocognitive test variables of the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST) were subjected to cluster analysis with data visualization using the test scores of both affected siblings. Family clusters derived were then used separately in family-based association tests for 64 single nucleotide polymorphisms covering the region of 6p24.3 and 6p22.3. Three clusters were derived from the family-based clustering, with deficit cluster 1 representing deficit on the CPT, deficit cluster 2 representing deficit on both the CPT and the WCST, and a third cluster of non-deficit. After adjustment using false discovery rate for multiple testing, SNP rs13873 and haplotype rs1225934-rs13873 on BMP6-TXNDC5 genes were significantly associated with schizophrenia for the deficit cluster 1 but not for the deficit cluster 2 or non-deficit cluster. Our results provide further evidence that the BMP6-TXNDC5 locus on 6p24.3 may play a role in the selective impairments on sustained attention of schizophrenia. PMID:19694819

Cluster Analysis of Acute Care Use Yields Insights for Tailored Pediatric Asthma Interventions.

PubMed

Abir, Mahshid; Truchil, Aaron; Wiest, Dawn; Nelson, Daniel B; Goldstick, Jason E; Koegel, Paul; Lozon, Marie M; Choi, Hwajung; Brenner, Jeffrey

2017-09-01

We undertake this study to understand patterns of pediatric asthma-related acute care use to inform interventions aimed at reducing potentially avoidable hospitalizations. Hospital claims data from 3 Camden city facilities for 2010 to 2014 were used to perform cluster analysis classifying patients aged 0 to 17 years according to their asthma-related hospital use. Clusters were based on 2 variables: asthma-related ED visits and hospitalizations. Demographics and a number of sociobehavioral and use characteristics were compared across clusters. Children who met the criteria (3,170) were included in the analysis. An examination of a scree plot showing the decline in within-cluster heterogeneity as the number of clusters increased confirmed that clusters of pediatric asthma patients according to hospital use exist in the data. Five clusters of patients with distinct asthma-related acute care use patterns were observed. Cluster 1 (62% of patients) showed the lowest rates of acute care use. These patients were least likely to have a mental health-related diagnosis, were less likely to have visited multiple facilities, and had no hospitalizations for asthma. Cluster 2 (19% of patients) had a low number of asthma ED visits and onetime hospitalization. Cluster 3 (11% of patients) had a high number of ED visits and low hospitalization rates, and the highest rates of multiple facility use. Cluster 4 (7% of patients) had moderate ED use for both asthma and other illnesses, and high rates of asthma hospitalizations; nearly one quarter received care at all facilities, and 1 in 10 had a mental health diagnosis. Cluster 5 (1% of patients) had extreme rates of acute care use. Differences observed between groups across multiple sociobehavioral factors suggest these clusters may represent children who differ along multiple dimensions, in addition to patterns of service use, with implications for tailored interventions. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

PubMed Central

Lind, Abigail L.; Wisecaver, Jennifer H.; Lameiras, Catarina; Wiemann, Philipp; Palmer, Jonathan M.; Keller, Nancy P.; Rodrigues, Fernando; Goldman, Gustavo H.

2017-01-01

Filamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here, we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen Aspergillus fumigatus. Investigation of genome-wide within-species variation revealed 5 general types of variation in SM gene clusters: nonfunctional gene polymorphisms; gene gain and loss polymorphisms; whole cluster gain and loss polymorphisms; allelic polymorphisms, in which different alleles corresponded to distinct, nonhomologous clusters; and location polymorphisms, in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative A. fumigatus SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms, the detection of which requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and nonhomologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, and genomic deletion and insertion events as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover within A. fumigatus have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns. PMID:29149178

Broiler Campylobacter Contamination and Human Campylobacteriosis in Iceland ▿ †

PubMed Central

Callicott, Kenneth A.; Harðardóttir, Hjördís; Georgsson, Franklín; Reiersen, Jarle; Friðriksdóttir, Vala; Gunnarsson, Eggert; Michel, Pascal; Bisaillon, Jean-Robert; Kristinsson, Karl G.; Briem, Haraldur; Hiett, Kelli L.; Needleman, David S.; Stern, Norman J.

2008-01-01

To examine whether there is a relationship between the degree of Campylobacter contamination observed in product lots of retail Icelandic broiler chicken carcasses and the incidence of human disease, 1,617 isolates from 327 individual product lots were genetically matched (using the flaA short variable region [SVR[) to 289 isolates from cases of human campylobacteriosis whose onset was within approximately 2 weeks from the date of processing. When there was genetic identity between broiler isolates and human isolates within the appropriate time frame, a retail product lot was classified as implicated in human disease. According to the results of this analysis, there were multiple clusters of human disease linked to the same process lot or lots. Implicated and nonimplicated retail product lots were compared for four lot descriptors: lot size, prevalence, mean contamination, and maximum contamination (as characterized by direct rinse plating). For retail product distributed fresh, Mann-Whitney U tests showed that implicated product lots had significantly (P = 0.0055) higher mean contamination than nonimplicated lots. The corresponding median values were 3.56 log CFU/carcass for implicated lots and 2.72 log CFU/carcass for nonimplicated lots. For frozen retail product, implicated lots were significantly (P = 0.0281) larger than nonimplicated lots. When the time frame was removed, retail product lots containing Campylobacter flaA SVR genotypes also seen in human disease had significantly higher mean and maximum contamination numbers than lots containing no genotypes seen in human disease for both fresh and frozen product. Our results suggest that cases of broiler-borne campylobacteriosis may occur in clusters and that the differences in mean contamination levels may provide a basis for regulatory action that is more specific than a presence-absence standard. PMID:18791017

A distance of 133-137 parsecs to the Pleiades star cluster.

PubMed

Pan, Xiaopei; Shao, M; Kulkarni, S R

2004-01-22

Nearby 'open' clusters of stars (those that are not gravitationally bound) have played a crucial role in the development of stellar astronomy because, as a consequence of the stars having a common age, they provide excellent natural laboratories to test theoretical stellar models. Clusters also play a fundamental part in determining distance scales. The satellite Hipparcos surprisingly found that an extensively studied open cluster--the Pleiades (also known as the Seven Sisters)--had a distance of D = 118 +/- 4 pc (refs 2, 3), about ten per cent smaller than the accepted value. The discrepancy generated a spirited debate because the implication was that either current stellar models were incorrect by a surprising amount or Hipparcos was giving incorrect distances. Here we report the orbital parameters of the bright double star Atlas in the Pleiades, using long-baseline optical/infrared interferometry. From the data we derive a firm lower bound of D > 127 pc, with the most likely range being 133 < D < 137 pc. Our result reaffirms the fidelity of current stellar models.

[Fish-caused illness: notify food-related outbreaks to the Municipal Health Services].

PubMed

Morroy, G; Ooms, D; Jansen, H J; Dijkstra, J; van Drunen-Kamp, K J; Batstra-Blokpoel, J

2018-01-01

When two or more people fall ill after eating the same food, this is called an outbreak of food poisoning or food-related infection. In the Netherlands, physicians have to notify the Municipal Health Services (GGD) of such outbreaks. The GGD informs the Netherlands Food and Consumer Product Safety Authority (NVWA). Two clusters of scombroid poisoning (histamine poisoning in this case after eating tuna) occurred in one month. Due to the quick reporting of patients by physicians, the GGD and the NVWA immediately tracked down the source. In both clusters the NVWA confirmed high histamine levels in tuna. In reaction to these findings and the first cluster, the supplier recalled the tuna batch. This may have prevented other cases of food poisoning. In the second cluster, the implicated tuna batch had already been sold. Timely notification by physicians of food poisoning or food-related outbreaks to the GGD enables swift tracing of the source and appropriate measures by the GGD and the NVWA..

Examining the relationship between coping strategies and suicidal desire in a sample of United States military personnel.

PubMed

Khazem, Lauren R; Law, Keyne C; Green, Bradley A; Anestis, Michael D

2015-02-01

Suicidal desire in the military has been previously examined through the lens of the Interpersonal-Psychological Theory of Suicide (IPTS). However, no research has examined the impact of specific coping strategies on perceived burdensomeness, thwarted belongingness, and suicidal ideation in a large population of individuals serving in the US military. Furthermore, the factor structure of previously utilized coping clusters did not apply to our sample of military personnel. Therefore, we found a three-factor solution to be tested in this sample. We hypothesized that specific types of coping behavior clusters (Adaptive and Maladaptive) would predict both IPTS constructs and suicidal ideation. Results indicated that Adaptive and Maladaptive coping clusters predicted the IPTS constructs in the hypothesized directions. However, only the Maladaptive cluster predicted suicidal ideation. These findings implicate the need for further research and suicide prevention efforts focusing on coping strategies, specifically those that are maladaptive in nature, in relation to suicidal ideation in military members. Copyright © 2014 Elsevier Inc. All rights reserved.

Dynein Clusters into Lipid Microdomains on Phagosomes to Drive Rapid Transport toward Lysosomes.

PubMed

Rai, Ashim; Pathak, Divya; Thakur, Shreyasi; Singh, Shampa; Dubey, Alok Kumar; Mallik, Roop

2016-02-11

Diverse cellular processes are driven by motor proteins that are recruited to and generate force on lipid membranes. Surprisingly little is known about how membranes control the force from motors and how this may impact specific cellular functions. Here, we show that dynein motors physically cluster into microdomains on the membrane of a phagosome as it matures inside cells. Such geometrical reorganization allows many dyneins within a cluster to generate cooperative force on a single microtubule. This results in rapid directed transport of the phagosome toward microtubule minus ends, likely promoting phagolysosome fusion and pathogen degradation. We show that lipophosphoglycan, the major molecule implicated in immune evasion of Leishmania donovani, inhibits phagosome motion by disrupting the clustering and therefore the cooperative force generation of dynein. These findings appear relevant to several pathogens that prevent phagosome-lysosome fusion by targeting lipid microdomains on phagosomes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Exploring Different Patterns of Love Attitudes among Chinese College Students.

PubMed

Zeng, Xianglong; Pan, Yiqin; Zhou, Han; Yu, Shi; Liu, Xiangping

2016-01-01

Individual differences in love attitudes and the relationship between love attitudes and other variables in Asian culture lack in-depth exploration. This study conducted cluster analysis with data regarding love attitudes obtained from 389 college students in mainland China. The result of cluster analysis based on love-attitude scales distinguished four types of students: game players, rational lovers, emotional lovers, and absence lovers. These four groups of students showed significant differences in sexual attitudes and personality traits of deliberation and dutifulness but not self-discipline. The study's implications for future studies on love attitudes in certain cultural groups were also discussed.

High-resolution X-ray spectroscopy of M87 with the Einstein observatory - The detection of an O VIII emission line

NASA Technical Reports Server (NTRS)

Canizares, C. R.; Clark, G. W.; Markert, T. H.; Berg, C.; Smedira, M.; Bardas, D.; Schnopper, H.; Kalata, K.

1979-01-01

The paper deals with high-resolution X-ray spectroscopy performed to study the extended source surrounding the giant elliptical galaxy, M87, in the Virgo cluster. From observations carried out with a focal plane crystal spectrometer, L-alpha emission was detected from hydrogenic oxygen (O VIII). Upper limits could be set on lines from intermediate ionization states of iron. The presence of a quantity of cooler matter surrounding M87 was revealed, which has important implications for cluster models and favors a radiatively controlled accretion mechanism.

HIFLUGCS: X-ray luminosity-dynamical mass relation and its implications for mass calibrations with the SPIDERS and 4MOST surveys

NASA Astrophysics Data System (ADS)

Zhang, Yu-Ying; Reiprich, Thomas H.; Schneider, Peter; Clerc, Nicolas; Merloni, Andrea; Schwope, Axel; Borm, Katharina; Andernach, Heinz; Caretta, César A.; Wu, Xiang-Ping

2017-03-01

We present the relation of X-ray luminosity versus dynamical mass for 63 nearby clusters of galaxies in a flux-limited sample, the HIghest X-ray FLUx Galaxy Cluster Sample (HIFLUGCS, consisting of 64 clusters). The luminosity measurements are obtained based on 1.3 Ms of clean XMM-Newton data and ROSAT pointed observations. The masses are estimated using optical spectroscopic redshifts of 13647 cluster galaxies in total. We classify clusters into disturbed and undisturbed based on a combination of the X-ray luminosity concentration and the offset between the brightest cluster galaxy and X-ray flux-weighted center. Given sufficient numbers (I.e., ≥45) of member galaxies when the dynamical masses are computed, the luminosity versus mass relations agree between the disturbed and undisturbed clusters. The cool-core clusters still dominate the scatter in the luminosity versus mass relation even when a core-corrected X-ray luminosity is used, which indicates that the scatter of this scaling relation mainly reflects the structure formation history of the clusters. As shown by the clusters with only few spectroscopically confirmed members, the dynamical masses can be underestimated and thus lead to a biased scaling relation. To investigate the potential of spectroscopic surveys to follow up high-redshift galaxy clusters or groups observed in X-ray surveys for the identifications and mass calibrations, we carried out Monte Carlo resampling of the cluster galaxy redshifts and calibrated the uncertainties of the redshift and dynamical mass estimates when only reduced numbers of galaxy redshifts per cluster are available. The resampling considers the SPIDERS and 4MOST configurations, designed for the follow-up of the eROSITA clusters, and was carried out for each cluster in the sample at the actual cluster redshift as well as at the assigned input cluster redshifts of 0.2, 0.4, 0.6, and 0.8. To follow up very distant clusters or groups, we also carried out the mass calibration based on the resampling with only ten redshifts per cluster, and redshift calibration based on the resampling with only five and ten redshifts per cluster, respectively. Our results demonstrate the power of combining upcoming X-ray and optical spectroscopic surveys for mass calibration of clusters. The scatter in the dynamical mass estimates for the clusters with at least ten members is within 50%.

Biochemical analysis of six genetic variants of error-prone human DNA polymerase ι involved in translesion DNA synthesis.

PubMed

Kim, Jinsook; Song, Insil; Jo, Ara; Shin, Joo-Ho; Cho, Hana; Eoff, Robert L; Guengerich, F Peter; Choi, Jeong-Yun

2014-10-20

DNA polymerase (pol) ι is the most error-prone among the Y-family polymerases that participate in translesion synthesis (TLS). Pol ι can bypass various DNA lesions, e.g., N(2)-ethyl(Et)G, O(6)-methyl(Me)G, 8-oxo-7,8-dihydroguanine (8-oxoG), and an abasic site, though frequently with low fidelity. We assessed the biochemical effects of six reported genetic variations of human pol ι on its TLS properties, using the recombinant pol ι (residues 1-445) proteins and DNA templates containing a G, N(2)-EtG, O(6)-MeG, 8-oxoG, or abasic site. The Δ1-25 variant, which is the N-terminal truncation of 25 residues resulting from an initiation codon variant (c.3G > A) and also is the formerly misassigned wild-type, exhibited considerably higher polymerase activity than wild-type with Mg(2+) (but not with Mn(2+)), coinciding with its steady-state kinetic data showing a ∼10-fold increase in kcat/Km for nucleotide incorporation opposite templates (only with Mg(2+)). The R96G variant, which lacks a R96 residue known to interact with the incoming nucleotide, lost much of its polymerase activity, consistent with the kinetic data displaying 5- to 72-fold decreases in kcat/Km for nucleotide incorporation opposite templates either with Mg(2+) or Mn(2+), except for that opposite N(2)-EtG with Mn(2+) (showing a 9-fold increase for dCTP incorporation). The Δ1-25 variant bound DNA 20- to 29-fold more tightly than wild-type (with Mg(2+)), but the R96G variant bound DNA 2-fold less tightly than wild-type. The DNA-binding affinity of wild-type, but not of the Δ1-25 variant, was ∼7-fold stronger with 0.15 mM Mn(2+) than with Mg(2+). The results indicate that the R96G variation severely impairs most of the Mg(2+)- and Mn(2+)-dependent TLS abilities of pol ι, whereas the Δ1-25 variation selectively and substantially enhances the Mg(2+)-dependent TLS capability of pol ι, emphasizing the potential translational importance of these pol ι genetic variations, e.g., individual differences in TLS, mutation, and cancer susceptibility to genotoxic carcinogens.

Biochemical Analysis of Six Genetic Variants of Error-Prone Human DNA Polymerase ι Involved in Translesion DNA Synthesis

PubMed Central

2015-01-01

DNA polymerase (pol) ι is the most error-prone among the Y-family polymerases that participate in translesion synthesis (TLS). Pol ι can bypass various DNA lesions, e.g., N2-ethyl(Et)G, O6-methyl(Me)G, 8-oxo-7,8-dihydroguanine (8-oxoG), and an abasic site, though frequently with low fidelity. We assessed the biochemical effects of six reported genetic variations of human pol ι on its TLS properties, using the recombinant pol ι (residues 1–445) proteins and DNA templates containing a G, N2-EtG, O6-MeG, 8-oxoG, or abasic site. The Δ1–25 variant, which is the N-terminal truncation of 25 residues resulting from an initiation codon variant (c.3G > A) and also is the formerly misassigned wild-type, exhibited considerably higher polymerase activity than wild-type with Mg2+ (but not with Mn2+), coinciding with its steady-state kinetic data showing a ∼10-fold increase in kcat/Km for nucleotide incorporation opposite templates (only with Mg2+). The R96G variant, which lacks a R96 residue known to interact with the incoming nucleotide, lost much of its polymerase activity, consistent with the kinetic data displaying 5- to 72-fold decreases in kcat/Km for nucleotide incorporation opposite templates either with Mg2+ or Mn2+, except for that opposite N2-EtG with Mn2+ (showing a 9-fold increase for dCTP incorporation). The Δ1–25 variant bound DNA 20- to 29-fold more tightly than wild-type (with Mg2+), but the R96G variant bound DNA 2-fold less tightly than wild-type. The DNA-binding affinity of wild-type, but not of the Δ1–25 variant, was ∼7-fold stronger with 0.15 mM Mn2+ than with Mg2+. The results indicate that the R96G variation severely impairs most of the Mg2+- and Mn2+-dependent TLS abilities of pol ι, whereas the Δ1–25 variation selectively and substantially enhances the Mg2+-dependent TLS capability of pol ι, emphasizing the potential translational importance of these pol ι genetic variations, e.g., individual differences in TLS, mutation, and cancer susceptibility to genotoxic carcinogens. PMID:25162224

Are U.S. Military Interventions Contagious over Time? Intervention Timing and Its Implications for Force Planning

DTIC Science & Technology

2013-01-01

29 3.5. ARIMA Models , Temporal Clustering of Conflicts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 3.6...39 3.9. ARIMA Models ...variance across a distribution. Autoregressive integrated moving average ( ARIMA ) models are used with time-series data sets and are designed to capture

Identifying Differences among Novice Database Users: Implications for Training Material Effectiveness.

ERIC Educational Resources Information Center

Antonucci, Yvonne Lederer; Wozny, Lucy Anne

1996-01-01

Identifies and describes sublevels of novices using a database management package, clustering those whose interaction is effective, partially effective, and totally ineffective. Among assistance documentation, functional tree diagrams (FTDs) were more beneficial to partially effective users than traditional reference material. The results have…

The ROSAT Brightest Cluster Sample - I. The compilation of the sample and the cluster log N-log S distribution

NASA Astrophysics Data System (ADS)

Ebeling, H.; Edge, A. C.; Bohringer, H.; Allen, S. W.; Crawford, C. S.; Fabian, A. C.; Voges, W.; Huchra, J. P.

1998-12-01

We present a 90 per cent flux-complete sample of the 201 X-ray-brightest clusters of galaxies in the northern hemisphere (delta>=0 deg), at high Galactic latitudes (|b|>=20 deg), with measured redshifts z<=0.3 and fluxes higher than 4.4x10^-12 erg cm^-2 s^-1 in the 0.1-2.4 keV band. The sample, called the ROSAT Brightest Cluster Sample (BCS), is selected from ROSAT All-Sky Survey data and is the largest X-ray-selected cluster sample compiled to date. In addition to Abell clusters, which form the bulk of the sample, the BCS also contains the X-ray-brightest Zwicky clusters and other clusters selected from their X-ray properties alone. Effort has been made to ensure the highest possible completeness of the sample and the smallest possible contamination by non-cluster X-ray sources. X-ray fluxes are computed using an algorithm tailored for the detection and characterization of X-ray emission from galaxy clusters. These fluxes are accurate to better than 15 per cent (mean 1sigma error). We find the cumulative logN-logS distribution of clusters to follow a power law kappa S^alpha with alpha=1.31^+0.06_-0.03 (errors are the 10th and 90th percentiles) down to fluxes of 2x10^-12 erg cm^-2 s^-1, i.e. considerably below the BCS flux limit. Although our best-fitting slope disagrees formally with the canonical value of -1.5 for a Euclidean distribution, the BCS logN-logS distribution is consistent with a non-evolving cluster population if cosmological effects are taken into account. Our sample will allow us to examine large-scale structure in the northern hemisphere, determine the spatial cluster-cluster correlation function, investigate correlations between the X-ray and optical properties of the clusters, establish the X-ray luminosity function for galaxy clusters, and discuss the implications of the results for cluster evolution.

Monothiol Glutaredoxins Can Bind Linear [Fe3S4]+ and [Fe4S4]2+ Clusters in Addition to [Fe2S2]2+ Clusters: Spectroscopic Characterization and Functional Implications

PubMed Central

Zhang, Bo; Bandyopadhyay, Sibali; Shakamuri, Priyanka; Naik, Sunil G.; Huynh, Boi Hanh; Couturier, Jérémy; Rouhier, Nicolas; Johnson, Michael K.

2013-01-01

Saccharomyces cerevisiae mitochondrial glutaredoxin 5 (Grx5) is the archetypical member of a ubiquitous class of monothiol glutaredoxins with a strictly conserved CGFS active-site sequence that has been shown to function in biological [Fe2S2]2+ cluster trafficking. In this work, we show that recombinant S. cerevisiae Grx5 purified aerobically after prolonged exposure of the cell-free extract to air or after anaerobic reconstitution in the presence of glutathione, predominantly contains a linear [Fe3S4]+ cluster. The excited state electronic properties and ground state electronic and vibrational properties of the linear [Fe3S4]+ cluster have been characterized using UV-visible absorption/CD/MCD, EPR, Mössbauer and resonance Raman spectroscopies. The results reveal a rhombic S = 5/2 linear [Fe3S4]+ cluster with properties similar to those reported for synthetic linear [Fe3S4]+ clusters and the linear [Fe3S4]+ clusters in purple aconitase. Moreover, the results indicate that the Fe-S cluster content previously reported for many monothiol Grxs has been misinterpreted exclusively in terms of [Fe2S2]2+ clusters, rather than linear [Fe3S4]+ clusters or mixtures of linear [Fe3S4]+ and [Fe2S2]2+ clusters. In the absence of GSH, anaerobic reconstitution of Grx5 yields a dimeric form containing one [Fe4S4]2+ cluster that competent for in vitro activation of apo-aconitase, via intact cluster transfer. The ligation of the linear [Fe3S4]+ and [Fe4S4]2+ clusters in Grx5 has been assessed by spectroscopic, mutational and analytical studies. Potential roles for monothiol Grx5 in scavenging and recycling linear [Fe3S4]+ clusters released during protein unfolding under oxidative stress conditions and in maturation of [Fe4S4]2+ cluster-containing proteins are discussed in light of these results. PMID:24032439

Microarray and comparative genomics-based identification of genes and gene regulatory regions of the mouse immune system

PubMed Central

Hutton, John J; Jegga, Anil G; Kong, Sue; Gupta, Ashima; Ebert, Catherine; Williams, Sarah; Katz, Jonathan D; Aronow, Bruce J

2004-01-01

Background In this study we have built and mined a gene expression database composed of 65 diverse mouse tissues for genes preferentially expressed in immune tissues and cell types. Using expression pattern criteria, we identified 360 genes with preferential expression in thymus, spleen, peripheral blood mononuclear cells, lymph nodes (unstimulated or stimulated), or in vitro activated T-cells. Results Gene clusters, formed based on similarity of expression-pattern across either all tissues or the immune tissues only, had highly significant associations both with immunological processes such as chemokine-mediated response, antigen processing, receptor-related signal transduction, and transcriptional regulation, and also with more general processes such as replication and cell cycle control. Within-cluster gene correlations implicated known associations of known genes, as well as immune process-related roles for poorly described genes. To characterize regulatory mechanisms and cis-elements of genes with similar patterns of expression, we used a new version of a comparative genomics-based cis-element analysis tool to identify clusters of cis-elements with compositional similarity among multiple genes. Several clusters contained genes that shared 5–6 cis-elements that included ETS and zinc-finger binding sites. cis-Elements AP2 EGRF ETSF MAZF SP1F ZF5F and AREB ETSF MZF1 PAX5 STAT were shared in a thymus-expressed set; AP4R E2FF EBOX ETSF MAZF SP1F ZF5F and CREB E2FF MAZF PCAT SP1F STAT cis-clusters occurred in activated T-cells; CEBP CREB NFKB SORY and GATA NKXH OCT1 RBIT occurred in stimulated lymph nodes. Conclusion This study demonstrates a series of analytic approaches that have allowed the implication of genes and regulatory elements that participate in the differentiation, maintenance, and function of the immune system. Polymorphism or mutation of these could adversely impact immune system functions. PMID:15504237

The clustering of galaxies in the completed SDSS-III Baryon Oscillation Spectroscopic Survey: Cosmological implications of the configuration-space clustering wedges

NASA Astrophysics Data System (ADS)

Sánchez, Ariel G.; Scoccimarro, Román; Crocce, Martín; Grieb, Jan Niklas; Salazar-Albornoz, Salvador; Dalla Vecchia, Claudio; Lippich, Martha; Beutler, Florian; Brownstein, Joel R.; Chuang, Chia-Hsun; Eisenstein, Daniel J.; Kitaura, Francisco-Shu; Olmstead, Matthew D.; Percival, Will J.; Prada, Francisco; Rodríguez-Torres, Sergio; Ross, Ashley J.; Samushia, Lado; Seo, Hee-Jong; Tinker, Jeremy; Tojeiro, Rita; Vargas-Magaña, Mariana; Wang, Yuting; Zhao, Gong-Bo

2017-01-01

We explore the cosmological implications of anisotropic clustering measurements in configuration space of the final galaxy samples from Data Release 12 of the Sloan Digital Sky Survey III Baryon Oscillation Spectroscopic Survey. We implement a new detailed modelling of the effects of non-linearities, bias and redshift-space distortions that can be used to extract unbiased cosmological information from our measurements for scales s ≳ 20 h-1 Mpc. We combined the information from Baryon Oscillation Spectroscopic Survey (BOSS) with the latest cosmic microwave background (CMB) observations and Type Ia supernovae samples and found no significant evidence for a deviation from the Λ cold dark matter (ΛCDM) cosmological model. In particular, these data sets can constrain the dark energy equation-of-state parameter to wDE = -0.996 ± 0.042 when to be assumed time independent, the curvature of the Universe to Ωk = -0.0007 ± 0.0030 and the sum of the neutrino masses to ∑mν < 0.25 eV at 95 per cent confidence levels. We explore the constraints on the growth rate of cosmic structures assuming f(z) = Ωm(z)γ and obtain γ = 0.609 ± 0.079, in good agreement with the predictions of general relativity of γ = 0.55. We compress the information of our clustering measurements into constraints on the parameter combinations DV(z)/rd, FAP(z) and fσ8(z) at zeff = 0.38, 0.51 and 0.61 with their respective covariance matrices and find good agreement with the predictions for these parameters obtained from the best-fitting ΛCDM model to the CMB data from the Planck satellite. This paper is part of a set that analyses the final galaxy clustering data set from BOSS. The measurements and likelihoods presented here are combined with others by Alam et al. to produce the final cosmological constraints from BOSS.

Chromosome thripsis by DNA double strand break clusters causes enhanced cell lethality, chromosomal translocations and 53BP1-recruitment

PubMed Central

Schipler, Agnes; Mladenova, Veronika; Soni, Aashish; Nikolov, Vladimir; Saha, Janapriya; Mladenov, Emil; Iliakis, George

2016-01-01

Chromosome translocations are hallmark of cancer and of radiation-induced cell killing, reflecting joining of incongruent DNA-ends that alter the genome. Translocation-formation requires DNA end-joining mechanisms and incompletely characterized, permissive chromatin conditions. We show that chromatin destabilization by clusters of DNA double-strand-breaks (DSBs) generated by the I-SceI meganuclease at multiple, appropriately engineered genomic sites, compromises c-NHEJ and markedly increases cell killing and translocation-formation compared to single-DSBs. Translocation-formation from DSB-clusters utilizes Parp1 activity, implicating alt-EJ in their formation. Immunofluorescence experiments show that single-DSBs and DSB-clusters uniformly provoke the formation of single γ-H2AX foci, suggesting similar activation of early DNA damage response (DDR). Live-cell imaging also shows similar single-focus recruitment of the early-response protein MDC1, to single-DSBs and DSB-clusters. Notably, the late DDR protein, 53BP1 shows in live-cell imaging strikingly stronger recruitment to DSB-clusters as compared to single-DSBs. This is the first report that chromatin thripsis, in the form of engineered DSB-clusters, compromises first-line DSB-repair pathways, allowing alt-EJ to function as rescuing-backup. DSB-cluster-formation is indirectly linked to the increased biological effectiveness of high ionization-density radiations, such as the alpha-particles emitted by radon gas or the heavy-ions utilized in cancer therapy. Our observations provide the first direct mechanistic explanation for this long-known effect. PMID:27257076

Tardigrade workbench: comparing stress-related proteins, sequence-similar and functional protein clusters as well as RNA elements in tardigrades

PubMed Central

2009-01-01

Background Tardigrades represent an animal phylum with extraordinary resistance to environmental stress. Results To gain insights into their stress-specific adaptation potential, major clusters of related and similar proteins are identified, as well as specific functional clusters delineated comparing all tardigrades and individual species (Milnesium tardigradum, Hypsibius dujardini, Echiniscus testudo, Tulinus stephaniae, Richtersius coronifer) and functional elements in tardigrade mRNAs are analysed. We find that 39.3% of the total sequences clustered in 58 clusters of more than 20 proteins. Among these are ten tardigrade specific as well as a number of stress-specific protein clusters. Tardigrade-specific functional adaptations include strong protein, DNA- and redox protection, maintenance and protein recycling. Specific regulatory elements regulate tardigrade mRNA stability such as lox P DICE elements whereas 14 other RNA elements of higher eukaryotes are not found. Further features of tardigrade specific adaption are rapidly identified by sequence and/or pattern search on the web-tool tardigrade analyzer http://waterbear.bioapps.biozentrum.uni-wuerzburg.de. The work-bench offers nucleotide pattern analysis for promotor and regulatory element detection (tardigrade specific; nrdb) as well as rapid COG search for function assignments including species-specific repositories of all analysed data. Conclusion Different protein clusters and regulatory elements implicated in tardigrade stress adaptations are analysed including unpublished tardigrade sequences. PMID:19821996

Relationship between Oral Malodor and the Global Composition of Indigenous Bacterial Populations in Saliva ▿

PubMed Central

Takeshita, Toru; Suzuki, Nao; Nakano, Yoshio; Shimazaki, Yoshihiro; Yoneda, Masahiro; Hirofuji, Takao; Yamashita, Yoshihisa

2010-01-01

Oral malodor develops mostly from the metabolic activities of indigenous bacterial populations within the oral cavity, but whether healthy or oral malodor-related patterns of the global bacterial composition exist remains unclear. In this study, the bacterial compositions in the saliva of 240 subjects complaining of oral malodor were divided into groups based on terminal-restriction fragment length polymorphism (T-RFLP) profiles using hierarchical cluster analysis, and the patterns of the microbial community composition of those exhibiting higher and lower malodor were explored. Four types of bacterial community compositions were detected (clusters I, II, III, and IV). Two parameters for measuring oral malodor intensity (the concentration of volatile sulfur compounds in mouth air and the organoleptic score) were noticeably lower in cluster I than in the other clusters. Using multivariate analysis, the differences in the levels of oral malodor were significant after adjustment for potential confounding factors such as total bacterial count, mean periodontal pocket depth, and tongue coating score (P < 0.001). Among the four clusters with different proportions of indigenous members, the T-RFLP profiles of cluster I were implicated as the bacterial populations with higher proportions of Streptococcus, Granulicatella, Rothia, and Treponema species than those of the other clusters. These results clearly correlate the global composition of indigenous bacterial populations with the severity of oral malodor. PMID:20228112

The contribution of psychological factors to recovery after mild traumatic brain injury: is cluster analysis a useful approach?

PubMed

Snell, Deborah L; Surgenor, Lois J; Hay-Smith, E Jean C; Williman, Jonathan; Siegert, Richard J

2015-01-01

Outcomes after mild traumatic brain injury (MTBI) vary, with slow or incomplete recovery for a significant minority. This study examines whether groups of cases with shared psychological factors but with different injury outcomes could be identified using cluster analysis. This is a prospective observational study following 147 adults presenting to a hospital-based emergency department or concussion services in Christchurch, New Zealand. This study examined associations between baseline demographic, clinical, psychological variables (distress, injury beliefs and symptom burden) and outcome 6 months later. A two-step approach to cluster analysis was applied (Ward's method to identify clusters, K-means to refine results). Three meaningful clusters emerged (high-adapters, medium-adapters, low-adapters). Baseline cluster-group membership was significantly associated with outcomes over time. High-adapters appeared recovered by 6-weeks and medium-adapters revealed improvements by 6-months. The low-adapters continued to endorse many symptoms, negative recovery expectations and distress, being significantly at risk for poor outcome more than 6-months after injury (OR (good outcome) = 0.12; CI = 0.03-0.53; p < 0.01). Cluster analysis supported the notion that groups could be identified early post-injury based on psychological factors, with group membership associated with differing outcomes over time. Implications for clinical care providers regarding therapy targets and cases that may benefit from different intensities of intervention are discussed.

Tardigrade workbench: comparing stress-related proteins, sequence-similar and functional protein clusters as well as RNA elements in tardigrades.

PubMed

Förster, Frank; Liang, Chunguang; Shkumatov, Alexander; Beisser, Daniela; Engelmann, Julia C; Schnölzer, Martina; Frohme, Marcus; Müller, Tobias; Schill, Ralph O; Dandekar, Thomas

2009-10-12

Tardigrades represent an animal phylum with extraordinary resistance to environmental stress. To gain insights into their stress-specific adaptation potential, major clusters of related and similar proteins are identified, as well as specific functional clusters delineated comparing all tardigrades and individual species (Milnesium tardigradum, Hypsibius dujardini, Echiniscus testudo, Tulinus stephaniae, Richtersius coronifer) and functional elements in tardigrade mRNAs are analysed. We find that 39.3% of the total sequences clustered in 58 clusters of more than 20 proteins. Among these are ten tardigrade specific as well as a number of stress-specific protein clusters. Tardigrade-specific functional adaptations include strong protein, DNA- and redox protection, maintenance and protein recycling. Specific regulatory elements regulate tardigrade mRNA stability such as lox P DICE elements whereas 14 other RNA elements of higher eukaryotes are not found. Further features of tardigrade specific adaption are rapidly identified by sequence and/or pattern search on the web-tool tardigrade analyzer http://waterbear.bioapps.biozentrum.uni-wuerzburg.de. The work-bench offers nucleotide pattern analysis for promotor and regulatory element detection (tardigrade specific; nrdb) as well as rapid COG search for function assignments including species-specific repositories of all analysed data. Different protein clusters and regulatory elements implicated in tardigrade stress adaptations are analysed including unpublished tardigrade sequences.

Biosynthetic Genes for the Tetrodecamycin Antibiotics

PubMed Central

Gverzdys, Tomas

2016-01-01

ABSTRACT We recently described 13-deoxytetrodecamycin, a new member of the tetrodecamycin family of antibiotics. A defining feature of these molecules is the presence of a five-membered lactone called a tetronate ring. By sequencing the genome of a producer strain, Streptomyces sp. strain WAC04657, and searching for a gene previously implicated in tetronate ring formation, we identified the biosynthetic genes responsible for producing 13-deoxytetrodecamycin (the ted genes). Using the ted cluster in WAC04657 as a reference, we found related clusters in three other organisms: Streptomyces atroolivaceus ATCC 19725, Streptomyces globisporus NRRL B-2293, and Streptomyces sp. strain LaPpAH-202. Comparing the four clusters allowed us to identify the cluster boundaries. Genetic manipulation of the cluster confirmed the involvement of the ted genes in 13-deoxytetrodecamycin biosynthesis and revealed several additional molecules produced through the ted biosynthetic pathway, including tetrodecamycin, dihydrotetrodecamycin, and another, W5.9, a novel molecule. Comparison of the bioactivities of these four molecules suggests that they may act through the covalent modification of their target(s). IMPORTANCE The tetrodecamycins are a distinct subgroup of the tetronate family of secondary metabolites. Little is known about their biosynthesis or mechanisms of action, making them an attractive subject for investigation. In this paper we present the biosynthetic gene cluster for 13-deoxytetrodecamycin in Streptomyces sp. strain WAC04657. We identify related clusters in several other organisms and show that they produce related molecules. PMID:27137499

Cognitive Clusters in Specific Learning Disorder.

PubMed

Poletti, Michele; Carretta, Elisa; Bonvicini, Laura; Giorgi-Rossi, Paolo

The heterogeneity among children with learning disabilities still represents a barrier and a challenge in their conceptualization. Although a dimensional approach has been gaining support, the categorical approach is still the most adopted, as in the recent fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. The introduction of the single overarching diagnostic category of specific learning disorder (SLD) could underemphasize interindividual clinical differences regarding intracategory cognitive functioning and learning proficiency, according to current models of multiple cognitive deficits at the basis of neurodevelopmental disorders. The characterization of specific cognitive profiles associated with an already manifest SLD could help identify possible early cognitive markers of SLD risk and distinct trajectories of atypical cognitive development leading to SLD. In this perspective, we applied a cluster analysis to identify groups of children with a Diagnostic and Statistical Manual-based diagnosis of SLD with similar cognitive profiles and to describe the association between clusters and SLD subtypes. A sample of 205 children with a diagnosis of SLD were enrolled. Cluster analyses (agglomerative hierarchical and nonhierarchical iterative clustering technique) were used successively on 10 core subtests of the Wechsler Intelligence Scale for Children-Fourth Edition. The 4-cluster solution was adopted, and external validation found differences in terms of SLD subtype frequencies and learning proficiency among clusters. Clinical implications of these findings are discussed, tracing directions for further studies.

Clustering Methods with Qualitative Data: A Mixed Methods Approach for Prevention Research with Small Samples

PubMed Central

Henry, David; Dymnicki, Allison B.; Mohatt, Nathaniel; Allen, James; Kelly, James G.

2016-01-01

Qualitative methods potentially add depth to prevention research, but can produce large amounts of complex data even with small samples. Studies conducted with culturally distinct samples often produce voluminous qualitative data, but may lack sufficient sample sizes for sophisticated quantitative analysis. Currently lacking in mixed methods research are methods allowing for more fully integrating qualitative and quantitative analysis techniques. Cluster analysis can be applied to coded qualitative data to clarify the findings of prevention studies by aiding efforts to reveal such things as the motives of participants for their actions and the reasons behind counterintuitive findings. By clustering groups of participants with similar profiles of codes in a quantitative analysis, cluster analysis can serve as a key component in mixed methods research. This article reports two studies. In the first study, we conduct simulations to test the accuracy of cluster assignment using three different clustering methods with binary data as produced when coding qualitative interviews. Results indicated that hierarchical clustering, K-Means clustering, and latent class analysis produced similar levels of accuracy with binary data, and that the accuracy of these methods did not decrease with samples as small as 50. Whereas the first study explores the feasibility of using common clustering methods with binary data, the second study provides a “real-world” example using data from a qualitative study of community leadership connected with a drug abuse prevention project. We discuss the implications of this approach for conducting prevention research, especially with small samples and culturally distinct communities. PMID:25946969

Effects of small-scale clustering of flowers on pollinator foraging behaviour and flower visitation rate.

PubMed

Akter, Asma; Biella, Paolo; Klecka, Jan

2017-01-01

Plants often grow in clusters of various sizes and have a variable number of flowers per inflorescence. This small-scale spatial clustering affects insect foraging strategies and plant reproductive success. In our study, we aimed to determine how visitation rate and foraging behaviour of pollinators depend on the number of flowers per plant and on the size of clusters of multiple plants using Dracocephalum moldavica (Lamiaceae) as a target species. We measured flower visitation rate by observations of insects visiting single plants and clusters of plants with different numbers of flowers. Detailed data on foraging behaviour within clusters of different sizes were gathered for honeybees, Apis mellifera, the most abundant visitor of Dracocephalum in the experiments. We found that the total number of flower visitors increased with the increasing number of flowers on individual plants and in larger clusters, but less then proportionally. Although individual honeybees visited more flowers in larger clusters, they visited a smaller proportion of flowers, as has been previously observed. Consequently, visitation rate per flower and unit time peaked in clusters with an intermediate number of flowers. These patterns do not conform to expectations based on optimal foraging theory and the ideal free distribution model. We attribute this discrepancy to incomplete information about the distribution of resources. Detailed observations and video recordings of individual honeybees also showed that the number of flowers had no effect on handling time of flowers by honeybees. We evaluated the implications of these patterns for insect foraging biology and plant reproduction.

Effects of small-scale clustering of flowers on pollinator foraging behaviour and flower visitation rate

PubMed Central

2017-01-01

Plants often grow in clusters of various sizes and have a variable number of flowers per inflorescence. This small-scale spatial clustering affects insect foraging strategies and plant reproductive success. In our study, we aimed to determine how visitation rate and foraging behaviour of pollinators depend on the number of flowers per plant and on the size of clusters of multiple plants using Dracocephalum moldavica (Lamiaceae) as a target species. We measured flower visitation rate by observations of insects visiting single plants and clusters of plants with different numbers of flowers. Detailed data on foraging behaviour within clusters of different sizes were gathered for honeybees, Apis mellifera, the most abundant visitor of Dracocephalum in the experiments. We found that the total number of flower visitors increased with the increasing number of flowers on individual plants and in larger clusters, but less then proportionally. Although individual honeybees visited more flowers in larger clusters, they visited a smaller proportion of flowers, as has been previously observed. Consequently, visitation rate per flower and unit time peaked in clusters with an intermediate number of flowers. These patterns do not conform to expectations based on optimal foraging theory and the ideal free distribution model. We attribute this discrepancy to incomplete information about the distribution of resources. Detailed observations and video recordings of individual honeybees also showed that the number of flowers had no effect on handling time of flowers by honeybees. We evaluated the implications of these patterns for insect foraging biology and plant reproduction. PMID:29136042

Physical Origins of Gas Motions in Galaxy Cluster Cores: Interpreting Hitomi Observations of the Perseus Cluster

NASA Astrophysics Data System (ADS)

Lau, Erwin T.; Gaspari, Massimo; Nagai, Daisuke; Coppi, Paolo

2017-11-01

The Hitomi X-ray satellite has provided the first direct measurements of the plasma velocity dispersion in a galaxy cluster. It finds a relatively “quiescent” gas with a line-of-sight velocity dispersion {σ }v,{los}≃ 160 {km} {{{s}}}-1, at 30-60 kpc from the cluster center. This is surprising given the presence of jets and X-ray cavities that indicates on-going activity and feedback from the active galactic nucleus (AGN) at the cluster center. Using a set of mock Hitomi observations generated from a suite of state-of-the-art cosmological cluster simulations, and an isolated but higher resolution simulation of gas physics in the cluster core, including the effects of cooling and AGN feedback, we examine the likelihood of Hitomi detecting a cluster with the observed velocities. As long as the Perseus has not experienced a major merger in the last few gigayears, and AGN feedback is operating in a “‘gentle” mode, we reproduce the level of gas motions observed by Hitomi. The frequent mechanical AGN feedback generates net line-of-sight velocity dispersions ˜ 100{--}200 {km} {{{s}}}-1, bracketing the values measured in the Perseus core. The large-scale velocity shear observed across the core, on the other hand, is generated mainly by cosmic accretion such as mergers. We discuss the implications of these results for AGN feedback physics and cluster cosmology and progress that needs to be made in both simulations and observations, including a Hitomi re-flight and calorimeter-based instruments with higher spatial resolution.

Clustering Methods with Qualitative Data: a Mixed-Methods Approach for Prevention Research with Small Samples.

PubMed

Henry, David; Dymnicki, Allison B; Mohatt, Nathaniel; Allen, James; Kelly, James G

2015-10-01

Qualitative methods potentially add depth to prevention research but can produce large amounts of complex data even with small samples. Studies conducted with culturally distinct samples often produce voluminous qualitative data but may lack sufficient sample sizes for sophisticated quantitative analysis. Currently lacking in mixed-methods research are methods allowing for more fully integrating qualitative and quantitative analysis techniques. Cluster analysis can be applied to coded qualitative data to clarify the findings of prevention studies by aiding efforts to reveal such things as the motives of participants for their actions and the reasons behind counterintuitive findings. By clustering groups of participants with similar profiles of codes in a quantitative analysis, cluster analysis can serve as a key component in mixed-methods research. This article reports two studies. In the first study, we conduct simulations to test the accuracy of cluster assignment using three different clustering methods with binary data as produced when coding qualitative interviews. Results indicated that hierarchical clustering, K-means clustering, and latent class analysis produced similar levels of accuracy with binary data and that the accuracy of these methods did not decrease with samples as small as 50. Whereas the first study explores the feasibility of using common clustering methods with binary data, the second study provides a "real-world" example using data from a qualitative study of community leadership connected with a drug abuse prevention project. We discuss the implications of this approach for conducting prevention research, especially with small samples and culturally distinct communities.

NEW CONSTRAINTS ON MASS-DEPENDENT DISRUPTION OF STAR CLUSTERS IN M51

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chandar, Rupali; Whitmore, Bradley C.; Regan, Michael

2011-02-01

We use UBVI H{alpha} images of the Whirlpool galaxy, M51, taken with the Advanced Camera for Surveys and WFPC2 cameras on the Hubble Space Telescope (HST) to select star clusters, and to estimate their masses and ages by comparing their observed colors with predictions from population synthesis models. We construct the mass function of intermediate-age (1-4 x 10{sup 8} yr) clusters, and find that it is well described by a power law, {psi}(M) {proportional_to} M{sup {beta}}, with {beta} = -2.1 {+-} 0.2, for clusters more massive than M {approx} 6 x 10{sup 3} M{sub sun}. This extends the mass functionmore » of intermediate-age clusters in M51 to masses lower by nearly a factor of five over previous determinations. The mass function does not show evidence for curvature at either the high or low mass end. This shape indicates that there is no evidence for the earlier disruption of lower mass clusters compared with their higher mass counterparts (i.e., no mass-dependent disruption) over the observed range of masses and ages, or for a physical upper mass limit M{sub C} with which clusters in M51 can form. These conclusions differ from previous suggestions based on poorer-quality HST observations. We discuss their implications for the formation and disruption of the clusters. Ages of clusters in two 'feathers', stellar features extending from the outer portion of a spiral arm, show that the feather with a larger pitch angle formed earlier, and over a longer period, than the other.« less

High–frequency cluster radio galaxies: Luminosity functions and implications for SZE–selected cluster samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Nikhel; Saro, A.; Mohr, J. J.

We study the overdensity of point sources in the direction of X-ray-selected galaxy clusters from the meta-catalogue of X-ray-detected clusters of galaxies (MCXC; < z > = 0.14) at South Pole Telescope (SPT) and Sydney University Molonglo Sky Survey (SUMSS) frequencies. Flux densities at 95, 150 and 220 GHz are extracted from the 2500 deg 2 SPT-SZ survey maps at the locations of SUMSS sources, producing a multifrequency catalogue of radio galaxies. In the direction of massive galaxy clusters, the radio galaxy flux densities at 95 and 150 GHz are biased low by the cluster Sunyaev–Zel’dovich Effect (SZE) signal, whichmore » is negative at these frequencies. We employ a cluster SZE model to remove the expected flux bias and then study these corrected source catalogues. We find that the high-frequency radio galaxies are centrally concentrated within the clusters and that their luminosity functions (LFs) exhibit amplitudes that are characteristically an order of magnitude lower than the cluster LF at 843 MHz. We use the 150 GHz LF to estimate the impact of cluster radio galaxies on an SPT-SZ like survey. The radio galaxy flux typically produces a small bias on the SZE signal and has negligible impact on the observed scatter in the SZE mass–observable relation. If we assume there is no redshift evolution in the radio galaxy LF then 1.8 ± 0.7 per cent of the clusters with detection significance ξ ≥ 4.5 would be lost from the sample. As a result, allowing for redshift evolution of the form (1 + z) 2.5 increases the incompleteness to 5.6 ± 1.0 per cent. Improved constraints on the evolution of the cluster radio galaxy LF require a larger cluster sample extending to higher redshift.« less

High–frequency cluster radio galaxies: Luminosity functions and implications for SZE–selected cluster samples

DOE PAGES

Gupta, Nikhel; Saro, A.; Mohr, J. J.; ...

2017-01-15

We study the overdensity of point sources in the direction of X-ray-selected galaxy clusters from the meta-catalogue of X-ray-detected clusters of galaxies (MCXC; < z > = 0.14) at South Pole Telescope (SPT) and Sydney University Molonglo Sky Survey (SUMSS) frequencies. Flux densities at 95, 150 and 220 GHz are extracted from the 2500 deg 2 SPT-SZ survey maps at the locations of SUMSS sources, producing a multifrequency catalogue of radio galaxies. In the direction of massive galaxy clusters, the radio galaxy flux densities at 95 and 150 GHz are biased low by the cluster Sunyaev–Zel’dovich Effect (SZE) signal, whichmore » is negative at these frequencies. We employ a cluster SZE model to remove the expected flux bias and then study these corrected source catalogues. We find that the high-frequency radio galaxies are centrally concentrated within the clusters and that their luminosity functions (LFs) exhibit amplitudes that are characteristically an order of magnitude lower than the cluster LF at 843 MHz. We use the 150 GHz LF to estimate the impact of cluster radio galaxies on an SPT-SZ like survey. The radio galaxy flux typically produces a small bias on the SZE signal and has negligible impact on the observed scatter in the SZE mass–observable relation. If we assume there is no redshift evolution in the radio galaxy LF then 1.8 ± 0.7 per cent of the clusters with detection significance ξ ≥ 4.5 would be lost from the sample. As a result, allowing for redshift evolution of the form (1 + z) 2.5 increases the incompleteness to 5.6 ± 1.0 per cent. Improved constraints on the evolution of the cluster radio galaxy LF require a larger cluster sample extending to higher redshift.« less

Estimating metallicities with isochrone fits to photometric data of open clusters

NASA Astrophysics Data System (ADS)

Monteiro, H.; Oliveira, A. F.; Dias, W. S.; Caetano, T. C.

2014-10-01

The metallicity is a critical parameter that affects the correct determination of stellar cluster's fundamental characteristics and has important implications in Galactic and Stellar evolution research. Fewer than 10% of the 2174 currently catalogued open clusters have their metallicity determined in the literature. In this work we present a method for estimating the metallicity of open clusters via non-subjective isochrone fitting using the cross-entropy global optimization algorithm applied to UBV photometric data. The free parameters distance, reddening, age, and metallicity are simultaneously determined by the fitting method. The fitting procedure uses weights for the observational data based on the estimation of membership likelihood for each star, which considers the observational magnitude limit, the density profile of stars as a function of radius from the center of the cluster, and the density of stars in multi-dimensional magnitude space. We present results of [Fe/H] for well-studied open clusters based on distinct UBV data sets. The [Fe/H] values obtained in the ten cases for which spectroscopic determinations were available in the literature agree, indicating that our method provides a good alternative to estimating [Fe/H] by using an objective isochrone fitting. Our results show that the typical precision is about 0.1 dex.

Mean-cluster approach indicates cell sorting time scales are determined by collective dynamics

NASA Astrophysics Data System (ADS)

Beatrici, Carine P.; de Almeida, Rita M. C.; Brunnet, Leonardo G.

2017-03-01

Cell migration is essential to cell segregation, playing a central role in tissue formation, wound healing, and tumor evolution. Considering random mixtures of two cell types, it is still not clear which cell characteristics define clustering time scales. The mass of diffusing clusters merging with one another is expected to grow as td /d +2 when the diffusion constant scales with the inverse of the cluster mass. Cell segregation experiments deviate from that behavior. Explanations for that could arise from specific microscopic mechanisms or from collective effects, typical of active matter. Here we consider a power law connecting diffusion constant and cluster mass to propose an analytic approach to model cell segregation where we explicitly take into account finite-size corrections. The results are compared with active matter model simulations and experiments available in the literature. To investigate the role played by different mechanisms we considered different hypotheses describing cell-cell interaction: differential adhesion hypothesis and different velocities hypothesis. We find that the simulations yield normal diffusion for long time intervals. Analytic and simulation results show that (i) cluster evolution clearly tends to a scaling regime, disrupted only at finite-size limits; (ii) cluster diffusion is greatly enhanced by cell collective behavior, such that for high enough tendency to follow the neighbors, cluster diffusion may become independent of cluster size; (iii) the scaling exponent for cluster growth depends only on the mass-diffusion relation, not on the detailed local segregation mechanism. These results apply for active matter systems in general and, in particular, the mechanisms found underlying the increase in cell sorting speed certainly have deep implications in biological evolution as a selection mechanism.

[3Fe-4S] to [4Fe-4S] cluster conversion in Desulfovibrio fructosovorans [NiFe] hydrogenase by site-directed mutagenesis

PubMed Central

Rousset, Marc; Montet, Yael; Guigliarelli, Bruno; Forget, Nicole; Asso, Marcel; Bertrand, Patrick; Fontecilla-Camps, Juan C.; Hatchikian, E. Claude

1998-01-01

The role of the high potential [3Fe-4S]1+,0 cluster of [NiFe] hydrogenase from Desulfovibrio species located halfway between the proximal and distal low potential [4Fe-4S]2+,1+ clusters has been investigated by using site-directed mutagenesis. Proline 238 of Desulfovibrio fructosovorans [NiFe] hydrogenase, which occupies the position of a potential ligand of the lacking fourth Fe-site of the [3Fe-4S] cluster, was replaced by a cysteine residue. The properties of the mutant enzyme were investigated in terms of enzymatic activity, EPR, and redox properties of the iron-sulfur centers and crystallographic structure. We have shown on the basis of both spectroscopic and x-ray crystallographic studies that the [3Fe-4S] cluster of D. fructosovorans hydrogenase was converted into a [4Fe-4S] center in the P238 mutant. The [3Fe-4S] to [4Fe-4S] cluster conversion resulted in a lowering of approximately 300 mV of the midpoint potential of the modified cluster, whereas no significant alteration of the spectroscopic and redox properties of the two native [4Fe-4S] clusters and the NiFe center occurred. The significant decrease of the midpoint potential of the intermediate Fe-S cluster had only a slight effect on the catalytic activity of the P238C mutant as compared with the wild-type enzyme. The implications of the results for the role of the high-potential [3Fe-4S] cluster in the intramolecular electron transfer pathway are discussed. PMID:9751716

Compact X-ray Binary Re-creation in Core Collapse: NGC 6397

NASA Astrophysics Data System (ADS)

Grindlay, J. E.; Bogdanov, S.; van den Berg, M.; Heinke, C.

2005-12-01

We report new Chandra observations of the core collapsed globular cluster NGC 6397. In comparison with our original Chandra observations (Grindlay et al 2001, ApJ, 563, L53), we now detect some 30 sources (vs. 20) in the cluster. A new CV is confirmed, though new HST/ACS optical observations (see Cohn et al this meeting) show that one of the original CV candidates is a background AGN). The 9 CVs (optically identified) yet only one MSP and one qLMXB suggest either a factor of 7 reduction in NSs/WDs vs. what we find in 47Tuc (see Grindlay 2005, Proc. Cefalu Conf. on Interacting Binaries) or that CVs are produced in the core collapse. The possible second MSP with main sequence companion, source U18 (see Grindlay et al 2001) is similar in its X-ray and optical properties to MSP-W in 47Tuc, which must have swapped its binary companion. Together with the one confirmed (radio) MSP in NGC 6397, with an evolved main sequence secondary, the process of enhanced partner swapping in the high stellar density of core collapse is implicated. At the same time, main sequence - main sequence binaries (active binaries) are depleted in the cluster core, presumably by "binary burning" in core collapse. These binary re-creation and destruction mechanisms in core collapse have profound implications for binary evolution and mergers in globulars that have undergone core collapse.

Beyond the Rayleigh instability limit for multicharged finite systems: From fission to Coulomb explosion

PubMed Central

Last, Isidore; Levy, Yaakov; Jortner, Joshua

2002-01-01

We address the stability of multicharged finite systems driven by Coulomb forces beyond the Rayleigh instability limit. Our exploration of the nuclear dynamics of heavily charged Morse clusters enabled us to vary the range of the pair potential and of the fissibility parameter, which results in distinct fragmentation patterns and in the angular distributions of the fragments. The Rayleigh instability limit separates between nearly binary (or tertiary) spatially unisotropic fission and spatially isotropic Coulomb explosion into a large number of small, ionic fragments. Implications are addressed for a broad spectrum of dynamics in chemical physics, radiation physics of ultracold gases, and biophysics, involving the fission of clusters and droplets, the realization of Coulomb explosion of molecular clusters, the isotropic expansion of optical molasses, and the Coulomb instability of “isolated” proteins. PMID:12093910

Some Psychometric and Design Implications of Game-Based Learning Analytics

ERIC Educational Resources Information Center

Gibson, David; Clarke-Midura, Jody

2013-01-01

The rise of digital game and simulation-based learning applications has led to new approaches in educational measurement that take account of patterns in time, high resolution paths of action, and clusters of virtual performance artifacts. The new approaches, which depart from traditional statistical analyses, include data mining, machine…

The ideal physician: implications for contemporary hospital marketing.

PubMed

Gochman, D S; Stukenborg, G J; Feler, A

1986-06-01

A questionnaire asking individuals to identify freely the characteristics most descriptive of physicians who are closest to their ideal was mailed to a systematically derived cluster sample in a medium-size metropolitan area. Respondents clearly valued psychosocial and interpersonal characteristics such as communicating and caring much more than technical medical skills.

Organization of a resistance gene cluster linked to rhizomania resistance in sugar beet

USDA-ARS?s Scientific Manuscript database

Genetic resistance to rhizomania has been in use for over 40 years. Characterization of the molecular basis for susceptibility and resistance has proved challenging. Nucleotide-binding leucine-rich-repeat-containing (NB-LRR) genes have been implicated in numerous gene-for-gene resistance interaction...

LAE1 regulates expression of multiple secondary metabolite gene clusters in Fusarium verticillioides

USDA-ARS?s Scientific Manuscript database

The filamentous fungus Fusarium verticillioides can cause disease of maize and is capable of producing the polyketide derived mycotoxins called fumonisins. Fumonisin contamination of maize kernels is a food safety concern. Fumonisins have been implicated in human esophageal cancer as well as in cau...

Initial Career and Work Meanings in Seven European Countries.

ERIC Educational Resources Information Center

Claes, Rita; Quintanilla, S. Antonio R.

1994-01-01

Explores initial careers of two target groups of young adults in seven European countries. Career patterns were constructed through cluster analysis on data gathered via self-report. Six career patterns were identified. Offers suggestions for further research and implications for career counseling, career education, and organizational career…

Congenital TORCH Infections in Infants and Young Children: Neurodevelopmental Sequelae and Implications for Intervention.

ERIC Educational Resources Information Center

Hutchinson, M. Katherine; Sandall, Susan R.

1995-01-01

This article describes TORCH infections, a congenital cluster of infections including toxoplasmosis, syphilis, rubella, cytomegalovirus, and herpes which often results in developmental disabilities for infected children. Methods of transmission, incidence, and developmental outcomes for common TORCH infections are described, as are program…

First isolation of West Nile virus from a dromedary camel

PubMed Central

Joseph, Sunitha; Wernery, Ulrich; Teng, Jade LL; Wernery, Renate; Huang, Yi; Patteril, Nissy AG; Chan, Kwok-Hung; Elizabeth, Shyna K; Fan, Rachel YY; Lau, Susanna KP; Kinne, Jörg; Woo, Patrick CY

2016-01-01

Although antibodies against West Nile virus (WNV) have been detected in the sera of dromedaries in the Middle East, North Africa and Spain, no WNV has been isolated or amplified from dromedary or Bactrian camels. In this study, WNV was isolated from Vero cells inoculated with both nasal swab and pooled trachea/lung samples from a dromedary calf in Dubai. Complete-genome sequencing and phylogenetic analysis using the near-whole-genome polyprotein revealed that the virus belonged to lineage 1a. There was no clustering of the present WNV with other WNVs isolated in other parts of the Middle East. Within lineage 1a, the dromedary WNV occupied a unique position, although it was most closely related to other WNVs of cluster 2. Comparative analysis revealed that the putative E protein encoded by the genome possessed the original WNV E protein glycosylation motif NYS at E154–156, which contained the N-linked glycosylation site at N-154 associated with increased WNV pathogenicity and neuroinvasiveness. In the putative NS1 protein, the A70S substitution observed in other cluster 2 WNVs and P250, which has been implicated in neuroinvasiveness, were present. In addition, the foo motif in the putative NS2A protein, which has been implicated in neuroinvasiveness, was detected. Notably, the amino-acid residues at 14 positions in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a, with the majority of these differences observed in the putative E and NS5 proteins. The present study is the first to demonstrate the isolation of WNV from dromedaries. This finding expands the possible reservoirs of WNV and sources of WNV infection. PMID:27273223

A FRAMEWORK FOR ATTRIBUTE-BASED COMMUNITY DETECTION WITH APPLICATIONS TO INTEGRATED FUNCTIONAL GENOMICS.

PubMed

Yu, Han; Hageman Blair, Rachael

2016-01-01

Understanding community structure in networks has received considerable attention in recent years. Detecting and leveraging community structure holds promise for understanding and potentially intervening with the spread of influence. Network features of this type have important implications in a number of research areas, including, marketing, social networks, and biology. However, an overwhelming majority of traditional approaches to community detection cannot readily incorporate information of node attributes. Integrating structural and attribute information is a major challenge. We propose a exible iterative method; inverse regularized Markov Clustering (irMCL), to network clustering via the manipulation of the transition probability matrix (aka stochastic flow) corresponding to a graph. Similar to traditional Markov Clustering, irMCL iterates between "expand" and "inflate" operations, which aim to strengthen the intra-cluster flow, while weakening the inter-cluster flow. Attribute information is directly incorporated into the iterative method through a sigmoid (logistic function) that naturally dampens attribute influence that is contradictory to the stochastic flow through the network. We demonstrate advantages and the exibility of our approach using simulations and real data. We highlight an application that integrates breast cancer gene expression data set and a functional network defined via KEGG pathways reveal significant modules for survival.

Identifying a gene expression signature of cluster headache in blood

PubMed Central

Eising, Else; Pelzer, Nadine; Vijfhuizen, Lisanne S.; Vries, Boukje de; Ferrari, Michel D.; ‘t Hoen, Peter A. C.; Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.

2017-01-01

Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Gene expression data were analysed by gene and by module of co-expressed genes with particular attention to previously implicated disease pathways including hypocretin dysregulation. Only moderate gene expression differences were identified and no associations were found with previously reported pathogenic mechanisms. At the level of functional gene sets, associations were observed for genes involved in several brain-related mechanisms such as GABA receptor function and voltage-gated channels. In addition, genes and modules of co-expressed genes showed a role for intracellular signalling cascades, mitochondria and inflammation. Although larger study samples may be required to identify the full range of involved pathways, these results indicate a role for mitochondria, intracellular signalling and inflammation in cluster headache. PMID:28074859

Interpersonal Subtypes Within Social Anxiety: The Identification of Distinct Social Features.

PubMed

Cooper, Danielle; Anderson, Timothy

2017-10-05

Although social anxiety disorder is defined by anxiety-related symptoms, little research has focused on the interpersonal features of social anxiety. Prior studies (Cain, Pincus, & Grosse Holtforth, 2010; Kachin, Newman, & Pincus, 2001) identified distinct subgroups of socially anxious individuals' interpersonal circumplex problems that were blends of agency and communion, and yet inconsistencies remain. We predicted 2 distinct interpersonal subtypes would exist for individuals with high social anxiety, and that these social anxiety subtypes would differ on empathetic concern, paranoia, received peer victimization, perspective taking, and emotional suppression. From a sample of 175 undergraduate participants, 51 participants with high social anxiety were selected as above a clinical cutoff on the social phobia scale. Cluster analyses identified 2 interpersonal subtypes of socially anxious individuals: low hostility-high submissiveness (Cluster 1) and high hostility-high submissiveness (Cluster 2). Cluster 1 reported higher levels of empathetic concern, lower paranoia, less peer victimization, and lower emotional suppression compared to Cluster 2. There were no differences between subtypes on perspective taking or cognitive reappraisal. Findings are consistent with an interpersonal conceptualization of social anxiety, and provide evidence of distinct social features between these subtypes. Findings have implications for the etiology, classification, and treatment of social anxiety.

Network Analysis of Fine Particulate Matter (PM2.5) Emissions in China

NASA Astrophysics Data System (ADS)

Yan, Shaomin; Wu, Guang

2016-09-01

Specification of PM2.5 spatial and temporal characteristics is important for understanding PM2.5 adverse effects and policymaking. We applied network analysis to studying the dataset MIX, which contains PM2.5 emissions recorded from 2168 monitoring stations in China in 2008 and 2010. The results showed that for PM2.5 emissions from industrial sector 8 clusters were found in 2008 but they merged together into a huge cluster in 2010, suggesting that industrial sector underwent an integrating process. For PM2.5 emissions from electricity generation sector, strong locality of clusters was revealed, implying that each region had its own electricity generation system. For PM2.5 emissions from residential sector, the same pattern of 10 clusters was uncovered in both years, implicating the household energy consumption unchanged from 2008 to 2010. For PM2.5 emissions from transportation sector, the same pattern of 5 clusters with many connections in-between was unraveled, indicating the high-speed development of transportation nationalwidely. Except for the known elements, mercury (Hg) surfaced as an element for particle nucleation. To our knowledge, this is the first network study in this field.

Viral Perturbations of Host Networks Reflect Disease Etiology

PubMed Central

Dricot, Amélie; Padi, Megha; Byrdsong, Danielle; Franchi, Rachel; Lee, Deok-Sun; Rozenblatt-Rosen, Orit; Mar, Jessica C.; Calderwood, Michael A.; Baldwin, Amy; Zhao, Bo; Santhanam, Balaji; Braun, Pascal; Simonis, Nicolas; Huh, Kyung-Won; Hellner, Karin; Grace, Miranda; Chen, Alyce; Rubio, Renee; Marto, Jarrod A.; Christakis, Nicholas A.; Kieff, Elliott; Roth, Frederick P.; Roecklein-Canfield, Jennifer; DeCaprio, James A.; Cusick, Michael E.; Quackenbush, John; Hill, David E.; Münger, Karl; Vidal, Marc; Barabási, Albert-László

2012-01-01

Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia. PMID:22761553

M31 Globular Clusters and Galaxy Formation

NASA Astrophysics Data System (ADS)

Gregg, M. D.; Karick, A. M.

2005-12-01

The brightest globular cluster in the halo of M31, cluster G1, has properties which suggest that it is not an ordinary globular but an ultra-compact dwarf galaxy: its velocity dispersion, M/L, and ellipticity are all atypically large, and its color-magnitude diagram suggests an abundance spread. Using the Keck Laser Guide Star Adaptive Optics system with NIRC2, we have begun an imaging campaign of globular clusters in M31 to measure their core sizes. Combining these data with high dispersion spectroscopy will produce masses and M/L ratios to determine if there are additional UCDs masquerading as M31 globulars. UCDs are thought to be the remnant nuclei from tidally stripped dwarf ellipticals or small spirals; finding additional examples in the cluster system of M31 has implications for galaxy formation processes. The K-band image quality during our first LGS run was very stable over many hours, with Strehl ratios of 0.35 or better, producing point sources with FWHM of 0\\farcs05. The core sizes of the clusters, which range from 0\\farcs2 to 0\\farcs8 can be easily measured from these data. The observing conditions were nearly as good in the J-band, and we obtained both colors for a number of clusters. We discuss our efforts to produce photometrically-calibrated color-magnitude diagrams of the clusters. This work is supported by National Science Foundation Grant No. 0407445 and was done at the Institute of Geophysics and Planetary Physics, under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract No. W-7405-Eng-48.

Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes

DOE PAGES

Graw, Frederik; Balagopal, Ashwin; Kandathil, Abraham J.; ...

2014-11-13

Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, wemore » are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from 4-50 infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Lastly, our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.« less

Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graw, Frederik; Balagopal, Ashwin; Kandathil, Abraham J.

Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, wemore » are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from 4-50 infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Lastly, our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.« less

Exploring Different Patterns of Love Attitudes among Chinese College Students

PubMed Central

Zeng, Xianglong; Pan, Yiqin; Zhou, Han; Yu, Shi; Liu, Xiangping

2016-01-01

Individual differences in love attitudes and the relationship between love attitudes and other variables in Asian culture lack in-depth exploration. This study conducted cluster analysis with data regarding love attitudes obtained from 389 college students in mainland China. The result of cluster analysis based on love-attitude scales distinguished four types of students: game players, rational lovers, emotional lovers, and absence lovers. These four groups of students showed significant differences in sexual attitudes and personality traits of deliberation and dutifulness but not self-discipline. The study’s implications for future studies on love attitudes in certain cultural groups were also discussed. PMID:27851784

Organizational flexibility as a strategic option: fostering dynamic capabilities of hospitals.

PubMed

Dias, Casimiro; Escoval, Ana

2014-01-01

The main purpose of this article is to examine how the internal and external dimensions of organizational flexibility impact hospital performance. Results reveal that matching internal and external flexibilities contributes to the development of capabilities to adopt new strategic options. Such interactions have a significant impact in terms of hospital performance. A cluster of dynamic hospitals, which is characterised by high levels of both internal and external flexibilities, (instead of that have high levels of both internal and external flexibilities) was found to have the double level of performance compared with other clusters. The implications for research and managerial practice are discussed. Copyright © 2014 Longwoods Publishing.

Systematics in lensing reconstruction: dark matter rings in the sky?

NASA Astrophysics Data System (ADS)

Ponente, P. P.; Diego, J. M.

2011-11-01

Context. Non-parametric lensing methods are a useful way of reconstructing the lensing mass of a cluster without making assumptions about the way the mass is distributed in the cluster. These methods are particularly powerful in the case of galaxy clusters with a large number of constraints. The advantage of not assuming implicitly that the luminous matter follows the dark matter is particularly interesting in those cases where the cluster is in a non-relaxed dynamical state. On the other hand, non-parametric methods have several limitations that should be taken into account carefully. Aims: We explore some of these limitations and focus on their implications for the possible ring of dark matter around the galaxy cluster CL0024+17. Methods: We project three background galaxies through a mock cluster of known radial profile density and obtain a map for the arcs (θ map). We also calculate the shear field associated with the mock cluster across the whole field of view (3.3 arcmin). Combining the positions of the arcs and the two-direction shear, we perform an inversion of the lens equation using two separate methods, the biconjugate gradient, and the quadratic programming (QADP) to reconstruct the convergence map of the mock cluster. Results: We explore the space of the solutions of the convergence map and compare the radial density profiles to the density profile of the mock cluster. When the inversion matrix algorithms are forced to find the exact solution, we encounter systematic effects resembling ring structures, that clearly depart from the original convergence map. Conclusions: Overfitting lensing data with a non-parametric method can produce ring-like structures similar to the alleged one in CL0024.

Identifying clusters of falls-related hospital admissions to inform population targets for prioritising falls prevention programmes

PubMed Central

Finch, Caroline F; Stephan, Karen; Shee, Anna Wong; Hill, Keith; Haines, Terry P; Clemson, Lindy; Day, Lesley

2015-01-01

Background There has been limited research investigating the relationship between injurious falls and hospital resource use. The aims of this study were to identify clusters of community-dwelling older people in the general population who are at increased risk of being admitted to hospital following a fall and how those clusters differed in their use of hospital resources. Methods Analysis of routinely collected hospital admissions data relating to 45 374 fall-related admissions in Victorian community-dwelling older adults aged ≥65 years that occurred during 2008/2009 to 2010/2011. Fall-related admission episodes were identified based on being admitted from a private residence to hospital with a principal diagnosis of injury (International Classification of Diseases (ICD)-10-AM codes S00 to T75) and having a first external cause of a fall (ICD-10-AM codes W00 to W19). A cluster analysis was performed to identify homogeneous groups using demographic details of patients and information on the presence of comorbidities. Hospital length of stay (LOS) was compared across clusters using competing risks regression. Results Clusters based on area of residence, demographic factors (age, gender, marital status, country of birth) and the presence of comorbidities were identified. Clusters representing hospitalised fallers with comorbidities were associated with longer LOS compared with other cluster groups. Clusters delineated by demographic factors were also associated with increased LOS. Conclusions All patients with comorbidity, and older women without comorbidities, stay in hospital longer following a fall and hence consume a disproportionate share of hospital resources. These findings have important implications for the targeting of falls prevention interventions for community-dwelling older people. PMID:25618735

Multi-temporal clustering of continental floods and associated atmospheric circulations

NASA Astrophysics Data System (ADS)

Liu, Jianyu; Zhang, Yongqiang

2017-12-01

Investigating clustering of floods has important social, economic and ecological implications. This study examines the clustering of Australian floods at different temporal scales and its possible physical mechanisms. Flood series with different severities are obtained by peaks-over-threshold (POT) sampling in four flood thresholds. At intra-annual scale, Cox regression and monthly frequency methods are used to examine whether and when the flood clustering exists, respectively. At inter-annual scale, dispersion indices with four-time variation windows are applied to investigate the inter-annual flood clustering and its variation. Furthermore, the Kernel occurrence rate estimate and bootstrap resampling methods are used to identify flood-rich/flood-poor periods. Finally, seasonal variation of horizontal wind at 850 hPa and vertical wind velocity at 500 hPa are used to investigate the possible mechanisms causing the temporal flood clustering. Our results show that: (1) flood occurrences exhibit clustering at intra-annual scale, which are regulated by climate indices representing the impacts of the Pacific and Indian Oceans; (2) the flood-rich months occur from January to March over northern Australia, and from July to September over southwestern and southeastern Australia; (3) stronger inter-annual clustering takes place across southern Australia than northern Australia; and (4) Australian floods are characterised by regional flood-rich and flood-poor periods, with 1987-1992 identified as the flood-rich period across southern Australia, but the flood-poor period across northern Australia, and 2001-2006 being the flood-poor period across most regions of Australia. The intra-annual and inter-annual clustering and temporal variation of flood occurrences are in accordance with the variation of atmospheric circulation. These results provide relevant information for flood management under the influence of climate variability, and, therefore, are helpful for developing flood hazard mitigation schemes.

WEIGHING GALAXY CLUSTERS WITH GAS. I. ON THE METHODS OF COMPUTING HYDROSTATIC MASS BIAS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lau, Erwin T.; Nagai, Daisuke; Nelson, Kaylea, E-mail: erwin.lau@yale.edu

2013-11-10

Mass estimates of galaxy clusters from X-ray and Sunyeav-Zel'dovich observations assume the intracluster gas is in hydrostatic equilibrium with their gravitational potential. However, since galaxy clusters are dynamically active objects whose dynamical states can deviate significantly from the equilibrium configuration, the departure from the hydrostatic equilibrium assumption is one of the largest sources of systematic uncertainties in cluster cosmology. In the literature there have been two methods for computing the hydrostatic mass bias based on the Euler and the modified Jeans equations, respectively, and there has been some confusion about the validity of these two methods. The word 'Jeans' wasmore » a misnomer, which incorrectly implies that the gas is collisionless. To avoid further confusion, we instead refer these methods as 'summation' and 'averaging' methods respectively. In this work, we show that these two methods for computing the hydrostatic mass bias are equivalent by demonstrating that the equation used in the second method can be derived from taking spatial averages of the Euler equation. Specifically, we identify the correspondences of individual terms in these two methods mathematically and show that these correspondences are valid to within a few percent level using hydrodynamical simulations of galaxy cluster formation. In addition, we compute the mass bias associated with the acceleration of gas and show that its contribution is small in the virialized regions in the interior of galaxy clusters, but becomes non-negligible in the outskirts of massive galaxy clusters. We discuss future prospects of understanding and characterizing biases in the mass estimate of galaxy clusters using both hydrodynamical simulations and observations and their implications for cluster cosmology.« less

Weighing Galaxy Clusters with Gas. I. On the Methods of Computing Hydrostatic Mass Bias

NASA Astrophysics Data System (ADS)

Lau, Erwin T.; Nagai, Daisuke; Nelson, Kaylea

2013-11-01

Mass estimates of galaxy clusters from X-ray and Sunyeav-Zel'dovich observations assume the intracluster gas is in hydrostatic equilibrium with their gravitational potential. However, since galaxy clusters are dynamically active objects whose dynamical states can deviate significantly from the equilibrium configuration, the departure from the hydrostatic equilibrium assumption is one of the largest sources of systematic uncertainties in cluster cosmology. In the literature there have been two methods for computing the hydrostatic mass bias based on the Euler and the modified Jeans equations, respectively, and there has been some confusion about the validity of these two methods. The word "Jeans" was a misnomer, which incorrectly implies that the gas is collisionless. To avoid further confusion, we instead refer these methods as "summation" and "averaging" methods respectively. In this work, we show that these two methods for computing the hydrostatic mass bias are equivalent by demonstrating that the equation used in the second method can be derived from taking spatial averages of the Euler equation. Specifically, we identify the correspondences of individual terms in these two methods mathematically and show that these correspondences are valid to within a few percent level using hydrodynamical simulations of galaxy cluster formation. In addition, we compute the mass bias associated with the acceleration of gas and show that its contribution is small in the virialized regions in the interior of galaxy clusters, but becomes non-negligible in the outskirts of massive galaxy clusters. We discuss future prospects of understanding and characterizing biases in the mass estimate of galaxy clusters using both hydrodynamical simulations and observations and their implications for cluster cosmology.

The relative vertex clustering value - a new criterion for the fast discovery of functional modules in protein interaction networks

PubMed Central

2015-01-01

Background Cellular processes are known to be modular and are realized by groups of proteins implicated in common biological functions. Such groups of proteins are called functional modules, and many community detection methods have been devised for their discovery from protein interaction networks (PINs) data. In current agglomerative clustering approaches, vertices with just a very few neighbors are often classified as separate clusters, which does not make sense biologically. Also, a major limitation of agglomerative techniques is that their computational efficiency do not scale well to large PINs. Finally, PIN data obtained from large scale experiments generally contain many false positives, and this makes it hard for agglomerative clustering methods to find the correct clusters, since they are known to be sensitive to noisy data. Results We propose a local similarity premetric, the relative vertex clustering value, as a new criterion allowing to decide when a node can be added to a given node's cluster and which addresses the above three issues. Based on this criterion, we introduce a novel and very fast agglomerative clustering technique, FAC-PIN, for discovering functional modules and protein complexes from a PIN data. Conclusions Our proposed FAC-PIN algorithm is applied to nine PIN data from eight different species including the yeast PIN, and the identified functional modules are validated using Gene Ontology (GO) annotations from DAVID Bioinformatics Resources. Identified protein complexes are also validated using experimentally verified complexes. Computational results show that FAC-PIN can discover functional modules or protein complexes from PINs more accurately and more efficiently than HC-PIN and CNM, the current state-of-the-art approaches for clustering PINs in an agglomerative manner. PMID:25734691

Quality of reporting of pilot and feasibility cluster randomised trials: a systematic review

PubMed Central

Chan, Claire L; Leyrat, Clémence; Eldridge, Sandra M

2017-01-01

Objectives To systematically review the quality of reporting of pilot and feasibility of cluster randomised trials (CRTs). In particular, to assess (1) the number of pilot CRTs conducted between 1 January 2011 and 31 December 2014, (2) whether objectives and methods are appropriate and (3) reporting quality. Methods We searched PubMed (2011–2014) for CRTs with ‘pilot’ or ‘feasibility’ in the title or abstract; that were assessing some element of feasibility and showing evidence the study was in preparation for a main effectiveness/efficacy trial. Quality assessment criteria were based on the Consolidated Standards of Reporting Trials (CONSORT) extensions for pilot trials and CRTs. Results Eighteen pilot CRTs were identified. Forty-four per cent did not have feasibility as their primary objective, and many (50%) performed formal hypothesis testing for effectiveness/efficacy despite being underpowered. Most (83%) included ‘pilot’ or ‘feasibility’ in the title, and discussed implications for progression from the pilot to the future definitive trial (89%), but fewer reported reasons for the randomised pilot trial (39%), sample size rationale (44%) or progression criteria (17%). Most defined the cluster (100%), and number of clusters randomised (94%), but few reported how the cluster design affected sample size (17%), whether consent was sought from clusters (11%), or who enrolled clusters (17%). Conclusions That only 18 pilot CRTs were identified necessitates increased awareness of the importance of conducting and publishing pilot CRTs and improved reporting. Pilot CRTs should primarily be assessing feasibility, avoiding formal hypothesis testing for effectiveness/efficacy and reporting reasons for the pilot, sample size rationale and progression criteria, as well as enrolment of clusters, and how the cluster design affects design aspects. We recommend adherence to the CONSORT extensions for pilot trials and CRTs. PMID:29122791

Biosynthetic Genes for the Tetrodecamycin Antibiotics.

PubMed

Gverzdys, Tomas; Nodwell, Justin R

2016-07-15

We recently described 13-deoxytetrodecamycin, a new member of the tetrodecamycin family of antibiotics. A defining feature of these molecules is the presence of a five-membered lactone called a tetronate ring. By sequencing the genome of a producer strain, Streptomyces sp. strain WAC04657, and searching for a gene previously implicated in tetronate ring formation, we identified the biosynthetic genes responsible for producing 13-deoxytetrodecamycin (the ted genes). Using the ted cluster in WAC04657 as a reference, we found related clusters in three other organisms: Streptomyces atroolivaceus ATCC 19725, Streptomyces globisporus NRRL B-2293, and Streptomyces sp. strain LaPpAH-202. Comparing the four clusters allowed us to identify the cluster boundaries. Genetic manipulation of the cluster confirmed the involvement of the ted genes in 13-deoxytetrodecamycin biosynthesis and revealed several additional molecules produced through the ted biosynthetic pathway, including tetrodecamycin, dihydrotetrodecamycin, and another, W5.9, a novel molecule. Comparison of the bioactivities of these four molecules suggests that they may act through the covalent modification of their target(s). The tetrodecamycins are a distinct subgroup of the tetronate family of secondary metabolites. Little is known about their biosynthesis or mechanisms of action, making them an attractive subject for investigation. In this paper we present the biosynthetic gene cluster for 13-deoxytetrodecamycin in Streptomyces sp. strain WAC04657. We identify related clusters in several other organisms and show that they produce related molecules. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Chaperone expression profiles correlate with distinct physiological states of Plasmodium falciparum in malaria patients

PubMed Central

2010-01-01

Background Molecular chaperones have been shown to be important in the growth of the malaria parasite Plasmodium falciparum and inhibition of chaperone function by pharmacological agents has been shown to abrogate parasite growth. A recent study has demonstrated that clinical isolates of the parasite have distinct physiological states, one of which resembles environmental stress response showing up-regulation of specific molecular chaperones. Methods Chaperone networks operational in the distinct physiological clusters in clinical malaria parasites were constructed using cytoscape by utilizing their clinical expression profiles. Results Molecular chaperones show distinct profiles in the previously defined physiologically distinct states. Further, expression profiles of the chaperones from different cellular compartments correlate with specific patient clusters. While cluster 1 parasites, representing a starvation response, show up-regulation of organellar chaperones, cluster 2 parasites, which resemble active growth based on glycolysis, show up-regulation of cytoplasmic chaperones. Interestingly, cytoplasmic Hsp90 and its co-chaperones, previously implicated as drug targets in malaria, cluster in the same group. Detailed analysis of chaperone expression in the patient cluster 2 reveals up-regulation of the entire Hsp90-dependent pro-survival circuitries. In addition, cluster 2 also shows up-regulation of Plasmodium export element (PEXEL)-containing Hsp40s thought to have regulatory and host remodeling roles in the infected erythrocyte. Conclusion In all, this study demonstrates an intimate involvement of parasite-encoded chaperones, PfHsp90 in particular, in defining pathogenesis of malaria. PMID:20719001

What is the role and authority of gatekeepers in cluster randomized trials in health research?

PubMed Central

2012-01-01

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the CRT is to be set on a firm ethical foundation. This paper addresses the sixth of the questions posed, namely, what is the role and authority of gatekeepers in CRTs in health research? ‘Gatekeepers’ are individuals or bodies that represent the interests of cluster members, clusters, or organizations. The need for gatekeepers arose in response to the difficulties in obtaining informed consent because of cluster randomization, cluster-level interventions, and cluster size. In this paper, we call for a more restrictive understanding of the role and authority of gatekeepers. Previous papers in this series have provided solutions to the challenges posed by informed consent in CRTs without the need to invoke gatekeepers. We considered that consent to randomization is not required when cluster members are approached for consent at the earliest opportunity and before any study interventions or data-collection procedures have started. Further, when cluster-level interventions or cluster size means that obtaining informed consent is not possible, a waiver of consent may be appropriate. In this paper, we suggest that the role of gatekeepers in protecting individual interests in CRTs should be limited. Generally, gatekeepers do not have the authority to provide proxy consent for cluster members. When a municipality or other community has a legitimate political authority that is empowered to make such decisions, cluster permission may be appropriate; however, gatekeepers may usefully protect cluster interests in other ways. Cluster consultation may ensure that the CRT addresses local health needs, and is conducted in accord with local values and customs. Gatekeepers may also play an important role in protecting the interests of organizations, such as hospitals, nursing homes, general practices, and schools. In these settings, permission to access the organization relies on resource implications and adherence to institutional policies. PMID:22834691

Probing C60

NASA Astrophysics Data System (ADS)

Curl, Robert F.; Smalley, Richard E.

1988-11-01

Experiments involving the laser vaporization of graphite have indicated that one particular cluster of carbon, C60, is preeminently stable; this special stability may be evidence that C60 can readily take the form of a hollow truncated icosahedron (a sort of molecular soccerball). If true, this structure for C60 would be the first example of a spherical aromatic molecule. In fact, because of symmetry properties unique to the number 60, it may be the most perfectly spherical, edgeless molecule possible. Its rapid formation in condensing carbon vapors and its extreme chemical and photophysical stability may have far-reaching implications in a number of areas, particularly combustion science and astrophysics. For these reasons C60 and other clusters of carbon have continued to be the subject of intense research. This article provides a short review of the many new experimental probes of the properties of C60 and related carbon clusters.

Nanoscale structure and morphology of sulfonated polyphenylenes via atomistic simulations

DOE PAGES

Abbott, Lauren J.; Frischknecht, Amalie L.

2017-01-23

We performed atomistic simulations on a series of sulfonated polyphenylenes systematically varying the degree of sulfonation and water content to determine their effect on the nanoscale structure, particularly for the hydrophilic domains formed by the ionic groups and water molecules. We found that the local structure around the ionic groups depended on the sulfonation and hydration levels, with the sulfonate groups and hydronium ions less strongly coupled at higher water contents. In addition, we characterized the morphology of the ionic domains employing two complementary clustering algorithms. At low sulfonation and hydration levels, clusters were more elongated in shape and poorlymore » connected throughout the system. As the degree of sulfonation and water content were increased, the clusters became more spherical, and a fully percolated ionic domain was formed. As a result, these structural details have important implications for ion transport.« less

Cadherin genes and evolutionary novelties in the octopus.

PubMed

Wang, Z Yan; Ragsdale, Clifton W

2017-09-01

All animals with large brains must have molecular mechanisms to regulate neuronal process outgrowth and prevent neurite self-entanglement. In vertebrates, two major gene families implicated in these mechanisms are the clustered protocadherins and the atypical cadherins. However, the molecular mechanisms utilized in complex invertebrate brains, such as those of the cephalopods, remain largely unknown. Recently, we identified protocadherins and atypical cadherins in the octopus. The octopus protocadherin expansion shares features with the mammalian clustered protocadherins, including enrichment in neural tissues, clustered head-to-tail orientations in the genome, and a large first exon encoding all cadherin domains. Other octopus cadherins, including a newly-identified cadherin with 77 extracellular cadherin domains, are elevated in the suckers, a striking cephalopod novelty. Future study of these octopus genes may yield insights into the general functions of protocadherins in neural wiring and cadherin-related proteins in complex morphogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical interpretation of the Spinal Cord Injury Functional Index (SCI-FI).

PubMed

Fyffe, Denise; Kalpakjian, Claire Z; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Kirshblum, Steven C; Tulsky, David S; Jette, Alan M

2016-09-01

To provide validation of functional ability levels for the Spinal Cord Injury - Functional Index (SCI-FI). Cross-sectional. Inpatient rehabilitation hospital and community settings. A sample of 855 individuals with traumatic spinal cord injury enrolled in 6 rehabilitation centers participating in the National Spinal Cord Injury Model Systems Network. Not Applicable. Spinal Cord Injury-Functional Index (SCI-FI). Cluster analyses identified three distinct groups that represent low, mid-range and high SCI-FI functional ability levels. Comparison of clusters on personal and other injury characteristics suggested some significant differences between groups. These results strongly support the use of SCI-FI functional ability levels to document the perceived functional abilities of persons with SCI. Results of the cluster analysis suggest that the SCI-FI functional ability levels capture function by injury characteristics. Clinical implications regarding tracking functional activity trajectories during follow-up visits are discussed.

Teacher student relationship quality type in elementary grades: Effects on trajectories for achievement and engagement

PubMed Central

Wu, Jiun-yu; Hughes, Jan N.; Kwok, Oi-man

2010-01-01

Teacher, peer, and student reports of the quality of the teacher-student relationship were obtained for an ethnically diverse and academically at-risk sample of 706 second and third grade students. Cluster analysis identified four types of relationships based on the consistency of child reports of support and conflict in the relationship with reports of others: Congruent positive, Congruent Negative, Incongruent Child Negative and Incongruent Child Positive. The cluster solution evidenced good internal consistency and construct validity. Cluster membership predicted growth trajectories for teacher-rated engagement and standardized achievement scores over the following three years, above prior performance. The predictive associations between child reports of teacher support and conflict and outcomes depended on whether child reports were consistent or inconsistent with reports of others. Study findings have implications for theory development, assessment of teacher-student relationships, and teacher professional development. PMID:20728688

The Origin of Clusters and Large-Scale Structures: Panoramic View of the High-z Universe

NASA Astrophysics Data System (ADS)

Ouchi, Masami

We will report results of our on-going survey for proto-clusters and large-scale structures at z=3-6. We carried out very wide and deep optical imaging down to i=27 for a 1 deg^2 field of the Subaru/XMM Deep Field with 8.2m Subaru Telescope. We obtain maps of the Universe traced by ~1,000 Ly-a galaxies at z=3, 4, and 6 and by ~10,000 Lyman break galaxies at z=3-6. These cosmic maps have a transverse dimension of ~150 Mpc x 150 Mpc in comoving units at these redshifts, and provide us, for the first time, a panoramic view of the high-z Universe from the scales of galaxies, clusters to large-scale structures. Major results and implications will be presented in our talk. (Part of this work is subject to press embargo.)

Planning a mentorship initiative for foster parents: Does gender matter?

PubMed

Jay Miller, J; Benner, Kalea; Thrasher, Shawndaya; Pope, Natalie; Dumas, Tamikia; Damron, Larry J; Segress, Melissa; Niu, Chunling

2017-10-01

Despite the use of mentoring programs in fields such as business, career training, and youth development, little is known about how mentoring can be used to train and support new foster parents. This paper describes how Concept Mapping was used with current foster parents to develop a conceptual framework suitable to plan a foster parent mentor program. A secondary aim of this study was to explore priority differences in the conceptualization by self-reported gender (foster mothers vs. foster fathers). Participant data was collected via three qualitative brainstorming sessions, and analyzed using non-metric multidimensional scaling and hierarchical cluster analysis. Findings indicate that foster parents participating in this study conceptualized effective mentor programs via a seven cluster solution. Study results also showed no significant differences in cluster ratings by gender. Implications for practice and program planning are identified, as well as areas for future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

The comptonization parameter from simulations of single-frequency, single-dish, dual-beam, cm-wave observations of galaxy clusters and mitigating CMB confusion using the Planck sky survey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lew, Bartosz; Roukema, Boudewijn F., E-mail: blew@astro.uni.torun.pl, E-mail: boud@astro.uni.torun.pl

2016-11-01

Systematic effects in dual-beam, differential, radio observations of extended objects are discussed in the context of the One Centimeter Receiver Array (OCRA). We use simulated samples of Sunyaev-Zel'dovich (SZ) galaxy clusters at low ( z < 0.4) and intermediate (0.4 < z < 1.0) redshifts to study the implications of operating at a single frequency (30 GHz) on the accuracy of extracting SZ flux densities and of reconstructing comptonization parameters with OCRA. We analyze dependences on cluster mass, redshift, observation strategy, and telescope pointing accuracy. Using Planck data to make primary cosmic microwave background (CMB) templates, we test the feasibilitymore » of mitigating CMB confusion effects in observations of SZ profiles at angular scales larger than the separation of the receiver beams.« less

Ambipolar SnOx thin-film transistors achieved at high sputtering power

NASA Astrophysics Data System (ADS)

Li, Yunpeng; Yang, Jia; Qu, Yunxiu; Zhang, Jiawei; Zhou, Li; Yang, Zaixing; Lin, Zhaojun; Wang, Qingpu; Song, Aimin; Xin, Qian

2018-04-01

SnO is the only oxide semiconductor to date that has exhibited ambipolar behavior in thin-film transistors (TFTs). In this work, ambipolar behavior was observed in SnOx TFTs fabricated at a high sputtering power of 200 W and post-annealed at 150-250 °C in ambient air. X-ray-diffraction patterns showed polycrystallisation of SnO and Sn in the annealed SnOx films. Scanning-electron-microscopy images revealed that microgrooves appeared after the films were annealed. Clusters subsequently segregated along the microgrooves, and our experiments suggest that they were most likely Sn clusters. Atomic force microscopy images indicate an abrupt increase in film roughness due to the cluster segregations. An important implication of this work is that excess Sn in the film, which has generally been thought to be detrimental to the film quality, may promote the ambipolar conduction when it is segregated from the film to enhance the stoichiometric balance.

Desorption electrospray ionization mass spectrometry of DNA nucleobases: implications for a liquid film model.

PubMed

Qiu, Bo; Luo, Hai

2009-05-01

Desorption electrospray ionization (DESI) mass spectrometry has been implemented on a commercial ion-trap mass spectrometer and used to optimize mass spectrometric conditions for DNA nucleobases: adenine, cytosine, thymine, and guanine. Experimental parameters including spray voltage, distance between mass spectrometer inlet and the sampled spot, and nebulizing gas inlet pressure were optimized. Cluster ions including some magic number clusters of nucleobases were observed for the first time using DESI mass spectrometry. The formation of the cluster species was found to vary with the nucleobases, acidification of the spray solvent, and the deposited sample amount. All the experimental results can be explained well using a liquid film model based on the two-step droplet pick-up mechanism. It is further suggested that solubility of the analytes in the spray solvent is an important factor to consider for their studies by using DESI. 2009 John Wiley & Sons, Ltd.

Bridging the gap: academic and practitioner perspectives to identify early career competencies needed in healthcare management.

PubMed

Shewchuk, Richard M; O'Connor, Stephen J; Fine, David J

2006-01-01

Healthcare organizations, health management professional associations, and educational institutions have begun to examine carefully what it means to be a fully competent healthcare executive. As a result, an upsurge in interest in healthcare management competencies has been observed recently. The present study uses two critically important groups of informants as participants: health management practitioners and faculty. Using the nominal group process, health administrators identified critical environmental issues perceived to have an impact on healthcare executives today. These issues were employed in a card-sort assessment and a survey was administered to a nationwide sample of health administrators. These data were used to create a map and five clusters of the environmental landscape of healthcare management. These clusters of environmental issues provided a framework for having groups of administrators and faculty members generate and rank perceived behavioral competencies relative to each cluster. Implications for healthcare management practice, education, and research are discussed.

Occupational Aptitude Patterns Map: Development and Implications for a Theory of Job Aptitude Requirements.

ERIC Educational Resources Information Center

Gottfredson, Linda S.

1986-01-01

United States Employment Service data on the cognitive and noncognitive aptitude requirements of different occupations were used to create an occupational classification--the Occupational Aptitude Patterns (OAP) Map. Thirteen job clusters are arrayed according to major differences in overall intellectual difficulty level and in functional focus…

Attachment Patterns in the Psychotherapy Relationship: Development of the Client Attachment to Therapist Scale.

ERIC Educational Resources Information Center

Mallinckrodt, Brent; And Others

1995-01-01

Describes development of an instrument, the Client Attachment to Therapist Scale (CATS). CATS factors correlated in expected directions with survey measures of object relations, client-rated working alliance, social self-efficacy, and adult attachment. Cluster analysis revealed four types of client attachment. Discusses implications of attachment…

Vineyard floor management influences 'Pinot noir' vine growth and productivity more than cluster thinning

USDA-ARS?s Scientific Manuscript database

Vigor and crop level management are important practices for premium wine grape production. The implications of crop thinning ‘Pinot noir’ (Vitis vinifera L.) vines of varying vigor were investigated in the Willamette Valley of Oregon in 2011 to 2013, to better understand the relationship between can...

A Typology of Family Social Environments for Institutionalized Juvenile Delinquents: Implications for Research and Treatment.

ERIC Educational Resources Information Center

Veneziano, Carol; Veneziano, Louis

1992-01-01

Family functioning of 411 incarcerated male juvenile delinquents (aged 12-16 years) was studied using the Family Environmental Scale. A typology of family social environments was developed using cluster analysis. Delinquents with the most serious behavioral difficulties come from family environments with few strengths and openly expressed conflict…

Child Development in Developing Countries: Child Rights and Policy Implications

ERIC Educational Resources Information Center

Britto, Pia Rebello; Ulkuer, Nurper

2012-01-01

The Multiple Indicator Cluster Survey was used to provide information on feeding practices, caregiving, discipline and violence, and the home environment for young children across 28 countries. The findings from the series of studies in this Special Section are the first of their kind because they provide information on the most proximal context…

Outbreak of Sporotrichosis, Western Australia

PubMed Central

Feeney, Kynan T.; Whittle, Amanda J.; Altman, Shelley A.; Speers, David J.

2007-01-01

A cluster of sporotrichosis cases occurred in the Busselton-Margaret River region of Western Australia from 2000 to 2003. Epidemiologic investigation and mycologic culture for Sporothrix schenckii implicated hay initially distributed through a commercial hay supplier as the source of the outbreak. Declining infection rates have occurred after various community measures were instigated. PMID:17953099

Callings in Career: A Typological Approach to Essential and Optional Components

ERIC Educational Resources Information Center

Hirschi, Andreas

2011-01-01

A sense of calling in career is supposed to have positive implications for individuals and organizations but current theoretical development is plagued with incongruent conceptualizations of what does or does not constitute a calling. The present study used cluster analysis to identify essential and optional components of a presence of calling…

Mitochondrial iron-sulfur cluster biogenesis from molecular understanding to clinical disease

PubMed Central

Alfadhel, Majid; Nashabat, Marwan; Ali, Qais Abu; Hundallah, Khalid

2017-01-01

Iron–sulfur clusters (ISCs) are known to play a major role in various protein functions. Located in the mitochondria, cytosol, endoplasmic reticulum and nucleus, they contribute to various core cellular functions. Until recently, only a few human diseases related to mitochondrial ISC biogenesis defects have been described. Such diseases include Friedreich ataxia, combined oxidative phosphorylation deficiency 19, infantile complex II/III deficiency defect, hereditary myopathy with lactic acidosis and mitochondrial muscle myopathy, lipoic acid biosynthesis defects, multiple mitochondrial dysfunctions syndromes and non ketotic hyperglycinemia due to glutaredoxin 5 gene defect. Disorders of mitochondrial import, export and translation, including sideroblastic anemia with ataxia, EVEN-PLUS syndrome and mitochondrial complex I deficiency due to nucleotide-binding protein-like protein gene defect, have also been implicated in ISC biogenesis defects. With advances in next generation sequencing technologies, more disorders related to ISC biogenesis defects are expected to be elucidated. In this article, we aim to shed the light on mitochondrial ISC biogenesis, related proteins and their function, pathophysiology, clinical phenotypes of related disorders, diagnostic approach, and future implications. PMID:28064324

Neuropsychological assessment of decision making in alcohol-dependent commercial pilots.

PubMed

Georgemiller, Randy; Machizawa, Sayaka; Young, Kathleen M; Martin, Cynthia N

2013-09-01

The aim of this exploratory archival study was to discern the utility of the Iowa Gambling Task (IGT) in identifying adaptive decision-making capacities among pilots with a history of alcohol dependence both with and without Cluster B personality features. Participants included 18 male airmen at the rank of captain with a history of receiving alcohol dependence treatment and subsequent referral for a fitness-for-duty evaluation. Data from prior comprehensive neuropsychological evaluations conducted in a private practice setting at the mandate of the FAA utilizing criteria outlined in the HIMS program was used. ANOVA was conducted to compare pilots with (N = 4) and without Cluster B personality features (N = 14) on measures of decisionmaking capacities, intelligence, and executive functioning. Pilots with Cluster B personality features were found to have a significantly lower Total Net T-Score on IGT (M = 35.00, SD = 9.27) than pilots without features of Cluster B (M = 56.36, SD = 9.55). Furthermore, with the exception of the first 20 cards (i.e., Net 1); the groups significantly differed in their Net scores. No statistically significant difference was found on airmen's intelligence and executive functioning. The present study found that alcohol-dependent airmen with Cluster B personality features evidenced significantly poorer decisionmaking capacities as measured by the ICT in comparison to alcohol dependent airman without Cluster B personality features. Implications and limitations of the study are discussed.

A New Look at the Molecular Gas in M42 and M43: Possible Evidence for Cloud–Cloud Collision that Triggered Formation of the OB Stars in the Orion Nebula Cluster

NASA Astrophysics Data System (ADS)

Fukui, Yasuo; Torii, Kazufumi; Hattori, Yusuke; Nishimura, Atsushi; Ohama, Akio; Shimajiri, Yoshito; Shima, Kazuhiro; Habe, Asao; Sano, Hidetoshi; Kohno, Mikito; Yamamoto, Hiroaki; Tachihara, Kengo; Onishi, Toshikazu

2018-06-01

The Orion Nebula Cluster toward the H II region M42 is the most outstanding young cluster at the smallest distance (410 pc) among the rich high-mass stellar clusters. By newly analyzing the archival molecular data of the 12CO(J = 1–0) emission at 21″ resolution, we identified at least three pairs of complementary distributions between two velocity components at 8 and 13 km s‑1. We present a hypothesis that the two clouds collided with each other and triggered formation of the high-mass stars, mainly toward two regions including the nearly 10 O stars in M42 and the B star, NU Ori, in M43. The timescale of the collision is estimated to be ∼0.1 Myr by a ratio of the cloud size and velocity corrected for projection, which is consistent with the age of the youngest cluster members less than 0.1 Myr. The majority of the low-mass cluster members were formed prior to the collision in the last Myr. We discuss the implications of the present hypothesis and the scenario of high-mass star formation by comparing with the other eight cases of triggered O-star formation via cloud–cloud collision.

Implications of hydrogen/halogen-bond in the stabilization of confined water and anion-water clusters by a cationic receptor

NASA Astrophysics Data System (ADS)

Hoque, Md. Najbul; Das, Gopal

2016-03-01

Anion complexation of benzene capped flexible tripodal receptor and solid state stabilization of discrete hybrid anion-water or infinite water clusters by various supramolecular interactions are reported here. The crystal structure of the receptor in protonated states shows all the three arms projected in one direction. We structurally demonstrate discrete fluoride-water cluster [F2-H2O]2- and square shaped chloride-water cluster [Cl2-(H2O)2]2- inside the cationic channel of the receptor. Structural analysis also reveals that these clusters are stabilized inside the channel through active participation of N/C/Ow‧H⋯Ow, N/C/Ow‧H⋯X- (X- = F-, Cl- and I-) H-bonds and electrostatic interactions. Moreover, C-H⋯π and π⋯π types weak intermolecular interactions appear to play crucial role in supramolecular assembly of receptor. Additionally, on treatment with hydroiodic acid (HI) L resulted zwitterionic iodide complex. Crystal structure reveals the presence of S···I halogen bonded dimer, I2···I halogen bond, 1D infinite water chain and neutral iodine molecules. It is comprehensible that ligand basal structure (benzene capped and N-bridge head in two tripodal) play crucial roles in the formation of diverse halide-water cluster. All structures were well examined by different techniques such as NMR, IR, TGA, DSC, PXRD and XRD.

DISCOVERY OF RR LYRAE STARS IN THE NUCLEAR BULGE OF THE MILKY WAY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minniti, Dante; Ramos, Rodrigo Contreras; Zoccali, Manuela

Galactic nuclei, such as that of the Milky Way, are extreme regions with high stellar densities, and in most cases, the hosts of a supermassive black hole. One of the scenarios proposed for the formation of the Galactic nucleus is merging of primordial globular clusters. An implication of this model is that this region should host stars that are characteristically found in old Milky Way globular clusters. RR Lyrae stars are primary distance indicators, well known representatives of old and metal-poor stellar populations, and therefore are regularly found in globular clusters. Here we report the discovery of a dozen RRmore » Lyrae type ab stars in the vicinity of the Galactic center, i.e., in the so-called nuclear stellar bulge of the Milky Way. This discovery provides the first direct observational evidence that the Galactic nuclear stellar bulge contains ancient stars (>10 Gyr old). Based on this we conclude that merging globular clusters likely contributed to the build-up of the high stellar density in the nuclear stellar bulge of the Milky Way.« less

Ce(x)O(y)⁻ (x = 2-3) + D₂O reactions: stoichiometric cluster formation from deuteroxide decomposition and anti-Arrhenius behavior.

PubMed

Felton, Jeremy A; Ray, Manisha; Waller, Sarah E; Kafader, Jared O; Jarrold, Caroline Chick

2014-10-30

Reactions between small cerium oxide cluster anions and deuterated water were monitored as a function of both water concentration and temperature in order to determine the temperature dependence of the rate constants. Sequential oxidation reactions of the Ce(x)O(y)⁻ (x = 2, 3) suboxide cluster anions were found to exhibit anti-Arrhenius behavior, with activation energies ranging from 0 to -18 kJ mol⁻¹. Direct oxidation of species up to y = x was observed, after which, -OD abstraction and D₂O addition reactions were observed. However, the stoichiometric Ce₂O₄⁻ and Ce₃O₆⁻ cluster anions also emerge in reactions between D₂O and the respective precursors, Ce₂O₃D⁻ and Ce₃O₅D₂⁻. Ce₂O₄⁻ and Ce₃O₆⁻ product intensities diminish relative to deuteroxide complex intensities with increasing temperature. The kinetics of these reactions are compared to the kinetics of the previously studied Mo(x)O(y)⁻ and W(x)O(y)⁻ reactions with water, and the possible implications for the reaction mechanisms are discussed.

Spatial autocorrelation among automated geocoding errors and its effects on testing for disease clustering

PubMed Central

Li, Jie; Fang, Xiangming

2010-01-01

Automated geocoding of patient addresses is an important data assimilation component of many spatial epidemiologic studies. Inevitably, the geocoding process results in positional errors. Positional errors incurred by automated geocoding tend to reduce the power of tests for disease clustering and otherwise affect spatial analytic methods. However, there are reasons to believe that the errors may often be positively spatially correlated and that this may mitigate their deleterious effects on spatial analyses. In this article, we demonstrate explicitly that the positional errors associated with automated geocoding of a dataset of more than 6000 addresses in Carroll County, Iowa are spatially autocorrelated. Furthermore, through two simulation studies of disease processes, including one in which the disease process is overlain upon the Carroll County addresses, we show that spatial autocorrelation among geocoding errors maintains the power of two tests for disease clustering at a level higher than that which would occur if the errors were independent. Implications of these results for cluster detection, privacy protection, and measurement-error modeling of geographic health data are discussed. PMID:20087879

Mechanism of unconfined dust explosions: Turbulent clustering and radiation-induced ignition.

PubMed

Liberman, Michael; Kleeorin, Nathan; Rogachevskii, Igor; Haugen, Nils Erland L

2017-05-01

It is known that unconfined dust explosions typically start off with a relatively weak primary flame followed by a severe secondary explosion. We show that clustering of dust particles in a temperature stratified turbulent flow ahead of the primary flame may give rise to a significant increase in the radiation penetration length. These particle clusters, even far ahead of the flame, are sufficiently exposed and heated by the radiation from the flame to become ignition kernels capable to ignite a large volume of fuel-air mixtures. This efficiently increases the total flame surface area and the effective combustion speed, defined as the rate of reactant consumption of a given volume. We show that this mechanism explains the high rate of combustion and overpressures required to account for the observed level of damage in unconfined dust explosions, e.g., at the 2005 Buncefield vapor-cloud explosion. The effect of the strong increase of radiation transparency due to turbulent clustering of particles goes beyond the state of the art of the application to dust explosions and has many implications in atmospheric physics and astrophysics.

Accurate Modeling of Galaxy Clustering on Small Scales: Testing the Standard ΛCDM + Halo Model

NASA Astrophysics Data System (ADS)

Sinha, Manodeep; Berlind, Andreas A.; McBride, Cameron; Scoccimarro, Roman

2015-01-01

The large-scale distribution of galaxies can be explained fairly simply by assuming (i) a cosmological model, which determines the dark matter halo distribution, and (ii) a simple connection between galaxies and the halos they inhabit. This conceptually simple framework, called the halo model, has been remarkably successful at reproducing the clustering of galaxies on all scales, as observed in various galaxy redshift surveys. However, none of these previous studies have carefully modeled the systematics and thus truly tested the halo model in a statistically rigorous sense. We present a new accurate and fully numerical halo model framework and test it against clustering measurements from two luminosity samples of galaxies drawn from the SDSS DR7. We show that the simple ΛCDM cosmology + halo model is not able to simultaneously reproduce the galaxy projected correlation function and the group multiplicity function. In particular, the more luminous sample shows significant tension with theory. We discuss the implications of our findings and how this work paves the way for constraining galaxy formation by accurate simultaneous modeling of multiple galaxy clustering statistics.

Neurocognitive deficits and history of childhood abuse in schizophrenia spectrum disorders: associations with Cluster B personality traits.

PubMed

Lysaker, Paul H; Wickett, Amanda M; Lancaster, Rebecca S; Davis, Louanne W

2004-05-01

Cluster B personality traits have been detected in persons with schizophrenia, at a rate exceeding that of the general population. Unclear, however, is how to account for such high rates of Cluster B traits. Accordingly, this study explored the hypothesis that the presence of these traits may be linked to impairments in neurocognition, and childhood abuse history. To test this, we simultaneously obtained an assessment of Cluster B traits using the Millon Clinical Multiaxial Inventory III, along with measures of attention, verbal memory, affect recognition, executive function and childhood abuse history among 37 persons with schizophrenia spectrum disorders in a post acute phases of illness. Pearson correlation coefficients revealed that higher levels of histrionic and narcissistic traits were related to poorer neurocognition while higher levels of narcissistic traits were negatively correlated with childhood physical abuse. Higher levels of borderline traits were uniquely related to the report of childhood sexual abuse while higher levels of antisocial traits were related to higher levels of childhood physical abuse. Theoretical and clinical implications are discussed.

Whole-brain structural topology in adult attention-deficit/hyperactivity disorder: Preserved global - disturbed local network organization.

PubMed

Sidlauskaite, Justina; Caeyenberghs, Karen; Sonuga-Barke, Edmund; Roeyers, Herbert; Wiersema, Jan R

2015-01-01

Prior studies demonstrate altered organization of functional brain networks in attention-deficit/hyperactivity disorder (ADHD). However, the structural underpinnings of these functional disturbances are poorly understood. In the current study, we applied a graph-theoretic approach to whole-brain diffusion magnetic resonance imaging data to investigate the organization of structural brain networks in adults with ADHD and unaffected controls using deterministic fiber tractography. Groups did not differ in terms of global network metrics - small-worldness, global efficiency and clustering coefficient. However, there were widespread ADHD-related effects at the nodal level in relation to local efficiency and clustering. The affected nodes included superior occipital, supramarginal, superior temporal, inferior parietal, angular and inferior frontal gyri, as well as putamen, thalamus and posterior cerebellum. Lower local efficiency of left superior temporal and supramarginal gyri was associated with higher ADHD symptom scores. Also greater local clustering of right putamen and lower local clustering of left supramarginal gyrus correlated with ADHD symptom severity. Overall, the findings indicate preserved global but altered local network organization in adult ADHD implicating regions underpinning putative ADHD-related neuropsychological deficits.

A multi-platform evaluation of the randomized CX low-rank matrix factorization in Spark

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gittens, Alex; Kottalam, Jey; Yang, Jiyan

We investigate the performance and scalability of the randomized CX low-rank matrix factorization and demonstrate its applicability through the analysis of a 1TB mass spectrometry imaging (MSI) dataset, using Apache Spark on an Amazon EC2 cluster, a Cray XC40 system, and an experimental Cray cluster. We implemented this factorization both as a parallelized C implementation with hand-tuned optimizations and in Scala using the Apache Spark high-level cluster computing framework. We obtained consistent performance across the three platforms: using Spark we were able to process the 1TB size dataset in under 30 minutes with 960 cores on all systems, with themore » fastest times obtained on the experimental Cray cluster. In comparison, the C implementation was 21X faster on the Amazon EC2 system, due to careful cache optimizations, bandwidth-friendly access of matrices and vector computation using SIMD units. We report these results and their implications on the hardware and software issues arising in supporting data-centric workloads in parallel and distributed environments.« less

Screening for PTSD among detained adolescents: Implications of the changes in the DSM-5.

PubMed

Modrowski, Crosby A; Bennett, Diana C; Chaplo, Shannon D; Kerig, Patricia K

2017-01-01

Screening for posttraumatic stress disorder (PTSD) is highly relevant for youth involved in the juvenile justice system given their high rates of trauma exposure and posttraumatic stress symptoms. However, to date, no studies have investigated the implications of the recent revisions to the Diagnostic and Statistical Manual for Mental Disorders (5th ed., DSM-5; American Psychiatric Association [APA], 2013) diagnostic criteria for PTSD for screening in this population. To this end, the present study compared PTSD screening rates using the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev., DSM-IV-TR; APA, 2013) versus DSM-5 criteria in a group of detained adolescents. Participants included 209 youth (60 girls) aged 13-19 (M = 15.97, SD = 1.24). Youth completed measures of lifetime trauma exposure and past-month posttraumatic stress symptoms. Over 95% of youth in the sample reported exposure to at least 1 type of traumatic event. Approximately 19.60% of the sample screened positive for PTSD according to the DSM-5 compared to 17.70% according to the DSM-IV-TR. Girls were more likely than boys to screen positive for PTSD according to the DSM-IV-TR compared to the DSM-5. The main factors accounting for the differences in screening rates across the versions of PTSD criteria involved the removal of Criterion A2 from the DSM-5, the separation of avoidance symptoms (Criterion C) into their own cluster, the addition of a cluster involving negative alterations in cognitions and mood (Criterion D), and revisions to the cluster of arousal symptoms (Criterion E). Future research should continue to investigate gender differences in PTSD symptoms in youth and consider the implications of these diagnostic changes for the accurate diagnosis and referral to treatment of adolescents who demonstrate posttraumatic stress reactions. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubinson, Emily H.; Prakasha Gowda, A.S.; Spratt, Thomas E.

DNA glycosylases that remove alkylated and deaminated purine nucleobases are essential DNA repair enzymes that protect the genome, and at the same time confound cancer alkylation therapy, by excising cytotoxic N3-methyladenine bases formed by DNA-targeting anticancer compounds. The basis for glycosylase specificity towards N3- and N7-alkylpurines is believed to result from intrinsic instability of the modified bases and not from direct enzyme functional group chemistry. Here we present crystal structures of the recently discovered Bacillus cereus AlkD glycosylase in complex with DNAs containing alkylated, mismatched and abasic nucleotides. Unlike other glycosylases, AlkD captures the extrahelical lesion in a solvent-exposed orientation,more » providing an illustration for how hydrolysis of N3- and N7-alkylated bases may be facilitated by increased lifetime out of the DNA helix. The structures and supporting biochemical analysis of base flipping and catalysis reveal how the HEAT repeats of AlkD distort the DNA backbone to detect non-Watson-Crick base pairs without duplex intercalation.« less

DNA bases thymine and adenine in bio-organic light emitting diodes.

PubMed

Gomez, Eliot F; Venkatraman, Vishak; Grote, James G; Steckl, Andrew J

2014-11-24

We report on the use of nucleic acid bases (NBs) in organic light emitting diodes (OLEDs). NBs are small molecules that are the basic building blocks of the larger DNA polymer. NBs readily thermally evaporate and integrate well into the vacuum deposited OLED fabrication. Adenine (A) and thymine (T) were deposited as electron-blocking/hole-transport layers (EBL/HTL) that resulted in increases in performance over the reference OLED containing the standard EBL material NPB. A-based OLEDs reached a peak current efficiency and luminance performance of 48 cd/A and 93,000 cd/m(2), respectively, while T-based OLEDs had a maximum of 76 cd/A and 132,000 cd/m(2). By comparison, the reference OLED yielded 37 cd/A and 113,000 cd/m(2). The enhanced performance of T-based devices is attributed to a combination of energy levels and structured surface morphology that causes more efficient and controlled hole current transport to the emitting layer.

Hydrolysis of N3-methyl-2'-deoxycytidine: model compound for reactivity of protonated cytosine residues in DNA.

PubMed

Sowers, L C; Sedwick, W D; Shaw, B R

1989-11-01

Protonation of cytosine residues at physiological pH may occur in DNA as a consequence of both alkylation and aberrant base-pair formation. When cytosine derivatives are protonated, they undergo hydrolysis reactions at elevated rates and can either deaminate to form the corresponding uracil derivatives or depyrimidinate generating abasic sites. The kinetic parameters for reaction of protonated cytosine are derived by studying the hydrolysis of N3-methyl-2'-deoxycytidine (m3dC), a cytosine analogue which is predominantly protonated at physiological pH. Both deamination and depyrimidimation reaction rates are shown to be linearly dependent upon the fraction of protonated molecules. We present here thermodynamic parameters which allow determination of hydrolysis rates of m3dC as functions of pH and temperature. Protonation of cytosine residues in DNA, as induced by aberrant base-pair formation or base modification, may accelerate the rate of both deamination and depyrimidation up to several thousand-fold under physiological conditions.

Hydration Changes upon DNA Folding Studied by Osmotic Stress Experiments

PubMed Central

Nakano, Shu-ichi; Yamaguchi, Daisuke; Tateishi-Karimata, Hisae; Miyoshi, Daisuke; Sugimoto, Naoki

2012-01-01

The thermal stability of nucleic acid structures is perturbed under the conditions that mimic the intracellular environment, typically rich in inert components and under osmotic stress. We now describe the thermodynamic stability of DNA oligonucleotide structures in the presence of high background concentrations of neutral cosolutes. Small cosolutes destabilize the basepair structures, and the DNA structures consisting of the same nearest-neighbor composition show similar thermodynamic parameters in the presence of various types of cosolutes. The osmotic stress experiments reveal that water binding to flexible loops, unstable mismatches, and an abasic site upon DNA folding are almost negligible, whereas the binding to stable mismatch pairs is significant. The studies using the basepair-mimic nucleosides and the peptide nucleic acid suggest that the sugar-phosphate backbone and the integrity of the basepair conformation make important contributions to the binding of water molecules to the DNA bases and helical grooves. The study of the DNA hydration provides the basis for understanding and predicting nucleic acid structures in nonaqueous solvent systems. PMID:22735531

Human DNA polymerase θ grasps the primer terminus to mediate DNA repair

DOE PAGES

Zahn, Karl E.; Averill, April M.; Aller, Pierre; ...

2015-03-16

DNA polymerase θ protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks. Polymerase θ is overexpressed in breast, lung and oral cancers, and reduction of its activity in mammalian cells increases sensitivity to double-strand break–inducing agents, including ionizing radiation. Reported in this paper are crystal structures of the C-terminal polymerase domain from human polymerase θ, illustrating two potential modes of dimerization. One structure depicts insertion of ddATP opposite an abasic-site analog during translesion DNA synthesis. The second structure describes a cognate ddGTP complex. Polymerase θ uses a specialized thumb subdomain to establish unique upstream contactsmore » to the primer DNA strand, including an interaction with the 3'-terminal phosphate from one of five distinctive insertion loops. Finally, these observations demonstrate how polymerase θ grasps the primer to bypass DNA lesions or extend poorly annealed DNA termini to mediate end-joining.« less

Surveying the repair of ancient DNA from bones via high-throughput sequencing.

PubMed

Mouttham, Nathalie; Klunk, Jennifer; Kuch, Melanie; Fourney, Ron; Poinar, Hendrik

2015-07-01

DNA damage in the form of abasic sites, chemically altered nucleotides, and strand fragmentation is the foremost limitation in obtaining genetic information from many ancient samples. Upon cell death, DNA continues to endure various chemical attacks such as hydrolysis and oxidation, but repair pathways found in vivo no longer operate. By incubating degraded DNA with specific enzyme combinations adopted from these pathways, it is possible to reverse some of the post-mortem nucleic acid damage prior to downstream analyses such as library preparation, targeted enrichment, and high-throughput sequencing. Here, we evaluate the performance of two available repair protocols on previously characterized DNA extracts from four mammoths. Both methods use endonucleases and glycosylases along with a DNA polymerase-ligase combination. PreCR Repair Mix increases the number of molecules converted to sequencing libraries, leading to an increase in endogenous content and a decrease in cytosine-to-thymine transitions due to cytosine deamination. However, the effects of Nelson Repair Mix on repair of DNA damage remain inconclusive.

A proteome view of structural, functional, and taxonomic characteristics of major protein domain clusters.

PubMed

Sun, Chia-Tsen; Chiang, Austin W T; Hwang, Ming-Jing

2017-10-27

Proteome-scale bioinformatics research is increasingly conducted as the number of completely sequenced genomes increases, but analysis of protein domains (PDs) usually relies on similarity in their amino acid sequences and/or three-dimensional structures. Here, we present results from a bi-clustering analysis on presence/absence data for 6,580 unique PDs in 2,134 species with a sequenced genome, thus covering a complete set of proteins, for the three superkingdoms of life, Bacteria, Archaea, and Eukarya. Our analysis revealed eight distinctive PD clusters, which, following an analysis of enrichment of Gene Ontology functions and CATH classification of protein structures, were shown to exhibit structural and functional properties that are taxa-characteristic. For examples, the largest cluster is ubiquitous in all three superkingdoms, constituting a set of 1,472 persistent domains created early in evolution and retained in living organisms and characterized by basic cellular functions and ancient structural architectures, while an Archaea and Eukarya bi-superkingdom cluster suggests its PDs may have existed in the ancestor of the two superkingdoms, and others are single superkingdom- or taxa (e.g. Fungi)-specific. These results contribute to increase our appreciation of PD diversity and our knowledge of how PDs are used in species, yielding implications on species evolution.

A general framework to test gravity using galaxy clusters - I. Modelling the dynamical mass of haloes in f(R) gravity

NASA Astrophysics Data System (ADS)

Mitchell, Myles A.; He, Jian-hua; Arnold, Christian; Li, Baojiu

2018-06-01

We propose a new framework for testing gravity using cluster observations, which aims to provide an unbiased constraint on modified gravity models from Sunyaev-Zel'dovich (SZ) and X-ray cluster counts and the cluster gas fraction, among other possible observables. Focusing on a popular f(R) model of gravity, we propose a novel procedure to recalibrate mass scaling relations from Λ cold dark matter (ΛCDM) to f(R) gravity for SZ and X-ray cluster observables. We find that the complicated modified gravity effects can be simply modelled as a dependence on a combination of the background scalar field and redshift, fR(z)/(1 + z), regardless of the f(R) model parameter. By employing a large suite of N-body simulations, we demonstrate that a theoretically derived tanh fitting formula is in excellent agreement with the dynamical mass enhancement of dark matter haloes for a large range of background field parameters and redshifts. Our framework is sufficiently flexible to allow for tests of other models and inclusion of further observables, and the one-parameter description of the dynamical mass enhancement can have important implications on the theoretical modelling of observables and on practical tests of gravity.

Clusters of community exposure to coastal flooding hazards based on storm and sea level rise scenarios—implications for adaptation networks in the San Francisco Bay region

USGS Publications Warehouse

Hummel, Michelle; Wood, Nathan J.; Schweikert, Amy; Stacey, Mark T.; Jones, Jeanne; Barnard, Patrick L.; Erikson, Li H.

2018-01-01

Sea level is projected to rise over the coming decades, further increasing the extent of flooding hazards in coastal communities. Efforts to address potential impacts from climate-driven coastal hazards have called for collaboration among communities to strengthen the application of best practices. However, communities currently lack practical tools for identifying potential partner communities based on similar hazard exposure characteristics. This study uses statistical cluster analysis to identify similarities in community exposure to flooding hazards for a suite of sea level rise and storm scenarios. We demonstrate this approach using 63 jurisdictions in the San Francisco Bay region of California (USA) and compare 21 distinct exposure variables related to residents, employees, and structures for six hazard scenario combinations of sea level rise and storms. Results indicate that cluster analysis can provide an effective mechanism for identifying community groupings. Cluster compositions changed based on the selected societal variables and sea level rise scenarios, suggesting that a community could participate in multiple networks to target specific issues or policy interventions. The proposed clustering approach can serve as a data-driven foundation to help communities identify other communities with similar adaptation challenges and to enhance regional efforts that aim to facilitate adaptation planning and investment prioritization.

Subspecialization in the human posterior medial cortex

PubMed Central

Bzdok, Danilo; Heeger, Adrian; Langner, Robert; Laird, Angela R.; Fox, Peter T.; Palomero-Gallagher, Nicola; Vogt, Brent A.; Zilles, Karl; Eickhoff, Simon B.

2014-01-01

The posterior medial cortex (PMC) is particularly poorly understood. Its neural activity changes have been related to highly disparate mental processes. We therefore investigated PMC properties with a data-driven exploratory approach. First, we subdivided the PMC by whole-brain coactivation profiles. Second, functional connectivity of the ensuing PMC regions was compared by task-constrained meta-analytic coactivation mapping (MACM) and task-unconstrained resting-state correlations (RSFC). Third, PMC regions were functionally described by forward/reverse functional inference. A precuneal cluster was mostly connected to the intraparietal sulcus, frontal eye fields, and right temporo-parietal junction; associated with attention and motor tasks. A ventral posterior cingulate cortex (PCC) cluster was mostly connected to the ventromedial prefrontal cortex and middle left inferior parietal cortex (IPC); associated with facial appraisal and language tasks. A dorsal PCC cluster was mostly connected to the dorsomedial prefrontal cortex, anterior/posterior IPC, posterior midcingulate cortex, and left dorsolateral prefrontal cortex; associated with delay discounting. A cluster in the retrosplenial cortex was mostly connected to the anterior thalamus and hippocampus. Furthermore, all PMC clusters were congruently coupled with the default mode network according to task-constrained but not task-unconstrained connectivity. We thus identified distinct regions in the PMC and characterized their neural networks and functional implications. PMID:25462801

Reduced response cluster size in early visual areas explains the acuity deficit in amblyopia.

PubMed

Huang, Yufeng; Feng, Lixia; Zhou, Yifeng

2017-05-03

Focal visual stimulation typically results in the activation of a large portion of the early visual cortex. This spread of activity is attributed to long-range lateral interactions. Such long-range interactions may serve to stabilize a visual representation or to simply modulate incoming signals, and any associated dysfunction in long-range activation may reduce sensitivity to visual information in conditions such as amblyopia. We sought to measure the dispersion of cortical activity following local visual stimulation in a group of patients with amblyopia and matched normal. Twenty adult anisometropic amblyopes and 10 normal controls participated in this study. Using a multifocal stimulation, we simultaneously measured cluster sizes to multiple stimulation points in the visual field. We found that the functional MRI (fMRI) response cluster size that corresponded to the fellow eye was significantly larger as opposed to that corresponding to the amblyopic eye and that the fMRI response cluster size at the two more central retinotopic locations correlated with amblyopia acuity deficit. Our results suggest that the amblyopic visual cortex has a diminished long-range communication as evidenced by significantly smaller cluster of activity as measured with fMRI. These results have important implications for models of amblyopia and approaches to treatment.

Properties of the probability distribution associated with the largest event in an earthquake cluster and their implications to foreshocks.

PubMed

Zhuang, Jiancang; Ogata, Yosihiko

2006-04-01

The space-time epidemic-type aftershock sequence model is a stochastic branching process in which earthquake activity is classified into background and clustering components and each earthquake triggers other earthquakes independently according to certain rules. This paper gives the probability distributions associated with the largest event in a cluster and their properties for all three cases when the process is subcritical, critical, and supercritical. One of the direct uses of these probability distributions is to evaluate the probability of an earthquake to be a foreshock, and magnitude distributions of foreshocks and nonforeshock earthquakes. To verify these theoretical results, the Japan Meteorological Agency earthquake catalog is analyzed. The proportion of events that have 1 or more larger descendants in total events is found to be as high as about 15%. When the differences between background events and triggered event in the behavior of triggering children are considered, a background event has a probability about 8% to be a foreshock. This probability decreases when the magnitude of the background event increases. These results, obtained from a complicated clustering model, where the characteristics of background events and triggered events are different, are consistent with the results obtained in [Ogata, Geophys. J. Int. 127, 17 (1996)] by using the conventional single-linked cluster declustering method.

Implicit Priors in Galaxy Cluster Mass and Scaling Relation Determinations

NASA Technical Reports Server (NTRS)

Mantz, A.; Allen, S. W.

2011-01-01

Deriving the total masses of galaxy clusters from observations of the intracluster medium (ICM) generally requires some prior information, in addition to the assumptions of hydrostatic equilibrium and spherical symmetry. Often, this information takes the form of particular parametrized functions used to describe the cluster gas density and temperature profiles. In this paper, we investigate the implicit priors on hydrostatic masses that result from this fully parametric approach, and the implications of such priors for scaling relations formed from those masses. We show that the application of such fully parametric models of the ICM naturally imposes a prior on the slopes of the derived scaling relations, favoring the self-similar model, and argue that this prior may be influential in practice. In contrast, this bias does not exist for techniques which adopt an explicit prior on the form of the mass profile but describe the ICM non-parametrically. Constraints on the slope of the cluster mass-temperature relation in the literature show a separation based the approach employed, with the results from fully parametric ICM modeling clustering nearer the self-similar value. Given that a primary goal of scaling relation analyses is to test the self-similar model, the application of methods subject to strong, implicit priors should be avoided. Alternative methods and best practices are discussed.

Compatible poliomyelitis cases in India during 2000.

PubMed Central

Kohler, Kathryn A.; Hlady, W. Gary; Banerjee, Kaushik; Gupta, Dhananjoy; Francis, Paul; Durrani, Sunita; Zuber, Patrick L. F.; Sutter, Roland W.

2003-01-01

OBJECTIVE: To describe the characteristics of compatible poliomyelitis cases and to assess the programmatic implications of clusters of such cases in India. METHODS: We described the characteristics of compatible poliomyelitis cases, identified clusters of compatible cases (two or more in the same district or neighbouring districts within two months), and examined their relationship to wild poliovirus cases. FINDINGS: There were 362 compatible cases in 2000. The incidence of compatible cases was higher in districts with laboratory-confirmed poliomyelitis cases than in districts without laboratory-confirmed cases. Of 580 districts, 96 reported one compatible case and 72 reported two or more compatible cases. Among these 168 districts with at least one compatible case, 123 had internal or cross- border clusters of compatible cases. In 27 districts with clusters of compatible cases, no wild poliovirus was isolated either in the same district or in neighbouring districts. Three of these 27 districts presented laboratory-confirmed poliomyelitis cases during 2001. CONCLUSION: Most clusters of compatible cases occurred in districts identified as areas with continuing wild poliovirus transmission and where mopping-up vaccination campaigns were carried out. As certification nears, areas with compatible poliomyelitis cases should be investigated and deficiencies in surveillance should be corrected in order to ensure that certification is justified. PMID:12640469

A Detailed Study of Chemical Enrichment History of Galaxy Clusters out to Virial Radius

NASA Astrophysics Data System (ADS)

Loewenstein, Michael

The origin of the metal enrichment of the intracluster medium (ICM) represents a fundamental problem in extragalactic astrophysics, with implications for our understanding of how stars and galaxies form, the nature of Type Ia supernova (SNIa) progenitors, and the thermal history of the ICM. These heavy elements are ultimately synthesized by supernova (SN) explosions; however, the details of the sites of metal production and mechanisms that transport metals to the ICM remain unclear. To make progress, accurate abundance profiles for multiple elements extending from the cluster core out to the virial radius (r180) are required for a significant cluster sample. We propose an X-ray spectroscopic study of a carefully-chosen sample of archival Suzaku and XMM-Newton observations of 23 clusters: XMM-Newton data probe the cluster temperature and abundances out to (0.5-1)r500, while Suzaku data probe the cluster outskirts. A method devised by our team to utilize all elements with emission lines in the X-ray bandpass to measure the relative contributions of supernova explosions by direct modeling of their X-ray spectra will be applied in order to constrain the demographics of the enriching supernova population. In addition we will conduct a stacking analysis of our already existing Suzaku and XMM-Newton cluster spectra to search for weak emssion lines that are important SN diagnostics, and to look for trends with cluster mass and redshift. The funding we propose here will also support the data analysis of our recent Suzaku observations of the archetypal cluster A3112 (200 ks each on the core and outskirts). Our data analysis, intepreted using theoretical models we have developed, will enable us to constrain the star formation history, SN demographics, and nature of SNIa progenitors associated with galaxy cluster stellar populations - and, hence, directly addresess NASA s Strategic Objective 2.4.2 in Astrophysics that aims to improve the understanding of how the Universe works, and explore how it began and evolved.

Galaxy Cluster Mass Reconstruction Project - II. Quantifying scatter and bias using contrasting mock catalogues

DOE PAGES

Old, L.; Wojtak, R.; Mamon, G. A.; ...

2015-03-26

Our paper is the second in a series in which we perform an extensive comparison of various galaxy-based cluster mass estimation techniques that utilize the positions, velocities and colours of galaxies. Our aim is to quantify the scatter, systematic bias and completeness of cluster masses derived from a diverse set of 25 galaxy-based methods using two contrasting mock galaxy catalogues based on a sophisticated halo occupation model and a semi-analytic model. Analysing 968 clusters, we find a wide range in the rms errors in log M200c delivered by the different methods (0.18–1.08 dex, i.e. a factor of ~1.5–12), with abundance-matchingmore » and richness methods providing the best results, irrespective of the input model assumptions. In addition, certain methods produce a significant number of catastrophic cases where the mass is under- or overestimated by a factor greater than 10. Given the steeply falling high-mass end of the cluster mass function, we recommend that richness- or abundance-matching-based methods are used in conjunction with these methods as a sanity check for studies selecting high-mass clusters. We also see a stronger correlation of the recovered to input number of galaxies for both catalogues in comparison with the group/cluster mass, however, this does not guarantee that the correct member galaxies are being selected. Finally, we did not observe significantly higher scatter for either mock galaxy catalogues. These results have implications for cosmological analyses that utilize the masses, richnesses, or abundances of clusters, which have different uncertainties when different methods are used.« less

New Cepheid variables in the young open clusters Berkeley 51 and Berkeley 55

NASA Astrophysics Data System (ADS)

Lohr, M. E.; Negueruela, I.; Tabernero, H. M.; Clark, J. S.; Lewis, F.; Roche, P.

2018-05-01

As part of a wider investigation of evolved massive stars in Galactic open clusters, we have spectroscopically identified three candidate classical Cepheids in the little-studied clusters Berkeley 51, Berkeley 55 and NGC 6603. Using new multi-epoch photometry, we confirm that Be 51 #162 and Be 55 #107 are bona fide Cepheids, with pulsation periods of 9.83±0.01 d and 5.850±0.005 d respectively, while NGC 6603 star W2249 does not show significant photometric variability. Using the period-luminosity relationship for Cepheid variables, we determine a distance to Be 51 of 5.3^{+1.0}_{-0.8} kpc and an age of 44^{+9}_{-8} Myr, placing it in a sparsely-attested region of the Perseus arm. For Be 55, we find a distance of 2.2±0.3 kpc and age of 63^{+12}_{-11} Myr, locating the cluster in the Local arm. Taken together with our recent discovery of a long-period Cepheid in the starburst cluster VdBH222, these represent an important increase in the number of young, massive Cepheids known in Galactic open clusters. We also consider new Gaia (data release 2) parallaxes and proper motions for members of Be 51 and Be 55; the uncertainties on the parallaxes do not allow us to refine our distance estimates to these clusters, but the well-constrained proper motion measurements furnish further confirmation of cluster membership. However, future final Gaia parallaxes for such objects should provide valuable independent distance measurements, improving the calibration of the period-luminosity relationship, with implications for the distance ladder out to cosmological scales.

Comprehensive Genomic Analyses of the OM43 Clade, Including a Novel Species from the Red Sea, Indicate Ecotype Differentiation among Marine Methylotrophs

PubMed Central

Jimenez-Infante, Francy; Ngugi, David Kamanda; Vinu, Manikandan; Alam, Intikhab; Kamau, Allan Anthony; Blom, Jochen; Bajic, Vladimir B.

2015-01-01

The OM43 clade within the family Methylophilaceae of Betaproteobacteria represents a group of methylotrophs that play important roles in the metabolism of C1 compounds in marine environments and other aquatic environments around the globe. Using dilution-to-extinction cultivation techniques, we successfully isolated a novel species of this clade (here designated MBRS-H7) from the ultraoligotrophic open ocean waters of the central Red Sea. Phylogenomic analyses indicate that MBRS-H7 is a novel species that forms a distinct cluster together with isolate KB13 from Hawaii (Hawaii-Red Sea [H-RS] cluster) that is separate from the cluster represented by strain HTCC2181 (from the Oregon coast). Phylogenetic analyses using the robust 16S-23S internal transcribed spacer revealed a potential ecotype separation of the marine OM43 clade members, which was further confirmed by metagenomic fragment recruitment analyses that showed trends of higher abundance in low-chlorophyll and/or high-temperature provinces for the H-RS cluster but a preference for colder, highly productive waters for the HTCC2181 cluster. This potential environmentally driven niche differentiation is also reflected in the metabolic gene inventories, which in the case of the H-RS cluster include those conferring resistance to high levels of UV irradiation, temperature, and salinity. Interestingly, we also found different energy conservation modules between these OM43 subclades, namely, the existence of the NADH:quinone oxidoreductase complex I (NUO) system in the H-RS cluster and the nonhomologous NADH:quinone oxidoreductase (NQR) system in the HTCC2181 cluster, which might have implications for their overall energetic yields. PMID:26655752

Redox Control of the Human Iron-Sulfur Repair Protein MitoNEET Activity via Its Iron-Sulfur Cluster*

PubMed Central

Golinelli-Cohen, Marie-Pierre; Lescop, Ewen; Mons, Cécile; Gonçalves, Sergio; Clémancey, Martin; Santolini, Jérôme; Guittet, Eric; Blondin, Geneviève; Latour, Jean-Marc; Bouton, Cécile

2016-01-01

Human mitoNEET (mNT) is the first identified Fe-S protein of the mammalian outer mitochondrial membrane. Recently, mNT has been implicated in cytosolic Fe-S repair of a key regulator of cellular iron homeostasis. Here, we aimed to decipher the mechanism by which mNT triggers its Fe-S repair capacity. By using tightly controlled reactions combined with complementary spectroscopic approaches, we have determined the differential roles played by both the redox state of the mNT cluster and dioxygen in cluster transfer and protein stability. We unambiguously demonstrated that only the oxidized state of the mNT cluster triggers cluster transfer to a generic acceptor protein and that dioxygen is neither required for the cluster transfer reaction nor does it affect the transfer rate. In the absence of apo-acceptors, a large fraction of the oxidized holo-mNT form is converted back to reduced holo-mNT under low oxygen tension. Reduced holo-mNT, which holds a [2Fe-2S]+ with a global protein fold similar to that of the oxidized form is, by contrast, resistant in losing its cluster or in transferring it. Our findings thus demonstrate that mNT uses an iron-based redox switch mechanism to regulate the transfer of its cluster. The oxidized state is the “active state,” which reacts promptly to initiate Fe-S transfer independently of dioxygen, whereas the reduced state is a “dormant form.” Finally, we propose that the redox-sensing function of mNT is a key component of the cellular adaptive response to help stress-sensitive Fe-S proteins recover from oxidative injury. PMID:26887944

A Multidimensional Approach to Explore the Understanding of the Notion of Absolute Value

ERIC Educational Resources Information Center

Gagatsis, Athanasios; Panaoura, Areti

2014-01-01

The study aimed to investigate students' conceptions on the notion of absolute value and their abilities in applying the specific notion in routine and non-routine situations. A questionnaire was constructed and administered to 17-year-old students. Data were analysed using the hierarchical clustering of variables and the implicative method, while…

Social Support, Academic Adversity and Academic Buoyancy: A Person-Centred Analysis and Implications for Academic Outcomes

ERIC Educational Resources Information Center

Collie, Rebecca J.; Martin, Andrew J.; Bottrell, Dorothy; Armstrong, Derrick; Ungar, Michael; Liebenberg, Linda

2017-01-01

The present study employed person-centred analyses that enabled identification of groups of students separated on the basis of their perceptions of social support (home and community), academic support, academic adversity and academic buoyancy. Among a sample of 249 young people, including many from high-needs communities, cluster analysis…

Patterns of forest phylogenetic community structure across the United States and their possible forest health implications

Treesearch

Kevin M. Potter; Frank H. Koch

2014-01-01

The analysis of phylogenetic relationships among co-occurring tree species offers insights into the ecological organization of forest communities from an evolutionary perspective and, when employed regionally across thousands of plots, can assist in forest health assessment. Phylogenetic clustering of species, when species are more closely related than expected by...

Intergroup Stereotypes of Working Class Blacks and Whites: Implications for Stereotype Threat.

ERIC Educational Resources Information Center

Niemann, Yolanda Flores; O'Connor, Elizabeth; McClorie, Randall

1998-01-01

Examined stereotypes of urban blacks and whites at a flea market with 68 black respondents, and at another flea market with 20 white respondents. Cluster-analysis results show that blacks have a relatively complex, multidimensional representation of themselves and of whites, while whites seem to have a more simplistic and negative view of blacks.…

Unrecognized Dengue Virus Infections in Children, Western Kenya, 2014-2015.

PubMed

Vu, David M; Mutai, Noah; Heath, Claire J; Vulule, John M; Mutuku, Francis M; Ndenga, Bryson A; LaBeaud, A Desiree

2017-11-01

We detected a cluster of dengue virus infections in children in Kenya during July 2014-June 2015. Most cases were serotype 1, but we detected all 4 serotypes, including co-infections with 2 serotypes. Our findings implicate dengue as a cause of febrile illness in this population and highlight a need for robust arbovirus surveillance.

Profiles of Attribution of Importance to Life Roles and Their Implications for the Work-Family Conflict

ERIC Educational Resources Information Center

Cinamon, Rachel Gali; Rich, Yisrael

2002-01-01

Cluster analysis identified 3 groups of individuals who differed systematically on attributions of relative importance to work and to family roles. Participants were 213 married computer workers and lawyers, 126 men and 87 women. Questionnaires gathered data on attributions of importance to life roles, work-family conflict, spousal and managerial…

Alternative states of a semiarid grassland ecosystem: implications for ecosystem services

USGS Publications Warehouse

Miller, Mark E.; Belote, R. Travis; Bowker, Matthew A.; Garman, Steven L.

2011-01-01

Ecosystems can shift between alternative states characterized by persistent differences in structure, function, and capacity to provide ecosystem services valued by society. We examined empirical evidence for alternative states in a semiarid grassland ecosystem where topographic complexity and contrasting management regimes have led to spatial variations in levels of livestock grazing. Using an inventory data set, we found that plots (n = 72) cluster into three groups corresponding to generalized alternative states identified in an a priori conceptual model. One cluster (biocrust) is notable for high coverage of a biological soil crust functional group in addition to vascular plants. Another (grass-bare) lacks biological crust but retains perennial grasses at levels similar to the biocrust cluster. A third (annualized-bare) is dominated by invasive annual plants. Occurrence of grass-bare and annualized-bare conditions in areas where livestock have been excluded for over 30 years demonstrates the persistence of these states. Significant differences among all three clusters were found for percent bare ground, percent total live cover, and functional group richness. Using data for vegetation structure and soil erodibility, we also found large among-cluster differences in average levels of dust emissions predicted by a wind-erosion model. Predicted emissions were highest for the annualized-bare cluster and lowest for the biocrust cluster, which was characterized by zero or minimal emissions even under conditions of extreme wind. Results illustrate potential trade-offs among ecosystem services including livestock production, soil retention, carbon storage, and biodiversity conservation. Improved understanding of these trade-offs may assist ecosystem managers when evaluating alternative management strategies.

Investigation of spacial clustering of rare diseases: childhood malignancies in North Humberside.

PubMed

Alexander, F; Cartwright, R; McKinney, P A; Ricketts, T J

1990-03-01

The aims of the study were (1) to test for uniformity of distribution of childhood leukaemias and other malignancies; and (2) to consider the aetiological implications of unusual distributions. A test for spacial clustering was applied using a method which allows for unequal distribution of the population at risk and avoids using census data to provide population denominators. When clustering was identified, four possible aetiological links which had already been suggested to the Leukaemia Research Fund Centre were examined in a local area. The study was carried out in the Yorkshire Health Region in the north of England. 144 children under 15 years of age with a diagnosis of malignant disease known to the Yorkshire Regional Childhood Tumour Registry between 1974 and 1986 were included in the analysis. Of these 53 had leukaemias and nine had lymphomas. Significant localised clustering was found in North Humberside, though not in the whole of the Yorkshire Health Region. A number of clustered cases were identified, some of whom were in a post code sector, Hull 10, to the west of Kingston-upon-Hull, about which concern had been expressed since 1985. There was however no evidence that disease clustering was confined to this area. Four previously suggested hypotheses about causation in this particular area were examined but the results were negative or inconclusive. The identification of spacial clustering must be seen as only the first step in a series of investigations; it can only rarely lead to aetiological conclusions by itself, but it can motivate and target other investigations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacLeod, Morgan; Ramirez-Ruiz, Enrico; Trenti, Michele

When embedded in dense cluster cores, intermediate-mass black holes (IMBHs) acquire close stellar or stellar-remnant companions. These companions are not only gravitationally bound, but also tend to hierarchically isolate from other cluster stars through series of multibody encounters. In this paper we study the demographics of IMBH companions in compact star clusters through direct N-body simulations. We study clusters initially composed of 10{sup 5} or 2 × 10{sup 5} stars with IMBHs of 75 and 150 solar masses, and we follow their evolution for 6–10 Gyr. A tight, innermost binary pair of IMBH and stellar object rapidly forms. The IMBH has amore » companion with an orbital semimajor axis at least three times tighter than the second-most-bound object over 90% of the time. These companionships have typical periods on the order of years and are subject to cycles of exchange and destruction. The most frequently observed, long-lived pairings persist for ∼10{sup 7} years. The demographics of IMBH companions in clusters are diverse: they include both main-sequence, giant stars and stellar remnants. Companion objects may reveal the presence of an IMBH in a cluster in one of several ways. The most-bound companion stars routinely suffer grazing tidal interactions with the IMBH, offering a dynamical mechanism to produce repeated flaring episodes like those seen in the IMBH candidate HLX-1. The stellar winds of companion stars provide a minimum quiescent accretion rate for IMBHs, with implications for radio searches for IMBH accretion in globular clusters. Finally, gravitational wave inspirals of compact objects occur with promising frequency.« less

Hubble Frontier Fields: systematic errors in strong lensing models of galaxy clusters - implications for cosmography

NASA Astrophysics Data System (ADS)

Acebron, Ana; Jullo, Eric; Limousin, Marceau; Tilquin, André; Giocoli, Carlo; Jauzac, Mathilde; Mahler, Guillaume; Richard, Johan

2017-09-01

Strong gravitational lensing by galaxy clusters is a fundamental tool to study dark matter and constrain the geometry of the Universe. Recently, the Hubble Space Telescope Frontier Fields programme has allowed a significant improvement of mass and magnification measurements but lensing models still have a residual root mean square between 0.2 arcsec and few arcseconds, not yet completely understood. Systematic errors have to be better understood and treated in order to use strong lensing clusters as reliable cosmological probes. We have analysed two simulated Hubble-Frontier-Fields-like clusters from the Hubble Frontier Fields Comparison Challenge, Ares and Hera. We use several estimators (relative bias on magnification, density profiles, ellipticity and orientation) to quantify the goodness of our reconstructions by comparing our multiple models, optimized with the parametric software lenstool, with the input models. We have quantified the impact of systematic errors arising, first, from the choice of different density profiles and configurations and, secondly, from the availability of constraints (spectroscopic or photometric redshifts, redshift ranges of the background sources) in the parametric modelling of strong lensing galaxy clusters and therefore on the retrieval of cosmological parameters. We find that substructures in the outskirts have a significant impact on the position of the multiple images, yielding tighter cosmological contours. The need for wide-field imaging around massive clusters is thus reinforced. We show that competitive cosmological constraints can be obtained also with complex multimodal clusters and that photometric redshifts improve the constraints on cosmological parameters when considering a narrow range of (spectroscopic) redshifts for the sources.

The Close Stellar Companions to Intermediate-mass Black Holes

NASA Astrophysics Data System (ADS)

MacLeod, Morgan; Trenti, Michele; Ramirez-Ruiz, Enrico

2016-03-01

When embedded in dense cluster cores, intermediate-mass black holes (IMBHs) acquire close stellar or stellar-remnant companions. These companions are not only gravitationally bound, but also tend to hierarchically isolate from other cluster stars through series of multibody encounters. In this paper we study the demographics of IMBH companions in compact star clusters through direct N-body simulations. We study clusters initially composed of 105 or 2 × 105 stars with IMBHs of 75 and 150 solar masses, and we follow their evolution for 6-10 Gyr. A tight, innermost binary pair of IMBH and stellar object rapidly forms. The IMBH has a companion with an orbital semimajor axis at least three times tighter than the second-most-bound object over 90% of the time. These companionships have typical periods on the order of years and are subject to cycles of exchange and destruction. The most frequently observed, long-lived pairings persist for ˜107 years. The demographics of IMBH companions in clusters are diverse: they include both main-sequence, giant stars and stellar remnants. Companion objects may reveal the presence of an IMBH in a cluster in one of several ways. The most-bound companion stars routinely suffer grazing tidal interactions with the IMBH, offering a dynamical mechanism to produce repeated flaring episodes like those seen in the IMBH candidate HLX-1. The stellar winds of companion stars provide a minimum quiescent accretion rate for IMBHs, with implications for radio searches for IMBH accretion in globular clusters. Finally, gravitational wave inspirals of compact objects occur with promising frequency.

Identification of Anxiety Symptom Clusters in Patients with COPD: Implications for Assessment and Treatment.

PubMed

Breland, Jessica Y; Hundt, Natalie E; Barrera, Terri L; Mignogna, Joseph; Petersen, Nancy J; Stanley, Melinda A; Cully, Jeffery A

2015-10-01

Treatment of chronic obstructive pulmonary disease (COPD) is palliative, and quality of life is important. Increased understanding of correlates of quality of life and its domains could help clinicians and researchers better tailor COPD treatments and better support patients engaging in those treatments or other important self-management behaviors. Anxiety is common in those with COPD; however, overlap of physical and emotional symptoms complicates its assessment. The current study aimed to identify anxiety symptom clusters and to assess the association of these symptom clusters with COPD-related quality of life. Participants (N = 162) with COPD completed the Beck Anxiety Inventory (BAI), Chronic Respiratory Disease Questionnaire, Patient Health Questionnaire-9, and Medical Research Council dyspnea scale. Anxiety clusters were identified, using principal component analysis (PCA) on the BAI's 21 items. Anxiety clusters, along with factors previously associated with quality of life, were entered into a multiple regression designed to predict COPD-related quality of life. PCA identified four symptom clusters related to (1) general somatic distress, (2) fear, (3) nervousness, and (4) respiration-related distress. Multiple regression analyses indicated that greater fear was associated with less perceived mastery over COPD (β = -0.19, t(149) = -2.69, p < 0.01). Anxiety symptoms associated with fear appear to be an important indicator of anxiety in patients with COPD. In particular, fear was associated with perceptions of mastery, an important psychological construct linked to disease self-management. Assessing the BAI symptom cluster associated with fear (five items) may be a valuable rapid assessment tool to improve COPD treatment and physical health outcomes.

Dark matter, long-range forces, and large-scale structure

NASA Technical Reports Server (NTRS)

Gradwohl, Ben-Ami; Frieman, Joshua A.

1992-01-01

If the dark matter in galaxies and clusters is nonbaryonic, it can interact with additional long-range fields that are invisible to experimental tests of the equivalence principle. We discuss the astrophysical and cosmological implications of a long-range force coupled only to the dark matter and find rather tight constraints on its strength. If the force is repulsive (attractive), the masses of galaxy groups and clusters (and the mean density of the universe inferred from them) have been systematically underestimated (overestimated). We explore the consequent effects on the two-point correlation function, large-scale velocity flows, and microwave background anisotropies, for models with initial scale-invariant adiabatic perturbations and cold dark matter.

Viscerotropic disease following yellow fever vaccination in Peru.

PubMed

Whittembury, Alvaro; Ramirez, Gladys; Hernández, Herminio; Ropero, Alba Maria; Waterman, Steve; Ticona, María; Brinton, Margo; Uchuya, Jorge; Gershman, Mark; Toledo, Washington; Staples, Erin; Campos, Clarense; Martínez, Mario; Chang, Gwong-Jen J; Cabezas, Cesar; Lanciotti, Robert; Zaki, Sherif; Montgomery, Joel M; Monath, Thomas; Hayes, Edward

2009-10-09

Five suspected cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) clustered in space and time following a vaccination campaign in Ica, Peru in 2007. All five people received the same lot of 17DD live attenuated yellow fever vaccine before their illness; four of the five died of confirmed YEL-AVD. The surviving case was classified as probable YEL-AVD. Intensive investigation yielded no abnormalities of the implicated vaccine lot and no common risk factors. This is the first described space-time cluster of yellow fever viscerotropic disease involving more than two cases. Mass yellow fever vaccination should be avoided in areas that present extremely low risk of yellow fever.

Predicting Adolescents' Bullying Participation from Developmental Trajectories of Social Status and Behavior.

PubMed

Pouwels, J Loes; Salmivalli, Christina; Saarento, Silja; van den Berg, Yvonne H M; Lansu, Tessa A M; Cillessen, Antonius H N

2017-03-28

The aim of this study was to determine how trajectory clusters of social status (social preference and perceived popularity) and behavior (direct aggression and prosocial behavior) from age 9 to age 14 predicted adolescents' bullying participant roles at age 16 and 17 (n = 266). Clusters were identified with multivariate growth mixture modeling (GMM). The findings showed that participants' developmental trajectories of social status and social behavior across childhood and early adolescence predicted their bullying participant role involvement in adolescence. Practical implications and suggestions for further research are discussed. © 2017 The Authors. Child Development published by Wiley Periodicals, Inc. on behalf of Society for Research in Child Development.

Could the clinical interpretability of subgroups detected using clustering methods be improved by using a novel two-stage approach?

PubMed

Kent, Peter; Stochkendahl, Mette Jensen; Christensen, Henrik Wulff; Kongsted, Alice

2015-01-01

Recognition of homogeneous subgroups of patients can usefully improve prediction of their outcomes and the targeting of treatment. There are a number of research approaches that have been used to recognise homogeneity in such subgroups and to test their implications. One approach is to use statistical clustering techniques, such as Cluster Analysis or Latent Class Analysis, to detect latent relationships between patient characteristics. Influential patient characteristics can come from diverse domains of health, such as pain, activity limitation, physical impairment, social role participation, psychological factors, biomarkers and imaging. However, such 'whole person' research may result in data-driven subgroups that are complex, difficult to interpret and challenging to recognise clinically. This paper describes a novel approach to applying statistical clustering techniques that may improve the clinical interpretability of derived subgroups and reduce sample size requirements. This approach involves clustering in two sequential stages. The first stage involves clustering within health domains and therefore requires creating as many clustering models as there are health domains in the available data. This first stage produces scoring patterns within each domain. The second stage involves clustering using the scoring patterns from each health domain (from the first stage) to identify subgroups across all domains. We illustrate this using chest pain data from the baseline presentation of 580 patients. The new two-stage clustering resulted in two subgroups that approximated the classic textbook descriptions of musculoskeletal chest pain and atypical angina chest pain. The traditional single-stage clustering resulted in five clusters that were also clinically recognisable but displayed less distinct differences. In this paper, a new approach to using clustering techniques to identify clinically useful subgroups of patients is suggested. Research designs, statistical methods and outcome metrics suitable for performing that testing are also described. This approach has potential benefits but requires broad testing, in multiple patient samples, to determine its clinical value. The usefulness of the approach is likely to be context-specific, depending on the characteristics of the available data and the research question being asked of it.

Oldest Known Objects May Be Surprisingly Immature

NASA Astrophysics Data System (ADS)

2008-04-01

Some of the oldest objects in the Universe may still have a long way to go, according to a new study using NASA’s Chandra X-ray Observatory. These new results indicate that globular clusters might be surprisingly less mature in their development than previously thought. Globular clusters, dense bunches of up to millions of stars found in all galaxies, are among the oldest known objects in the Universe, with most estimates of their ages ranging from 9 to 13 billions of years old. As such they contain some of the first stars to form in a galaxy and understanding their evolution is critical to understanding the evolution of galaxies. Animation The Evolution of a Globular Cluster "For many years, globular clusters have been used as wonderful natural laboratories to study the evolution and interaction of stars," said John Fregeau of Northwestern University, who conducted the study. "So, it’s exciting to discover something that may be new and fundamental about the way they evolve." Conventional wisdom is that globular clusters pass through three phases of evolution or development of their structure, corresponding to adolescence, middle age, and old age. These "ages" refer to the evolutionary state of the cluster, not the physical ages of the individual stars. People Who Read This Also Read... Milky Way's Super-efficient Particle Accelerators Caught in The Act Discovery of Most Recent Supernova in Our Galaxy Action Replay of Powerful Stellar Explosion Jet Power and Black Hole Assortment Revealed in New Chandra Image In the adolescent phase, the stars near the center of the cluster collapse inward. Middle age refers to a phase when the interactions of double stars near the center of the cluster prevents it from further collapse. Finally, old age describes when binaries in the center of the cluster are disrupted or ejected, and the center of the cluster collapses inwards. For years, it has been thought that most globular clusters are middle- aged with a few being toward the end of their evolution. However, Chandra data along with theoretical work suggest this may not be the case. When single and double stars interact in the crowded centers of globular clusters, double stars can form that transfer mass and give off X-rays. Since such double stars are expected to mostly be formed in the middle of a globular cluster’s evolution and then lost in old age, the relative number of X-ray sources gives clues about the stage of evolution the cluster is in. A new study by Fregeau of 13 globular clusters in the Milky Way shows that three of them have unusually large number of X-ray sources, or X- ray binaries, suggesting the clusters are middle-aged. Previously, these globular clusters had been classified as being in old age because they had very tight concentrations of stars in their centers, another litmus test of age used by astronomers. The implication is that most globular clusters, including the other ten studied by Fregeau, are not in the middle age of their evolution, as previously thought, but are actually in adolescence. "It’s remarkable that these objects, which are thought to be some of the oldest in the Universe, may really be very immature in their development," said Fregeau whose paper appears in The Astrophysical Journal. "This would represent a major change in thinking about the current evolutionary status of globular clusters." If confirmed, this result would help reconcile other observations with recent theoretical work that suggest the tightness of the central concentration of stars in the most evolved globular clusters is consistent with them being in a middle, rather than an advanced phase of evolution. Other theoretical studies have suggested it can take longer than the current age of the Universe for globular clusters to reach old age. Besides improving the understanding of the basic evolution of globular clusters, this result has implications for understanding stellar interactions in dense environments. It also removes the need for exotic mechanisms - some involving black holes - that were thought to be needed to prevent the many middle-aged clusters from collapsing. "Some exotic scenarios, including some of my own, have been invoked to try to make sense of the observations and save the old theory," said Fregeau. "If this result holds up, we don't have to worry about the exotic scenarios any more." NASA's Marshall Space Flight Center, Huntsville, Ala., manages the Chandra program for the agency’s Science Mission Directorate. The Smithsonian Astrophysical Observatory controls science and flight operations from the Chandra X-ray Center in Cambridge, Mass.

[Occurrence of genotypes of porcine circovirus (PCV2) in pig farms using different vaccination strategies against PCV2].

PubMed

Eddicks, Matthias; Szikora, Florian; Walhöfer, Nils; Sauter Louis, Carola; Reese, Sven; Banholzer, Elisabeth; Reiner, Gerald; Sutter, Gerd; Ritzmann, Mathias; Fux, Robert

2017-04-19

Since 2004/2005 a worldwide shift of the detection rate of porcine circovirus (PCV) has been observed from PCV2a towards PCV2b. Currently commercially available vaccines are based on genotype PCV2a. The study was conducted as a pilot study to evaluate the occurrence of PCV2a and PCV2b in farms with different vaccination strategies against PCV2. For this purpose a total of 405 piglets originating from nine farms (three farms with sow vaccination [SI], piglet vaccination [FI] and no vaccination [NI] against PCV2, respectively) were enrolled and followed from day 3 of life until slaughter. Serum of the piglets was examined for PCV2-DNA by quantitative PCR, genotype differentiating duplex PCR, and after sequencing of the total genome, PCV2 isolates were phylogenetically assigned. The evaluation included the data from 383 animals. In eight farms PCV2 could be detected (1x PCV2a; 6x PCV2b; 1x PCV2a and PCV2b). PCV2b was found in SI-, NI- and FI-farms, whereas PCV2a was only detected in SI- and NI-farms. A proportion of 55.4% was PCV2-positive at least once during the entire study period (FI: 7.8%, SI: 65.4%, NI: 93.7%). Of these samples 4.7% were PCV2a-, 92.2% PCV2b- and 2.4% PCV2a- and PCV2b-positive. The mean content of PCV2-DNA in the serum of PCV2b positive animals was significantly higher than from PCV2a positive animals. PCV2 isolates were identified as PCV2b-1A (5/9 farms), PCV2b-1B (1/9 farms) und PCV2a-2D (2/9 farms). The increased detection rate of PCV2b in comparison to PCV2a could be confirmed. The present study gives hint that the vaccination of piglets using PCV2a-based vaccines may lead to a further shift of the detection rate from PCV2a to PCV2b. To assess the clinical relevance of this observation, extensive comparative studies should be taken into account, which also evaluate the efficacy of PCV2a-based vaccines in PCV2a- and PCV2b-positive farms.

Size and clustering of ethnic groups and rates of psychiatric admission in England.

PubMed

Venkatesan, Gayathri; Weich, Scott; McBride, Orla; Twigg, Liz; Parsons, Helen; Scott, Jan; Bhui, Kamaldeep; Keown, Patrick

2018-05-11

Aims and methodTo compare rates of admission for different types of severe mental illness between ethnic groups, and to test the hypothesis that larger and more clustered ethnic groups will have lower admission rates. This was a descriptive study of routinely collected data from the National Health Service in England. There was an eightfold difference in admission rates between ethnic groups for schizophreniform and mania admissions, and a fivefold variation in depression admissions. On average, Black and minority ethnic (BME) groups had higher rates of admission for schizophreniform and mania admissions but not for depression. This increased rate was greatest in the teenage years and early adulthood. Larger ethnic group size was associated with lower admission rates. However, greater clustering was associated with higher admission rates.Clinical implicationsOur findings support the hypothesis that larger ethnic groups have lower rates of admission. This was a between-group comparison rather than within each group. Our findings do not support the hypothesis that more clustered groups have lower rates of admission. In fact, they suggest the opposite: groups with low clustering had lower admission rates. The BME population in the UK is increasing in size and becoming less clustered. Our results suggest that both of these factors should ameliorate the overrepresentation of BME groups among psychiatric in-patients. However, this overrepresentation continues, and our results suggest a possible explanation, namely, changes in the delivery of mental health services, particularly the marked reduction in admissions for depression.Declaration of interestNone.

Early Environment and Neurobehavioral Development Predict Adult Temperament Clusters

PubMed Central

Congdon, Eliza; Service, Susan; Wessman, Jaana; Seppänen, Jouni K.; Schönauer, Stefan; Miettunen, Jouko; Turunen, Hannu; Koiranen, Markku; Joukamaa, Matti; Järvelin, Marjo-Riitta; Veijola, Juha; Mannila, Heikki; Paunio, Tiina; Freimer, Nelson B.

2012-01-01

Background Investigation of the environmental influences on human behavioral phenotypes is important for our understanding of the causation of psychiatric disorders. However, there are complexities associated with the assessment of environmental influences on behavior. Methods/Principal Findings We conducted a series of analyses using a prospective, longitudinal study of a nationally representative birth cohort from Finland (the Northern Finland 1966 Birth Cohort). Participants included a total of 3,761 male and female cohort members who were living in Finland at the age of 16 years and who had complete temperament scores. Our initial analyses (Wessman et al., in press) provide evidence in support of four stable and robust temperament clusters. Using these temperament clusters, as well as independent temperament dimensions for comparison, we conducted a data-driven analysis to assess the influence of a broad set of life course measures, assessed pre-natally, in infancy, and during adolescence, on adult temperament. Results Measures of early environment, neurobehavioral development, and adolescent behavior significantly predict adult temperament, classified by both cluster membership and temperament dimensions. Specifically, our results suggest that a relatively consistent set of life course measures are associated with adult temperament profiles, including maternal education, characteristics of the family’s location and residence, adolescent academic performance, and adolescent smoking. Conclusions Our finding that a consistent set of life course measures predict temperament clusters indicate that these clusters represent distinct developmental temperament trajectories and that information about a subset of life course measures has implications for adult health outcomes. PMID:22815688

Comparing Dark Energy Survey and HST –CLASH observations of the galaxy cluster RXC J2248.7-4431: implications for stellar mass versus dark matter

DOE PAGES

Palmese, A.; Lahav, O.; Banerji, M.; ...

2016-08-20

We derive the stellar mass fraction in the galaxy cluster RXC J2248.7-4431 observed with the Dark Energy Survey (DES) during the Science Verification period. We compare the stellar mass results from DES (5 filters) with those from the Hubble Space Telescope CLASH (17 filters). When the cluster spectroscopic redshift is assumed, we show that stellar masses from DES can be estimated within 25% of CLASH values. We compute the stellar mass contribution coming from red and blue galaxies, and study the relation between stellar mass and the underlying dark matter using weak lensing studies with DES and CLASH. An analysismore » of the radial profiles of the DES total and stellar mass yields a stellar-to-total fraction of f*=7.0+-2.2x10^-3 within a radius of r_200c~3 Mpc. Our analysis also includes a comparison of photometric redshifts and star/galaxy separation efficiency for both datasets. We conclude that space-based small field imaging can be used to calibrate the galaxy properties in DES for the much wider field of view. The technique developed to derive the stellar mass fraction in galaxy clusters can be applied to the ~100 000 clusters that will be observed within this survey. The stacking of all the DES clusters would reduce the errors on f* estimates and deduce important information about galaxy evolution.« less

The impact of collaborations between universities and private organizations on cluster development and competitiveness in Romania

NASA Astrophysics Data System (ADS)

Stoicovici, D.; Bănică, M.; Ungureanu, M.; Stoicovici, M.

2017-05-01

While the European Union has put a lot of emphasis on cluster development due to their inherent advantages such as lower transaction costs, technological transfer and regional development, little is known about how clusters emerge and what can facilitate their competitiveness. This paper aims to study the impact of public-private cooperation between universities and organizations on cluster development and competitiveness. A literature review is employed to develop the model while 4 qualitative case studies provide the initial test of its validity. The analysis suggests that cooperating with research institutions impacts cluster development first through education of industrial staff, but also by developing innovation processes through the facilitation of the appearance of innovative ideas and also of knowledge sharing among organizations. The research has several implications both for organizations and for government officials. First of all, R&D and top management should actively seek to cooperate with research institutions both for training of their staff but also in seeking new ideas and as a way of collaborating with other organizations within the field without fear of losing competitive advantage. Second, government officials should try to create more incentives both for organizations (through for example tax returns) and for universities (extra funding or salary incentives) that can increase collaboration between these actors. This paper is the first one to asses empirically how cooperation with research institutions affect cluster competitiveness and development, especially within the developing region of Eastern Europe, Romania.

A scan statistic to extract causal gene clusters from case-control genome-wide rare CNV data.

PubMed

Nishiyama, Takeshi; Takahashi, Kunihiko; Tango, Toshiro; Pinto, Dalila; Scherer, Stephen W; Takami, Satoshi; Kishino, Hirohisa

2011-05-26

Several statistical tests have been developed for analyzing genome-wide association data by incorporating gene pathway information in terms of gene sets. Using these methods, hundreds of gene sets are typically tested, and the tested gene sets often overlap. This overlapping greatly increases the probability of generating false positives, and the results obtained are difficult to interpret, particularly when many gene sets show statistical significance. We propose a flexible statistical framework to circumvent these problems. Inspired by spatial scan statistics for detecting clustering of disease occurrence in the field of epidemiology, we developed a scan statistic to extract disease-associated gene clusters from a whole gene pathway. Extracting one or a few significant gene clusters from a global pathway limits the overall false positive probability, which results in increased statistical power, and facilitates the interpretation of test results. In the present study, we applied our method to genome-wide association data for rare copy-number variations, which have been strongly implicated in common diseases. Application of our method to a simulated dataset demonstrated the high accuracy of this method in detecting disease-associated gene clusters in a whole gene pathway. The scan statistic approach proposed here shows a high level of accuracy in detecting gene clusters in a whole gene pathway. This study has provided a sound statistical framework for analyzing genome-wide rare CNV data by incorporating topological information on the gene pathway.

Galaxy Cluster IDCS J1426

NASA Image and Video Library

2016-01-07

Astronomers have made the most detailed study yet of an extremely massive young galaxy cluster using three of NASA's Great Observatories. This multi-wavelength image shows this galaxy cluster, called IDCS J1426.5+3508 (IDCS 1426 for short), in X-rays recorded by the Chandra X-ray Observatory in blue, visible light observed by the Hubble Space Telescope in green, and infrared light detected by the Spitzer Space Telescope in red. This rare galaxy cluster, which is located 10 billion light-years from Earth, is almost as massive as 500 trillion suns. This object has important implications for understanding how such megastructures formed and evolved early in the universe. The light astronomers observed from IDCS 1426 began its journey to Earth when the universe was less than a third of its current age. It is the most massive galaxy cluster detected at such an early time. First discovered by the Spitzer Space Telescope in 2012, IDCS 1426 was then observed using the Hubble Space Telescope and the Keck Observatory to determine its distance. Observations from the Combined Array for Millimeter-wave Astronomy indicated it was extremely massive. New data from the Chandra X-ray Observatory confirm the galaxy cluster's mass and show that about 90 percent of this mass is in the form of dark matter -- the mysterious substance that has so far been detected only through its gravitational pull on normal matter composed of atoms. http://photojournal.jpl.nasa.gov/catalog/PIA20063

Comparing Dark Energy Survey and HST-CLASH observations of the galaxy cluster RXC J2248.7-4431: implications for stellar mass versus dark matter

NASA Astrophysics Data System (ADS)

Palmese, A.; Lahav, O.; Banerji, M.; Gruen, D.; Jouvel, S.; Melchior, P.; Aleksić, J.; Annis, J.; Diehl, H. T.; Hartley, W. G.; Jeltema, T.; Romer, A. K.; Rozo, E.; Rykoff, E. S.; Seitz, S.; Suchyta, E.; Zhang, Y.; Abbott, T. M. C.; Abdalla, F. B.; Allam, S.; Benoit-Lévy, A.; Bertin, E.; Brooks, D.; Buckley-Geer, E.; Burke, D. L.; Capozzi, D.; Carnero Rosell, A.; Carrasco Kind, M.; Carretero, J.; Crocce, M.; Cunha, C. E.; D'Andrea, C. B.; da Costa, L. N.; Desai, S.; Dietrich, J. P.; Doel, P.; Estrada, J.; Evrard, A. E.; Flaugher, B.; Frieman, J.; Gerdes, D. W.; Goldstein, D. A.; Gruendl, R. A.; Gutierrez, G.; Honscheid, K.; James, D. J.; Kuehn, K.; Kuropatkin, N.; Li, T. S.; Lima, M.; Maia, M. A. G.; Marshall, J. L.; Miller, C. J.; Miquel, R.; Nord, B.; Ogando, R.; Plazas, A. A.; Roodman, A.; Sanchez, E.; Scarpine, V.; Sevilla-Noarbe, I.; Smith, R. C.; Soares-Santos, M.; Sobreira, F.; Swanson, M. E. C.; Tarle, G.; Thomas, D.; Tucker, D.; Vikram, V.

2016-12-01

We derive the stellar mass fraction in the galaxy cluster RXC J2248.7-4431 observed with the Dark Energy Survey (DES) during the Science Verification period. We compare the stellar mass results from DES (five filters) with those from the Hubble Space Telescope Cluster Lensing And Supernova Survey (CLASH; 17 filters). When the cluster spectroscopic redshift is assumed, we show that stellar masses from DES can be estimated within 25 per cent of CLASH values. We compute the stellar mass contribution coming from red and blue galaxies, and study the relation between stellar mass and the underlying dark matter using weak lensing studies with DES and CLASH. An analysis of the radial profiles of the DES total and stellar mass yields a stellar-to-total fraction of f⋆ = (6.8 ± 1.7) × 10-3 within a radius of r200c ≃ 2 Mpc. Our analysis also includes a comparison of photometric redshifts and star/galaxy separation efficiency for both data sets. We conclude that space-based small field imaging can be used to calibrate the galaxy properties in DES for the much wider field of view. The technique developed to derive the stellar mass fraction in galaxy clusters can be applied to the ˜100 000 clusters that will be observed within this survey and yield important information about galaxy evolution.

Comparing Dark Energy Survey and HST –CLASH observations of the galaxy cluster RXC J2248.7-4431: implications for stellar mass versus dark matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palmese, A.; Lahav, O.; Banerji, M.

We derive the stellar mass fraction in the galaxy cluster RXC J2248.7-4431 observed with the Dark Energy Survey (DES) during the Science Verification period. We compare the stellar mass results from DES (5 filters) with those from the Hubble Space Telescope CLASH (17 filters). When the cluster spectroscopic redshift is assumed, we show that stellar masses from DES can be estimated within 25% of CLASH values. We compute the stellar mass contribution coming from red and blue galaxies, and study the relation between stellar mass and the underlying dark matter using weak lensing studies with DES and CLASH. An analysismore » of the radial profiles of the DES total and stellar mass yields a stellar-to-total fraction of f*=7.0+-2.2x10^-3 within a radius of r_200c~3 Mpc. Our analysis also includes a comparison of photometric redshifts and star/galaxy separation efficiency for both datasets. We conclude that space-based small field imaging can be used to calibrate the galaxy properties in DES for the much wider field of view. The technique developed to derive the stellar mass fraction in galaxy clusters can be applied to the ~100 000 clusters that will be observed within this survey. The stacking of all the DES clusters would reduce the errors on f* estimates and deduce important information about galaxy evolution.« less

Comparing Dark Energy Survey and HST –CLASH observations of the galaxy cluster RXC J2248.7-4431: implications for stellar mass versus dark matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palmese, A.; Lahav, O.; Banerji, M.

We derive the stellar mass fraction in the galaxy cluster RXC J2248.7-4431 observed with the Dark Energy Survey (DES) during the Science Verification period. We compare the stellar mass results from DES (five filters) with those from the Hubble Space Telescope Cluster Lensing And Supernova Survey (CLASH; 17 filters). When the cluster spectroscopic redshift is assumed, we show that stellar masses from DES can be estimated within 25 per cent of CLASH values. We compute the stellar mass contribution coming from red and blue galaxies, and study the relation between stellar mass and the underlying dark matter using weak lensingmore » studies with DES and CLASH. An analysis of the radial profiles of the DES total and stellar mass yields a stellar-to-total fraction of f(star) = (6.8 +/- 1.7) x 10(-3) within a radius of r(200c) similar or equal to 2 Mpc. Our analysis also includes a comparison of photometric redshifts and star/galaxy separation efficiency for both data sets. We conclude that space-based small field imaging can be used to calibrate the galaxy properties in DES for the much wider field of view. The technique developed to derive the stellar mass fraction in galaxy clusters can be applied to the similar to 100 000 clusters that will be observed within this survey and yield important information about galaxy evolution.« less

Sibling relationship patterns and their associations with child competence and problem behavior.

PubMed

Buist, Kirsten L; Vermande, Marjolijn

2014-08-01

The present study is the first to examine patterns in sibling relationship quality and the associations of these patterns with internalizing and externalizing problem behavior, as well as self-perceived competence, in middle childhood. Self-report questionnaires (e.g., Sibling Relationship Questionnaire, Self-Perception Profile for Children, Youth Self Report) were administered among 1,670 Dutch children (Mage = 11.40 years, SD = .83) attending 51 different Dutch schools. Three sibling relationship clusters were found: a conflictual cluster (low on warmth, high on conflict), an affect-intense cluster (above average on warmth and conflict), and a harmonious cluster (high on warmth, low on conflict). Sister pairs were underrepresented in the conflictual cluster and overrepresented in the harmonious cluster. Children with conflictual sibling relationships reported significantly more internalizing and externalizing problems, and lower academic and social competence and global self-worth, than children with harmonious sibling relationships. Children with affect-intense sibling relationships reported less aggression and better social competence than children with conflictual sibling relationships. Our findings indicate that it is fruitful to combine indices of sibling warmth and conflict to examine sibling relationship types. Relationship types differed significantly concerning internalizing and externalizing problems, but also concerning self-perceived competence. These findings extend our knowledge about sibling relationship types and their impact on different aspects of child adjustment. Whereas harmonious sibling relationships are the most beneficial for adjustment, sibling conflict mainly has a negative effect on adjustment in combination with lack of sibling warmth. Implications and future directions are discussed.

Intensive management affects composition of betaproteobacterial ammonia oxidizers in turfgrass systems.

PubMed

Dell, Emily A; Bowman, Daniel; Rufty, Thomas; Shi, Wei

2008-07-01

Turfgrass is a highly managed ecosystem subject to frequent fertilization, mowing, irrigation, and application of pesticides. Turf management practices may create a perturbed environment for ammonia oxidizers, a key microbial group responsible for nitrification. To elucidate the long-term effects of turf management on these bacteria, we assessed the composition of betaproteobacterial ammonia oxidizers in a chronosequence of turfgrass systems (i.e., 1, 6, 23, and 95 years old) and the adjacent native pines by using both 16S rRNA and amoA gene fragments specific to ammonia oxidizers. Based on the Shannon-Wiener diversity index of denaturing gradient gel electrophoresis patterns and the rarefaction curves of amoA clones, turf management did not change the relative diversity and richness of ammonia oxidizers in turf soils as compared to native pine soils. Ammonia oxidizers in turfgrass systems comprised a suite of phylogenetic clusters common to other terrestrial ecosystems. Nitrosospira clusters 0, 2, 3, and 4; Nitrosospira sp. Nsp65-like sequences; and Nitrosomonas clusters 6 and 7 were detected in the turfgrass chronosequence with Nitrosospira clusters 3 and 4 being dominant. However, both turf age and land change (pine to turf) effected minor changes in ammonia oxidizer composition. Nitrosospira cluster 0 was observed only in older turfgrass systems (i.e., 23 and 95 years old); fine-scale differences within Nitrosospira cluster 3 were seen between native pines and turf. Further investigations are needed to elucidate the ecological implications of the compositional differences.

Broadband pulsations from PSR B1821–24: Implications for emission models and the pulsar population of M28

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, T. J.; Guillemot, L.; Freire, P. C. C.

2013-12-01

We report a 5.4σ detection of pulsed gamma rays from PSR B1821–24 in the globular cluster M28 using ∼44 months of Fermi Large Area Telescope (LAT) data that have been reprocessed with improved instrument calibration constants. We constructed a phase-coherent ephemeris, with post-fit residual rms of 3 μs, using radio data spanning ∼23.2 yr, enabling measurements of the multi-wavelength light-curve properties of PSR B1821–24 at the milliperiod level. We fold RXTE observations of PSR B1821–24 from 1996 to 2007 and discuss implications on the emission zones. The gamma-ray light curve consists of two peaks separated by 0.41 ± 0.02 inmore » phase, with the first gamma-ray peak lagging behind the first radio peak by 0.05 ± 0.02 in phase, consistent with the phase of giant radio pulses. We observe significant emission in the off-peak interval of PSR B1821–24 with a best-fit LAT position inconsistent with the core of M28. We do not detect significant gamma-ray pulsations at the spin or orbital periods from any other known pulsar in M28, and we place limits on the number of energetic pulsars in the cluster. The derived gamma-ray efficiency, ∼2%, is typical of other gamma-ray pulsars with comparable spin-down power, suggesting that the measured spin-down rate (2.2 × 10{sup 36} erg s{sup –1}) is not appreciably distorted by acceleration in the cluster potential. This confirms PSR B1821–24 as the second very energetic millisecond pulsar in a globular cluster and raises the question of whether these represent a separate class of objects that only form in regions of very high stellar density.« less

Broadband pulsations from PSR B1821-24: Implications for emission models and the pulsar population of M28

DOE PAGES

Johnson, Tyrel J.; Guillemot, L.; Kerr, M.; ...

2013-11-11

Here, we report a 5.4σ detection of pulsed gamma rays from PSR B1821–24 in the globular cluster M28 using ~44 months of Fermi Large Area Telescope (LAT) data that have been reprocessed with improved instrument calibration constants. We constructed a phase-coherent ephemeris, with post-fit residual rms of 3 μs, using radio data spanning ~23.2 yr, enabling measurements of the multi-wavelength light-curve properties of PSR B1821–24 at the milliperiod level. We fold RXTE observations of PSR B1821–24 from 1996 to 2007 and discuss implications on the emission zones. The gamma-ray light curve consists of two peaks separated by 0.41 ± 0.02more » in phase, with the first gamma-ray peak lagging behind the first radio peak by 0.05 ± 0.02 in phase, consistent with the phase of giant radio pulses. We observe significant emission in the off-peak interval of PSR B1821–24 with a best-fit LAT position inconsistent with the core of M28. We do not detect significant gamma-ray pulsations at the spin or orbital periods from any other known pulsar in M28, and we place limits on the number of energetic pulsars in the cluster. The derived gamma-ray efficiency, ~2%, is typical of other gamma-ray pulsars with comparable spin-down power, suggesting that the measured spin-down rate (2.2 × 10 36 erg s –1) is not appreciably distorted by acceleration in the cluster potential. This confirms PSR B1821–24 as the second very energetic millisecond pulsar in a globular cluster and raises the question of whether these represent a separate class of objects that only form in regions of very high stellar density.« less

Packing a pinch: functional implications of chela shapes in scorpions using finite element analysis

PubMed Central

van der Meijden, Arie; Kleinteich, Thomas; Coelho, Pedro

2012-01-01

Scorpions depend on their pedipalps for prey capture, defense, mating and sensing their environment. Some species additionally use their pedipalps for burrowing or climbing. Because the pincers or chelae at the end of the pedipalps vary widely in shape, they have been used as part of a suite of characters to delimit ecomorphotypes. We here evaluate the influence of the different chela cuticular shapes on their performance under natural loading conditions. Chelae of 20 species, representing seven families and spanning most of the range of chela morphologies, were assigned to clusters based on chela shape parameters using hierarchical cluster analysis. Several clusters were identified corresponding approximately to described scorpion ecomorphotypes. Finite element models of the chela cuticulae were constructed from CT scans and loaded with estimated pinch forces based on in vivo force measurements. Chela shape clusters differed significantly in mean Von Mises stress and strain energy. Normalized FEA showed that chela shape significantly influenced Von Mises stress and strain energy in the chela cuticula, with Von Mises stress varying up to an order of magnitude and strain energy up to two orders of magnitude. More elongate, high-aspect ratio chela forms showed significantly higher mean stress compared with more robust low-aspect ratio forms. This suggests that elongate chelae are at a higher risk of failure when operating near the maximum pinch force. Phylogenetic independent contrasts (PIC) were calculated based on a partly resolved phylogram with branch lengths based on an alignment of the 12S, 16S and CO1 mitochondrial genes. PIC showed that cuticular stress and strain in the chela were correlated with several shape parameters, such as aspect ratio, movable finger length, and chela height, independently of phylogenetic history. Our results indicate that slender chela morphologies may be less suitable for high-force functions such as burrowing and defense. Further implications of these findings for the ecology and evolution of the different chela morphologies are discussed. PMID:22360433

miR-17-92 Cluster Promotes Cholangiocarcinoma Growth

PubMed Central

Zhu, Hanqing; Han, Chang; Lu, Dongdong; Wu, Tong

2015-01-01

miR-17-92 is an oncogenic miRNA cluster implicated in the development of several cancers; however, it remains unknown whether the miR-17-92 cluster is able to regulate cholangiocarcinogenesis. This study was designed to investigate the biological functions and molecular mechanisms of the miR-17-92 cluster in cholangiocarcinoma. In situ hybridization and quantitative RT-PCR analysis showed that the miR-17-92 cluster is highly expressed in human cholangiocarcinoma cells compared with the nonneoplastic biliary epithelial cells. Forced overexpression of the miR-17-92 cluster or its members, miR-92a and miR-19a, in cultured human cholangiocarcinoma cells enhanced tumor cell proliferation, colony formation, and invasiveness, in vitro. Overexpression of the miR-17-92 cluster or miR-92a also enhanced cholangiocarcinoma growth in vivo in hairless outbred mice with severe combined immunodeficiency (SHO-PrkdcscidHrhr). The tumor-suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), was identified as a bona fide target of both miR-92a and miR-19a in cholangiocarcinoma cells via sequence prediction, 3′ untranslated region luciferase activity assay, and Western blot analysis. Accordingly, overexpression of the PTEN open reading frame protein (devoid of 3′ untranslated region) prevented miR-92a– or miR-19a–induced cholangiocarcinoma cell growth. Microarray analysis revealed additional targets of the miR-17-92 cluster in human cholangiocarcinoma cells, including APAF-1 and PRDM2. Moreover, we observed that the expression of the miR-17-92 cluster is regulated by IL-6/Stat3, a key oncogenic signaling pathway pivotal in cholangiocarcinogenesis. Taken together, our findings disclose a novel IL-6/Stat3–miR-17-92 cluster–PTEN signaling axis that is crucial for cholangiocarcinogenesis and tumor progression. PMID:25239565

Laboratory Study of Air Turbulence-Particle Coupling

NASA Astrophysics Data System (ADS)

Petersen, A.; Baker, L.; Coletti, F.

2017-12-01

Inertial particles suspended in a turbulent flow are unable to follow the fluid's rapid velocity fluctuations, leading to high concentrations in regions where fluid strain dominates vorticity. This phenomenon is known as preferential concentration or clustering and is thought to affect natural processes ranging from the collisional growth of raindrops to the formation of planetesimals in proto-planetary nebulas. In the present study, we use a large jet-stirred chamber to generate homogeneous air turbulence into which we drop particles with an aerodynamic response time comparable to the flow time scales. Using laser imaging we find that turbulence can lead to a multi-fold increase of settling velocity compared to still-air conditions. We then employ Voronoi tessellation to examine the particle spatial distribution, finding strong evidence of turbulence-driven particle clustering over a wide range of experimental conditions. We observe individual clusters of a larger size range than seen previously, sometimes beyond the integral length scale of the turbulence. We also investigate cluster topology and find that they (i) exhibit a fractal structure, (ii) have a nearly constant particle concentration over their entire size range, and (iii) are most often vertically oriented. Furthermore, clustered particles tend to fall faster than those outside clusters, and larger clusters fall faster on average than smaller ones. Finally, by simultaneous measurement of particle and air velocity fields, we provide the first experimental evidence of preferential sweeping, a mechanism previously proposed to explain the increase in particle settling velocity found in numerical simulations, and find it especially effective for clustered particles. These results are significant for the micro-scale physics of atmospheric clouds. The large cluster size range has implications for how droplets will influence the local environment through condensation, evaporation, drag and latent heat effects. Our results also suggest that large collections of droplets will interact due to differential settling, possibly enhancing raindrop formation.

CTCF Occupation of the Herpes Simplex Virus 1 Genome Is Disrupted at Early Times Postreactivation in a Transcription-Dependent Manner

PubMed Central

Ertel, Monica K.; Cammarata, Amy L.; Hron, Rebecca J.

2012-01-01

In herpes simplex virus 1 (HSV-1), binding clusters enriched in CTCF during latency have been previously identified. We hypothesized that CTCF binding to CTCF clusters in HSV-1 would be disrupted in a reactivation event. To investigate, CTCF occupation of three CTCF binding clusters in HSV-1 was analyzed following sodium butyrate (NaB)- and explant-induced reactivation in the mouse. Our data show that the CTCF domains positioned within the HSV-1 genome, specifically around the latency-associated transcript (LAT) and ICP0 and ICP4 regions of the genome, lose CTCF occupancy following the application of reactivation stimuli in wild-type virus. We also found that CTCF binding clusters upstream of the ICP0 and ICP4 promoters both function as classical insulators capable of acting as enhancer blockers of the LAT enhancer. Finally, our results suggest that CTCF occupation of domains in HSV-1 may be differentially regulated both during latency and at early times following reactivation by the presence of lytic transcripts and further implicate epigenetic regulation of HSV-1 as a critical component of the latency-reactivation transition. PMID:22973047

Cluster formation in liverwort-associated methylobacteria and its implications.

PubMed

Kutschera, U; Thomas, J; Hornschuh, M

2007-08-01

Pink-pigmented methylotropic bacteria of the genus Methylobacterium inhabit the surfaces of plant organs. In bryophytes, these methylobacteria enhance cell growth, but the nature of this plant-microbe interaction is largely unknown. In this study, methylobacteria were isolated from the upper surface of the free-living thalli of the liverwort Marchantia polymorpha L. Identification of one strain by 16S ribosomal RNA (rRNA) gene-targeted polymerase chain reaction (PCR) and other data show that these microbes represent an undescribed species of the genus Methylobacterium (Methylobacterium sp.). The growth-promoting activity of these wild-type methylobacteria was tested and compared with that of the type strain Methylobacterium mesophilicum. Both types of methylobacteria stimulated surface expansion of isolated gemmae from Marchantia polymorpha by about 350%. When suspended in water, the liverwort-associated bacteria (Methylobacterium sp.) formed dense clusters of up to 600 cells. In liquid cultures of Methylobacterium mesophilicum, single cells were observed, but no clustering occurred. We suggest that the liverwort-associated methylobacteria are co-evolved symbionts of the plants: Cluster formation may be a behavior that enhances the survival of the epiphytic microbes during periods of drought of these desiccation-tolerant lower plants.

Fingerprints of resistant Escherichia coli O157:H7 from vegetables and environmental samples.

PubMed

Abakpa, Grace Onyukwo; Umoh, Veronica J; Kamaruzaman, Sijam; Ibekwe, Mark

2018-01-01

Some routes of transmission of Escherichia coli O157:H7 to fresh produce include contaminated irrigation water and manure polluted soils. The aim of the present study was to determine the genetic relationships of E. coli O157:H7 isolated from some produce growing region in Nigeria using enterobacterial repetitive intergenic consensus (ERIC) DNA fingerprinting analysis. A total of 440 samples comprising leafy greens, irrigation water, manure and soil were obtained from vegetable producing regions in Kano and Plateau States, Nigeria. Genes coding for the quinolone resistance-determinant (gyrA) and plasmid (pCT) coding for multidrug resistance (MDR) were determined using polymerase chain reaction (PCR) in 16 isolates that showed MDR. Cluster analysis of the ERIC-PCR profiles based on band sizes revealed six main clusters from the sixteen isolates analysed. The largest cluster (cluster 3) grouped isolates from vegetables and manure at a similarity coefficient of 0.72. The present study provides data that support the potential transmission of resistant strains of E. coli O157:H7 from vegetables and environmental sources to humans with potential public health implications, especially in developing countries. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Theoretical study on the structure and stabilities of molecular clusters of oxalic acid with water.

PubMed

Weber, Kevin H; Morales, Francisco J; Tao, Fu-Ming

2012-11-29

The importance of aerosols to humankind is well-known, playing an integral role in determining Earth's climate and influencing human health. Despite this fact, much remains unknown about the initial events of nucleation. In this work, the molecular properties of common organic atmospheric pollutant oxalic acid and its gas phase interactions with water have been thoroughly examined. Local minima single-point energies for the monomer conformations were calculated at the B3LYP and MP2 level of theory with both 6-311++G(d,p) and aug-cc-pVDZ basis sets and are compared with previous works. Optimized geometries, relative energies, and free energy changes for the stable clusters of oxalic acid conformers with up to six waters were then obtained from B3LYP calculations with 6-31+G(d) and 6-311++G(d,p) basis sets. Initially, cooperative binding is predicted to be the most important factor in nucleation, but as the clusters grow, dipole cancellations are found to play a pivotal role. The clusters of oxalic acid hydrated purely with water tend to produce extremely stable and neutral core systems. Free energies of formation and atmospheric implications are discussed.

Cluster formation in liverwort-associated methylobacteria and its implications

NASA Astrophysics Data System (ADS)

Kutschera, U.; Thomas, J.; Hornschuh, M.

2007-08-01

Pink-pigmented methylotropic bacteria of the genus Methylobacterium inhabit the surfaces of plant organs. In bryophytes, these methylobacteria enhance cell growth, but the nature of this plant-microbe interaction is largely unknown. In this study, methylobacteria were isolated from the upper surface of the free-living thalli of the liverwort Marchantia polymorpha L. Identification of one strain by 16S ribosomal RNA (rRNA) gene-targeted polymerase chain reaction (PCR) and other data show that these microbes represent an undescribed species of the genus Methylobacterium ( Methylobacterium sp.). The growth-promoting activity of these wild-type methylobacteria was tested and compared with that of the type strain Methylobacterium mesophilicum. Both types of methylobacteria stimulated surface expansion of isolated gemmae from Marchantia polymorpha by about 350%. When suspended in water, the liverwort-associated bacteria ( Methylobacterium sp.) formed dense clusters of up to 600 cells. In liquid cultures of Methylobacterium mesophilicum, single cells were observed, but no clustering occurred. We suggest that the liverwort-associated methylobacteria are co-evolved symbionts of the plants: Cluster formation may be a behavior that enhances the survival of the epiphytic microbes during periods of drought of these desiccation-tolerant lower plants.

Sampling affects the detection of genetic subdivision and conservation implications for fisher in the Sierra Nevada

Treesearch

Jody M. Tucker; Michael K. Schwartz; Richard L. Truex; Samantha M. Wisely; Fred W. Allendorf

2014-01-01

The small population of fisher (Pekania pennanti) in the southern Sierra Nevada is completely geographically and genetically isolated putting it at increased risk of extinction. Previous research using a clustered sampling scheme found a high amount of genetic subdivision within the southern Sierra Nevada population hypothesized to be caused by the Kings River Canyon....

Forest products cluster development in central Arizona—implications for landscape-scale forest restoration

Treesearch

David Nicholls

2014-01-01

Since 2004, close to 50,000 ac of hazardous fuels have been mechanically treated in east-central Arizona as part of the USDA Forest Service's first 10-year stewardship project on national forest lands. The need for coordinated wood products and biomass utilization in Arizona is likely to increase as broad-scale restoration treatments across Arizona's national...

Patterns of Depressive Symptoms, Drinking Motives, and Sexual Behavior among Substance Abusing Adolescents: Implications for Health Risk

ERIC Educational Resources Information Center

Tubman, Jonathan G.; Wagner, Eric F.; Langer, Lilly M.

2003-01-01

Adolescents with substance use problems were classified into four distinct and meaningful subgroups based on patterns of depressive symptoms and motives for drinking before sex (i.e., avoidance, enhancement and social motives) using cluster analysis. Data were collected in face-to-face interviews from 120 adolescents and young adults (87 men, 33…

2016: Signaling Breakthroughs of the Year.

PubMed

Adler, Elizabeth M

2017-01-03

Signaling breakthroughs of 2016 clustered mainly in the areas of neuroscience, immunology, and metabolism, with excursions into plant hormone signaling and bacterial manipulation of host signaling pathways. Perhaps reflecting the growing maturity of the discipline of cell signaling, many of this year's breakthroughs have implications for the pathogenesis or treatment of human disease. Copyright © 2017, American Association for the Advancement of Science.

What's Eating into School Recess? Implications of Extended Eating for Free Play and Physical Activity

ERIC Educational Resources Information Center

Wyver, Shirley; Engelen, Lina; Bundy, Anita; Naughton, Geraldine

2012-01-01

An assumption made when designing recess interventions in schools is that there is a clear demarcation between eating time and play time. We used observational data conducted as part of the Sydney Playground Project to test if this assumption was correct. The Sydney Playground Project is a cluster randomised controlled trial of a recess…

Identifying the facets of impulsivity that explain the relation between ADHD symptoms and substance use in a nonclinical sample

PubMed Central

Roberts, Walter; Peters, Jessica R.; Adams, Zachary W.; Lynam, Donald R.; Milich, Richard

2014-01-01

Adults with attention-deficit/hyperactivity disorder (ADHD) are at higher risk to use substances than their nonclinical peers. Increased levels of impulsivity are generally thought to contribute to their increased levels of risk. Impulsivity is a multifaceted construct, however, and little research to date has attempted to identify which facets of impulsivity contribute to the increased rates of substance abuse among individuals with ADHD. The current study examined the relation among ADHD symptom clusters (i.e., hyperactivity/impulsivity and inattention), substance use rates (i.e., alcohol use, nicotine use, and marijuana use), and personality processes associated with impulsive behavior in a group of young adults. Participants were 361 undergraduate students. Both symptom clusters were positively associated with rates of substance use. Specifically, hyperactive/impulsive symptoms were associated with alcohol and nicotine use, and inattentive symptoms were associated with alcohol use. Several pathways from hyperactive/impulsive symptoms to alcohol, nicotine, and marijuana use via specific facets of impulsivity were identified. These findings have implications for understanding the relation between ADHD symptoms and substance use, as well as clinical implications for preventing and treating substance use problems in individuals with symptoms of ADHD. PMID:24813555

The performance implications of pharmacy information system at the university teaching hospitals of Shiraz, Iran: Cluster approach

PubMed Central

Bayati, Saeede; Bastani, Peivand; Sagheb, Zahra Mahmoodzade; Jamalabadi, Sara; Samadbeik, Mahnaz

2017-01-01

Pharmacy information system (PIS) is becoming vital in assisting pharmacists to do their responsibilities. The aim of this study was to identify the current PIS implications in teaching hospitals affiliated with Shiraz University of Medical Science. This cross-sectional study was conducted in teaching hospitals affiliated with Shiraz University of Medical Science over the year 2016. Data were collected by observing the PIS as well as interviewing its users based on the researcher-made checklist. The checklist was prepared based on reviewing the Persian and English literature and its content validity was approved by the experts. To determine the reliability of the checklist, inter-rater reliability was used. Data were analyzed using SPSS16, and hospitals were clustered using SK-means method. In this study, the least conformity to the standards was shown in smart clinical features (4.54%), pharmaceutical companies' relationship (32.6%), and optimization of drug therapy (34.6%). In contrast, the highest conformity to the standards was shown in reporting capabilities (77.3%) and entry information and input (70.4%). Medication stock checking and optimization of drug therapy were effective features that have made a distinction between hospitals and lead to 95% variance between clusters. Based on the results, the current PIS design pays less attention to clinical features. Besides, clinical information for pharmacists and outside organization relationship were not provided by the current system. Thus, emphasis should be placed on the implementation of corrective actions to eliminate the current system's deficiencies. PMID:29184843

Dark matter self-interactions and small scale structure

NASA Astrophysics Data System (ADS)

Tulin, Sean; Yu, Hai-Bo

2018-02-01

We review theories of dark matter (DM) beyond the collisionless paradigm, known as self-interacting dark matter (SIDM), and their observable implications for astrophysical structure in the Universe. Self-interactions are motivated, in part, due to the potential to explain long-standing (and more recent) small scale structure observations that are in tension with collisionless cold DM (CDM) predictions. Simple particle physics models for SIDM can provide a universal explanation for these observations across a wide range of mass scales spanning dwarf galaxies, low and high surface brightness spiral galaxies, and clusters of galaxies. At the same time, SIDM leaves intact the success of ΛCDM cosmology on large scales. This report covers the following topics: (1) small scale structure issues, including the core-cusp problem, the diversity problem for rotation curves, the missing satellites problem, and the too-big-to-fail problem, as well as recent progress in hydrodynamical simulations of galaxy formation; (2) N-body simulations for SIDM, including implications for density profiles, halo shapes, substructure, and the interplay between baryons and self-interactions; (3) semi-analytic Jeans-based methods that provide a complementary approach for connecting particle models with observations; (4) merging systems, such as cluster mergers (e.g., the Bullet Cluster) and minor infalls, along with recent simulation results for mergers; (5) particle physics models, including light mediator models and composite DM models; and (6) complementary probes for SIDM, including indirect and direct detection experiments, particle collider searches, and cosmological observations. We provide a summary and critical look for all current constraints on DM self-interactions and an outline for future directions.

Studies of cluster X-ray sources, energy spectra for the Perseus, Virgo, and Coma clusters

NASA Technical Reports Server (NTRS)

Kellogg, E.; Baldwin, J. R.; Koch, D.

1975-01-01

Final Uhuru X-ray differential-energy spectra are presented for the Perseus, Virgo, and Coma clusters. Power-law and isothermal bremsstrahlung model spectra with low-energy cutoffs are given, and the energy-dependent Gaunt factor is calculated for the bremsstrahlung. The spectra, which are best fits to the Uhuru data between 2 and 10 keV, are compared with previous observations of these sources in the energy range from 0.1 to 100 keV. The problem of parameter estimation is discussed, error bars with 68% confidence are given for the independently determined slope and cutoff parameters, and the 68% confidence limits are plotted for the fitted spectral functions. The data for Perseus above 20 keV marginally favor the bremsstrahlung fit, those for Virgo between 0.25 and 1.0 keV clearly favor that curve, and those for Coma indicate a low-energy turnover or cutoff. Implications of such a cutoff are briefly discussed.

Spatial, Temporal and Spatio-Temporal Patterns of Maritime Piracy.

PubMed

Marchione, Elio; Johnson, Shane D

2013-11-01

To examine patterns in the timing and location of incidents of maritime piracy to see whether, like many urban crimes, attacks cluster in space and time. Data for all incidents of maritime piracy worldwide recorded by the National Geospatial Intelligence Agency are analyzed using time-series models and methods originally developed to detect disease contagion. At the macro level, analyses suggest that incidents of pirate attacks are concentrated in five subregions of the earth's oceans and that the time series for these different subregions differ. At the micro level, analyses suggest that for the last 16 years (or more), pirate attacks appear to cluster in space and time suggesting that patterns are not static but are also not random. Much like other types of crime, pirate attacks cluster in space, and following an attack at one location the risk of others at the same location or nearby is temporarily elevated. The identification of such regularities has implications for the understanding of maritime piracy and for predicting the future locations of attacks.

Constraining the baryon-dark matter relative velocity with the large-scale 3-point correlation function of the SDSS BOSS DR12 CMASS galaxies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slepian, Zachary; Slosar, Anze; Eisenstein, Daniel J.

We search for a galaxy clustering bias due to a modulation of galaxy number with the baryon-dark matter relative velocity resulting from recombination-era physics. We find no detected signal and place the constraint bv <0.01 on the relative velocity bias for the CMASS galaxies. This bias is an important potential systematic of Baryon Acoustic Oscillation (BAO) method measurements of the cosmic distance scale using the 2-point clustering. Our limit on the relative velocity bias indicates a systematic shift of no more than 0.3% rms in the distance scale inferred from the BAO feature in the BOSS 2-point clustering, well belowmore » the 1% statistical error of this measurement. In conclusion, this constraint is the most stringent currently available and has important implications for the ability of upcoming large-scale structure surveys such as DESI to self-protect against the relative velocity as a possible systematic.« less

Structural determinants of adhesion by Protocadherin-19 and implications for its role in epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooper, Sharon R.; Jontes, James D.; Sotomayor, Marcos

2016-10-26

Non-clustered δ-protocadherins are homophilic cell adhesion molecules essential for the development of the vertebrate nervous system, as several are closely linked to neurodevelopmental disorders. Mutations inprotocadherin-19(PCDH19) result in a female-limited, infant-onset form of epilepsy (PCDH19-FE). Over 100 mutations inPCDH19have been identified in patients with PCDH19-FE, about half of which are missense mutations in the adhesive extracellular domain. Neither the mechanism of homophilic adhesion by PCDH19, nor the biochemical effects of missense mutations are understood. Here we present a crystallographic structure of the minimal adhesive fragment of the zebrafish Pcdh19 extracellular domain. This structure reveals the adhesive interface for Pcdh19, whichmore » is broadly relevant to both non-clustered δ and clustered protocadherin subfamilies. In addition, we show that several PCDH19-FE missense mutations localize to the adhesive interface and abolish Pcdh19 adhesion inin vitroassays, thus revealing the biochemical basis of their pathogenic effects during brain development.« less

Clinical interpretation of the Spinal Cord Injury Functional Index (SCI-FI)

PubMed Central

Fyffe, Denise; Kalpakjian, Claire Z.; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Kirshblum, Steven C.; Tulsky, David S.; Jette, Alan M.

2016-01-01

Objective: To provide validation of functional ability levels for the Spinal Cord Injury – Functional Index (SCI-FI). Design: Cross-sectional. Setting: Inpatient rehabilitation hospital and community settings. Participants: A sample of 855 individuals with traumatic spinal cord injury enrolled in 6 rehabilitation centers participating in the National Spinal Cord Injury Model Systems Network. Interventions: Not Applicable. Main Outcome Measures: Spinal Cord Injury-Functional Index (SCI-FI). Results: Cluster analyses identified three distinct groups that represent low, mid-range and high SCI-FI functional ability levels. Comparison of clusters on personal and other injury characteristics suggested some significant differences between groups. Conclusions: These results strongly support the use of SCI-FI functional ability levels to document the perceived functional abilities of persons with SCI. Results of the cluster analysis suggest that the SCI-FI functional ability levels capture function by injury characteristics. Clinical implications regarding tracking functional activity trajectories during follow-up visits are discussed. PMID:26781769

X-ray insights into star and planet formation.

PubMed

Feigelson, Eric D

2010-04-20

Although stars and planets form in cold environments, X-rays are produced in abundance by young stars. This review examines the implications of stellar X-rays for star and planet formation studies, highlighting the contributions of NASA's (National Aeronautics and Space Administration) Chandra X-ray Observatory. Seven topics are covered: X-rays from protostellar outflow shocks, X-rays from the youngest protostars, the stellar initial mass function, the structure of young stellar clusters, the fate of massive stellar winds, X-ray irradiation of protoplanetary disks, and X-ray flare effects on ancient meteorites. Chandra observations of star-forming regions often show dramatic star clusters, powerful magnetic reconnection flares, and parsec-scale diffuse plasma. X-ray selected samples of premain sequence stars significantly advance studies of star cluster formation, the stellar initial mass function, triggered star-formation processes, and protoplanetary disk evolution. Although X-rays themselves may not play a critical role in the physics of star formation, they likely have important effects on protoplanetary disks by heating and ionizing disk gases.

Structural changes in white matter are uniquely related to children’s reading development

PubMed Central

Myers, Chelsea A.; Vandermosten, Maaike; Farris, Emily A.; Hancock, Roeland; Gimenez, Paul; Black, Jessica M.; Casto, Brandi; Drahos, Miroslav; Tumber, Mandeep; Hendren, Robert L.; Hulme, Charles; Hoeft, Fumiko

2014-01-01

This study examined whether variations in brain development between kindergarten and Grade 3 predicted individual differences in reading ability at the latter time point. Structural MRI measurements indicated that increases in volume of two left temporo-parietal white matter clusters are unique predictors of reading outcome at Grade 3. Using diffusion MRI, the larger of these two clusters was identified as a location where fibers of the long segment of arcuate fasciculus and superior corona radiata intersect, and the smaller cluster as the posterior arcuate fasciculus. Bias-free regression analyses using regions-of-interest from prior literature revealed white matter volume changes in temporo-parietal white matter, together with preliteracy measures, predicted 56% of the variance in reading outcomes. Our findings demonstrate the important contribution of developmental differences in areas of left dorsal white matter, often implicated in phonological processing, as a sensitive early biomarker for later reading abilities, and by extension, reading difficulties. PMID:25212581

The unique associations between rape acknowledgment and the DSM-5 PTSD symptom clusters.

PubMed

Wilson, Laura C; Scarpa, Angela

2017-11-01

It is well documented in the sexual assault literature that more than half of rape survivors do not label their experience as rape. This is called unacknowledged rape. Although this phenomenon is common and undoubtedly has huge implications for psychotherapy, the impact of acknowledgment status on psychological adjustment is unclear. The present study aimed to delineate the unique impact of rape acknowledgment on psychopathology by examining PTSD symptoms at the cluster level. To examine this, 178 female college students who reported rape completed an online survey, including an assessment of PTSD symptoms in the past month. The results suggested that, after accounting for several covariates, acknowledged rape survivors reported significantly greater levels of intrusion and avoidance symptoms compared to unacknowledged rape survivors. The findings suggest that examining PTSD symptoms at the cluster level may provide more insight into the process of recovery following rape and therefore may better inform treatment decisions. Copyright © 2017 Elsevier B.V. All rights reserved.

Clusters of Behaviors and Beliefs Predicting Adolescent Depression: Implications for Prevention

PubMed Central

Paunesku, David; Ellis, Justin; Fogel, Joshua; Kuwabara, Sachiko A; Gollan, Jackie; Gladstone, Tracy; Reinecke, Mark; Van Voorhees, Benjamin W.

2009-01-01

OBJECTIVE Risk factors for various disorders are known to cluster. However, the factor structure for behaviors and beliefs predicting depressive disorder in adolescents is not known. Knowledge of this structure can facilitate prevention planning. METHODS We used the National Longitudinal Study of Adolescent Health (AddHealth) data set to conduct an exploratory factor analysis to identify clusters of behaviors/experiences predicting the onset of major depressive disorder (MDD) at 1-year follow-up (N=4,791). RESULTS Four factors were identified: family/interpersonal relations, self-emancipation, avoidant problem solving/low self-worth, and religious activity. Strong family/interpersonal relations were the most significantly protective against depression at one year follow-up. Avoidant problem solving/low self-worth was not predictive of MDD on its own, but significantly amplified the risks associated with delinquency. CONCLUSION Depression prevention interventions should consider giving family relationships a more central role in their efforts. Programs teaching problem solving skills may be most appropriate for reducing MDD risk in delinquent youth. PMID:20502621

The Embeddedness of Adolescent Friendship Nominations: The Formation of Social Capital in Emergent Network Structures

PubMed Central

Frank, Kenneth A.; Muller, Chandra; Mueller, Anna S.

2014-01-01

Although research on social embeddedness and social capital con-firms the value of friendship networks, little has been written about how social relations form and are structured by social institutions. Using data from the Adolescent Health and Academic Achievement study and the National Longitudinal Study of Adolescent Health, the authors show that the odds of a new friendship nomination were 1.77 times greater within clusters of high school students taking courses together than between them. The estimated effect cannot be attributed to exposure to peers in similar grade levels, indirect friendship links, or pair-level course overlap, and the finding is robust to alternative model specifications. The authors also show how tendencies associated with status hierarchy inhering in triadic friendship nominations are neutralized within the clusters. These results have implications for the production and distribution of social capital within social systems such as schools, giving the clusters social salience as “local positions.” PMID:25364011

Clustering of temperamental and cognitive risk factors for anxiety in a college sample of late adolescents.

PubMed

Viana, Andres G; Gratz, Kim L; Bierman, Karen L

2013-01-01

Temperamental vulnerabilities (e.g., behavioral inhibition, anxiety sensitivity) and cognitive biases (e.g., interpretive and judgment biases) may exacerbate feelings of stress and anxiety, particularly among late adolescents during the early years of college. The goal of the present study was to apply person-centered analyses to explore possible heterogeneity in the patterns of these four risk factors in late adolescence, and to examine associations with several anxiety outcomes (i.e., worry, anxiety symptoms, and trait anxiety). Cluster analyses in a college sample of 855 late adolescents revealed a Low-Risk group, along with four reliable clusters with distinct profiles of risk factors and anxiety outcomes (Inhibited, Sensitive, Cognitively-Biased, and Multi-Risk). Of the risk profiles, Multi-Risk youth experienced the highest levels of anxiety outcomes, whereas Inhibited youth experienced the lowest levels of anxiety outcomes. Sensitive and Cognitively-Biased youth experienced comparable levels of anxiety-related outcomes, despite different constellations of risk factors. Implications for interventions and future research are discussed.

X-ray insights into star and planet formation

PubMed Central

Feigelson, Eric D.

2010-01-01

Although stars and planets form in cold environments, X-rays are produced in abundance by young stars. This review examines the implications of stellar X-rays for star and planet formation studies, highlighting the contributions of NASA’s (National Aeronautics and Space Administration) Chandra X-ray Observatory. Seven topics are covered: X-rays from protostellar outflow shocks, X-rays from the youngest protostars, the stellar initial mass function, the structure of young stellar clusters, the fate of massive stellar winds, X-ray irradiation of protoplanetary disks, and X-ray flare effects on ancient meteorites. Chandra observations of star-forming regions often show dramatic star clusters, powerful magnetic reconnection flares, and parsec-scale diffuse plasma. X-ray selected samples of premain sequence stars significantly advance studies of star cluster formation, the stellar initial mass function, triggered star-formation processes, and protoplanetary disk evolution. Although X-rays themselves may not play a critical role in the physics of star formation, they likely have important effects on protoplanetary disks by heating and ionizing disk gases. PMID:20404197

The relationship between grain boundary structure, defect mobility, and grain boundary sink efficiency

PubMed Central

Uberuaga, Blas Pedro; Vernon, Louis J.; Martinez, Enrique; Voter, Arthur F.

2015-01-01

Nanocrystalline materials have received great attention due to their potential for improved functionality and have been proposed for extreme environments where the interfaces are expected to promote radiation tolerance. However, the precise role of the interfaces in modifying defect behavior is unclear. Using long-time simulations methods, we determine the mobility of defects and defect clusters at grain boundaries in Cu. We find that mobilities vary significantly with boundary structure and cluster size, with larger clusters exhibiting reduced mobility, and that interface sink efficiency depends on the kinetics of defects within the interface via the in-boundary annihilation rate of defects. Thus, sink efficiency is a strong function of defect mobility, which depends on boundary structure, a property that evolves with time. Further, defect mobility at boundaries can be slower than in the bulk, which has general implications for the properties of polycrystalline materials. Finally, we correlate defect energetics with the volumes of atomic sites at the boundary. PMID:25766999

The relationship between grain boundary structure, defect mobility, and grain boundary sink efficiency

DOE PAGES

Uberuaga, Blas Pedro; Vernon, Louis J.; Martinez, Enrique; ...

2015-03-13

Nanocrystalline materials have received great attention due to their potential for improved functionality and have been proposed for extreme environments where the interfaces are expected to promote radiation tolerance. However, the precise role of the interfaces in modifying defect behavior is unclear. Using long-time simulations methods, we determine the mobility of defects and defect clusters at grain boundaries in Cu. We find that mobilities vary significantly with boundary structure and cluster size, with larger clusters exhibiting reduced mobility, and that interface sink efficiency depends on the kinetics of defects within the interface via the in-boundary annihilation rate of defects. Thus,more » sink efficiency is a strong function of defect mobility, which depends on boundary structure, a property that evolves with time. Further, defect mobility at boundaries can be slower than in the bulk, which has general implications for the properties of polycrystalline materials. Finally, we correlate defect energetics with the volumes of atomic sites at the boundary.« less

Solubility of aqueous methane under metastable conditions: implications for gas hydrate nucleation.

PubMed

Guo, Guang-Jun; Rodger, P Mark

2013-05-30

To understand the prenucleation stage of methane hydrate formation, we measured methane solubility under metastable conditions using molecular dynamics simulations. Three factors that influence solubility are considered: temperature, pressure, and the strength of the modeled van der Waals attraction between methane and water. Moreover, the naturally formed water cages and methane clusters in the methane solutions are analyzed. We find that both lowering the temperature and increasing the pressure increase methane solubility, but lowering the temperature is more effective than increasing the pressure in promoting hydrate nucleation because the former induces more water cages to form while the latter makes them less prevalent. With an increase in methane solubility, the chance of forming large methane clusters increases, with the distribution of cluster sizes being exponential. The critical solubility, beyond which the metastable solutions spontaneously form hydrate, is estimated to be ~0.05 mole fraction in this work, corresponding to the concentration of 1.7 methane molecules/nm(3). This value agrees well with the cage adsorption hypothesis of hydrate nucleation.