Mesenchymal stem cells promote the sustained expression of CD69 on activated T lymphocytes: roles of canonical and non-canonical NF-κB signalling

PubMed Central

Saldanha-Araujo, Felipe; Haddad, Rodrigo; de Farias, Kelen C R Malmegrim; Souza, Alessandra de Paula Alves; Palma, Patrícia V; Araujo, Amélia G; Orellana, Maristela D; Voltarelli, Julio C; Covas, Dimas T; Zago, Marco A; Panepucci, Rodrigo A

2012-01-01

Abstract Mesenchymal stem cells (MSCs) are known to induce the conversion of activated T cells into regulatory T cells in vitro. The marker CD69 is a target of canonical nuclear factor kappa-B (NF-κB) signalling and is transiently expressed upon activation; however, stable CD69 expression defines cells with immunoregulatory properties. Given its enormous therapeutic potential, we explored the molecular mechanisms underlying the induction of regulatory cells by MSCs. Peripheral blood CD3+ T cells were activated and cultured in the presence or absence of MSCs. CD4+ cell mRNA expression was then characterized by microarray analysis. The drug BAY11-7082 (BAY) and a siRNA against v-rel reticuloendotheliosis viral oncogene homolog B (RELB) were used to explore the differential roles of canonical and non-canonical NF-κB signalling, respectively. Flow cytometry and real-time PCR were used for analyses. Genes with immunoregulatory functions, CD69 and non-canonical NF-κB subunits (RELB and NFKB2) were all expressed at higher levels in lymphocytes co-cultured with MSCs. The frequency of CD69+ cells among lymphocytes cultured alone progressively decreased after activation. In contrast, the frequency of CD69+ cells increased significantly following activation in lymphocytes co-cultured with MSCs. Inhibition of canonical NF-κB signalling by BAY immediately following activation blocked the induction of CD69; however, inhibition of canonical NF-κB signalling on the third day further induced the expression of CD69. Furthermore, late expression of CD69 was inhibited by RELB siRNA. These results indicate that the canonical NF-κB pathway controls the early expression of CD69 after activation; however, in an immunoregulatory context, late and sustained CD69 expression is promoted by the non-canonical pathway and is inhibited by canonical NF-κB signalling. PMID:21777379

Remarks on the "Non-canonicity Puzzle": Lagrangian Symmetries of the Einstein-Hilbert Action

NASA Astrophysics Data System (ADS)

Kiriushcheva, N.; Komorowski, P. G.; Kuzmin, S. V.

2012-07-01

Given the non-canonical relationship between variables used in the Hamiltonian formulations of the Einstein-Hilbert action (due to Pirani, Schild, Skinner (PSS) and Dirac) and the Arnowitt-Deser-Misner (ADM) action, and the consequent difference in the gauge transformations generated by the first-class constraints of these two formulations, the assumption that the Lagrangians from which they were derived are equivalent leads to an apparent contradiction that has been called "the non-canonicity puzzle". In this work we shall investigate the group properties of two symmetries derived for the Einstein-Hilbert action: diffeomorphism, which follows from the PSS and Dirac formulations, and the one that arises from the ADM formulation. We demonstrate that unlike the diffeomorphism transformations, the ADM transformations (as well as others, which can be constructed for the Einstein-Hilbert Lagrangian using Noether's identities) do not form a group. This makes diffeomorphism transformations unique (the term "canonical" symmetry might be suggested). If the two Lagrangians are to be called equivalent, canonical symmetry must be preserved. The interplay between general covariance and the canonicity of the variables used is discussed.

The tangled web of non-canonical Wnt signalling in neural migration.

PubMed

Clark, Charlotte E J; Nourse, C Cathrin; Cooper, Helen M

2012-01-01

In all multicellular animals, successful embryogenesis is dependent on the ability of cells to detect the status of the local environment and respond appropriately. The nature of the extracellular environment is communicated to the intracellular compartment by ligand/receptor interactions at the cell surface. The Wnt canonical and non-canonical signalling pathways are found in the most primitive metazoans, and they play an essential role in the most fundamental developmental processes in all multicellular organisms. Vertebrates have expanded the number of Wnts and Frizzled receptors and have additionally evolved novel Wnt receptor families (Ryk, Ror). The multiplicity of potential interactions between Wnts, their receptors and downstream effectors has exponentially increased the complexity of the signal transduction network. Signalling through each of the Wnt pathways, as well as crosstalk between them, plays a critical role in the establishment of the complex architecture of the vertebrate central nervous system. In this review, we explore the signalling networks triggered by non-canonical Wnt/receptor interactions, focussing on the emerging roles of the non-conventional Wnt receptors Ryk and Ror. We describe the role of these pathways in neural tube formation and axon guidance where Wnt signalling controls tissue polarity, coordinated cell migration and axon guidance via remodelling of the cytoskeleton. Copyright © 2012 S. Karger AG, Basel.

Canonical Drude Weight for Non-integrable Quantum Spin Chains

NASA Astrophysics Data System (ADS)

Mastropietro, Vieri; Porta, Marcello

2018-03-01

The Drude weight is a central quantity for the transport properties of quantum spin chains. The canonical definition of Drude weight is directly related to Kubo formula of conductivity. However, the difficulty in the evaluation of such expression has led to several alternative formulations, accessible to different methods. In particular, the Euclidean, or imaginary-time, Drude weight can be studied via rigorous renormalization group. As a result, in the past years several universality results have been proven for such quantity at zero temperature; remarkably, the proofs work for both integrable and non-integrable quantum spin chains. Here we establish the equivalence of Euclidean and canonical Drude weights at zero temperature. Our proof is based on rigorous renormalization group methods, Ward identities, and complex analytic ideas.

Canonical Gravity, Non-Inertial Frames, Relativistic Metrology and Dark Matter

NASA Astrophysics Data System (ADS)

Lusanna, Luca

Clock synchronization leads to the definition of instantaneous 3-spaces (to be used as Cauchy surfaces) in non-inertial frames, the only ones allowed by the equivalence principle. ADM canonical tetrad gravity in asymptotically Minkowskian space-times can be described in this framework. This allows to find the York canonical basis in which the inertial (gauge) and tidal (physical) degrees of freedom of the gravitational field can be identified. A Post-Minkowskian linearization with respect to the asymptotic Minkowski metric (asymptotic background) allows to solve the Dirac constraints in non-harmonic 3-orthogonal gauges and to find non-harmonic TT gravitational waves. The inertial gauge variable York time (the trace of the extrinsic curvature of the 3-space) describes the general relativistic freedom in clock synchronization. After a digression on the gauge problem in general relativity and its connection with relativistic metrology, it is shown that dark matter, whose experimental signatures are the rotation curves and the mass of galaxies, may be described (at least partially) as an inertial relativistic effect (absent in Newtonian gravity) connected with the York time, namely with the non-Euclidean nature of 3-spaces as 3-sub-manifolds of space-time.

Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells

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

Kim, Byeong-Moo; Department of Medicine, Harvard Medical School, Boston, MA 02115; Choi, Michael Y., E-mail: mchoi@partners.org

2012-09-21

Highlights: Black-Right-Pointing-Pointer Embryonic stem cells (ESCs) lacking non-canonical miRNAs proliferate slower. Black-Right-Pointing-Pointer miR-320 and miR-702 are two non-canonical miRNAs expressed in ESCs. Black-Right-Pointing-Pointer miR-320 and miR-702 promote proliferation of Dgcr8-deficient ESCs. Black-Right-Pointing-Pointer miR-320 targets p57 and helps to release Dgcr8-deficient ESCs from G1 arrest. Black-Right-Pointing-Pointer miR-702 targets p21 and helps to release Dgcr8-deficient ESCs from G1 arrest. -- Abstract: MicroRNAs are known to contribute significantly to stem cell phenotype by post-transcriptionally regulating gene expression. Most of our knowledge of microRNAs comes from the study of canonical microRNAs that require two sequential cleavages by the Drosha/Dgcr8 heterodimer and Dicer to generatemore » mature products. In contrast, non-canonical microRNAs bypass the cleavage by the Drosha/Dgcr8 heterodimer within the nucleus but still require cytoplasmic cleavage by Dicer. The function of non-canonical microRNAs in embryonic stem cells (ESCs) remains obscure. It has been hypothesized that non-canonical microRNAs have important roles in ESCs based upon the phenotypes of ESC lines that lack these specific classes of microRNAs; Dicer-deficient ESCs lacking both canonical and non-canonical microRNAs have much more severe proliferation defect than Dgcr8-deficient ESCs lacking only canonical microRNAs. Using these cell lines, we identified two non-canonical microRNAs, miR-320 and miR-702, that promote proliferation of Dgcr8-deficient ESCs by releasing them from G1 arrest. This is accomplished by targeting the 3 Prime -untranslated regions of the cell cycle inhibitors p57 and p21 and thereby inhibiting their expression. This is the first report of the crucial role of non-canonical microRNAs in ESCs.« less

Production of non-canonical sentences in agrammatic aphasia: limits in representation or rule application?

PubMed

Burchert, Frank; Meissner, Nadine; De Bleser, Ria

2008-02-01

The study reported here compares two linguistically informed hypotheses on agrammatic sentence production, the TPH [Friedmann, N., & Grodzinsky, Y. (1997). Tense and agreement in agrammatic production: Pruning the syntactic tree. Brain and Language, 56, 397-425.] and the DOP [Bastiaanse, R., & van Zonneveld, R. (2005). Sentence production with verbs of alternating transitivity in agrammatic Broca's aphasia. Journal of Neurolinguistics, 18, 59-66]. To explain impaired production of non-canonical sentences in agrammatism, the TPH basically relies on deleted or pruned clause structure positions in the left periphery, whereas the DOP appeals to limitations in the application of movement rules. Certain non-canonical sentences such as object-questions and object-relative clauses require the availability of nodes in the left periphery as well as movement to these nodes. In languages with relatively fixed word order such as English, the relevant test cases generally involve a coincidence of left periphery and movement, such that the predictions of the TPH and the DOP are identical although for different reasons. In languages with relatively free word order such as German, on the other hand, it is possible to devise specific tests of the different predictions due to the availability of scrambling. Scrambled object sentences, for example, do not involve the left periphery but do require application of movement in a domain below the left periphery. A study was conducted with German agrammatic subjects which elicited canonical sentences without object movement and non-canonical scrambled sentences with object movement. The results show that agrammatic speakers have a particular problem with the production of scrambled sentences. Further evidence reported in the study from spontaneous speech, elicitation of object relatives, questions and passives and with different agrammatic subjects confirms that non-canonical sentences are generally harder to produce for agrammatics. These

Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway

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

Lin, Qiu-Ru; Li, Chen-Guang; Zha, Qing-Bing

Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1β (IL-1β) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1β release similar to that of ATP. Consistent with this, activated caspase-1 responsible for pro-IL-1β maturation was undetectablemore » in gossypol-treated peritoneal macrophages. Besides, RAW 264.7 cells lacking ASC expression and caspase-1 activation also underwent pyroptotic cell death upon gossypol treatment. In further support of pyroptosis induction, both pan-caspase inhibitor and caspase-1 subfamily inhibitor, but not caspase-3 inhibitor, could sharply suppress gossypol-induced cell death. Other canonical pyroptotic inhibitors, including potassium chloride and N-acetyl-L-cysteine, could suppress ATP-induced pyroptosis but failed to inhibit or even enhanced gossypol-induced cell death, whereas nonspecific pore-formation inhibitor glycine could attenuate this process, suggesting involvement of a non-canonical pathway. Of note, gossypol treatment eliminated thioglycollate-induced macrophages in the peritoneal cavity with recruitment of other leukocytes. Moreover, gossypol administration markedly decreased the survival of mice in a bacterial sepsis model. Collectively, these results suggested that gossypol induced pyroptosis in mouse macrophages via a non-canonical inflammasome pathway, which raises a concern for its in vivo cytotoxicity to macrophages. - Highlights: • Gossypol induces pyroptosis in mouse peritoneal and RAW 264.7 macrophages. • In LPS

The non-canonical functions of the heme oxygenases

PubMed Central

Tibullo, Daniele; Forte, Stefano; Zappalà, Agata; Volti, Giovanni Li

2016-01-01

Heme oxygenase (HO) isoforms catalyze the conversion of heme to carbon monoxide (CO) and biliverdin with a concurrent release of iron, which can drive the synthesis of ferritin for iron sequestration. Most of the studies so far were directed at evaluating the protective effect of these enzymes because of their ability to generate antioxidant and antiapoptotic molecules such as CO and bilirubin. Recent evidences are suggesting that HO may possess other important physiological functions, which are not related to its enzymatic activity and for which we would like to introduce for the first time the term “non canonical functions”. Recent evidence suggest that both HO isoforms may form protein-protein interactions (i.e. cytochrome P450, adiponectin, CD91) thus serving as chaperone-like protein. In addition, truncated HO-1 isoform was localized in the nuclear compartment under certain experimental conditions (i.e. excitotoxicity, hypoxia) regulating the activity of important nuclear transcription factors (i.e. Nrf2) and DNA repair. In the present review, we discuss three potential signaling mechanisms that we refer to as the non-canonical functions of the HO isoforms: protein-protein interaction, intracellular compartmentalization, and extracellular secretion. The aim of the present review is to describe each of this mechanism and all the aspects warranting additional studies in order to unravel all the functions of the HO system. PMID:27626166

XEDAR activates the non-canonical NF-κB pathway

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

Verhelst, Kelly, E-mail: Kelly.Verhelst@irc.VIB-UGent.be; Department of Biomedical Molecular Biology, Ghent University, Ghent; Gardam, Sandra, E-mail: s.gardam@garvan.org.au

2015-09-18

Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR hasmore » been reported to activate canonical nuclear factor κB (NF-κB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-κB pathway, characterized by the processing of p100 (NF-κB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKα. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. - Highlights: • XEDAR activates the non-canonical NF-κB pathway. • XEDAR-induced processing of p100 depends on XEDAR interaction with TRAF3 and TRAF6. • XEDAR-induced processing of p100 depends on NIK and IKKα activity. • Overexpression of XEDAR leads to NIK accumulation. • XEDAR-induced processing of p100 is negatively regulated by TRAF3 cIAP1 and A20.« less

Carbon-14 decay as a source of non-canonical bases in DNA.

PubMed

Sassi, Michel; Carter, Damien J; Uberuaga, Blas P; Stanek, Chris R; Marks, Nigel A

2014-01-01

Significant experimental effort has been applied to study radioactive beta-decay in biological systems. Atomic-scale knowledge of this transmutation process is lacking due to the absence of computer simulations. Carbon-14 is an important beta-emitter, being ubiquitous in the environment and an intrinsic part of the genetic code. Over a lifetime, around 50 billion (14)C decays occur within human DNA. We apply ab initio molecular dynamics to quantify (14)C-induced bond rupture in a variety of organic molecules, including DNA base pairs. We show that double bonds and ring structures confer radiation resistance. These features, present in the canonical bases of the DNA, enhance their resistance to (14)C-induced bond-breaking. In contrast, the sugar group of the DNA and RNA backbone is vulnerable to single-strand breaking. We also show that Carbon-14 decay provides a mechanism for creating mutagenic wobble-type mispairs. The observation that DNA has a resistance to natural radioactivity has not previously been recognized. We show that (14)C decay can be a source for generating non-canonical bases. Our findings raise questions such as how the genetic apparatus deals with the appearance of an extra nitrogen in the canonical bases. It is not obvious whether or not the DNA repair mechanism detects this modification nor how DNA replication is affected by a non-canonical nucleobase. Accordingly, (14)C may prove to be a source of genetic alteration that is impossible to avoid due to the universal presence of radiocarbon in the environment. © 2013.

Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites.

PubMed

Betel, Doron; Koppal, Anjali; Agius, Phaedra; Sander, Chris; Leslie, Christina

2010-01-01

mirSVR is a new machine learning method for ranking microRNA target sites by a down-regulation score. The algorithm trains a regression model on sequence and contextual features extracted from miRanda-predicted target sites. In a large-scale evaluation, miRanda-mirSVR is competitive with other target prediction methods in identifying target genes and predicting the extent of their downregulation at the mRNA or protein levels. Importantly, the method identifies a significant number of experimentally determined non-canonical and non-conserved sites.

Wnt3a regulates proliferation and migration of HUVEC via canonical and non-canonical Wnt signaling pathways

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

Samarzija, Ivana; Sini, Patrizia; Schlange, Thomas

2009-08-28

Untangling the signaling pathways involved in endothelial cell biology is of central interest for the development of antiangiogenesis based therapies. Here we report that Wnt3a induces the proliferation and migration of HUVECs, but does not affect their survival. Wnt3a-induced proliferation was VEGFR signaling independent, but reduced upon CamKII inhibition. In a search for the downstream mediators of Wnt3a's effects on HUVEC biology, we found that Wnt3a treatment leads to phosphorylation of DVL3 and stabilization of {beta}-catenin. Moreover, under the same conditions we observed an upregulation in c-MYC, TIE-2 and GJA1 mRNA transcripts. Although treatment of HUVECs with Wnt5a induced DVL3more » phosphorylation, we did not observe any of the other effects seen upon Wnt3a stimulation. Taken together, our data indicate that Wnt3a induces canonical and non-canonical Wnt signaling in HUVECs, and stimulates their proliferation and migration.« less

Explicit high-order non-canonical symplectic particle-in-cell algorithms for Vlasov-Maxwell systems

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

Xiao, Jianyuan; Qin, Hong; Liu, Jian

2015-11-01

Explicit high-order non-canonical symplectic particle-in-cell algorithms for classical particle-field systems governed by the Vlasov-Maxwell equations are developed. The algorithms conserve a discrete non-canonical symplectic structure derived from the Lagrangian of the particle-field system, which is naturally discrete in particles. The electromagnetic field is spatially discretized using the method of discrete exterior calculus with high-order interpolating differential forms for a cubic grid. The resulting time-domain Lagrangian assumes a non-canonical symplectic structure. It is also gauge invariant and conserves charge. The system is then solved using a structure-preserving splitting method discovered by He et al. [preprint arXiv: 1505.06076 (2015)], which produces fivemore » exactly soluble sub-systems, and high-order structure-preserving algorithms follow by combinations. The explicit, high-order, and conservative nature of the algorithms is especially suitable for long-term simulations of particle-field systems with extremely large number of degrees of freedom on massively parallel supercomputers. The algorithms have been tested and verified by the two physics problems, i.e., the nonlinear Landau damping and the electron Bernstein wave. (C) 2015 AIP Publishing LLC.« less

The non-canonical Wnt receptor Ryk regulates hematopoietic stem cell repopulation in part by controlling proliferation and apoptosis.

PubMed

Famili, Farbod; Perez, Laura Garcia; Naber, Brigitta Ae; Noordermeer, Jasprina N; Fradkin, Lee G; Staal, Frank Jt

2016-11-24

The development of blood and immune cells requires strict control by various signaling pathways in order to regulate self-renewal, differentiation and apoptosis in stem and progenitor cells. Recent evidence indicates critical roles for the canonical and non-canonical Wnt pathways in hematopoiesis. The non-canonical Wnt pathway is important for establishment of cell polarity and cell migration and regulates apoptosis in the thymus. We here investigate the role of the non-canonical Wnt receptor Ryk in hematopoiesis and lymphoid development. We show that there are dynamic changes in Ryk expression during development and in different hematopoietic tissues. Functionally, Ryk regulates NK cell development in a temporal fashion. Moreover, Ryk-deficient mice show diminished, but not absent self-renewal of hematopoietic stem cells (HSC), via effects on mildly increased proliferation and apoptosis. Thus, Ryk deficiency in HSCs from fetal liver reduces their quiescence, leading to proliferation-induced apoptosis and decreased self-renewal.

Spontaneous CRISPR loci generation in vivo by non-canonical spacer integration

PubMed Central

Nivala, Jeff; Shipman, Seth L.; Church, George M.

2018-01-01

The adaptation phase of CRISPR-Cas immunity depends on the precise integration of short segments of foreign DNA (spacers) into a specific genomic location within the CRISPR locus by the Cas1-Cas2 integration complex. Although off-target spacer integration outside of canonical CRISPR arrays has been described in vitro, no evidence of non-specific integration activity has been found in vivo. Here, we show that non-canonical off-target integrations can occur within bacterial chromosomes at locations that resemble the native CRISPR locus by characterizing hundreds of off-target integration locations within Escherichia coli. Considering whether such promiscuous Cas1-Cas2 activity could have an evolutionary role through the genesis of neo-CRISPR loci, we combed existing CRISPR databases and available genomes for evidence of off-target integration activity. This search uncovered several putative instances of naturally occurring off-target spacer integration events within the genomes of Yersinia pestis and Sulfolobus islandicus. These results are important in understanding alternative routes to CRISPR array genesis and evolution, as well as in the use of spacer acquisition in technological applications. PMID:29379209

Regulation of mitochondrial bioenergetics by the non-canonical roles of mitochondrial dynamics proteins in the heart.

PubMed

Wang, Wang; Fernandez-Sanz, Celia; Sheu, Shey-Shing

2018-05-01

Recent advancement in mitochondrial research has significantly extended our knowledge on the role and regulation of mitochondria in health and disease. One important breakthrough is the delineation of how mitochondrial morphological changes, termed mitochondrial dynamics, are coupled to the bioenergetics and signaling functions of mitochondria. In general, it is believed that fusion leads to an increased mitochondrial respiration efficiency and resistance to stress-induced dysfunction while fission does the contrary. This concept seems not applicable to adult cardiomyocytes. The mitochondria in adult cardiomyocytes exhibit fragmented morphology (tilted towards fission) and show less networking and movement as compared to other cell types. However, being the most energy-demanding cells, cardiomyocytes in the adult heart possess vast number of mitochondria, high level of energy flow, and abundant mitochondrial dynamics proteins. This apparent discrepancy could be explained by recently identified new functions of the mitochondrial dynamics proteins. These "non-canonical" roles of mitochondrial dynamics proteins range from controlling inter-organelle communication to regulating cell viability and survival under metabolic stresses. Here, we summarize the newly identified non-canonical roles of mitochondrial dynamics proteins. We focus on how these fission and fusion independent roles of dynamics proteins regulate mitochondrial bioenergetics. We also discuss potential molecular mechanisms, unique intracellular location, and the cardiovascular disease relevance of these non-canonical roles of the dynamics proteins. We propose that future studies are warranted to differentiate the canonical and non-canonical roles of dynamics proteins and to identify new approaches for the treatment of heart diseases. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and

New insights into transcription fidelity: thermal stability of non-canonical structures in template DNA regulates transcriptional arrest, pause, and slippage.

PubMed

Tateishi-Karimata, Hisae; Isono, Noburu; Sugimoto, Naoki

2014-01-01

The thermal stability and topology of non-canonical structures of G-quadruplexes and hairpins in template DNA were investigated, and the effect of non-canonical structures on transcription fidelity was evaluated quantitatively. We designed ten template DNAs: A linear sequence that does not have significant higher-order structure, three sequences that form hairpin structures, and six sequences that form G-quadruplex structures with different stabilities. Templates with non-canonical structures induced the production of an arrested, a slipped, and a full-length transcript, whereas the linear sequence produced only a full-length transcript. The efficiency of production for run-off transcripts (full-length and slipped transcripts) from templates that formed the non-canonical structures was lower than that from the linear. G-quadruplex structures were more effective inhibitors of full-length product formation than were hairpin structure even when the stability of the G-quadruplex in an aqueous solution was the same as that of the hairpin. We considered that intra-polymerase conditions may differentially affect the stability of non-canonical structures. The values of transcription efficiencies of run-off or arrest transcripts were correlated with stabilities of non-canonical structures in the intra-polymerase condition mimicked by 20 wt% polyethylene glycol (PEG). Transcriptional arrest was induced when the stability of the G-quadruplex structure (-ΔG°37) in the presence of 20 wt% PEG was more than 8.2 kcal mol(-1). Thus, values of stability in the presence of 20 wt% PEG are an important indicator of transcription perturbation. Our results further our understanding of the impact of template structure on the transcription process and may guide logical design of transcription-regulating drugs.

New Insights into Transcription Fidelity: Thermal Stability of Non-Canonical Structures in Template DNA Regulates Transcriptional Arrest, Pause, and Slippage

PubMed Central

Tateishi-Karimata, Hisae; Isono, Noburu; Sugimoto, Naoki

2014-01-01

The thermal stability and topology of non-canonical structures of G-quadruplexes and hairpins in template DNA were investigated, and the effect of non-canonical structures on transcription fidelity was evaluated quantitatively. We designed ten template DNAs: A linear sequence that does not have significant higher-order structure, three sequences that form hairpin structures, and six sequences that form G-quadruplex structures with different stabilities. Templates with non-canonical structures induced the production of an arrested, a slipped, and a full-length transcript, whereas the linear sequence produced only a full-length transcript. The efficiency of production for run-off transcripts (full-length and slipped transcripts) from templates that formed the non-canonical structures was lower than that from the linear. G-quadruplex structures were more effective inhibitors of full-length product formation than were hairpin structure even when the stability of the G-quadruplex in an aqueous solution was the same as that of the hairpin. We considered that intra-polymerase conditions may differentially affect the stability of non-canonical structures. The values of transcription efficiencies of run-off or arrest transcripts were correlated with stabilities of non-canonical structures in the intra-polymerase condition mimicked by 20 wt% polyethylene glycol (PEG). Transcriptional arrest was induced when the stability of the G-quadruplex structure (−ΔGo 37) in the presence of 20 wt% PEG was more than 8.2 kcal mol−1. Thus, values of stability in the presence of 20 wt% PEG are an important indicator of transcription perturbation. Our results further our understanding of the impact of template structure on the transcription process and may guide logical design of transcription-regulating drugs. PMID:24594642

Canonical methods in classical and quantum gravity: An invitation to canonical LQG

NASA Astrophysics Data System (ADS)

Reyes, Juan D.

2018-04-01

Loop Quantum Gravity (LQG) is a candidate quantum theory of gravity still under construction. LQG was originally conceived as a background independent canonical quantization of Einstein’s general relativity theory. This contribution provides some physical motivations and an overview of some mathematical tools employed in canonical Loop Quantum Gravity. First, Hamiltonian classical methods are reviewed from a geometric perspective. Canonical Dirac quantization of general gauge systems is sketched next. The Hamiltonian formultation of gravity in geometric ADM and connection-triad variables is then presented to finally lay down the canonical loop quantization program. The presentation is geared toward advanced undergradute or graduate students in physics and/or non-specialists curious about LQG.

Construction Method of Analytical Solutions to the Mathematical Physics Boundary Problems for Non-Canonical Domains

NASA Astrophysics Data System (ADS)

Mobarakeh, Pouyan Shakeri; Grinchenko, Victor T.

2015-06-01

The majority of practical cases of acoustics problems requires solving the boundary problems in non-canonical domains. Therefore construction of analytical solutions of mathematical physics boundary problems for non-canonical domains is both lucrative from the academic viewpoint, and very instrumental for elaboration of efficient algorithms of quantitative estimation of the field characteristics under study. One of the main solving ideologies for such problems is based on the superposition method that allows one to analyze a wide class of specific problems with domains which can be constructed as the union of canonically-shaped subdomains. It is also assumed that an analytical solution (or quasi-solution) can be constructed for each subdomain in one form or another. However, this case implies some difficulties in the construction of calculation algorithms, insofar as the boundary conditions are incompletely defined in the intervals, where the functions appearing in the general solution are orthogonal to each other. We discuss several typical examples of problems with such difficulties, we study their nature and identify the optimal methods to overcome them.

4-Hydroxynonenal activates Src through a non-canonical pathway that involves EGFR/PTP1B

PubMed Central

Zhang, Hongqiao; Forman, Henry Jay

2015-01-01

Src, a non-receptor protein tyrosine kinase involved in many biological processes, can be activated through both redox-dependent and independent mechanisms. 4-Hydroxy-2-nonenal (HNE) is a lipid peroxidation product that is increased in pathophysiological conditions associated with Src activation. This study examined how HNE activates human c-Src. In the canonical pathway Src activation is initiated by dephosphorylation of pTyr530 followed by conformational change that causes Src auto-phosphorylation at Tyr419 and its activation. HNE increased Src activation in both dose- and time-dependent manner, while it also increased Src phosphorylation at Tyr530 (pTyr530 Src), suggesting that HNE activated Src via a non-canonical mechanism. Protein tyrosine phosphatase 1B inhibitor (539741), at concentrations that increased basal pTyr530 Src, also increased basal Src activity and significantly reduced HNE-mediated Src activation. The EGFR inhibitor, AG1478, and EGFR silencing, abrogated HNE-mediated EGFR activation and inhibited basal and HNE-induced Src activity. In addition, AG1478 also eliminated the increase of basal Src activation by a PTP1B inhibitor. Taken together these data suggest that HNE can activate Src partly through a non-canonical pathway involving activation of EGFR and inhibition of PTP1B. PMID:26453921

RNAHelix: computational modeling of nucleic acid structures with Watson-Crick and non-canonical base pairs.

PubMed

Bhattacharyya, Dhananjay; Halder, Sukanya; Basu, Sankar; Mukherjee, Debasish; Kumar, Prasun; Bansal, Manju

2017-02-01

Comprehensive analyses of structural features of non-canonical base pairs within a nucleic acid double helix are limited by the availability of a small number of three dimensional structures. Therefore, a procedure for model building of double helices containing any given nucleotide sequence and base pairing information, either canonical or non-canonical, is seriously needed. Here we describe a program RNAHelix, which is an updated version of our widely used software, NUCGEN. The program can regenerate duplexes using the dinucleotide step and base pair orientation parameters for a given double helical DNA or RNA sequence with defined Watson-Crick or non-Watson-Crick base pairs. The original structure and the corresponding regenerated structure of double helices were found to be very close, as indicated by the small RMSD values between positions of the corresponding atoms. Structures of several usual and unusual double helices have been regenerated and compared with their original structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high agreements have been noted. RNAHelix can also be used to generate a structure with a sequence completely different from an experimentally determined one or to introduce single to multiple mutation, but with the same set of parameters and hence can also be an important tool in homology modeling and study of mutation induced structural changes.

The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes.

PubMed

Fletcher, Katherine; Ulferts, Rachel; Jacquin, Elise; Veith, Talitha; Gammoh, Noor; Arasteh, Julia M; Mayer, Ulrike; Carding, Simon R; Wileman, Thomas; Beale, Rupert; Florey, Oliver

2018-02-15

A hallmark of macroautophagy is the covalent lipidation of LC3 and insertion into the double-membrane phagophore, which is driven by the ATG16L1/ATG5-ATG12 complex. In contrast, non-canonical autophagy is a pathway through which LC3 is lipidated and inserted into single membranes, particularly endolysosomal vacuoles during cell engulfment events such as LC3-associated phagocytosis. Factors controlling the targeting of ATG16L1 to phagophores are dispensable for non-canonical autophagy, for which the mechanism of ATG16L1 recruitment is unknown. Here we show that the WD repeat-containing C-terminal domain (WD40 CTD) of ATG16L1 is essential for LC3 recruitment to endolysosomal membranes during non-canonical autophagy, but dispensable for canonical autophagy. Using this strategy to inhibit non-canonical autophagy specifically, we show a reduction of MHC class II antigen presentation in dendritic cells from mice lacking the WD40 CTD Further, we demonstrate activation of non-canonical autophagy dependent on the WD40 CTD during influenza A virus infection. This suggests dependence on WD40 CTD distinguishes between macroautophagy and non-canonical use of autophagy machinery. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Endothelial RSPO3 Controls Vascular Stability and Pruning through Non-canonical WNT/Ca(2+)/NFAT Signaling.

PubMed

Scholz, Beate; Korn, Claudia; Wojtarowicz, Jessica; Mogler, Carolin; Augustin, Iris; Boutros, Michael; Niehrs, Christof; Augustin, Hellmut G

2016-01-11

The WNT signaling enhancer R-spondin3 (RSPO3) is prominently expressed in the vasculature. Correspondingly, embryonic lethality of Rspo3-deficient mice is caused by vessel remodeling defects. Yet the mechanisms underlying vascular RSPO3 function remain elusive. Inducible endothelial Rspo3 deletion (Rspo3-iECKO) resulted in perturbed developmental and tumor vascular remodeling. Endothelial cell apoptosis and vascular pruning led to reduced microvessel density in Rspo3-iECKO mice. Rspo3-iECKO mice strikingly phenocopied the non-canonical WNT signaling-induced vascular defects of mice deleted for the WNT secretion factor Evi/Wls. An endothelial screen for RSPO3 and EVI/WLS co-regulated genes identified Rnf213, Usp18, and Trim30α. RNF213 targets filamin A and NFAT1 for proteasomal degradation attenuating non-canonical WNT/Ca(2+) signaling. Likewise, USP18 and TRIM5α inhibited NFAT1 activation. Consequently, NFAT protein levels were decreased in endothelial cells of Rspo3-iECKO mice and pharmacological NFAT inhibition phenocopied Rspo3-iECKO mice. The data identify endothelial RSPO3-driven non-canonical WNT/Ca(2+)/NFAT signaling as a critical maintenance pathway of the remodeling vasculature. Copyright © 2016 Elsevier Inc. All rights reserved.

WIF1 re-expression in glioblastoma inhibits migration through attenuation of non-canonical WNT signaling by downregulating the lncRNA MALAT1.

PubMed

Vassallo, I; Zinn, P; Lai, M; Rajakannu, P; Hamou, M-F; Hegi, M E

2016-01-07

Glioblastoma is the most aggressive primary brain tumor in adults and due to the invasive nature cannot be completely removed. The WNT inhibitory factor 1 (WIF1), a secreted inhibitor of WNTs, is systematically downregulated in glioblastoma and acts as strong tumor suppressor. The aim of this study was the dissection of WIF1-associated tumor-suppressing effects mediated by canonical and non-canonical WNT signaling. We found that WIF1 besides inhibiting the canonical WNT pathway selectively downregulates the WNT/calcium pathway associated with significant reduction of p38-MAPK (p38-mitogen-activated protein kinase) phosphorylation. Knockdown of WNT5A, the only WNT ligand overexpressed in glioblastoma, phenocopied this inhibitory effect. WIF1 expression inhibited cell migration in vitro and in an orthotopic brain tumor model, in accordance with the known regulatory function of the WNT/Ca(2+) pathway on migration and invasion. In search of a mediator for this function differential gene expression profiles of WIF1-expressing cells were performed. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA and key positive regulator of invasion, emerged as the top downregulated gene. Indeed, knockdown of MALAT1 reduced migration in glioblastoma cells, without effect on proliferation. Hence, loss of WIF1 enhances the migratory potential of glioblastoma through WNT5A that activates the WNT/Ca(2+) pathway and MALAT1. These data suggest the involvement of canonical and non-canonical WNT pathways in glioblastoma promoting key features associated with this deadly disease, proliferation on one hand and invasion on the other. Successful targeting will require a dual strategy affecting both canonical and non-canonical WNT pathways.

Consistent Discretization and Canonical, Classical and Quantum Regge Calculus

NASA Astrophysics Data System (ADS)

Gambini, Rodolfo; Pullin, Jorge

We apply the "consistent discretization" technique to the Regge action for (Euclidean and Lorentzian) general relativity in arbitrary number of dimensions. The result is a well-defined canonical theory that is free of constraints and where the dynamics is implemented as a canonical transformation. In the Lorentzian case, the framework appears to be naturally free of the "spikes" that plague traditional formulations. It also provides a well-defined recipe for determining the integration measure for quantum Regge calculus.

Faddeev–Jackiw quantization of an Abelian and non-Abelian exotic action for gravity in three dimensions

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

Escalante, Alberto, E-mail: aescalan@ifuap.buap.mx; Manuel-Cabrera, J., E-mail: jmanuel@ifuap.buap.mx

2015-10-15

A detailed Faddeev–Jackiw quantization of an Abelian and non-Abelian exotic action for gravity in three dimensions is performed. We obtain for the theories under study the constraints, the gauge transformations, the generalized Faddeev–Jackiw brackets and we perform the counting of physical degrees of freedom. In addition, we compare our results with those found in the literature where the canonical analysis is developed, in particular, we show that both the generalized Faddeev–Jackiw brackets and Dirac’s brackets coincide to each other. Finally we discuss some remarks and prospects. - Highlights: • A detailed Faddeev–Jackiw analysis for exotic action of gravity is performed.more » • We show that Dirac’s brackets and Generalized [FJ] brackets are equivalent. • Without fixing the gauge exotic action is a non-commutative theory. • The fundamental gauge transformations of the theory are found. • Dirac and Faddeev–Jackiw approaches are compared.« less

Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling

PubMed Central

Franco, Claudio A; Jones, Martin L; Bernabeu, Miguel O; Vion, Anne-Clemence; Barbacena, Pedro; Fan, Jieqing; Mathivet, Thomas; Fonseca, Catarina G; Ragab, Anan; Yamaguchi, Terry P; Coveney, Peter V; Lang, Richard A; Gerhardt, Holger

2016-01-01

Endothelial cells respond to molecular and physical forces in development and vascular homeostasis. Deregulation of endothelial responses to flow-induced shear is believed to contribute to many aspects of cardiovascular diseases including atherosclerosis. However, how molecular signals and shear-mediated physical forces integrate to regulate vascular patterning is poorly understood. Here we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/Wnt11 renders endothelial cells more sensitive to shear, resulting in axial polarization and migration against flow at lower shear levels. Integration of flow modelling and polarity analysis in entire vascular networks demonstrates that polarization against flow is achieved differentially in artery, vein, capillaries and the primitive sprouting front. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus. DOI: http://dx.doi.org/10.7554/eLife.07727.001 PMID:26845523

The biochemistry and immunology of non-canonical forms of HLA-B27.

PubMed

Shaw, Jacqueline; Hatano, Hiroko; Kollnberger, Simon

2014-01-01

HLA-B27 (B27) is strongly associated with the spondyloarthritides. B27 is expressed at the cell surface of antigen presenting cells (APC) both as canonical β2m-associated and non-canonical β2m-free heavy chain (FHC) forms which include B27 dimers (termed B272). B27 FHC forms arise in an endosomal compartment from recycling β2m-associated B27. Formation of cell surface FHC dimers is critically dependent on an unpaired reactive cysteine 67 in the α1 helix of the class I heavy chain. HLA-B27 also form redox-inducible β2m-associated dimers on exosomes and apoptosing cells. By contrast with cell surface expressed cysteine 67-dependent heavy chain dimers these dimers are dependent on a cytoplasmic cysteine 325 for their formation. HLA-B27 binds to immunoregulatory receptors including members of the Killer cell Immunoglobulin-like (KIR) and Leukocyte Immunoglobulin-like receptor family. B27 FHC bind to different but overlapping sets of these immunoreceptors compared to classical β2m-associated HLA-B27. B27 FHC bind more strongly to KIR3DL2 and LILRB2 immune receptor than other β2m-associated HLA-class I ligands. Genetic studies have implicated genes which control production of the important proinflammatory cytokine IL-17 in the pathogenesis of spondyloarthritis. Cell surface HLA-B27 FHC binding to these immune receptors or acting through other mechanisms could impact on the pathogenesis of spondyloarthritis by promoting immune cell production of IL-17. Here we review the literature on these non-canonical forms of HLA-B27 and the immune receptors they bind to and discuss the possible relevance of these interactions to the pathogenesis of spondyloarthropathy. Copyright © 2013 Elsevier Ltd. All rights reserved.

On the relativistic micro-canonical ensemble and relativistic kinetic theory for N relativistic particles in inertial and non-inertial rest frames

NASA Astrophysics Data System (ADS)

Alba, David; Crater, Horace W.; Lusanna, Luca

2015-03-01

A new formulation of relativistic classical mechanics allows a reconsideration of old unsolved problems in relativistic kinetic theory and in relativistic statistical mechanics. In particular a definition of the relativistic micro-canonical partition function is given strictly in terms of the Poincaré generators of an interacting N-particle system both in the inertial and non-inertial rest frames. The non-relativistic limit allows a definition of both the inertial and non-inertial micro-canonical ensemble in terms of the Galilei generators.

2D non-separable linear canonical transform (2D-NS-LCT) based cryptography

NASA Astrophysics Data System (ADS)

Zhao, Liang; Muniraj, Inbarasan; Healy, John J.; Malallah, Ra'ed; Cui, Xiao-Guang; Ryle, James P.; Sheridan, John T.

2017-05-01

The 2D non-separable linear canonical transform (2D-NS-LCT) can describe a variety of paraxial optical systems. Digital algorithms to numerically evaluate the 2D-NS-LCTs are not only important in modeling the light field propagations but also of interest in various signal processing based applications, for instance optical encryption. Therefore, in this paper, for the first time, a 2D-NS-LCT based optical Double-random- Phase-Encryption (DRPE) system is proposed which offers encrypting information in multiple degrees of freedom. Compared with the traditional systems, i.e. (i) Fourier transform (FT); (ii) Fresnel transform (FST); (iii) Fractional Fourier transform (FRT); and (iv) Linear Canonical transform (LCT), based DRPE systems, the proposed system is more secure and robust as it encrypts the data with more degrees of freedom with an augmented key-space.

Non-canonical NF-κB signalling and ETS1/2 cooperatively drive C250T mutant TERT promoter activation

PubMed Central

Li, Yinghui; Zhou, Qi-Ling; Sun, Wenjie; Chandrasekharan, Prashant; Cheng, Hui Shan; Ying, Zhe; Lakshmanan, Manikandan; Raju, Anandhkumar; Tenen, Daniel G.; Cheng, Shi-Yuan; Chuang, Kai-Hsiang; Li, Jun; Prabhakar, Shyam; Li, Mengfeng; Tergaonkar, Vinay

2016-01-01

Transcriptional reactivation of TERT, the catalytic subunit of telomerase, is necessary for cancer progression in about 90% of human cancers. The recent discovery of two prevalent somatic mutations—C250T and C228T—in the TERT promoter in various cancers has provided insight into a plausible mechanism of TERT reactivation. Although the two hotspot mutations create a similar binding motif for E-twenty-six (ETS) transcription factors, we show that they are functionally distinct, in that the C250T unlike the C228T TERT promoter is driven by non-canonical NF-κB signalling. We demonstrate that binding of ETS to the mutant TERT promoter is insufficient in driving its transcription but this process requires non-canonical NF-κB signalling for stimulus responsiveness, sustained telomerase activity and hence cancer progression. Our findings highlight a previously unrecognized role of non-canonical NF-κB signalling in tumorigenesis and elucidate a fundamental mechanism for TERT reactivation in cancers, which if targeted could have immense therapeutic implications. PMID:26389665

Non-canonical NF-κB signalling and ETS1/2 cooperatively drive C250T mutant TERT promoter activation.

PubMed

Li, Yinghui; Zhou, Qi-Ling; Sun, Wenjie; Chandrasekharan, Prashant; Cheng, Hui Shan; Ying, Zhe; Lakshmanan, Manikandan; Raju, Anandhkumar; Tenen, Daniel G; Cheng, Shi-Yuan; Chuang, Kai-Hsiang; Li, Jun; Prabhakar, Shyam; Li, Mengfeng; Tergaonkar, Vinay

2015-10-01

Transcriptional reactivation of TERT, the catalytic subunit of telomerase, is necessary for cancer progression in about 90% of human cancers. The recent discovery of two prevalent somatic mutations-C250T and C228T-in the TERT promoter in various cancers has provided insight into a plausible mechanism of TERT reactivation. Although the two hotspot mutations create a similar binding motif for E-twenty-six (ETS) transcription factors, we show that they are functionally distinct, in that the C250T unlike the C228T TERT promoter is driven by non-canonical NF-κB signalling. We demonstrate that binding of ETS to the mutant TERT promoter is insufficient in driving its transcription but this process requires non-canonical NF-κB signalling for stimulus responsiveness, sustained telomerase activity and hence cancer progression. Our findings highlight a previously unrecognized role of non-canonical NF-κB signalling in tumorigenesis and elucidate a fundamental mechanism for TERT reactivation in cancers, which if targeted could have immense therapeutic implications.

Ligand-activated epidermal growth factor receptor (EGFR) signaling governs endocytic trafficking of unliganded receptor monomers by non-canonical phosphorylation.

PubMed

Tanaka, Tomohiro; Zhou, Yue; Ozawa, Tatsuhiko; Okizono, Ryuya; Banba, Ayako; Yamamura, Tomohiro; Oga, Eiji; Muraguchi, Atsushi; Sakurai, Hiroaki

2018-02-16

The canonical description of transmembrane receptor function is initial binding of ligand, followed by initiation of intracellular signaling and then internalization en route to degradation or recycling to the cell surface. It is known that low concentrations of extracellular ligand lead to a higher proportion of receptor that is recycled and that non-canonical mechanisms of receptor activation, including phosphorylation by the kinase p38, can induce internalization and recycling. However, no connections have been made between these pathways; i.e. it has yet to be established what happens to unbound receptors following stimulation with ligand. Here we demonstrate that a minimal level of activation of epidermal growth factor receptor (EGFR) tyrosine kinase by low levels of ligand is sufficient to fully activate downstream mitogen-activated protein kinase (MAPK) pathways, with most of the remaining unbound EGFR molecules being efficiently phosphorylated at intracellular serine/threonine residues by activated mitogen-activated protein kinase. This non-canonical, p38-mediated phosphorylation of the C-tail of EGFR, near Ser-1015, induces the clathrin-mediated endocytosis of the unliganded EGFR monomers, which occurs slightly later than the canonical endocytosis of ligand-bound EGFR dimers via tyrosine autophosphorylation. EGFR endocytosed via the non-canonical pathway is largely recycled back to the plasma membrane as functional receptors, whereas p38-independent populations are mainly sorted for lysosomal degradation. Moreover, ligand concentrations balance these endocytic trafficking pathways. These results demonstrate that ligand-activated EGFR signaling controls unliganded receptors through feedback phosphorylation, identifying a dual-mode regulation of the endocytic trafficking dynamics of EGFR. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

A non-canonical transferred DNA insertion at the BRI1 locus in Arabidopsis thaliana.

PubMed

Zhao, Zhong; Zhu, Yan; Erhardt, Mathieu; Ruan, Ying; Shen, Wen-Hui

2009-04-01

Agrobacterium-mediated transformation is widely used in transgenic plant engineering and has been proven to be a powerful tool for insertional mutagenesis of the plant genome. The transferred DNA (T-DNA) from Agrobacterium is integrated into the plant genome through illegitimate recombination between the T-DNA and the plant DNA. Contrasting to the canonical insertion, here we report on a locus showing a complex mutation associated with T-DNA insertion at the BRI1 gene in Arabidopsis thaliana. We obtained a mutant line, named salade for its phenotype of dwarf stature and proliferating rosette. Molecular characterization of this mutant revealed that in addition to T-DNA a non-T-DNA-localized transposon from bacteria was inserted in the Arabidopsis genome and that a region of more than 11.5 kb of the Arabidopsis genome was deleted at the insertion site. The deleted region contains the brassinosteroid receptor gene BRI1 and the transcription factor gene WRKY13. Our finding reveals non-canonical T-DNA insertion, implicating horizontal gene transfer and cautioning the use of T-DNA as mutagen in transgenic research.

Toward a generalized equation for the Reynolds stress: Turbulence momentum balance in non-canonical flows

NASA Astrophysics Data System (ADS)

Lee, T.-W.

2017-11-01

Recently, we developed a theoretical basis for determination of the Reynolds stress in canonical flows. Writing momentum balance for a control volume moving at the local mean velocity, along with a differential transform ∂/∂x =C1 U∂/∂y , a turbulence momentum balance is discovered which includes the Reynolds stress as a function of root turbulence parameters: ∂(u'v')/∂y = -C1 U∂u'2/∂y +νm∂2urms'/∂y2 . Then, the Reynolds stress can simply be computed by integrating in the y-direction using the right-hand side (RHS). This is obviously a far simplification of complex modeling of the Reynolds stress, but contains the correct physics, as borne out by comparisons with experimental and DNS data in canonical flows in our earlier works (e.g. in APS 2016). The RHS contains only two parameters, U and u'. In this work, we seek extensions of this solution to non-canonical flows such as wakes, flow over a step, and mixing layers. Comparisons with experimental and DNS data will be presented.

Canonical field anticommutators in the extended gauged Rarita-Schwinger theory

NASA Astrophysics Data System (ADS)

Adler, Stephen L.; Henneaux, Marc; Pais, Pablo

2017-10-01

We reexamine canonical quantization of the gauged Rarita-Schwinger theory using the extended theory, incorporating a dimension 1/2 auxiliary spin-1/2 field Λ , in which there is an exact off-shell gauge invariance. In Λ =0 gauge, which reduces to the original unextended theory, our results agree with those found by Johnson and Sudarshan, and later verified by Velo and Zwanziger, which give a canonical Rarita-Schwinger field Dirac bracket that is singular for small gauge fields. In gauge covariant radiation gauge, the Dirac bracket of the Rarita-Schwinger fields is nonsingular, but does not correspond to a positive semidefinite anticommutator, and the Dirac bracket of the auxiliary fields has a singularity of the same form as found in the unextended theory. These results indicate that gauged Rarita-Schwinger theory is somewhat pathological, and cannot be canonically quantized within a conventional positive semidefinite metric Hilbert space. We leave open the questions of whether consistent quantizations can be achieved by using an indefinite metric Hilbert space, by path integral methods, or by appropriate couplings to conventional dimension 3/2 spin-1/2 fields.

Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction

PubMed Central

Sowers, L. P.; Loo, L.; Wu, Y.; Campbell, E.; Ulrich, J. D.; Wu, S.; Paemka, L.; Wassink, T.; Meyer, K.; Bing, X.; El-Shanti, H.; Usachev, Y. M.; Ueno, N.; Manak, R. J.; Shepherd, A. J.; Ferguson, P. J.; Darbro, B. W.; Richerson, G. B.; Mohapatra, D. P.; Wemmie, J. A.; Bassuk, A. G.

2014-01-01

Autism spectrum disorders (ASDs) have been suggested to arise from abnormalities in the canonical and non-canonical Wnt signaling pathways. However, a direct connection between a human variant in a Wnt pathway gene and ASD-relevant brain pathology has not been established. Prickle2 (Pk2) is a post-synaptic non-canonical Wnt signaling protein shown to interact with post synaptic density 95 (PSD-95). Here we show that mice with disruption in Prickle2 display behavioral abnormalities including altered social interaction, learning abnormalities, and behavioral inflexibility. Prickle2 disruption in mouse hippocampal neurons led to reductions in dendrite branching, synapse number, and post-synaptic density size. Consistent with these findings, Prickle2 null neurons show decreased frequency and size of spontaneous miniature synaptic currents. These behavioral and physiological abnormalities in Prickle2 disrupted mice are consistent with ASD-like phenotypes present in other mouse models of ASDs. In 384 individuals with autism, we identified two with distinct, heterozygous, rare, non-synonymous PRICKLE2 variants (p.E8Q and p.V153I) that were shared by their affected siblings and inherited paternally. Unlike wild-type PRICKLE2, the PRICKLE2 variants found in ASD patients exhibit deficits in morphological and electrophysiological assays. These data suggest that these PRICKLE2 variants cause a critical loss of PRICKLE2 function. The data presented here provide new insight into the biological roles of Prickle2, its behavioral importance, and suggest disruptions in non-canonical Wnt genes such as PRICKLE2 may contribute to synaptic abnormalities underlying ASDs. PMID:23711981

MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of multiple genes from the non-canonical TGF-β signalling pathway

PubMed Central

Lynch, Jennifer; Fay, Joanna; Meehan, Maria; Bryan, Kenneth; Watters, Karen M.; Murphy, Derek M.; Stallings, Raymond L.

2012-01-01

Transforming growth factor-β (TGF-β) signaling regulates many diverse cellular activities through both canonical (SMAD-dependent) and non-canonical branches, which includes the mitogen-activated protein kinase (MAPK), Rho-like guanosine triphosphatase and phosphatidylinositol-3-kinase/AKT pathways. Here, we demonstrate that miR-335 directly targets and downregulates genes in the TGF-β non-canonical pathways, including the Rho-associated coiled-coil containing protein (ROCK1) and MAPK1, resulting in reduced phosphorylation of downstream pathway members. Specifically, inhibition of ROCK1 and MAPK1 reduces phosphorylation levels of the motor protein myosin light chain (MLC) leading to a significant inhibition of the invasive and migratory potential of neuroblastoma cells. Additionally, miR-335 targets the leucine-rich alpha-2-glycoprotein 1 (LRG1) messenger RNA, which similarly results in a significant reduction in the phosphorylation status of MLC and a decrease in neuroblastoma cell migration and invasion. Thus, we link LRG1 to the migratory machinery of the cell, altering its activity presumably by exerting its effect within the non-canonical TGF-β pathway. Moreover, we demonstrate that the MYCN transcription factor, whose coding sequence is highly amplified in a particularly clinically aggressive neuroblastoma tumor subtype, directly binds to a region immediately upstream of the miR-335 transcriptional start site, resulting in transcriptional repression. We conclude that MYCN contributes to neuroblastoma cell migration and invasion, by directly downregulating miR-335, resulting in the upregulation of the TGF-β signaling pathway members ROCK1, MAPK1 and putative member LRG1, which positively promote this process. Our results provide novel insight into the direct regulation of TGF-β non-canonical signaling by miR-335, which in turn is downregulated by MYCN. PMID:22382496

A Non-canonical Feedback Circuit for Rapid Interactions between Somatosensory Cortices.

PubMed

Minamisawa, Genki; Kwon, Sung Eun; Chevée, Maxime; Brown, Solange P; O'Connor, Daniel H

2018-05-29

Sensory perception depends on interactions among cortical areas. These interactions are mediated by canonical patterns of connectivity in which higher areas send feedback projections to lower areas via neurons in superficial and deep layers. Here, we probed the circuit basis of interactions among two areas critical for touch perception in mice, whisker primary (wS1) and secondary (wS2) somatosensory cortices. Neurons in layer 4 of wS2 (S2 L4 ) formed a major feedback pathway to wS1. Feedback from wS2 to wS1 was organized somatotopically. Spikes evoked by whisker deflections occurred nearly as rapidly in wS2 as in wS1, including among putative S2 L4 → S1 feedback neurons. Axons from S2 L4 → S1 neurons sent stimulus orientation-specific activity to wS1. Optogenetic excitation of S2 L4 neurons modulated activity across both wS2 and wS1, while inhibition of S2 L4 reduced orientation tuning among wS1 neurons. Thus, a non-canonical feedback circuit, originating in layer 4 of S2, rapidly modulates early tactile processing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Fyn/Yes and non-canonical Wnt signalling converge on RhoA in vertebrate gastrulation cell movements

PubMed Central

Jopling, Chris; den Hertog, Jeroen

2005-01-01

Convergent extension (CE) cell movements during gastrulation mediate extension of the anterior–posterior body axis of vertebrate embryos. Non-canonical Wnt5 and Wnt11 signalling is essential for normal CE movements in vertebrate gastrulation. Here, we show that morpholino (MO)-mediated double knock-down of the Fyn and Yes tyrosine kinases in zebrafish embryos impaired normal CE cell movements, resembling the silberblick and pipetail mutants, caused by mutations in wnt11 and wnt5, respectively. Co-injection of Fyn/Yes- and Wnt11- or Wnt5-MO was synergistic, but wnt11 or wnt5 RNA did not rescue the Fyn/Yes knockdown or vice versa. Remarkably, active RhoA rescued the Fyn/Yes knockdown as well as the Wnt11 knockdown, indicating that Fyn/Yes and Wnt11 signalling converged on RhoA. Our results show that Fyn and Yes act together with non-canonical Wnt signalling via RhoA in CE cell movements during gastrulation. PMID:15815683

Vanishing of local non-Gaussianity in canonical single field inflation

NASA Astrophysics Data System (ADS)

Bravo, Rafael; Mooij, Sander; Palma, Gonzalo A.; Pradenas, Bastián

2018-05-01

We study the production of observable primordial local non-Gaussianity in two opposite regimes of canonical single field inflation: attractor (standard single field slow-roll inflation) and non attractor (ultra slow-roll inflation). In the attractor regime, the standard derivation of the bispectrum's squeezed limit using co-moving coordinates gives the well known Maldacena's consistency relation fNL = 5 (1‑ns) / 12. On the other hand, in the non-attractor regime, the squeezed limit offers a substantial violation of this relation given by fNL = 5/2. In this work we argue that, independently of whether inflation is attractor or non-attractor, the size of the observable primordial local non-Gaussianity is predicted to be fNLobs = 0 (a result that was already understood to hold in the case of attractor models). To show this, we follow the use of the so-called Conformal Fermi Coordinates (CFC), recently introduced in the literature. These coordinates parametrize the local environment of inertial observers in a perturbed FRW spacetime, allowing one to identify and compute gauge invariant quantities, such as n-point correlation functions. Concretely, we find that during inflation, after all the modes have exited the horizon, the squeezed limit of the 3-point correlation function of curvature perturbations vanishes in the CFC frame, regardless of the inflationary regime. We argue that such a cancellation should persist after inflation ends.

SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling.

PubMed

Cortez, Victor S; Ulland, Tyler K; Cervantes-Barragan, Luisa; Bando, Jennifer K; Robinette, Michelle L; Wang, Qianli; White, Andrew J; Gilfillan, Susan; Cella, Marina; Colonna, Marco

2017-09-01

Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from natural killer (NK) cells is a gene signature indicative of 'imprinting' by cytokines of the TGF-β family. We studied mice in which ILC1s and NK cells lacked SMAD4, a signal transducer that facilitates the canonical signaling pathway common to all cytokines of the TGF-β family. While SMAD4 deficiency did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like gene signature and were unable to control tumor metastasis or viral infection. Mechanistically, SMAD4 restrained non-canonical TGF-β signaling mediated by the cytokine receptor TGFβR1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-β. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-β signaling in NK cells.

SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling

PubMed Central

Cortez, Victor S; Ulland, Tyler K; Cervantes-Barragan, Luisa; Bando, Jennifer K; Robinette, Michelle L; Wang, Qianli; White, Andrew J; Gilfillan, Susan; Cella, Marina; Colonna, Marco

2017-01-01

Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from natural killer (NK) cells is a gene signature indicative of ‘imprinting’ by cytokines of the TGF-β family. We examined mice in which ILC1s and NK cells lacked SMAD4, a signal transducer that facilitates the canonical signaling pathway common to all cytokines of the TGF-β family. While SMAD4 deficiency did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like gene signature and were unable to control tumor metastasis or viral infection. Mechanistically, SMAD4 restrained non-canonical TGF-β signaling mediated by the cytokine receptor TGF-βR1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-β. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-β signaling in NK cells. PMID:28759002

Subcellular Localization of a Plant Catalase-Phenol Oxidase, AcCATPO, from Amaranthus and Identification of a Non-canonical Peroxisome Targeting Signal

PubMed Central

Chen, Ning; Teng, Xiao-Lu; Xiao, Xing-Guo

2017-01-01

AcCATPO is a plant catalase-phenol oxidase recently identified from red amaranth. Its physiological function remains unexplored. As the starting step of functional analysis, here we report its subcellular localization and a non-canonical targeting signal. Commonly used bioinformatics programs predicted a peroxisomal localization for AcCATPO, but failed in identification of canonical peroxisomal targeting signals (PTS). The C-terminal GFP tagging led the fusion protein AcCATPO-GFP to the cytosol and the nucleus, but N-terminal tagging directed the GFP-AcCATPO to peroxisomes and nuclei, in transgenic tobacco. Deleting the tripeptide (PTM) at the extreme C-terminus almost ruled out the peroxisomal localization of GFP-AcCATPOΔ3, and removing the C-terminal decapeptide completely excluded peroxisomes as the residence of GFP-AcCATPOΔ10. Furthermore, this decapeptide as a targeting signal could import GFP-10aa to the peroxisome exclusively. Taken together, these results demonstrate that AcCATPO is localized to the peroxisome and the nucleus, and its peroxisomal localization is attributed to a non-canonical PTS1, the C-terminal decapeptide which contains an internal SRL motif and a conserved tripeptide P-S/T-I/M at the extreme of C-terminus. This work may further the study as to the physiological function of AcCATPO, especially clarify its involvement in betalain biosynthesis, and provide a clue to elucidate more non-canonic PTS. PMID:28824680

Subcellular Localization of a Plant Catalase-Phenol Oxidase, AcCATPO, from Amaranthus and Identification of a Non-canonical Peroxisome Targeting Signal.

PubMed

Chen, Ning; Teng, Xiao-Lu; Xiao, Xing-Guo

2017-01-01

AcCATPO is a plant catalase-phenol oxidase recently identified from red amaranth. Its physiological function remains unexplored. As the starting step of functional analysis, here we report its subcellular localization and a non-canonical targeting signal. Commonly used bioinformatics programs predicted a peroxisomal localization for AcCATPO, but failed in identification of canonical peroxisomal targeting signals (PTS). The C-terminal GFP tagging led the fusion protein AcCATPO-GFP to the cytosol and the nucleus, but N-terminal tagging directed the GFP-AcCATPO to peroxisomes and nuclei, in transgenic tobacco. Deleting the tripeptide (PTM) at the extreme C-terminus almost ruled out the peroxisomal localization of GFP-AcCATPOΔ3, and removing the C-terminal decapeptide completely excluded peroxisomes as the residence of GFP-AcCATPOΔ10. Furthermore, this decapeptide as a targeting signal could import GFP-10aa to the peroxisome exclusively. Taken together, these results demonstrate that AcCATPO is localized to the peroxisome and the nucleus, and its peroxisomal localization is attributed to a non-canonical PTS1, the C-terminal decapeptide which contains an internal SRL motif and a conserved tripeptide P-S/T-I/M at the extreme of C-terminus. This work may further the study as to the physiological function of AcCATPO, especially clarify its involvement in betalain biosynthesis, and provide a clue to elucidate more non-canonic PTS.

A Novel Non-canonical Forkhead-associated (FHA) Domain-binding Interface Mediates the Interaction between Rad53 and Dbf4 Proteins*

PubMed Central

Matthews, Lindsay A.; Selvaratnam, Rajeevan; Jones, Darryl R.; Akimoto, Madoka; McConkey, Brendan J.; Melacini, Giuseppe; Duncker, Bernard P.; Guarné, Alba

2014-01-01

Forkhead-associated (FHA) and BRCA1 C-terminal (BRCT) domains are overrepresented in DNA damage and replication stress response proteins. They function primarily as phosphoepitope recognition modules but can also mediate non-canonical interactions. The latter are rare, and only a few have been studied at a molecular level. We have identified a crucial non-canonical interaction between the N-terminal FHA1 domain of the checkpoint effector kinase Rad53 and the BRCT domain of the regulatory subunit of the Dbf4-dependent kinase that is critical to suppress late origin firing and to stabilize stalled forks during replication stress. The Rad53-Dbf4 interaction is phosphorylation-independent and involves a novel non-canonical interface on the FHA1 domain. Mutations within this surface result in hypersensitivity to genotoxic stress. Importantly, this surface is not conserved in the FHA2 domain of Rad53, suggesting that the FHA domains of Rad53 gain specificity by engaging additional interaction interfaces beyond their phosphoepitope-binding site. In general, our results point to FHA domains functioning as complex logic gates rather than mere phosphoepitope-targeting modules. PMID:24285546

Induction of CXC chemokines in human mesenchymal stem cells by stimulation with secreted frizzled-related proteins through non-canonical Wnt signaling.

PubMed

Bischoff, David S; Zhu, Jian-Hua; Makhijani, Nalini S; Yamaguchi, Dean T

2015-12-26

To investigate the effect of secreted frizzled-related proteins (sFRPs) on CXC chemokine expression in human mesenchymal stem cells (hMSCs). CXC chemokines such as CXCL5 and CXCL8 are induced in hMSCs during differentiation with osteogenic differentiation medium (OGM) and may be involved in angiogenic stimulation during bone repair. hMSCs were treated with conditioned medium (CM) from L-cells expressing non-canonical Wnt5a protein, or with control CM from wild type L-cells, or directly with sFRPs for up to 10 d in culture. mRNA expression levels of both CXCL5 and CXCL8 were quantitated by real-time reverse transcriptase-polymerase chain reaction and secreted protein levels of these proteins determined by ELISA. Dose- (0-500 ng/mL) and time-response curves were generated for treatment with sFRP1. Signal transduction pathways were explored by western blot analysis with pan- or phosphorylation-specific antibodies, through use of specific pathway inhibitors, and through use of siRNAs targeting specific frizzled receptors (Fzd)-2 and 5 or the receptor tyrosine kinase-like orphan receptor-2 (RoR2) prior to treatment with sFRPs. CM from L-cells expressing Wnt5a, a non-canonical Wnt, stimulated an increase in CXCL5 mRNA expression and protein secretion in comparison to control L-cell CM. sFRP1, which should inhibit both canonical and non-canonical Wnt signaling, surprisingly enhanced the expression of CXCL5 at 7 and 10 d. Dickkopf1, an inhibitor of canonical Wnt signaling prevented the sFRP-stimulated induction of CXCL5 and actually inhibited basal levels of CXCL5 expression at 7 but not at 10 d post treatment. In addition, all four sFRPs isoforms induced CXCL8 expression in a dose- and time-dependent manner with maximum expression at 7 d with treatment at 150 ng/mL. The largest increases in CXCL5 expression were seen from stimulation with sFRP1 or sFRP2. Analysis of mitogen-activated protein kinase signaling pathways in the presence of OGM showed sFRP1-induced

Induction of CXC chemokines in human mesenchymal stem cells by stimulation with secreted frizzled-related proteins through non-canonical Wnt signaling

PubMed Central

Bischoff, David S; Zhu, Jian-Hua; Makhijani, Nalini S; Yamaguchi, Dean T

2015-01-01

AIM: To investigate the effect of secreted frizzled-related proteins (sFRPs) on CXC chemokine expression in human mesenchymal stem cells (hMSCs). METHODS: CXC chemokines such as CXCL5 and CXCL8 are induced in hMSCs during differentiation with osteogenic differentiation medium (OGM) and may be involved in angiogenic stimulation during bone repair. hMSCs were treated with conditioned medium (CM) from L-cells expressing non-canonical Wnt5a protein, or with control CM from wild type L-cells, or directly with sFRPs for up to 10 d in culture. mRNA expression levels of both CXCL5 and CXCL8 were quantitated by real-time reverse transcriptase-polymerase chain reaction and secreted protein levels of these proteins determined by ELISA. Dose- (0-500 ng/mL) and time-response curves were generated for treatment with sFRP1. Signal transduction pathways were explored by western blot analysis with pan- or phosphorylation-specific antibodies, through use of specific pathway inhibitors, and through use of siRNAs targeting specific frizzled receptors (Fzd)-2 and 5 or the receptor tyrosine kinase-like orphan receptor-2 (RoR2) prior to treatment with sFRPs. RESULTS: CM from L-cells expressing Wnt5a, a non-canonical Wnt, stimulated an increase in CXCL5 mRNA expression and protein secretion in comparison to control L-cell CM. sFRP1, which should inhibit both canonical and non-canonical Wnt signaling, surprisingly enhanced the expression of CXCL5 at 7 and 10 d. Dickkopf1, an inhibitor of canonical Wnt signaling prevented the sFRP-stimulated induction of CXCL5 and actually inhibited basal levels of CXCL5 expression at 7 but not at 10 d post treatment. In addition, all four sFRPs isoforms induced CXCL8 expression in a dose- and time-dependent manner with maximum expression at 7 d with treatment at 150 ng/mL. The largest increases in CXCL5 expression were seen from stimulation with sFRP1 or sFRP2. Analysis of mitogen-activated protein kinase signaling pathways in the presence of OGM showed s

Non-canonical NOTCH3 signalling limits tumour angiogenesis.

PubMed

Lin, Shuheng; Negulescu, Ana; Bulusu, Sirisha; Gibert, Benjamin; Delcros, Jean-Guy; Ducarouge, Benjamin; Rama, Nicolas; Gadot, Nicolas; Treilleux, Isabelle; Saintigny, Pierre; Meurette, Olivier; Mehlen, Patrick

2017-07-18

Notch signalling is a causal determinant of cancer and efforts have been made to develop targeted therapies to inhibit the so-called canonical pathway. Here we describe an unexpected pro-apoptotic role of Notch3 in regulating tumour angiogenesis independently of the Notch canonical pathway. The Notch3 ligand Jagged-1 is upregulated in a fraction of human cancer and our data support the view that Jagged-1, produced by cancer cells, is inhibiting the apoptosis induced by the aberrant Notch3 expression in tumour vasculature. We thus present Notch3 as a dependence receptor inducing endothelial cell death while this pro-apoptotic activity is blocked by Jagged-1. Along this line, using Notch3 mutant mice, we demonstrate that tumour growth and angiogenesis are increased when Notch3 is silenced in the stroma. Consequently, we show that the well-documented anti-tumour effect mediated by γ-secretase inhibition is at least in part dependent on the apoptosis triggered by Notch3 in endothelial cells.

Non-canonical NOTCH3 signalling limits tumour angiogenesis

PubMed Central

Lin, Shuheng; Negulescu, Ana; Bulusu, Sirisha; Gibert, Benjamin; Delcros, Jean-Guy; Ducarouge, Benjamin; Rama, Nicolas; Gadot, Nicolas; Treilleux, Isabelle; Saintigny, Pierre; Meurette, Olivier; Mehlen, Patrick

2017-01-01

Notch signalling is a causal determinant of cancer and efforts have been made to develop targeted therapies to inhibit the so-called canonical pathway. Here we describe an unexpected pro-apoptotic role of Notch3 in regulating tumour angiogenesis independently of the Notch canonical pathway. The Notch3 ligand Jagged-1 is upregulated in a fraction of human cancer and our data support the view that Jagged-1, produced by cancer cells, is inhibiting the apoptosis induced by the aberrant Notch3 expression in tumour vasculature. We thus present Notch3 as a dependence receptor inducing endothelial cell death while this pro-apoptotic activity is blocked by Jagged-1. Along this line, using Notch3 mutant mice, we demonstrate that tumour growth and angiogenesis are increased when Notch3 is silenced in the stroma. Consequently, we show that the well-documented anti-tumour effect mediated by γ-secretase inhibition is at least in part dependent on the apoptosis triggered by Notch3 in endothelial cells. PMID:28719575

Alteration of Wnt5a expression and of the non-canonical Wnt/PCP and Wnt/PKC-Ca2+ pathways in human osteoarthritis osteoblasts

PubMed Central

Martineau, Xavier; Abed, Élie; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Lajeunesse, Daniel

2017-01-01

Objective Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblasts (Ob) is involved in the progression and/or onset of osteoarthritis (OA). Human Ob isolated from sclerotic subchondral OA bone tissue show an altered phenotype, a decreased canonical Wnt/β-catenin signaling pathway (cWnt), and a reduced mineralization in vitro. In addition to the cWnt pathway, at least two non-canonical signaling pathways, the Wnt/PKC and Wnt/PCP pathway have been described. However, there are no reports of either pathway in OA Ob. Here, we studied the two non-canonical pathways in OA Ob and if they influence their phenotype. Methods Human primary subchondral Ob were isolated from the subchondral bone plate of tibial plateaus of OA patients undergoing total knee arthroplasty, or of normal individuals at autopsy. The expression of genes involved in non-canonical Wnt signaling was evaluated by qRT-PCR and their protein production by Western blot analysis. Alkaline phosphatase activity and osteocalcin secretion (OC) were determined with substrate hydrolysis and EIA, respectively. Mineralization levels were evaluated with Alizarin Red Staining, Wnt/PKC and Wnt/PCP pathways by target gene expression and their respective activity using the NFAT and AP-1 luciferase reporter assays. Results OA Ob showed an altered phenotype as illustrated by an increased alkaline phosphatase activity and osteocalcin release compared to normal Ob. The expression of the non-canonical Wnt5a ligand was increased in OA Ob compared to normal. Whereas, the expression of LGR5 was significantly increased in OA Ob compared to normal Ob, the expression of LGR4 was similar. Wnt5a directly stimulated the expression and production of LGR5, contrasting, Wnt5a did not stimulate the expression of LGR4. Wnt5a also stimulated the phosphorylation of both JNK and PKC, as well as the activity of both NFAT and AP-1 transcription factors. The inhibition of Wnt5a expression partially

A non-canonical site reveals the cooperative mechanisms of microRNA-mediated silencing.

PubMed

Flamand, Mathieu N; Gan, Hin Hark; Mayya, Vinay K; Gunsalus, Kristin C; Duchaine, Thomas F

2017-07-07

Although strong evidence supports the importance of their cooperative interactions, microRNA (miRNA)-binding sites are still largely investigated as functionally independent regulatory units. Here, a survey of alternative 3΄UTR isoforms implicates a non-canonical seedless site in cooperative miRNA-mediated silencing. While required for target mRNA deadenylation and silencing, this site is not sufficient on its own to physically recruit miRISC. Instead, it relies on facilitating interactions with a nearby canonical seed-pairing site to recruit the Argonaute complexes. We further show that cooperation between miRNA target sites is necessary for silencing in vivo in the C. elegans embryo, and for the recruitment of the Ccr4-Not effector complex. Using a structural model of cooperating miRISCs, we identified allosteric determinants of cooperative miRNA-mediated silencing that are required for both embryonic and larval miRNA functions. Our results delineate multiple cooperative mechanisms in miRNA-mediated silencing and further support the consideration of target site cooperation as a fundamental characteristic of miRNA function. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Three dimensional canonical singularity and five dimensional N = 1 SCFT

NASA Astrophysics Data System (ADS)

Xie, Dan; Yau, Shing-Tung

2017-06-01

We conjecture that every three dimensional canonical singularity defines a five dimensional N = 1 SCFT. Flavor symmetry can be found from singularity structure: non-abelian flavor symmetry is read from the singularity type over one dimensional singular locus. The dimension of Coulomb branch is given by the number of compact crepant divisors from a crepant resolution of singularity. The detailed structure of Coulomb branch is described as follows: a) a chamber of Coulomb branch is described by a crepant resolution, and this chamber is given by its Nef cone and the prepotential is computed from triple intersection numbers; b) Crepant resolution is not unique and different resolutions are related by flops; Nef cones from crepant resolutions form a fan which is claimed to be the full Coulomb branch.

Perceived Emotional Intelligence and Learning Strategies in Spanish University Students: A New Perspective from a Canonical Non-symmetrical Correspondence Analysis.

PubMed

Vega-Hernández, María C; Patino-Alonso, María C; Cabello, Rosario; Galindo-Villardón, María P; Fernández-Berrocal, Pablo

2017-01-01

Recent studies have revealed that emotional competences are relevant to the student's learning process and, more specifically, in the use of learning strategies (LSs). The aim of this study is twofold. First, we aim to analyze the relationship between perceived emotional intelligence (PEI) and LSs applying the scales TMMS-24 and Abridged ACRA to a sample of 2334 Spanish university students, whilst also exploring possible gender differences. Second, we aim to propose a methodological alternative based on the Canonical non-symmetrical correspondence analysis (CNCA), as an alternative to the methods traditionally used in Psychology and Education. Our results show that PEI has an impact on the LS of the students. Male participants with high scores on learning support strategies are positively related to high attention, clarity, and emotional repair. However, the use of cognitive and control LS is related to low values on the PEI dimensions. For women, high scores on cognitive, control, and learning support LS are related to high emotional attention, whereas dimensions such as study habits and learning support are related to adequate emotional repair. Participants in the 18-19 and 22-23 years age groups showed similar behavior. High scores on learning support strategies are related to high values on three dimensions of the PEI, and high values of study habits show high values for clarity and low values for attention and repair. The 20-21 and older than 24 years age groups behaved similarly. High scores on learning support strategies are related to low values on clarity, and study habits show high values for clarity and repair. This article presents the relationship between PEI and LS in university students, the differences by gender and age, and CNCA as an alternative method to techniques used in this field to study this association.

Perceived Emotional Intelligence and Learning Strategies in Spanish University Students: A New Perspective from a Canonical Non-symmetrical Correspondence Analysis

PubMed Central

Vega-Hernández, María C.; Patino-Alonso, María C.; Cabello, Rosario; Galindo-Villardón, María P.; Fernández-Berrocal, Pablo

2017-01-01

Recent studies have revealed that emotional competences are relevant to the student’s learning process and, more specifically, in the use of learning strategies (LSs). The aim of this study is twofold. First, we aim to analyze the relationship between perceived emotional intelligence (PEI) and LSs applying the scales TMMS-24 and Abridged ACRA to a sample of 2334 Spanish university students, whilst also exploring possible gender differences. Second, we aim to propose a methodological alternative based on the Canonical non-symmetrical correspondence analysis (CNCA), as an alternative to the methods traditionally used in Psychology and Education. Our results show that PEI has an impact on the LS of the students. Male participants with high scores on learning support strategies are positively related to high attention, clarity, and emotional repair. However, the use of cognitive and control LS is related to low values on the PEI dimensions. For women, high scores on cognitive, control, and learning support LS are related to high emotional attention, whereas dimensions such as study habits and learning support are related to adequate emotional repair. Participants in the 18–19 and 22–23 years age groups showed similar behavior. High scores on learning support strategies are related to high values on three dimensions of the PEI, and high values of study habits show high values for clarity and low values for attention and repair. The 20–21 and older than 24 years age groups behaved similarly. High scores on learning support strategies are related to low values on clarity, and study habits show high values for clarity and repair. This article presents the relationship between PEI and LS in university students, the differences by gender and age, and CNCA as an alternative method to techniques used in this field to study this association. PMID:29163272

A Non-canonical Reticular-Limbic Central Auditory Pathway via Medial Septum Contributes to Fear Conditioning.

PubMed

Zhang, Guang-Wei; Sun, Wen-Jian; Zingg, Brian; Shen, Li; He, Jufang; Xiong, Ying; Tao, Huizhong W; Zhang, Li I

2018-01-17

In the mammalian brain, auditory information is known to be processed along a central ascending pathway leading to auditory cortex (AC). Whether there exist any major pathways beyond this canonical auditory neuraxis remains unclear. In awake mice, we found that auditory responses in entorhinal cortex (EC) cannot be explained by a previously proposed relay from AC based on response properties. By combining anatomical tracing and optogenetic/pharmacological manipulations, we discovered that EC received auditory input primarily from the medial septum (MS), rather than AC. A previously uncharacterized auditory pathway was then revealed: it branched from the cochlear nucleus, and via caudal pontine reticular nucleus, pontine central gray, and MS, reached EC. Neurons along this non-canonical auditory pathway responded selectively to high-intensity broadband noise, but not pure tones. Disruption of the pathway resulted in an impairment of specifically noise-cued fear conditioning. This reticular-limbic pathway may thus function in processing aversive acoustic signals. Copyright © 2017 Elsevier Inc. All rights reserved.

Repetitive DNA loci and their modulation by the non-canonical nucleic acid structures R-loops and G-quadruplexes

PubMed Central

Hall, Amanda C.; Ostrowski, Lauren A.; Mekhail, Karim

2017-01-01

ABSTRACT Cells have evolved intricate mechanisms to maintain genome stability despite allowing mutational changes to drive evolutionary adaptation. Repetitive DNA sequences, which represent the bulk of most genomes, are a major threat to genome stability often driving chromosome rearrangements and disease. The major source of repetitive DNA sequences and thus the most vulnerable constituents of the genome are the rDNA (rDNA) repeats, telomeres, and transposable elements. Maintaining the stability of these loci is critical to overall cellular fitness and lifespan. Therefore, cells have evolved mechanisms to regulate rDNA copy number, telomere length and transposon activity, as well as DNA repair at these loci. In addition, non-canonical structure-forming DNA motifs can also modulate the function of these repetitive DNA loci by impacting their transcription, replication, and stability. Here, we discuss key mechanisms that maintain rDNA repeats, telomeres, and transposons in yeast and human before highlighting emerging roles for non-canonical DNA structures at these repetitive loci. PMID:28406751

Quantum canonical ensemble: A projection operator approach

NASA Astrophysics Data System (ADS)

Magnus, Wim; Lemmens, Lucien; Brosens, Fons

2017-09-01

Knowing the exact number of particles N, and taking this knowledge into account, the quantum canonical ensemble imposes a constraint on the occupation number operators. The constraint particularly hampers the systematic calculation of the partition function and any relevant thermodynamic expectation value for arbitrary but fixed N. On the other hand, fixing only the average number of particles, one may remove the above constraint and simply factorize the traces in Fock space into traces over single-particle states. As is well known, that would be the strategy of the grand-canonical ensemble which, however, comes with an additional Lagrange multiplier to impose the average number of particles. The appearance of this multiplier can be avoided by invoking a projection operator that enables a constraint-free computation of the partition function and its derived quantities in the canonical ensemble, at the price of an angular or contour integration. Introduced in the recent past to handle various issues related to particle-number projected statistics, the projection operator approach proves beneficial to a wide variety of problems in condensed matter physics for which the canonical ensemble offers a natural and appropriate environment. In this light, we present a systematic treatment of the canonical ensemble that embeds the projection operator into the formalism of second quantization while explicitly fixing N, the very number of particles rather than the average. Being applicable to both bosonic and fermionic systems in arbitrary dimensions, transparent integral representations are provided for the partition function ZN and the Helmholtz free energy FN as well as for two- and four-point correlation functions. The chemical potential is not a Lagrange multiplier regulating the average particle number but can be extracted from FN+1 -FN, as illustrated for a two-dimensional fermion gas.

Canonical forms of multidimensional steady inviscid flows

NASA Technical Reports Server (NTRS)

Taasan, Shlomo

1993-01-01

Canonical forms and canonical variables for inviscid flow problems are derived. In these forms the components of the system governed by different types of operators (elliptic and hyperbolic) are separated. Both the incompressible and compressible cases are analyzed, and their similarities and differences are discussed. The canonical forms obtained are block upper triangular operator form in which the elliptic and non-elliptic parts reside in different blocks. The full nonlinear equations are treated without using any linearization process. This form enables a better analysis of the equations as well as better numerical treatment. These forms are the analog of the decomposition of the one dimensional Euler equations into characteristic directions and Riemann invariants.

The search of "canonical" explanations for the cerebral cortex.

PubMed

Plebe, Alessio

2018-06-15

This paper addresses a fundamental line of research in neuroscience: the identification of a putative neural processing core of the cerebral cortex, often claimed to be "canonical". This "canonical" core would be shared by the entire cortex, and would explain why it is so powerful and diversified in tasks and functions, yet so uniform in architecture. The purpose of this paper is to analyze the search for canonical explanations over the past 40 years, discussing the theoretical frameworks informing this research. It will highlight a bias that, in my opinion, has limited the success of this research project, that of overlooking the dimension of cortical development. The earliest explanation of the cerebral cortex as canonical was attempted by David Marr, deriving putative cortical circuits from general mathematical laws, loosely following a deductive-nomological account. Although Marr's theory turned out to be incorrect, one of its merits was to have put the issue of cortical circuit development at the top of his agenda. This aspect has been largely neglected in much of the research on canonical models that has followed. Models proposed in the 1980s were conceived as mechanistic. They identified a small number of components that interacted as a basic circuit, with each component defined as a function. More recent models have been presented as idealized canonical computations, distinct from mechanistic explanations, due to the lack of identifiable cortical components. Currently, the entire enterprise of coming up with a single canonical explanation has been criticized as being misguided, and the premise of the uniformity of the cortex has been strongly challenged. This debate is analyzed here. The legacy of the canonical circuit concept is reflected in both positive and negative ways in recent large-scale brain projects, such as the Human Brain Project. One positive aspect is that these projects might achieve the aim of producing detailed simulations of cortical

[Non-linear canonical correlation analysis between anthropometric indicators and multiple metabolic abnormalities].

PubMed

Fu, Xiaoli; Liu, Li; Ping, Zhiguang; Li, Linlin

2013-09-01

To define the general correlation between anthropometric indicators and multiple metabolic abnormalities, and to put forward some particular suggestions for the prevention of multiple metabolic abnormalities. A random cluster sampling was carried out in one county of Henan Province. Questionnaire, physical examination and biochemical tests were admitted to the adult inhabitants. Non-linear canonical correlation analysis (NLCCA) was applied with OVERALS of SPSS 13.0. The coefficients of canonical correlation and multiple correlation were calculated. The plot of centroids labeled by variables showed the correlation among various indicators. In total, 2,914 objects were investigated. It included 1,134 (38.9%) males and 1,780 (61.1%) females (60.0%). The average age was (50.58 +/- 13.70) years old. The fitting result of NLCCA were as follows: the loss of 0.577 accounting for 28.8% of the total variation was relatively small, and indicated that the two sets of variables of this study, namely sets of biochemical indicators (including serum total cholesterol, total triglyceride, high-density lipoprotein cholesterol, low density lipoprotein cholesterol and fasting plasma glucose) and sets of others (including gender, BMI and waist circumference) were closely related and often changed synchronously. Multivariate correlation coefficient showed that internal indicators of the above two sets were closely related respectively and often showed the multiple anomalies of the same set. The diagram of the center of gravity of the association of various indicators showed that the symptoms of metabolic abnormalities increased with age. Women were more liable to have metabolic abnormalities. Overweight and obese people often suffer multiple metabolic disorders. Waist circumference was positively correlated with metabolic abnormalities. (1) Biochemical indicators and anthropometric often change in combination. (2) Much attention should be paid to older people especially middle-aged or

A Non-Canonical Initiation Site Is Required for Efficient Translation of the Dendritically Localized Shank1 mRNA

PubMed Central

Studtmann, Katrin; Ölschläger-Schütt, Janin; Buck, Friedrich; Richter, Dietmar; Sala, Carlo; Bockmann, Jürgen; Kindler, Stefan; Kreienkamp, Hans-Jürgen

2014-01-01

Local protein synthesis in dendrites enables neurons to selectively change the protein complement of individual postsynaptic sites. Though it is generally assumed that this mechanism requires tight translational control of dendritically transported mRNAs, it is unclear how translation of dendritic mRNAs is regulated. We have analyzed here translational control elements of the dendritically localized mRNA coding for the postsynaptic scaffold protein Shank1. In its 5′ region, the human Shank1 mRNA exhibits two alternative translation initiation sites (AUG+1 and AUG+214), three canonical upstream open reading frames (uORFs1-3) and a high GC content. In reporter assays, fragments of the 5′UTR with high GC content inhibit translation, suggesting a contribution of secondary structures. uORF3 is most relevant to translation control as it overlaps with the first in frame start codon (AUG+1), directing translation initiation to the second in frame start codon (AUG+214). Surprisingly, our analysis points to an additional uORF initiated at a non-canonical ACG start codon. Mutation of this start site leads to an almost complete loss of translation initiation at AUG+1, demonstrating that this unconventional uORF is required for Shank1 synthesis. Our data identify a novel mechanism whereby initiation at a non-canonical site allows for translation of the main Shank1 ORF despite a highly structured 5′UTR. PMID:24533096

[3D structure of DKK1 indicates its involvement in both canonical and non-canonical Wnt pathways].

PubMed

Khalili, S; Rasaee, M J; Bamdad, T

2017-01-01

Dikkoppf-1 (DKK1) is an antagonist of the canonical Wnt signaling pathway. The importance of DKK1 as a diagnostic and therapeutic agent in a wide range of diseases along with its significance in a variety of biological processes accentuate the necessity to decipher its 3D structure that would pave the way towards the development of relevant selective inhibitors. A DKK1 structure model predicted by the Robetta server with structural refinements including a 10 ns molecular dynamics run was subjected to functional and docking analyses. We hypothesize that the N-terminal region of the DKK1 molecule could be functionally important for both canonical and noncanonical Wnt pathways. Moreover, it seems that DKK1 could be involved in interactions with the Frizzled receptors, leading to the activation of the Planar Cell Polarity (PCP) pathway (activation of Jun N-terminal kinase (JNK) Pathway) and Wnt/Ca^(2+) pathway (activation of CamKII).

Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models

PubMed Central

2011-01-01

Background Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA) models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Results Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC) models that extend the power-law formalism to deal with saturation and cooperativity. Conclusions Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task. PMID:21867520

Perceived Dimensions of Parenting and Non-Suicidal Self-Injury in Young Adults

ERIC Educational Resources Information Center

Bureau, Jean-Francois; Martin, Jodi; Freynet, Nathalie; Poirier, Alexane Ali; Lafontaine, Marie-France; Cloutier, Paula

2010-01-01

Family experiences are influential in the development of non-suicidal self-injury (NSSI). The current study aimed to identify specific dimensions underlying early parent-child relationships in association with NSSI. It was hypothesized that all relationship dimensions would be related with NSSI, with some dimensions being stronger predictors when…

Non-canonical IDH1 and IDH2 mutations: a clonal and relevant event in an Italian cohort of gliomas classified according to the 2016 World Health Organization (WHO) criteria.

PubMed

Visani, Michela; Acquaviva, Giorgia; Marucci, Gianluca; Paccapelo, Alexandro; Mura, Antonella; Franceschi, Enrico; Grifoni, Daniela; Pession, Annalisa; Tallini, Giovanni; Brandes, Alba A; de Biase, Dario

2017-11-01

According to the 2016 World Health Organization (WHO) classification of tumors of the central nervous system, assessment of exon 4 mutations in isocitrate dehydrogenase 1 or 2 genes (IDH1 or IDH2) is an essential step in the characterization of gliomas. The p.R132H mutation is the most frequent alteration in IDH genes, however other non-canonical IDH mutations can be identified. The aim of this study is to investigate in depth the prevalence of non-R132H IDH ("non-canonical") mutations in brain tumors classified according to the 2016 WHO scheme and their clonal distribution in neoplastic cells. A total of 288 consecutive cases of brain gliomas (grade II-IV) were analyzed for exon 4 IDH1 and IDH2 mutations. IDH1 and IDH2 analysis was performed using next generation sequencing. Non-canonical IDH mutations were identified in 13/52 (25.0%) grade II gliomas (astrocytomas: 8/31, 25.8%; oligodendrogliomas: 5/21, 23.8%) and in 5/40 (12.5%) grade III gliomas (astrocytomas: 3/25, 12.0%; oligodendrogliomas: 2/15, 13.3%). They were not identified in 196 grade IV gliomas (192 glioblastomas, 4 gliosarcomas). In the large majority (>80%) of tumors IDH mutations, both IDH1-R132H and the non-canonical ones, were present in the large majority (>80%) of neoplastic cells. Our data highlight the importance of investigating not only the IDH1-R132H mutation but also the non-canonical ones. These mutations are clonally distributed, with proportions of mutated neoplastic cells overlapping with those of p.R132H, a finding consistent with their driver role in gliomagenesis.

Drosophila melanogaster Hedgehog cooperates with Frazzled to guide axons through a non-canonical signalling pathway.

PubMed

Ricolo, Delia; Butí, Elisenda; Araújo, Sofia J

2015-08-01

We report that the morphogen Hedgehog (Hh) is an axonal chemoattractant in the midline of Drosophila melanogaster embryos. Hh is present in the ventral nerve cord during axonal guidance and overexpression of hh in the midline causes ectopic midline crossing of FasII-positive axonal tracts. In addition, we show that Hh influences axonal guidance via a non-canonical signalling pathway dependent on Ptc. Our results reveal that the Hh pathway cooperates with the Netrin/Frazzled pathway to guide axons through the midline in invertebrates. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Interrelations between different canonical descriptions of dissipative systems

NASA Astrophysics Data System (ADS)

Schuch, D.; Guerrero, J.; López-Ruiz, F. F.; Aldaya, V.

2015-04-01

There are many approaches for the description of dissipative systems coupled to some kind of environment. This environment can be described in different ways; only effective models are being considered here. In the Bateman model, the environment is represented by one additional degree of freedom and the corresponding momentum. In two other canonical approaches, no environmental degree of freedom appears explicitly, but the canonical variables are connected with the physical ones via non-canonical transformations. The link between the Bateman approach and those without additional variables is achieved via comparison with a canonical approach using expanding coordinates, as, in this case, both Hamiltonians are constants of motion. This leads to constraints that allow for the elimination of the additional degree of freedom in the Bateman approach. These constraints are not unique. Several choices are studied explicitly, and the consequences for the physical interpretation of the additional variable in the Bateman model are discussed.

Dimensions of Intuition: First-Round Validation Studies

ERIC Educational Resources Information Center

Vrugtman, Rosanne

2009-01-01

This study utilized confirmatory factor analysis (CFA), canonical correlation analysis (CCA), regression analysis (RA), and correlation analysis (CA) for first-round validation of the researcher's Dimensions of Intuition (DOI) instrument. The DOI examined 25 personal characteristics and situations purportedly predictive of intuition. Data was…

The non-canonical BMP and Wnt/β-catenin signaling pathways orchestrate early tooth development

PubMed Central

Yuan, Guohua; Yang, Guobin; Zheng, Yuqian; Zhu, Xiaojing; Chen, Zhi; Zhang, Zunyi; Chen, YiPing

2015-01-01

BMP and Wnt signaling pathways play a crucial role in organogenesis, including tooth development. Despite extensive studies, the exact functions, as well as if and how these two pathways act coordinately in regulating early tooth development, remain elusive. In this study, we dissected regulatory functions of BMP and Wnt pathways in early tooth development using a transgenic noggin (Nog) overexpression model (K14Cre;pNog). It exhibits early arrested tooth development, accompanied by reduced cell proliferation and loss of odontogenic fate marker Pitx2 expression in the dental epithelium. We demonstrated that overexpression of Nog disrupted BMP non-canonical activity, which led to a dramatic reduction of cell proliferation rate but did not affect Pitx2 expression. We further identified a novel function of Nog by inhibiting Wnt/β-catenin signaling, causing loss of Pitx2 expression. Co-immunoprecipitation and TOPflash assays revealed direct binding of Nog to Wnts to functionally prevent Wnt/β-catenin signaling. In situ PLA and immunohistochemistry on Nog mutants confirmed in vivo interaction between endogenous Nog and Wnts and modulation of Wnt signaling by Nog in tooth germs. Genetic rescue experiments presented evidence that both BMP and Wnt signaling pathways contribute to cell proliferation regulation in the dental epithelium, with Wnt signaling also controlling the odontogenic fate. Reactivation of both BMP and Wnt signaling pathways, but not of only one of them, rescued tooth developmental defects in K14Cre;pNog mice, in which Wnt signaling can be substituted by transgenic activation of Pitx2. Our results reveal the orchestration of non-canonical BMP and Wnt/β-catenin signaling pathways in the regulation of early tooth development. PMID:25428587

Intracrine prostaglandin E2 pro-tumoral actions in prostate epithelial cells originate from non-canonical pathways.

PubMed

Madrigal-Martínez, Antonio; Fernández-Martínez, Ana B; Lucio Cazaña, Francisco J

2018-04-01

Prostaglandin E 2 (PGE 2 ) increases cell proliferation and stimulates migratory and angiogenic abilities in prostate cancer cells. However, the effects of PGE 2 on non-transformed prostate epithelial cells are unknown, despite the fact that PGE 2 overproduction has been found in benign hyperplastic prostates. In the present work we studied the effects of PGE 2 in immortalized, non-malignant prostate epithelial RWPE-1 cells and found that PGE 2 increased cell proliferation, cell migration, and production of vascular endothelial growth factor-A, and activated in vitro angiogenesis. These actions involved a non-canonic intracrine mechanism in which the actual effector was intracellular PGE 2 (iPGE 2 ) instead of extracellular PGE 2 : inhibition of the prostaglandin uptake transporter (PGT) or antagonism of EP receptors prevented the effects of PGE 2 , which indicated that PGE 2 activity depended on its carrier-mediated translocation from the outside to the inside of cells and that EP receptors located intracellularly (iEP) mediated the effects of PGE 2 . iPGE 2 acted through transactivation of epidermal growth factor-receptor (EGFR) by iEP, leading to increased expression and activity of hypoxia-inducible factor-1α (HIF-1α). Interestingly, iPGE 2 also mediates the effects of PGE 2 on prostate cancer PC3 cells through the axis iPGE 2 -iEP receptors-EGFR-HIF-1α. Thus, this axis might be responsible for the growth-stimulating effects of PGE 2 on prostate epithelial cells, thereby contributing to prostate proliferative diseases associated with chronic inflammation. Since this PGT-dependent non-canonic intracrine mechanism of PGE 2 action operates in both benign and malignant prostate epithelial cells, PGT inhibitors should be tested as a novel therapeutic modality to treat prostate proliferative disease. © 2017 Wiley Periodicals, Inc.

Celecoxib Ameliorates Non-Alcoholic Steatohepatitis in Type 2 Diabetic Rats via Suppression of the Non-Canonical Wnt Signaling Pathway Expression

PubMed Central

Tian, Feng; Zhang, Ya Jie; Li, Yu; Xie, Ying

2014-01-01

Our aim was to test whether pharmacological inhibition of cycloxygenase-2 (COX-2) reverses non-alcoholic steatohepatitis (NASH) in type 2 diabetes mellitus (T2DM) rats via suppression of the non-canonical Wnt signaling pathway expression. Twenty-four male Sprague-Dawley rats were randomly distributed to two groups and were fed with a high fat and sucrose (HF-HS) diet or a normal chow diet, respectively. After four weeks, rats fed with a HF-HS diet were made diabetic with low-dose streptozotocin. At the 9th week the diabetic rats fed with a HF-HS diet or the non-diabetic rats fed with a normal chow diet were further divided into two subgroups treated with vehicle or celecoxib (a selective COX-2 inhibitor, 10 mg/Kg/day, gavage) for the last 4 weeks, respectively. At the end of the 12th week, rats were anesthetized. NASH was assessed by histology. Related cytokine expression was measured at both the protein and gene levels through immunohistochemistry (IHC), Western blot and real-time PCR. T2DM rats fed with a HF-HS diet developed steatohepatitis and insulin resistance associated with elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin levels and the non-alcoholic fatty liver disease (NAFLD) activity score (NAS). The expression of Wnt5a, JNK1, NF-κB p65, and COX-2 were all significantly increased in the T2DM-NASH group compared with the control and control-cele group. Hepatic injury was improved by celecoxib in T2DM-NASH-Cele group indicated by reduced serum ALT and AST levels and hepatic inflammation was reduced by celecoxib showed by histology and the NAFLD activity score (NAS). Serum related metabolic parameters, HOMA-IR and insulin sensitivity index were all improved by celecoxib. The expression of Wnt5a, JNK1, NF-κB p65, and COX-2 expression were all suppressed by celecoxib in T2DM-NASH-Cele group. The results of the present study indicated that celecoxib ameliorated NASH in T2DM rats via suppression of the non-canonical Wnt

Regional bankfull-channel dimensions of non-urban wadeable streams in Indiana

USGS Publications Warehouse

Robinson, Bret A.

2013-01-01

During floods, damage to properties and community infrastructure may result from inundation and the processes of erosion. The damages imparted by erosion are collectively termed the fluvial erosion hazard (FEH), and the Indiana Silver Jackets Multi-agency Hazard Mitigation Taskforce is supporting a program to build tools that will assist Indiana property owners and communities with FEH-mitigation efforts. As part of that program, regional channel-dimension relations are identified for non-urban wadeable streams in Indiana. With a site-selection process that targeted the three largest physiographic regions of the state, field work was completed to measure channel-dimension and channel-geometry characteristics across Indiana. In total, 82 sites were identified for data collection; 25 in the Northern Moraine and Lake region, 31 in the Central Till Plain region, and 26 in the Southern Hills and Lowlands region. Following well established methods, for each data-collection site, effort was applied to identify bankfull stage, determine bankfull-channel dimensions, and document channel-geometry characteristics that allowed for determinations of channel classification. In this report, regional bankfull-channel dimension results are presented as a combination of plots and regression equations that identify the relations between drainage area and the bankfull-channel dimensions of width, mean depth, and cross-sectional area. This investigation found that the channel-dimension data support independent relations for each of the three physiographic regions noted above. Furthermore, these relations show that, for any given drainage area, northern Indiana channels have the smallest predicted dimensions, southern Indiana channels have the largest predicted dimensions, and central Indiana channels are intermediate in their predicted dimensions. When considering the suite of variables that influence bankfull-channel dimensions, it appears that contrasting runoff characteristics

Broken Scale Invariance and Anomalous Dimensions

DOE R&D Accomplishments Database

Wilson, K. G.

1970-05-01

Mack and Kastrup have proposed that broken scale invariance is a symmetry of strong interactions. There is evidence from the Thirring model and perturbation theory that the dimensions of fields defined by scale transformations will be changed by the interaction from their canonical values. We review these ideas and their consequences for strong interactions.

Neutrophils Express Distinct RNA Receptors in a Non-canonical Way*

PubMed Central

Berger, Michael; Hsieh, Chin-Yuan; Bakele, Martina; Marcos, Veronica; Rieber, Nikolaus; Kormann, Michael; Mays, Lauren; Hofer, Laura; Neth, Olaf; Vitkov, Ljubomir; Krautgartner, Wolf Dietrich; von Schweinitz, Dietrich; Kappler, Roland; Hector, Andreas; Weber, Alexander; Hartl, Dominik

2012-01-01

RNAs are capable of modulating immune responses by binding to specific receptors. Neutrophils represent the major fraction of circulating immune cells, but receptors and mechanisms by which neutrophils sense RNA are poorly defined. Here, we analyzed the mRNA and protein expression patterns and the subcellular localization of the RNA receptors RIG-I, MDA-5, TLR3, TLR7, and TLR8 in primary neutrophils and immortalized neutrophil-like differentiated HL-60 cells. Our results demonstrate that both neutrophils and differentiated HL-60 cells express RIG-I, MDA-5, and TLR8 at the mRNA and protein levels, whereas TLR3 and TLR7 are not expressed at the protein level. Subcellular fractionation, flow cytometry, confocal laser scanning microscopy, and immuno-transmission electron microscopy provided evidence that, besides the cytoplasm, RIG-I and MDA-5 are stored in secretory vesicles of neutrophils and showed that RIG-I and its ligand, 3p-RNA, co-localize at the cell surface without triggering neutrophil activation. In summary, this study demonstrates that neutrophils express a distinct pattern of RNA recognition receptors in a non-canonical way, which could have essential implications for future RNA-based therapeutics. PMID:22532562

Non-Abelian fractional topological insulators in three spatial dimensions from coupled wires

NASA Astrophysics Data System (ADS)

Iadecola, Thomas; Neupert, Titus; Chamon, Claudio; Mudry, Christopher

The study of topological order in three spatial dimensions constitutes a major frontier in theoretical condensed matter physics. Recently, substantial progress has been made in constructing (3+1)-dimensional Abelian topological states of matter from arrays of coupled quantum wires. In this talk, I will illustrate how wire constructions based on non-Abelian bosonization can be used to build and characterize non-Abelian symmetry-enriched topological phases in three dimensions. In particular, I will describe a family of states of matter, constructed in this way, that constitute a natural non-Abelian generalization of strongly correlated three dimensional fractional topological insulators. These states of matter support strongly interacting symmetry-protected gapless surface states, and host non-Abelian pointlike and linelike excitations in the bulk.

Stepping towards new parameterizations for non-canonical atmospheric surface-layer conditions

NASA Astrophysics Data System (ADS)

Calaf, M.; Margairaz, F.; Pardyjak, E.

2017-12-01

-dynamics parameter is introduced to differentiate dispersive fluxes driven by surface thermal heterogeneities from those induced by surface shear. We believe that results from this research are a first step in developing new parameterizations appropriate for non-canonical ASL conditions.

Common position of indels that cause deviations from canonical genome organization in different measles virus strains.

PubMed

Ivancic-Jelecki, Jelena; Slovic, Anamarija; Šantak, Maja; Tešović, Goran; Forcic, Dubravko

2016-07-29

The canonical genome organization of measles virus (MV) is characterized by total size of 15 894 nucleotides (nts) and defined length of every genomic region, both coding and non-coding. Only rarely have reports of strains possessing non-canonical genomic properties (possessing indels, with or without the change of total genome length) been published. The observed mutations are mutually compensatory in a sense that the total genome length remains polyhexameric. Although programmed and highly precise pseudo-templated nucleotide additions during transcription are inherent to polymerases of all viruses belonging to family Paramyxoviridae, a similar mechanism that would serve to non-randomly correct genome length, if an indel has occurred during replication, has so far not been described in the context of a complete virus genome. We compiled all complete MV genomic sequences (64 in total) available in open access sequence databases. Multiple sequence comparisons and phylogenetic analyses were performed with the aim of exploring whether non-recombinant and non-evolutionary linked measles strains that show deviations from canonical genome organization possess a common genetic characteristic. In 11 MV sequences we detected deviations from canonical genome organization due to short indels located within homopolymeric stretches or next to them. In nine out of 11 identified non-canonical MV sequences, a common feature was observed: one mutation, either an insertion or a deletion, was located in a 28 nts long region in F gene 5' untranslated region (positions 5051-5078 in genomic cDNA of canonical strains). This segment is composed of five tandemly linked homopolymeric stretches, its consensus sequence is G6-7C7-8A6-7G1-3C5-6. Although none of the mononucleotide repeats within this segment has fixed length, the total number of nts in canonical strains is always 28. These nine non-canonical strains, as well as the tenth (not mutated in 5051-5078 segment), can be grouped in

Non-canonical distribution and non-equilibrium transport beyond weak system-bath coupling regime: A polaron transformation approach

NASA Astrophysics Data System (ADS)

Xu, Dazhi; Cao, Jianshu

2016-08-01

The concept of polaron, emerged from condense matter physics, describes the dynamical interaction of moving particle with its surrounding bosonic modes. This concept has been developed into a useful method to treat open quantum systems with a complete range of system-bath coupling strength. Especially, the polaron transformation approach shows its validity in the intermediate coupling regime, in which the Redfield equation or Fermi's golden rule will fail. In the polaron frame, the equilibrium distribution carried out by perturbative expansion presents a deviation from the canonical distribution, which is beyond the usual weak coupling assumption in thermodynamics. A polaron transformed Redfield equation (PTRE) not only reproduces the dissipative quantum dynamics but also provides an accurate and efficient way to calculate the non-equilibrium steady states. Applications of the PTRE approach to problems such as exciton diffusion, heat transport and light-harvesting energy transfer are presented.

Revisiting Interpretation of Canonical Correlation Analysis: A Tutorial and Demonstration of Canonical Commonality Analysis

ERIC Educational Resources Information Center

Nimon, Kim; Henson, Robin K.; Gates, Michael S.

2010-01-01

In the face of multicollinearity, researchers face challenges interpreting canonical correlation analysis (CCA) results. Although standardized function and structure coefficients provide insight into the canonical variates produced, they fall short when researchers want to fully report canonical effects. This article revisits the interpretation of…

Non-equilibrium thermodynamical description of rhythmic motion patterns of active systems: a canonical-dissipative approach.

PubMed

Dotov, D G; Kim, S; Frank, T D

2015-02-01

We derive explicit expressions for the non-equilibrium thermodynamical variables of a canonical-dissipative limit cycle oscillator describing rhythmic motion patterns of active systems. These variables are statistical entropy, non-equilibrium internal energy, and non-equilibrium free energy. In particular, the expression for the non-equilibrium free energy is derived as a function of a suitable control parameter. The control parameter determines the Hopf bifurcation point of the deterministic active system and describes the effective pumping of the oscillator. In analogy to the equilibrium free energy of the Landau theory, it is shown that the non-equilibrium free energy decays as a function of the control parameter. In doing so, a similarity between certain equilibrium and non-equilibrium phase transitions is pointed out. Data from an experiment on human rhythmic movements is presented. Estimates for pumping intensity as well as the thermodynamical variables are reported. It is shown that in the experiment the non-equilibrium free energy decayed when pumping intensity was increased, which is consistent with the theory. Moreover, pumping intensities close to zero could be observed at relatively slow intended rhythmic movements. In view of the Hopf bifurcation underlying the limit cycle oscillator model, this observation suggests that the intended limit cycle movements were actually more similar to trajectories of a randomly perturbed stable focus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Non-contact measurement of linear external dimensions of the mouse eye

PubMed Central

Wisard, Jeffrey; Chrenek, Micah A.; Wright, Charles; Dalal, Nupur; Pardue, Machelle T.; Boatright, Jeffrey H.; Nickerson, John M.

2010-01-01

Biometric analyses of quantitative traits in eyes of mice can reveal abnormalities related to refractive or ocular development. Due to the small size of the mouse eye, highly accurate and precise measurements are needed to detect meaningful differences. We sought a non-contact measuring technique to obtain highly accurate and precise linear dimensions of the mouse eye. Laser micrometry was validated with gauge block standards. Simple procedures to measure eye dimensions on three axes were devised. Mouse eyes from C57BL/6J and rd10 on a C57BL/6J background were dissected and extraocular muscle and fat removed. External eye dimensions of axial length (anterior-posterior (A-P) axis) and equatorial diameter (superior-inferior (S-I) and nasal-temporal (N-T) axes) were obtained with a laser micrometer. Several approaches to prevent or ameliorate evaporation due to room air were employed. The resolution of the laser micrometer was less than 0.77 microns, and it provided accurate and precise non-contact measurements of eye dimensions on three axes. External dimensions of the eye strongly correlated with eye weight. The N-T and S-I dimensions of the eye correlated with each other most closely from among the 28 pair-wise combinations of the several parameters that were collected. The equatorial axis measurements correlated well from the right and left eye of each mouse. The A-P measurements did not correlate or correlated poorly in each pair of eyes. The instrument is well suited for the measurement of enucleated eyes and other structures from most commonly used species in experimental vision research and ophthalmology. PMID:20067806

Non-contact measurement of linear external dimensions of the mouse eye.

PubMed

Wisard, Jeffrey; Chrenek, Micah A; Wright, Charles; Dalal, Nupur; Pardue, Machelle T; Boatright, Jeffrey H; Nickerson, John M

2010-03-30

Biometric analyses of quantitative traits in eyes of mice can reveal abnormalities related to refractive or ocular development. Due to the small size of the mouse eye, highly accurate and precise measurements are needed to detect meaningful differences. We sought a non-contact measuring technique to obtain highly accurate and precise linear dimensions of the mouse eye. Laser micrometry was validated with gauge block standards. Simple procedures to measure eye dimensions on three axes were devised. Mouse eyes from C57BL/6J and rd10 on a C57BL/6J background were dissected and extraocular muscle and fat removed. External eye dimensions of axial length (anterior-posterior (A-P) axis) and equatorial diameter (superior-inferior (S-I) and nasal-temporal (N-T) axes) were obtained with a laser micrometer. Several approaches to prevent or ameliorate evaporation due to room air were employed. The resolution of the laser micrometer was less than 0.77 microm, and it provided accurate and precise non-contact measurements of eye dimensions on three axes. External dimensions of the eye strongly correlated with eye weight. The N-T and S-I dimensions of the eye correlated with each other most closely from among the 28 pair-wise combinations of the several parameters that were collected. The equatorial axis measurements correlated well from the right and left eye of each mouse. The A-P measurements did not correlate or correlated poorly in each pair of eyes. The instrument is well suited for the measurement of enucleated eyes and other structures from most commonly used species in experimental vision research and ophthalmology. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Unidirectional invisibility and non-reciprocal transmission in two and three dimensions.

PubMed

Loran, Farhang; Mostafazadeh, Ali

2016-07-01

We explore the phenomenon of unidirectional invisibility in two dimensions, examine its optical realizations and discuss its three-dimensional generalization. In particular, we construct an infinite class of unidirectionally invisible optical potentials that describe the scattering of normally incident transverse electric waves by an infinite planar slab with refractive-index modulations along both the normal directions to the electric field. A by-product of this investigation is a demonstration of non-reciprocal transmission in two dimensions. To elucidate this phenomenon, we state and prove a general reciprocity theorem that applies to quantum scattering theory of real and complex potentials in two and three dimensions.

Geometric integrator for simulations in the canonical ensemble

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

Tapias, Diego, E-mail: diego.tapias@nucleares.unam.mx; Sanders, David P., E-mail: dpsanders@ciencias.unam.mx; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139

2016-08-28

We introduce a geometric integrator for molecular dynamics simulations of physical systems in the canonical ensemble that preserves the invariant distribution in equations arising from the density dynamics algorithm, with any possible type of thermostat. Our integrator thus constitutes a unified framework that allows the study and comparison of different thermostats and of their influence on the equilibrium and non-equilibrium (thermo-)dynamic properties of a system. To show the validity and the generality of the integrator, we implement it with a second-order, time-reversible method and apply it to the simulation of a Lennard-Jones system with three different thermostats, obtaining good conservationmore » of the geometrical properties and recovering the expected thermodynamic results. Moreover, to show the advantage of our geometric integrator over a non-geometric one, we compare the results with those obtained by using the non-geometric Gear integrator, which is frequently used to perform simulations in the canonical ensemble. The non-geometric integrator induces a drift in the invariant quantity, while our integrator has no such drift, thus ensuring that the system is effectively sampling the correct ensemble.« less

Glia initiate brain assembly through non-canonical Chimaerin/Furin axon guidance in C. elegans

PubMed Central

Rapti, Georgia; Li, Chang; Shan, Alan; Lu, Yun; Shaham, Shai

2017-01-01

Brain assembly is hypothesized to begin when pioneer axons extend over non-neuronal cells, forming tracts guiding follower axons. Yet pioneer-neuron identities, their guidance substrates, and their interactions, are not well understood. Here, using time-lapse embryonic imaging, genetics, protein-interaction, and functional studies, we uncover the early events of C. elegans brain assembly. We demonstrate that C. elegans glia are key for assembly initiation, guiding pioneer and follower axons using distinct signals. Pioneer sublateral neurons, with unique growth properties, anatomy, and innervation, cooperate with glia to mediate follower-axon guidance. We further identify a CHIN-1/Chimaerin-KPC-1/Furin double mutant that severely disrupts assembly. CHIN-1/Chimaerin and KPC-1/Furin function non-canonically in glia and pioneer neurons for guidance-cue trafficking. We exploit this bottleneck to define roles for glial Netrin and Semaphorin in pioneer- and follower-axon guidance, respectively, and for glial and pioneer-neuron Flamingo/CELSR in follower-axon navigation. Altogether, our studies reveal previously-unknown glial roles in pioneer-axon guidance, suggesting conserved brain-assembly principles. PMID:28846083

Basic Brackets of a 2D Model for the Hodge Theory Without its Canonical Conjugate Momenta

NASA Astrophysics Data System (ADS)

Kumar, R.; Gupta, S.; Malik, R. P.

2016-06-01

We deduce the canonical brackets for a two (1+1)-dimensional (2D) free Abelian 1-form gauge theory by exploiting the beauty and strength of the continuous symmetries of a Becchi-Rouet-Stora-Tyutin (BRST) invariant Lagrangian density that respects, in totality, six continuous symmetries. These symmetries entail upon this model to become a field theoretic example of Hodge theory. Taken together, these symmetries enforce the existence of exactly the same canonical brackets amongst the creation and annihilation operators that are found to exist within the standard canonical quantization scheme. These creation and annihilation operators appear in the normal mode expansion of the basic fields of this theory. In other words, we provide an alternative to the canonical method of quantization for our present model of Hodge theory where the continuous internal symmetries play a decisive role. We conjecture that our method of quantization is valid for a class of field theories that are tractable physical examples for the Hodge theory. This statement is true in any arbitrary dimension of spacetime.

Canonical Correlation: Terms and Descriptions.

ERIC Educational Resources Information Center

Pugh, Richard C.; Hu, Yuehluen

The use of terms to describe and interpret results from canonical correlation analysis has been inconsistent across research studies. This study assembled the terminology related to the use and interpretation of canonical correlation analysis from research articles, textbooks, and computer manuals. Research articles using canonical correlation…

Database of non-canonical base pairs found in known RNA structures

NASA Technical Reports Server (NTRS)

Nagaswamy, U.; Voss, N.; Zhang, Z.; Fox, G. E.

2000-01-01

Atomic resolution RNA structures are being published at an increasing rate. It is common to find a modest number of non-canonical base pairs in these structures in addition to the usual Watson-Crick pairs. This database summarizes the occurrence of these rare base pairs in accordance with standard nomenclature. The database, http://prion.bchs.uh.edu/, contains information such as sequence context, sugar pucker conformation, anti / syn base conformations, chemical shift, p K (a)values, melting temperature and free energy. Of the 29 anticipated pairs with two or more hydrogen bonds, 20 have been encountered to date. In addition, four unexpected pairs with two hydrogen bonds have been reported bringing the total to 24. Single hydrogen bond versions of five of the expected geometries have been encountered among the single hydrogen bond interactions. In addition, 18 different types of base triplets have been encountered, each of which involves three to six hydrogen bonds. The vast majority of the rare base pairs are antiparallel with the bases in the anti configuration relative to the ribose. The most common are the GU wobble, the Sheared GA pair, the Reverse Hoogsteen pair and the GA imino pair.

A non-canonical mechanism for Crm1-export cargo complex assembly.

PubMed

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Faza, Marius Boulos; Panse, Vikram Govind

2015-04-21

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export.

A non-canonical mechanism for Crm1-export cargo complex assembly

PubMed Central

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Boulos Faza, Marius; Panse, Vikram Govind

2015-01-01

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export. DOI: http://dx.doi.org/10.7554/eLife.05745.001 PMID:25895666

Planck limits on non-canonical generalizations of large-field inflation models

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

Stein, Nina K.; Kinney, William H., E-mail: ninastei@buffalo.edu, E-mail: whkinney@buffalo.edu

2017-04-01

In this paper, we consider two case examples of Dirac-Born-Infeld (DBI) generalizations of canonical large-field inflation models, characterized by a reduced sound speed, c {sub S} < 1. The reduced speed of sound lowers the tensor-scalar ratio, improving the fit of the models to the data, but increases the equilateral-mode non-Gaussianity, f {sup equil.}{sub NL}, which the latest results from the Planck satellite constrain by a new upper bound. We examine constraints on these models in light of the most recent Planck and BICEP/Keck results, and find that they have a greatly decreased window of viability. The upper bound onmore » f {sup equil.}{sub NL} corresponds to a lower bound on the sound speed and a corresponding lower bound on the tensor-scalar ratio of r ∼ 0.01, so that near-future Cosmic Microwave Background observations may be capable of ruling out entire classes of DBI inflation models. The result is, however, not universal: infrared-type DBI inflation models, where the speed of sound increases with time, are not subject to the bound.« less

cGAS drives non-canonical inflammasome activation in age-related macular degeneration

PubMed Central

Kerur, Nagaraj; Fukuda, Shinichi; Banerjee, Daipayan; Kim, Younghee; Fu, Dongxu; Apicella, Ivana; Varshney, Akhil; Yasuma, Reo; Fowler, Benjamin J.; Baghdasaryan, Elmira; Marion, Kenneth M.; Huang, Xiwen; Yasuma, Tetsuhiro; Hirano, Yoshio; Serbulea, Vlad; Ambati, Meenakshi; Ambati, Vidya L.; Kajiwara, Yuji; Ambati, Kameshwari; Bastos-Carvalho, Ana; Ogura, Yuichiro; Terasaki, Hiroko; Oshika, Tetsuro; Kim, Kyung Bo; Hinton, David R.; Leitinger, Norbert; Cambier, John C.; Buxbaum, Joseph D.; Kenney, M. Cristina; Jazwinski, S. Michal; Nagai, Hiroshi; Hara, Isao; West, A. Phillip; Fitzgerald, Katherine A.; Sadda, SriniVas R.; Gelfand, Bradley D.; Ambati, Jayakrishna

2017-01-01

Geographic atrophy is a blinding form of age-related macular degeneration characterized by death of the retinal pigmented epithelium (RPE). In this disease, the RPE displays evidence of DICER1 deficiency, resultant accumulation of endogenous Alu retroelement RNA, and NLRP3 inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human cell culture and in mouse models is driven by a non-canonical inflammasome pathway that results in activation of caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β (IFN-β) production and gasdermin D-dependent interleukin-18 (IL-18) secretion. Reduction of DICER1 levelsor accumulation of Alu RNA triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, IFN-β, and cGAS levels are elevated in the RPE of human eyes with geographic atrophy. Collectively, these data highlight an unexpected role for cGAS in responding to mobile element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial damage-induced inflammasome activation, expand the immune sensing repertoire of cGAS and caspase-4 to non-infectious human disease, and identify new potential targets for treatment of a major cause of blindness. PMID:29176737

Polynomial meta-models with canonical low-rank approximations: Numerical insights and comparison to sparse polynomial chaos expansions

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

Konakli, Katerina, E-mail: konakli@ibk.baug.ethz.ch; Sudret, Bruno

2016-09-15

The growing need for uncertainty analysis of complex computational models has led to an expanding use of meta-models across engineering and sciences. The efficiency of meta-modeling techniques relies on their ability to provide statistically-equivalent analytical representations based on relatively few evaluations of the original model. Polynomial chaos expansions (PCE) have proven a powerful tool for developing meta-models in a wide range of applications; the key idea thereof is to expand the model response onto a basis made of multivariate polynomials obtained as tensor products of appropriate univariate polynomials. The classical PCE approach nevertheless faces the “curse of dimensionality”, namely themore » exponential increase of the basis size with increasing input dimension. To address this limitation, the sparse PCE technique has been proposed, in which the expansion is carried out on only a few relevant basis terms that are automatically selected by a suitable algorithm. An alternative for developing meta-models with polynomial functions in high-dimensional problems is offered by the newly emerged low-rank approximations (LRA) approach. By exploiting the tensor–product structure of the multivariate basis, LRA can provide polynomial representations in highly compressed formats. Through extensive numerical investigations, we herein first shed light on issues relating to the construction of canonical LRA with a particular greedy algorithm involving a sequential updating of the polynomial coefficients along separate dimensions. Specifically, we examine the selection of optimal rank, stopping criteria in the updating of the polynomial coefficients and error estimation. In the sequel, we confront canonical LRA to sparse PCE in structural-mechanics and heat-conduction applications based on finite-element solutions. Canonical LRA exhibit smaller errors than sparse PCE in cases when the number of available model evaluations is small with respect to the

A Novel Role for the BMP Antagonist Noggin in Sensitizing Cells to Non-canonical Wnt-5a/Ror2/Disheveled Pathway Activation

PubMed Central

Bernatik, Ondrej; Radaszkiewicz, Tomasz; Behal, Martin; Dave, Zankruti; Witte, Florian; Mahl, Annika; Cernohorsky, Nicole H.; Krejci, Pavel; Stricker, Sigmar; Bryja, Vitezslav

2017-01-01

Mammalian limb development is driven by the integrative input from several signaling pathways; a failure to receive or a misinterpretation of these signals results in skeletal defects. The brachydactylies, a group of overlapping inherited human hand malformation syndromes, are mainly caused by mutations in BMP signaling pathway components. Two closely related forms, Brachydactyly type B2 (BDB2) and BDB1 are caused by mutations in the BMP antagonist Noggin (NOG) and the atypical receptor tyrosine kinase ROR2 that acts as a receptor in the non-canonical Wnt pathway. Genetic analysis of Nog and Ror2 functional interaction via crossing Noggin and Ror2 mutant mice revealed a widening of skeletal elements in compound but not in any of the single mutants, thus indicating genetic interaction. Since ROR2 is a non-canonical Wnt co-receptor specific for Wnt-5a we speculated that this phenotype might be a result of deregulated Wnt-5a signaling activation, which is known to be essential for limb skeletal elements growth and patterning. We show that Noggin potentiates activation of the Wnt-5a-Ror2-Disheveled (Dvl) pathway in mouse embryonic fibroblast (MEF) cells in a Ror2-dependent fashion. Rat chondrosarcoma chondrocytes (RCS), however, are not able to respond to Noggin in this fashion unless growth arrest is induced by FGF2. In summary, our data demonstrate genetic interaction between Noggin and Ror2 and show that Noggin can sensitize cells to Wnt-5a/Ror2-mediated non-canonical Wnt signaling, a feature that in cartilage may depend on the presence of active FGF signaling. These findings indicate an unappreciated function of Noggin that will help to understand BMP and Wnt/PCP signaling pathway interactions. PMID:28523267

NLRP12 Suppresses Colon Inflammation and Tumorigenesis through the Negative Regulation of Non-canonical NF-κB Signaling and MAP Kinase Activation

PubMed Central

Allen, Irving C.; Wilson, Justin E.; Schneider, Monika; Lich, John D.; Roberts, Reid A.; Arthur, Janelle C.; Woodford, Rita-Marie T.; Davis, Beckley K.; Uronis, Joshua M.; Herfarth, Hans H.; Jobin, Christian; Rogers, Arlin B.; Ting, Jenny P.-Y.

2013-01-01

SUMMARY In vitro data suggest that a subgroup of NLR proteins, including NLRP12, inhibits the transcription factor NF-κB, although physiologic and disease-relevant evidence is largely missing. Dysregulated NF-κB activity is associated with colonic inflammation and cancer, and we found Nlrp12-/- mice were highly susceptible to colitis and colitis-associated colon cancer. Polyps isolated from Nlrp12-/- mice showed elevated non-canonical NF-κB activation and increased expression of target genes that were associated with cancer, including Cxcl13 and Cxcl12. NLRP12 negatively regulated ERK and AKT signaling pathways in affected tumor tissues. Both hematopoietic and nonhematopoietic-derived NLRP12 contributed to inflammation, but the latter dominantly contributed to tumorigenesis. The non-canonical NF-κB pathway was regulated upon degradation of TRAF3 and activation of NIK. NLRP12 interacted with both NIK and TRAF3, and Nlrp12-/- cells have constitutively elevated NIK, p100 processing to p52 and reduced TRAF3. Thus, NLRP12 is a checkpoint of noncanonical NF-κB, inflammation and tumorigenesis. PMID:22503542

Canonical Transformations of Kepler Trajectories

ERIC Educational Resources Information Center

Mostowski, Jan

2010-01-01

In this paper, canonical transformations generated by constants of motion in the case of the Kepler problem are discussed. It is shown that canonical transformations generated by angular momentum are rotations of the trajectory. Particular attention is paid to canonical transformations generated by the Runge-Lenz vector. It is shown that these…

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids.

PubMed

Nickling, Jessica H; Baumann, Tobias; Schmitt, Franz-Josef; Bartholomae, Maike; Kuipers, Oscar P; Friedrich, Thomas; Budisa, Nediljko

2018-05-04

Nature has a variety of possibilities to create new protein functions by modifying the sequence of the individual amino acid building blocks. However, all variations are based on the 20 canonical amino acids (cAAs). As a way to introduce additional physicochemical properties into polypeptides, the incorporation of non-canonical amino acids (ncAAs) is increasingly used in protein engineering. Due to their relatively short length, the modification of ribosomally synthesized and post-translationally modified peptides by ncAAs is particularly attractive. New functionalities and chemical handles can be generated by specific modifications of individual residues. The selective pressure incorporation (SPI) method utilizes auxotrophic host strains that are deprived of an essential amino acid in chemically defined growth media. Several structurally and chemically similar amino acid analogs can then be activated by the corresponding aminoacyl-tRNA synthetase and provide residue-specific cAA(s) → ncAA(s) substitutions in the target peptide or protein sequence. Although, in the context of the SPI method, ncAAs are also incorporated into the host proteome during the phase of recombinant gene expression, the majority of the cell's resources are assigned to the expression of the target gene. This enables efficient residue-specific incorporation of ncAAs often accompanied with high amounts of modified target. The presented work describes the in vivo incorporation of six proline analogs into the antimicrobial peptide nisin, a lantibiotic naturally produced by Lactococcus lactis. Antimicrobial properties of nisin can be changed and further expanded during its fermentation and expression in auxotrophic Escherichia coli strains in defined growth media. Thereby, the effects of residue-specific replacement of cAAs with ncAAs can deliver changes in antimicrobial activity and specificity. Antimicrobial activity assays and fluorescence microscopy are used to test the new nisin variants

The impairment of HCCS leads to MLS syndrome by activating a non-canonical cell death pathway in the brain and eyes

PubMed Central

Indrieri, Alessia; Conte, Ivan; Chesi, Giancarlo; Romano, Alessia; Quartararo, Jade; Tatè, Rosarita; Ghezzi, Daniele; Zeviani, Massimo; Goffrini, Paola; Ferrero, Ileana; Bovolenta, Paola; Franco, Brunella

2013-01-01

Mitochondrial-dependent (intrinsic) programmed cell death (PCD) is an essential homoeostatic mechanism that selects bioenergetically proficient cells suitable for tissue/organ development. However, the link between mitochondrial dysfunction, intrinsic apoptosis and developmental anomalies has not been demonstrated to date. Now we provide the evidence that non-canonical mitochondrial-dependent apoptosis explains the phenotype of microphthalmia with linear skin lesions (MLS), an X-linked developmental disorder caused by mutations in the holo-cytochrome c-type synthase (HCCS) gene. By taking advantage of a medaka model that recapitulates the MLS phenotype we demonstrate that downregulation of hccs, an essential player of the mitochondrial respiratory chain (MRC), causes increased cell death via an apoptosome-independent caspase-9 activation in brain and eyes. We also show that the unconventional activation of caspase-9 occurs in the mitochondria and is triggered by MRC impairment and overproduction of reactive oxygen species (ROS). We thus propose that HCCS plays a key role in central nervous system (CNS) development by modulating a novel non-canonical start-up of cell death and provide the first experimental evidence for a mechanistic link between mitochondrial dysfunction, intrinsic apoptosis and developmental disorders. PMID:23239471

Application of Canonical Effective Methods to Background-Independent Theories

NASA Astrophysics Data System (ADS)

Buyukcam, Umut

Effective formalisms play an important role in analyzing phenomena above some given length scale when complete theories are not accessible. In diverse exotic but physically important cases, the usual path-integral techniques used in a standard Quantum Field Theory approach seldom serve as adequate tools. This thesis exposes a new effective method for quantum systems, called the Canonical Effective Method, which owns particularly wide applicability in backgroundindependent theories as in the case of gravitational phenomena. The central purpose of this work is to employ these techniques to obtain semi-classical dynamics from canonical quantum gravity theories. Application to non-associative quantum mechanics is developed and testable results are obtained. Types of non-associative algebras relevant for magnetic-monopole systems are discussed. Possible modifications of hypersurface deformation algebra and the emergence of effective space-times are presented. iii.

Infants' Recognition of Objects Using Canonical Color

ERIC Educational Resources Information Center

Kimura, Atsushi; Wada, Yuji; Yang, Jiale; Otsuka, Yumiko; Dan, Ippeita; Masuda, Tomohiro; Kanazawa, So; Yamaguchi, Masami K.

2010-01-01

We explored infants' ability to recognize the canonical colors of daily objects, including two color-specific objects (human face and fruit) and a non-color-specific object (flower), by using a preferential looking technique. A total of 58 infants between 5 and 8 months of age were tested with a stimulus composed of two color pictures of an object…

Chimeric Vaccine Stimulation of Human Dendritic Cell Indoleamine 2, 3-Dioxygenase Occurs via the Non-Canonical NF-κB Pathway

PubMed Central

Kim, Nan-Sun; Mbongue, Jacques C.; Nicholas, Dequina A.; Esebanmen, Grace E.; Unternaehrer, Juli J.; Firek, Anthony F.; Langridge, William H. R.

2016-01-01

A chimeric protein vaccine composed of the cholera toxin B subunit fused to proinsulin (CTB-INS) was shown to suppress type 1 diabetes onset in NOD mice and upregulate biosynthesis of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1) in human dendritic cells (DCs). Here we demonstrate siRNA inhibition of the NF-κB-inducing kinase (NIK) suppresses vaccine-induced IDO1 biosynthesis as well as IKKα phosphorylation. Chromatin immunoprecipitation (ChIP) analysis of CTB-INS inoculated DCs showed that RelB bound to NF-κB consensus sequences in the IDO1 promoter, suggesting vaccine stimulation of the non-canonical NF-κB pathway activates IDO1 expression in vivo. The addition of Tumor Necrosis Factor Associated Factors (TRAF) TRAF 2, 3 and TRAF6 blocking peptides to vaccine inoculated DCs was shown to inhibit IDO1 biosynthesis. This experimental outcome suggests vaccine activation of the TNFR super-family receptor pathway leads to upregulation of IDO1 biosynthesis in CTB-INS inoculated dendritic cells. Together, our experimental data suggest the CTB-INS vaccine uses a TNFR-dependent signaling pathway of the non-canonical NF-κB signaling pathway resulting in suppression of dendritic cell mediated type 1 diabetes autoimmunity. PMID:26881431

Cryptic indole hydroxylation by a non-canonical terpenoid cyclase parallels bacterial xenobiotic detoxification

NASA Astrophysics Data System (ADS)

Kugel, Susann; Baunach, Martin; Baer, Philipp; Ishida-Ito, Mie; Sundaram, Srividhya; Xu, Zhongli; Groll, Michael; Hertweck, Christian

2017-06-01

Terpenoid natural products comprise a wide range of molecular architectures that typically result from C-C bond formations catalysed by classical type I/II terpene cyclases. However, the molecular diversity of biologically active terpenoids is substantially increased by fully unrelated, non-canonical terpenoid cyclases. Their evolutionary origin has remained enigmatic. Here we report the in vitro reconstitution of an unusual flavin-dependent bacterial indoloterpenoid cyclase, XiaF, together with a designated flavoenzyme-reductase (XiaP) that mediates a key step in xiamycin biosynthesis. The crystal structure of XiaF with bound FADH2 (at 2.4 Å resolution) and phylogenetic analyses reveal that XiaF is, surprisingly, most closely related to xenobiotic-degrading enzymes. Biotransformation assays show that XiaF is a designated indole hydroxylase that can be used for the production of indigo and indirubin. We unveil a cryptic hydroxylation step that sets the basis for terpenoid cyclization and suggest that the cyclase has evolved from xenobiotics detoxification enzymes.

A field theory approach to the evolution of canonical helicity and energy

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

You, S.

A redefinition of the Lagrangian of a multi-particle system in fields reformulates the single-particle, kinetic, and fluid equations governing fluid and plasma dynamics as a single set of generalized Maxwell's equations and Ohm's law for canonical force-fields. The Lagrangian includes new terms representing the coupling between the motion of particle distributions, between distributions and electromagnetic fields, with relativistic contributions. The formulation shows that the concepts of self-organization and canonical helicity transport are applicable across single-particle, kinetic, and fluid regimes, at classical and relativistic scales. The theory gives the basis for comparing canonical helicity change to energy change in general systems.more » For example, in a fixed, isolated system subject to non-conservative forces, a species' canonical helicity changes less than total energy only if gradients in density or distribution function are shallow.« less

Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase.

PubMed

Fenwick, Michael K; Mehta, Angad P; Zhang, Yang; Abdelwahed, Sameh H; Begley, Tadhg P; Ealick, Steven E

2015-03-27

Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical. Canonical radical SAM enzymes are characterized by a β-barrel-like fold and SAM anchors to the differentiated iron of the cluster, which is located near the amino terminus and within the β-barrel, through its amino and carboxylate groups. Here we show that ThiC, the thiamin pyrimidine synthase in plants and bacteria, contains a tethered cluster-binding domain at its carboxy terminus that moves in and out of the active site during catalysis. In contrast to canonical radical SAM enzymes, we predict that SAM anchors to an additional active site metal through its amino and carboxylate groups. Superimposition of the catalytic domains of ThiC and glutamate mutase shows that these two enzymes share similar active site architectures, thus providing strong evidence for an evolutionary link between the radical SAM and adenosylcobalamin-dependent enzyme superfamilies.

Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase

DOE PAGES

Fenwick, Michael K.; Mehta, Angad P.; Zhang, Yang; ...

2015-03-27

Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical. Canonical radical SAM enzymes are characterized by a β-barrel-like fold and SAM anchors to the differentiated iron of the cluster, which is located near the amino terminus and within the β-barrel, through its amino and carboxylate groups. Here we show that ThiC, the thiamin pyrimidine synthase in plants and bacteria, contains a tethered cluster-binding domain at its carboxy terminus that moves in and out of the active site during catalysis. In contrast to canonical radical SAM enzymes, we predict that SAM anchors to an additional active sitemore » metal through its amino and carboxylate groups. Superimposition of the catalytic domains of ThiC and glutamate mutase shows that these two enzymes share similar active site architectures, thus providing strong evidence for an evolutionary link between the radical SAM and adenosylcobalamin-dependent enzyme superfamilies.« less

ADER schemes for scalar non-linear hyperbolic conservation laws with source terms in three-space dimensions

NASA Astrophysics Data System (ADS)

Toro, E. F.; Titarev, V. A.

2005-01-01

In this paper we develop non-linear ADER schemes for time-dependent scalar linear and non-linear conservation laws in one-, two- and three-space dimensions. Numerical results of schemes of up to fifth order of accuracy in both time and space illustrate that the designed order of accuracy is achieved in all space dimensions for a fixed Courant number and essentially non-oscillatory results are obtained for solutions with discontinuities. We also present preliminary results for two-dimensional non-linear systems.

Designer tRNAs for efficient incorporation of non-canonical amino acids by the pyrrolysine system in mammalian cells

PubMed Central

Serfling, Robert; Lorenz, Christian; Etzel, Maja; Schicht, Gerda; Böttke, Thore; Mörl, Mario

2018-01-01

Abstract The pyrrolysyl-tRNA synthetase/tRNAPyl pair is the most versatile and widespread system for the incorporation of non-canonical amino acids (ncAAs) into proteins in mammalian cells. However, low yields of ncAA incorporation severely limit its applicability to relevant biological targets. Here, we generate two tRNAPyl variants that significantly boost the performance of the pyrrolysine system. Compared to the original tRNAPyl, the engineered tRNAs feature a canonical hinge between D- and T-loop, show higher intracellular concentrations and bear partially distinct post-transcriptional modifications. Using the new tRNAs, we demonstrate efficient ncAA incorporation into a G-protein coupled receptor (GPCR) and simultaneous ncAA incorporation at two GPCR sites. Moreover, by incorporating last-generation ncAAs for bioorthogonal chemistry, we achieve GPCR labeling with small organic fluorophores on the live cell and visualize stimulus-induced GPCR internalization. Such a robust system for incorporation of single or multiple ncAAs will facilitate the application of a wide pool of chemical tools for structural and functional studies of challenging biological targets in live mammalian cells. PMID:29177436

Anti-cell growth and anti-cancer stem cell activities of the non-canonical hedgehog inhibitor GANT61 in triple-negative breast cancer cells.

PubMed

Koike, Yoshikazu; Ohta, Yusuke; Saitoh, Wataru; Yamashita, Tetsumasa; Kanomata, Naoki; Moriya, Takuya; Kurebayashi, Junichi

2017-09-01

Triple-negative breast cancer (TNBC) exhibits biologically aggressive behavior and has a poor prognosis. Novel molecular targeting agents are needed to control TNBC. Recent studies revealed that the non-canonical hedgehog (Hh) signaling pathway plays important roles in the regulation of cancer stem cells (CSCs) in breast cancer. Therefore, the anti-cell growth and anti-CSC effects of the non-canonical Hh inhibitor GANT61 were investigated in TNBC cells. The effects of GANT61 on cell growth, cell cycle progression, apoptosis, and the proportion of CSCs were investigated in three TNBC cell lines. Four ER-positive breast cancer cell lines were also used for comparisons. The expression levels of effector molecules in the Hh pathway: glioma-associated oncogene (GLI) 1 and GLI2, were measured. The combined effects of GANT61 and paclitaxel on anti-cell growth and anti-CSC activities were also investigated. Basal expression levels of GLI1 and GLI2 were significantly higher in TNBC cells than in ER-positive breast cancer cells. GANT61 dose-dependently decreased cell growth in association with G1-S cell cycle retardation and increased apoptosis. GANT61 significantly decreased the CSC proportion in all TNBC cell lines. Paclitaxel decreased cell growth, but not the CSC proportion. Combined treatments of GANT61 and paclitaxel more than additively enhanced anti-cell growth and/or anti-CSC activities. The non-canonical Hh inhibitor GANT61 decreased not only cell growth, but also the CSC population in TNBC cells. GANT61 enhanced the anti-cell growth activity of paclitaxel in these cells. These results suggest for the first time that GANT61 has potential as a therapeutic agent in the treatment of patients with TNBC.

Marcus canonical integral for non-Gaussian processes and its computation: pathwise simulation and tau-leaping algorithm.

PubMed

Li, Tiejun; Min, Bin; Wang, Zhiming

2013-03-14

The stochastic integral ensuring the Newton-Leibnitz chain rule is essential in stochastic energetics. Marcus canonical integral has this property and can be understood as the Wong-Zakai type smoothing limit when the driving process is non-Gaussian. However, this important concept seems not well-known for physicists. In this paper, we discuss Marcus integral for non-Gaussian processes and its computation in the context of stochastic energetics. We give a comprehensive introduction to Marcus integral and compare three equivalent definitions in the literature. We introduce the exact pathwise simulation algorithm and give the error analysis. We show how to compute the thermodynamic quantities based on the pathwise simulation algorithm. We highlight the information hidden in the Marcus mapping, which plays the key role in determining thermodynamic quantities. We further propose the tau-leaping algorithm, which advance the process with deterministic time steps when tau-leaping condition is satisfied. The numerical experiments and its efficiency analysis show that it is very promising.

A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish

NASA Astrophysics Data System (ADS)

Alcaraz-Pérez, Francisca; García-Castillo, Jesús; García-Moreno, Diana; López-Muñoz, Azucena; Anchelin, Monique; Angosto, Diego; Zon, Leonard I.; Mulero, Victoriano; Cayuela, María L.

2014-02-01

Dyskeratosis congenita (DC) is an inherited disorder with mutations affecting telomerase or telomeric proteins. DC patients usually die of bone marrow failure. Here we show that genetic depletion of the telomerase RNA component (TR) in the zebrafish results in impaired myelopoiesis, despite normal development of haematopoietic stem cells (HSCs). The neutropenia caused by TR depletion is independent of telomere length and telomerase activity. Genetic analysis shows that TR modulates the myeloid-erythroid fate decision by controlling the levels of the master myeloid and erythroid transcription factors spi1 and gata1, respectively. The alteration in spi1 and gata1 levels occurs through stimulation of gcsf and mcsf. Our model of TR deficiency in the zebrafish illuminates the non-canonical roles of TR, and could establish therapeutic targets for DC.

Complement factor H family proteins in their non-canonical role as modulators of cellular functions.

PubMed

Józsi, Mihály; Schneider, Andrea E; Kárpáti, Éva; Sándor, Noémi

2018-01-04

Complement factor H is a major regulator of the alternative pathway of the complement system. The factor H-related proteins are less characterized, but recent data indicate that they rather promote complement activation. These proteins have some common ligands with factor H and have both overlapping and distinct functions depending on domain composition and the degree of conservation of amino acid sequence. Factor H and some of the factor H-related proteins also appear in a non-canonical function that is beyond their role in the modulation of complement activation. This review covers our current understanding on this emerging role of factor H family proteins in modulating the activation and function of various cells by binding to receptors or receptor ligands. Copyright © 2018 Elsevier Ltd. All rights reserved.

Constraints to solve parallelogram grid problems in 2D non separable linear canonical transform

NASA Astrophysics Data System (ADS)

Zhao, Liang; Healy, John J.; Muniraj, Inbarasan; Cui, Xiao-Guang; Malallah, Ra'ed; Ryle, James P.; Sheridan, John T.

2017-05-01

The 2D non-separable linear canonical transform (2D-NS-LCT) can model a range of various paraxial optical systems. Digital algorithms to evaluate the 2D-NS-LCTs are important in modeling the light field propagations and also of interest in many digital signal processing applications. In [Zhao 14] we have reported that a given 2D input image with rectangular shape/boundary, in general, results in a parallelogram output sampling grid (generally in an affine coordinates rather than in a Cartesian coordinates) thus limiting the further calculations, e.g. inverse transform. One possible solution is to use the interpolation techniques; however, it reduces the speed and accuracy of the numerical approximations. To alleviate this problem, in this paper, some constraints are derived under which the output samples are located in the Cartesian coordinates. Therefore, no interpolation operation is required and thus the calculation error can be significantly eliminated.

Generalized canonical ensembles and ensemble equivalence

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

Costeniuc, M.; Ellis, R.S.; Turkington, B.

2006-02-15

This paper is a companion piece to our previous work [J. Stat. Phys. 119, 1283 (2005)], which introduced a generalized canonical ensemble obtained by multiplying the usual Boltzmann weight factor e{sup -{beta}}{sup H} of the canonical ensemble with an exponential factor involving a continuous function g of the Hamiltonian H. We provide here a simplified introduction to our previous work, focusing now on a number of physical rather than mathematical aspects of the generalized canonical ensemble. The main result discussed is that, for suitable choices of g, the generalized canonical ensemble reproduces, in the thermodynamic limit, all the microcanonical equilibriummore » properties of the many-body system represented by H even if this system has a nonconcave microcanonical entropy function. This is something that in general the standard (g=0) canonical ensemble cannot achieve. Thus a virtue of the generalized canonical ensemble is that it can often be made equivalent to the microcanonical ensemble in cases in which the canonical ensemble cannot. The case of quadratic g functions is discussed in detail; it leads to the so-called Gaussian ensemble.« less

Functional Multiple-Set Canonical Correlation Analysis

ERIC Educational Resources Information Center

Hwang, Heungsun; Jung, Kwanghee; Takane, Yoshio; Woodward, Todd S.

2012-01-01

We propose functional multiple-set canonical correlation analysis for exploring associations among multiple sets of functions. The proposed method includes functional canonical correlation analysis as a special case when only two sets of functions are considered. As in classical multiple-set canonical correlation analysis, computationally, the…

K-Fold Crossvalidation in Canonical Analysis.

ERIC Educational Resources Information Center

Liang, Kun-Hsia; And Others

1995-01-01

A computer-assisted, K-fold cross-validation technique is discussed in the framework of canonical correlation analysis of randomly generated data sets. Analysis results suggest that this technique can effectively reduce the contamination of canonical variates and canonical correlations by sample-specific variance components. (Author/SLD)

A non-canonical DNA structure enables homologous recombination in various genetic systems.

PubMed

Masuda, Tokiha; Ito, Yutaka; Terada, Tohru; Shibata, Takehiko; Mikawa, Tsutomu

2009-10-30

Homologous recombination, which is critical to genetic diversity, depends on homologous pairing (HP). HP is the switch from parental to recombinant base pairs, which requires expansion of inter-base pair spaces. This expansion unavoidably causes untwisting of the parental double-stranded DNA. RecA/Rad51-catalyzed ATP-dependent HP is extensively stimulated in vitro by negative supercoils, which compensates for untwisting. However, in vivo, double-stranded DNA is relaxed by bound proteins and thus is an unfavorable substrate for RecA/Rad51. In contrast, Mhr1, an ATP-independent HP protein required for yeast mitochondrial homologous recombination, catalyzes HP without the net untwisting of double-stranded DNA. Therefore, we questioned whether Mhr1 uses a novel strategy to promote HP. Here, we found that, like RecA, Mhr1 induced the extension of bound single-stranded DNA. In addition, this structure was induced by all evolutionarily and structurally distinct HP proteins so far tested, including bacterial RecO, viral RecT, and human Rad51. Thus, HP includes the common non-canonical DNA structure and uses a common core mechanism, independent of the species of HP proteins. We discuss the significance of multiple types of HP proteins.

Analysis of Plasma Detachment through Magnetic Nozzle via Canonical Field Theory

NASA Astrophysics Data System (ADS)

Takagaki, Yu

In this paper, I have investigated the mechanism of plasma detachment through magnetic nozzle via canonical field theory, especially by considering canonical vorticity flux Psisigma contour and dissipative force vector Rsigma. As one of the most recent experimental proofs of plasma detachment, Olsen et al., observed and investigated three key indications of plasma detachment. However, after solving for numerical fits with their experimental data, I found that constant ion flux lines did not actually separate from constant magnetic flux lines. Thus, their first key indication becomes incorrect now. Whereas, my analytical results are consistent with the other two key indications. At the beginning, plasma detached from canonical vorticity flux contours due to non-zero dissipative force and attached on magnetic flux lines instead. However, vector Rsigma [is asymptotically equal to] 0 force makes plasma re-attach on canonical vorticity flux contours around the plume edge region. As the most significant and notable result through my analysis, I confirmed the existence of returning plasma flow around the plume edge region.

Lagrange multiplier and Wess-Zumino variable as extra dimensions in the torus universe

NASA Astrophysics Data System (ADS)

Nejad, Salman Abarghouei; Dehghani, Mehdi; Monemzadeh, Majid

2018-01-01

We study the effect of the simplest geometry which is imposed via the topology of the universe by gauging non-relativistic particle model on torus and 3-torus with the help of symplectic formalism of constrained systems. Also, we obtain generators of gauge transformations for gauged models. Extracting corresponding Poisson structure of existed constraints, we show the effect of the shape of the universe on canonical structure of phase-spaces of models and suggest some phenomenology to prove the topology of the universe and probable non-commutative structure of the space. In addition, we show that the number of extra dimensions in the phase-spaces of gauged embedded models are exactly two. Moreover, in classical form, we talk over modification of Newton's second law in order to study the origin of the terms appeared in the gauged theory.

Engineering 'Golden' Fluorescence by Selective Pressure Incorporation of Non-canonical Amino Acids and Protein Analysis by Mass Spectrometry and Fluorescence.

PubMed

Baumann, Tobias; Schmitt, Franz-Josef; Pelzer, Almut; Spiering, Vivian Jeanette; Freiherr von Sass, Georg Johannes; Friedrich, Thomas; Budisa, Nediljko

2018-04-27

Fluorescent proteins are fundamental tools for the life sciences, in particular for fluorescence microscopy of living cells. While wild-type and engineered variants of the green fluorescent protein from Aequorea victoria (avGFP) as well as homologs from other species already cover large parts of the optical spectrum, a spectral gap remains in the near-infrared region, for which avGFP-based fluorophores are not available. Red-shifted fluorescent protein (FP) variants would substantially expand the toolkit for spectral unmixing of multiple molecular species, but the naturally occurring red-shifted FPs derived from corals or sea anemones have lower fluorescence quantum yield and inferior photo-stability compared to the avGFP variants. Further manipulation and possible expansion of the chromophore's conjugated system towards the far-red spectral region is also limited by the repertoire of 20 canonical amino acids prescribed by the genetic code. To overcome these limitations, synthetic biology can achieve further spectral red-shifting via insertion of non-canonical amino acids into the chromophore triad. We describe the application of SPI to engineer avGFP variants with novel spectral properties. Protein expression is performed in a tryptophan-auxotrophic E. coli strain and by supplementing growth media with suitable indole precursors. Inside the cells, these precursors are converted to the corresponding tryptophan analogs and incorporated into proteins by the ribosomal machinery in response to UGG codons. The replacement of Trp-66 in the enhanced "cyan" variant of avGFP (ECFP) by an electron-donating 4-aminotryptophan results in GdFP featuring a 108 nm Stokes shift and a strongly red-shifted emission maximum (574 nm), while being thermodynamically more stable than its predecessor ECFP. Residue-specific incorporation of the non-canonical amino acid is analyzed by mass spectrometry. The spectroscopic properties of GdFP are characterized by time-resolved fluorescence

Non-canonical Wnt4 prevents skeletal aging and inflammation by inhibiting NF-κB

PubMed Central

Yu, Bo; Chang, Jia; Liu, Yunsong; Li, Jiong; Kevork, Kareena; Al-Hezaimi, Khalid; Graves, Dana T; Park, No-Hee; Wang, Cun-Yu

2014-01-01

Aging-related bone loss and osteoporosis affect millions of patients worldwide. Chronic inflammation associated with aging and arthritis promotes bone resorption and impairs bone formation. Here we show that Wnt4 attenuated bone loss in osteoporosis and skeletal aging by inhibiting nuclear factor-kappa B (NF-κB) via non-canonical Wnt signaling. Transgenic mice expressing Wnt4 from osteoblasts were significantly protected from bone loss and chronic inflammation induced by ovariectomy, tumor necrosis factor or natural aging. In addition to promoting bone formation, Wnt4 could inhibit osteoclast formation and bone resorption. Mechanistically, Wnt4 inhibited transforming growth factor beta-activated kinase 1-mediated NF-κB activation in macrophages and osteoclast precursors independent of β-catenin. Moreover, recombinant Wnt4 proteins were able to alleviate osteoporotic bone loss and inflammation by inhibiting NF-κB in vivo. Taken together, our results suggest that Wnt4 might be used as a therapeutic agent for treating osteoporosis by attenuating NF-κB. PMID:25108526

Characterizing psychological dimensions in non-pathological subjects through autonomic nervous system dynamics

PubMed Central

Nardelli, Mimma; Valenza, Gaetano; Cristea, Ioana A.; Gentili, Claudio; Cotet, Carmen; David, Daniel; Lanata, Antonio; Scilingo, Enzo P.

2015-01-01

The objective assessment of psychological traits of healthy subjects and psychiatric patients has been growing interest in clinical and bioengineering research fields during the last decade. Several experimental evidences strongly suggest that a link between Autonomic Nervous System (ANS) dynamics and specific dimensions such as anxiety, social phobia, stress, and emotional regulation might exist. Nevertheless, an extensive investigation on a wide range of psycho-cognitive scales and ANS non-invasive markers gathered from standard and non-linear analysis still needs to be addressed. In this study, we analyzed the discerning and correlation capabilities of a comprehensive set of ANS features and psycho-cognitive scales in 29 non-pathological subjects monitored during resting conditions. In particular, the state of the art of standard and non-linear analysis was performed on Heart Rate Variability, InterBreath Interval series, and InterBeat Respiration series, which were considered as monovariate and multivariate measurements. Experimental results show that each ANS feature is linked to specific psychological traits. Moreover, non-linear analysis outperforms the psychological assessment with respect to standard analysis. Considering that the current clinical practice relies only on subjective scores from interviews and questionnaires, this study provides objective tools for the assessment of psychological dimensions. PMID:25859212

Are neoclassical canons valid for southern Chinese faces?

PubMed

Jayaratne, Yasas S N; Deutsch, Curtis K; McGrath, Colman P J; Zwahlen, Roger A

2012-01-01

Proportions derived from neoclassical canons, initially described by Renaissance sculptors and painters, are still being employed as aesthetic guidelines during the clinical assessment of the facial morphology. 1. to determine the applicability of neoclassical canons for Southern Chinese faces and 2. to explore gender differences in relation to the applicability of the neoclassical canons and their variants. 3-D photographs acquired from 103 young adults (51 males and 52 females) without facial dysmorphology were used to test applicability of four neoclassical canons. Standard anthropometric measurements that determine the facial canons were made on these 3-D images. The validity of the canons as well as their different variants were quantified. The neoclassical cannons seldom applied to these individuals, and facial three-section and orbital canons did not apply at all. The orbitonasal canon was most frequently applicable, with a frequency of 19%. Significant sexual dimorphism was found relative to the prevalence of the variants of facial three-section and orbitonasal canons. The neoclassical canons did not appear to apply to our sample when rigorous quantitative measurements were employed. Thus, they should not be used as esthetic goals for craniofacial surgical interventions.

Are Neoclassical Canons Valid for Southern Chinese Faces?

PubMed Central

Jayaratne, Yasas S. N.; Deutsch, Curtis K.; McGrath, Colman P. J.; Zwahlen, Roger A.

2012-01-01

Background Proportions derived from neoclassical canons, initially described by Renaissance sculptors and painters, are still being employed as aesthetic guidelines during the clinical assessment of the facial morphology. Objective 1. to determine the applicability of neoclassical canons for Southern Chinese faces and 2. to explore gender differences in relation to the applicability of the neoclassical canons and their variants. Methodology 3-D photographs acquired from 103 young adults (51 males and 52 females) without facial dysmorphology were used to test applicability of four neoclassical canons. Standard anthropometric measurements that determine the facial canons were made on these 3-D images. The validity of the canons as well as their different variants were quantified. Principal Findings The neoclassical cannons seldom applied to these individuals, and facial three-section and orbital canons did not apply at all. The orbitonasal canon was most frequently applicable, with a frequency of 19%. Significant sexual dimorphism was found relative to the prevalence of the variants of facial three-section and orbitonasal canons. Conclusion The neoclassical canons did not appear to apply to our sample when rigorous quantitative measurements were employed. Thus, they should not be used as esthetic goals for craniofacial surgical interventions. PMID:23285105

Probing eudesmane cation-π interactions in catalysis by aristolochene synthase with non-canonical amino acids.

PubMed

Faraldos, Juan A; Antonczak, Alicja K; González, Verónica; Fullerton, Rebecca; Tippmann, Eric M; Allemann, Rudolf K

2011-09-07

Stabilization of the reaction intermediate eudesmane cation (3) through interaction with Trp 334 during catalysis by aristolochene synthase from Penicillium roqueforti was investigated by site-directed incorporation of proteinogenic and non-canonical aromatic amino acids. The amount of germacrene A (2) generated by the mutant enzymes served as a measure of the stabilization of 3. 2 is a neutral intermediate, from which 3 is formed during PR-AS catalysis by protonation of the C6,C7 double bond. The replacement of Trp 334 with para-substituted phenylalanines of increasing electron-withdrawing properties led to a progressive accumulation of 2 that showed a good correlation with the interaction energies of simple cations such as Na(+) with substituted benzenes. These results provide compelling evidence for the stabilizing role played by Trp 334 in aristolochene synthase catalysis for the energetically demanding transformation of 2 to 3.

Influence in Canonical Correlation Analysis.

ERIC Educational Resources Information Center

Romanazzi, Mario

1992-01-01

The perturbation theory of the generalized eigenproblem is used to derive influence functions of each squared canonical correlation coefficient and the corresponding canonical vector pair. Three sample versions of these functions are described, and some properties are noted. Two obvious applications, multiple correlation and correspondence…

Failure in activation of the canonical NF-κB pathway by human T-cell leukemia virus type 1 Tax in non-hematopoietic cell lines

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

Mizukoshi, Terumi; Komori, Hideyuki; Mizuguchi, Mariko

2013-09-01

Human T-cell leukemia virus type 1 (HTLV-1) Tax (Tax1) plays crucial roles in leukemogenesis in part through activation of NF-κB. In this study, we demonstrated that Tax1 activated an NF-κB binding (gpκB) site of the gp34/OX40 ligand gene in a cell type-dependent manner. Our examination showed that the gpκΒ site and authentic NF-κB (IgκB) site were activated by Tax1 in hematopoietic cell lines. Non-hematopoietic cell lines including hepatoma and fibroblast cell lines were not permissive to Tax1-mediated activation of the gpκB site, while the IgκB site was activated in those cells in association with binding of RelB. However RelA bindingmore » was not observed in the gpκB and IgκB sites. Our results suggest that HTLV-1 Tax1 fails to activate the canonical pathway of NF-κB in non-hematopoietic cell lines. Cell type-dependent activation of NF-κB by Tax1 could be associated with pathogenesis by HTLV-1 infection. - Highlights: • HTLV-1 Tax1 does not activate RelA of NF-κB in non-hematopoietic cell lines. • Tax1 activates the NF-κB non-canonical pathway in non-hematopoietic cell lines. • Tax1 does not induce RelA nuclear translocation in those cell lines, unlike TNFα. • The OX40L promoter κB site is activated by ectopic, but not endogenous, RelA.« less

The canonical Wnt signaling pathway in autism.

PubMed

Zhang, Yinghua; Yuan, Xiangshan; Wang, Zhongping; Li, Ruixi

2014-01-01

Mounting attention is being focused on the canonical Wnt signaling pathway which has been implicated in the pathogenesis of autism in some our and other recent studies. The canonical Wnt pathway is involved in cell proliferation, differentiation and migration, especially during nervous system development. Given its various functions, dysfunction of the canonical Wnt pathway may exert adverse effects on neurodevelopment and therefore leads to the pathogenesis of autism. Here, we review human and animal studies that implicate the canonical Wnt signal transduction pathway in the pathogenesis of autism. We also describe the crosstalk between the canonical Wnt pathway and the Notch signaling pathway in several types of autism spectrum disorders, including Asperger syndrome and Fragile X. Further research on the crosstalk between the canonical Wnt signaling pathway and other signaling cascades in autism may be an efficient avenue to understand the etiology of autism and ultimately lead to alternative medications for autism-like phenotypes.

A non-canonical peptide synthetase adenylates 3-methyl-2-oxovaleric acid for auriculamide biosynthesis.

PubMed

Braga, Daniel; Hoffmeister, Dirk; Nett, Markus

2016-01-01

Auriculamide is the first natural product known from the predatory bacterium Herpetosiphon aurantiacus. It is composed of three unusual building blocks, including the non-proteinogenic amino acid 3-chloro-L-tyrosine, the α-hydroxy acid L-isoleucic acid, and a methylmalonyl-CoA-derived ethane unit. A candidate genetic locus for auriculamide biosynthesis was identified and encodes four enzymes. Among them, the non-canonical 199 kDa four-domain nonribosomal peptide synthetase, AulA, is extraordinary in that it features two consecutive adenylation domains. Here, we describe the functional characterization of the recombinantly produced AulA. The observed activation of 3-methyl-2-oxovaleric acid by the enzyme supports the hypothesis that it participates in the biosynthesis of auriculamide. An artificially truncated version of AulA that lacks the first adenylation domain activated this substrate like the full-length enzyme which shows that the first adenylation domain is dispensable. Additionally, we provide evidence that the enzyme tolerates structural variation of the substrate. α-Carbon substituents significantly affected the substrate turnover. While all tested aliphatic α-keto acids were accepted by the enzyme and minor differences in chain size and branches did not interfere with the enzymatic activity, molecules with methylene α-carbons led to low turnover. Such enzymatic plasticity is an important attribute to help in the perpetual search for novel molecules and to access a greater structural diversity by mutasynthesis.

Regularized Generalized Canonical Correlation Analysis

ERIC Educational Resources Information Center

Tenenhaus, Arthur; Tenenhaus, Michel

2011-01-01

Regularized generalized canonical correlation analysis (RGCCA) is a generalization of regularized canonical correlation analysis to three or more sets of variables. It constitutes a general framework for many multi-block data analysis methods. It combines the power of multi-block data analysis methods (maximization of well identified criteria) and…

Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (Review).

PubMed

Katoh, Masaru

2017-11-01

Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49). Aberrant canonical and non-canonical WNT signaling in human malignancies, including breast, colorectal, gastric, lung, ovary, pancreatic, prostate and uterine cancers, leukemia and melanoma, are involved in CSC survival, bulk-tumor expansion and invasion/metastasis. WNT signaling-targeted therapeutics, such as anti-FZD1/2/5/7/8 monoclonal antibody (mAb) (vantictumab), anti-LGR5 antibody-drug conjugate (ADC) (mAb-mc-vc-PAB-MMAE), anti-PTK7 ADC (PF-06647020), anti-ROR1 mAb (cirmtuzumab), anti-RSPO3 mAb (rosmantuzumab), small-molecule porcupine inhibitors (ETC-159, WNT-C59 and WNT974), tankyrase inhibitors (AZ1366, G007-LK, NVP-TNKS656 and XAV939) and β-catenin inhibitors (BC2059, CWP232228, ICG-001 and PRI-724), are in clinical trials or preclinical studies for the treatment of patients with WNT-driven cancers. WNT signaling-targeted therapeutics are applicable for combination therapy with BCR-ABL, EGFR, FLT3, KIT or RET inhibitors to treat a subset of tyrosine kinase-driven cancers because WNT and tyrosine kinase signaling cascades converge to β-catenin for the maintenance and expansion of CSCs. WNT signaling-targeted therapeutics might also be applicable for combination therapy with immune checkpoint blockers, such as atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab and pembrolizumab, to treat cancers

Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (Review)

PubMed Central

Katoh, Masaru

2017-01-01

Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49). Aberrant canonical and non-canonical WNT signaling in human malignancies, including breast, colorectal, gastric, lung, ovary, pancreatic, prostate and uterine cancers, leukemia and melanoma, are involved in CSC survival, bulk-tumor expansion and invasion/metastasis. WNT signaling-targeted therapeutics, such as anti-FZD1/2/5/7/8 monoclonal antibody (mAb) (vantictumab), anti-LGR5 antibody-drug conjugate (ADC) (mAb-mc-vc-PAB-MMAE), anti-PTK7 ADC (PF-06647020), anti-ROR1 mAb (cirmtuzumab), anti-RSPO3 mAb (rosmantuzumab), small-molecule porcupine inhibitors (ETC-159, WNT-C59 and WNT974), tankyrase inhibitors (AZ1366, G007-LK, NVP-TNKS656 and XAV939) and β-catenin inhibitors (BC2059, CWP232228, ICG-001 and PRI-724), are in clinical trials or preclinical studies for the treatment of patients with WNT-driven cancers. WNT signaling-targeted therapeutics are applicable for combination therapy with BCR-ABL, EGFR, FLT3, KIT or RET inhibitors to treat a subset of tyrosine kinase-driven cancers because WNT and tyrosine kinase signaling cascades converge to β-catenin for the maintenance and expansion of CSCs. WNT signaling-targeted therapeutics might also be applicable for combination therapy with immune checkpoint blockers, such as atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab and pembrolizumab, to treat cancers

The contributions of non-numeric dimensions to number encoding, representations, and decision-making factors.

PubMed

Odic, Darko

2017-01-01

Leibovich et al. suggest that congruency effects in number perception (biases towards smaller, denser, etc., dots) are evidence for the number's dependence on these dimensions. I argue that they fail to differentiate between effects at three distinct levels of number perception - encoding, representations, and decision making - and that differentiating between these allows the number to be independent from, but correlated with, non-numeric dimensions.

Bethe/Gauge correspondence in odd dimension: modular double, non-perturbative corrections and open topological strings

NASA Astrophysics Data System (ADS)

Sciarappa, Antonio

2016-10-01

Bethe/Gauge correspondence as it is usually stated is ill-defined in five dimensions and needs a "non-perturbative" completion; a related problem also appears in three dimensions. It has been suggested that this problem, probably due to incompleteness of Omega background regularization in odd dimension, may be solved if we consider gauge theory on compact S 5 and S 3 geometries. We will develop this idea further by giving a full Bethe/Gauge correspondence dictionary on S 5 and S 3 focussing mainly on the eigenfunctions of (open and closed) relativistic 2-particle Toda chain and its quantized spectral curve: these are most properly written in terms of non-perturbatively completed NS open topological strings. A key ingredient is Faddeev's modular double structure which is naturally implemented by the S 5 and S 3 geometries.

Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site

NASA Astrophysics Data System (ADS)

Liu, Chuang; Perilla, Juan R.; Ning, Jiying; Lu, Manman; Hou, Guangjin; Ramalho, Ruben; Himes, Benjamin A.; Zhao, Gongpu; Bedwell, Gregory J.; Byeon, In-Ja; Ahn, Jinwoo; Gronenborn, Angela M.; Prevelige, Peter E.; Rousso, Itay; Aiken, Christopher; Polenova, Tatyana; Schulten, Klaus; Zhang, Peijun

2016-03-01

The host cell factor cyclophilin A (CypA) interacts directly with the HIV-1 capsid and regulates viral infectivity. Although the crystal structure of CypA in complex with the N-terminal domain of the HIV-1 capsid protein (CA) has been known for nearly two decades, how CypA interacts with the viral capsid and modulates HIV-1 infectivity remains unclear. We determined the cryoEM structure of CypA in complex with the assembled HIV-1 capsid at 8-Å resolution. The structure exhibits a distinct CypA-binding pattern in which CypA selectively bridges the two CA hexamers along the direction of highest curvature. EM-guided all-atom molecular dynamics simulations and solid-state NMR further reveal that the CypA-binding pattern is achieved by single-CypA molecules simultaneously interacting with two CA subunits, in different hexamers, through a previously uncharacterized non-canonical interface. These results provide new insights into how CypA stabilizes the HIV-1 capsid and is recruited to facilitate HIV-1 infection.

Non-Canonical Role of IKKα in the Regulation of STAT1 Phosphorylation in Antiviral Signaling

PubMed Central

Xing, Fei; Matsumiya, Tomoh; Shiba, Yuko; Hayakari, Ryo; Yoshida, Hidemi; Imaizumi, Tadaatsu

2016-01-01

Non-self RNA is recognized by retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), inducing type I interferons (IFNs). Type I IFN promotes the expression of IFN-stimulated genes (ISGs), which requires the activation of signal transducer and activator of transcription-1 (STAT1). We previously reported that dsRNA induced STAT1 phosphorylation via a type I IFN-independent pathway in addition to the well-known type I IFN-dependent pathway. IκB kinase α (IKKα) is involved in antiviral signaling induced by dsRNA; however, its role is incompletely understood. Here, we explored the function of IKKα in RLR-mediated STAT1 phosphorylation. Silencing of IKKα markedly decreased the level of IFN-β and STAT1 phosphorylation inHeH response to dsRNA. However, the inhibition of IKKα did not alter the RLR signaling-mediated dimerization of interferon responsive factor 3 (IRF3) or the nuclear translocation of nuclear factor-κB (NFκB). These results suggest a non-canonical role of IKKα in RLR signaling. Furthermore, phosphorylation of STAT1 was suppressed by IKKα knockdown in cells treated with a specific neutralizing antibody for the type I IFN receptor (IFNAR) and in IFNAR-deficient cells. Collectively, the dual regulation of STAT1 by IKKα in antiviral signaling suggests a role for IKKα in the fine-tuning of antiviral signaling in response to non-self RNA. PMID:27992555

Opinion: uracil DNA glycosylase (UNG) plays distinct and non-canonical roles in somatic hypermutation and class switch recombination.

PubMed

Yousif, Ashraf S; Stanlie, Andre; Begum, Nasim A; Honjo, Tasuku

2014-10-01

Activation-induced cytidine deaminase (AID) is essential to class switch recombination (CSR) and somatic hypermutation (SHM). Uracil DNA glycosylase (UNG), a member of the base excision repair complex, is required for CSR. The role of UNG in CSR and SHM is extremely controversial. AID deficiency in mice abolishes both CSR and SHM, while UNG-deficient mice have drastically reduced CSR but augmented SHM raising a possibility of differential functions of UNG in CSR and SHM. Interestingly, UNG has been associated with a CSR-specific repair adapter protein Brd4, which interacts with acetyl histone 4, γH2AX and 53BP1 to promote non-homologous end joining during CSR. A non-canonical scaffold function of UNG, but not the catalytic activity, can be attributed to the recruitment of essential repair proteins associated with the error-free repair during SHM, and the end joining during CSR. © The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The role of word order in the interpretation of canonical and non-canonical graphic symbol utterances: A developmental study.

PubMed

Trudeau, Natacha; Morford, Jill P; Sutton, Ann

2010-06-01

Graphic symbols are often used to represent words in Augmentative and Alternative Communication systems. Previous findings suggest that different processes operate when using graphic symbols and when using speech. This study assessed the ability of native speakers of French with no communication disorders from four age groups to interpret graphic-symbol sequences of varying length and canonicity. Results reveal that, as they get older, participants show an increase in their capacity to interpret graphic-symbol sequences. Constituent order played an important role in the interpretation of the sequences. However, the specific word-order strategies used varied depending on the age group and the type of sequence presented.

Positive geometries and canonical forms

NASA Astrophysics Data System (ADS)

Arkani-Hamed, Nima; Bai, Yuntao; Lam, Thomas

2017-11-01

Recent years have seen a surprising connection between the physics of scattering amplitudes and a class of mathematical objects — the positive Grassmannian, positive loop Grassmannians, tree and loop Amplituhedra — which have been loosely referred to as "positive geometries". The connection between the geometry and physics is provided by a unique differential form canonically determined by the property of having logarithmic singularities (only) on all the boundaries of the space, with residues on each boundary given by the canonical form on that boundary. The structures seen in the physical setting of the Amplituhedron are both rigid and rich enough to motivate an investigation of the notions of "positive geometries" and their associated "canonical forms" as objects of study in their own right, in a more general mathematical setting. In this paper we take the first steps in this direction. We begin by giving a precise definition of positive geometries and canonical forms, and introduce two general methods for finding forms for more complicated positive geometries from simpler ones — via "triangulation" on the one hand, and "push-forward" maps between geometries on the other. We present numerous examples of positive geometries in projective spaces, Grassmannians, and toric, cluster and flag varieties, both for the simplest "simplex-like" geometries and the richer "polytope-like" ones. We also illustrate a number of strategies for computing canonical forms for large classes of positive geometries, ranging from a direct determination exploiting knowledge of zeros and poles, to the use of the general triangulation and push-forward methods, to the representation of the form as volume integrals over dual geometries and contour integrals over auxiliary spaces. These methods yield interesting representations for the canonical forms of wide classes of positive geometries, ranging from the simplest Amplituhedra to new expressions for the volume of arbitrary convex

Preserving Catholic identity in mergers--an ethical and Canon Law perspective.

PubMed

Vowell, T H

1992-03-01

A merger or joint venture between a Catholic healthcare facility and a non-Catholic healthcare facility that provides procedures the Catholic Church believes to violate moral principles raises a number of issues to be considered by diocesan bishops. The 1983 Code of Canon Law provides bishops with guidelines to help establish the Catholicity of a Catholic hospital that has affiliated with a non-Catholic hospital. The diocesan bishop exercises his authority through a threefold ministry of teaching, sanctifying, and governing. These ministries stand as a reminder of his decision-making authority in matters that affect the spiritual state and growth of those entrusted to his care. Catholic identity, as it is presented in the Code of Canon Law, can be determined through the presence of a relationship between an institution and ecclesiastical authorities, the legal establishment of the entity, and a degree of control that the Church exercises over the institution. When evaluating a possible merger of joint venture between a Catholic hospital and a non-Catholic hospital that is performing procedures not in accord with Catholic Church teaching, the diocesan bishop must consider what limits must be observed. The good effects of the affiliation must be intended and direct, and the harmful effects must be perceived as unintended and indirect. The difficulties in determining and protecting the identity of Catholic hospitals in possible mergers or joint ventures should not prevent facilities from considering alternative forms of corporate structures. The Code of Canon Law and the Church's ethical teachings provide guidelines to ensure these possibilities.

The integrated model of sport confidence: a canonical correlation and mediational analysis.

PubMed

Koehn, Stefan; Pearce, Alan J; Morris, Tony

2013-12-01

The main purpose of the study was to examine crucial parts of Vealey's (2001) integrated framework hypothesizing that sport confidence is a mediating variable between sources of sport confidence (including achievement, self-regulation, and social climate) and athletes' affect in competition. The sample consisted of 386 athletes, who completed the Sources of Sport Confidence Questionnaire, Trait Sport Confidence Inventory, and Dispositional Flow Scale-2. Canonical correlation analysis revealed a confidence-achievement dimension underlying flow. Bias-corrected bootstrap confidence intervals in AMOS 20.0 were used in examining mediation effects between source domains and dispositional flow. Results showed that sport confidence partially mediated the relationship between achievement and self-regulation domains and flow, whereas no significant mediation was found for social climate. On a subscale level, full mediation models emerged for achievement and flow dimensions of challenge-skills balance, clear goals, and concentration on the task at hand.

On a canonical quantization of 3D Anti de Sitter pure gravity

NASA Astrophysics Data System (ADS)

Kim, Jihun; Porrati, Massimo

2015-10-01

We perform a canonical quantization of pure gravity on AdS 3 using as a technical tool its equivalence at the classical level with a Chern-Simons theory with gauge group SL(2,{R})× SL(2,{R}) . We first quantize the theory canonically on an asymptotically AdS space -which is topologically the real line times a Riemann surface with one connected boundary. Using the "constrain first" approach we reduce canonical quantization to quantization of orbits of the Virasoro group and Kähler quantization of Teichmüller space. After explicitly computing the Kähler form for the torus with one boundary component and after extending that result to higher genus, we recover known results, such as that wave functions of SL(2,{R}) Chern-Simons theory are conformal blocks. We find new restrictions on the Hilbert space of pure gravity by imposing invariance under large diffeomorphisms and normalizability of the wave function. The Hilbert space of pure gravity is shown to be the target space of Conformal Field Theories with continuous spectrum and a lower bound on operator dimensions. A projection defined by topology changing amplitudes in Euclidean gravity is proposed. It defines an invariant subspace that allows for a dual interpretation in terms of a Liouville CFT. Problems and features of the CFT dual are assessed and a new definition of the Hilbert space, exempt from those problems, is proposed in the case of highly-curved AdS 3.

A field theoretic generalization of Hajicek and Kuchar's quantization scheme in 3+1 canonical quantum gravity

NASA Astrophysics Data System (ADS)

Melas, Evangelos

2011-07-01

The 3+1 (canonical) decomposition of all geometries admitting two-dimensional space-like surfaces is exhibited as a generalization of a previous work. A proposal, consisting of a specific re-normalization Assumption and an accompanying Requirement, which has been put forward in the 2+1 case is now generalized to 3+1 dimensions. This enables the canonical quantization of these geometries through a generalization of Kuchař's quantization scheme in the case of infinite degrees of freedom. The resulting Wheeler-deWitt equation is based on a re-normalized manifold parameterized by three smooth scalar functionals. The entire space of solutions to this equation is analytically given, a fact that is entirely new to the present case. This is made possible by exploiting the freedom left by the imposition of the Requirement and contained in the third functional.

Structure and energy of non-canonical basepairs: comparison of various computational chemistry methods with crystallographic ensembles.

PubMed

Panigrahi, Swati; Pal, Rahul; Bhattacharyya, Dhananjay

2011-12-01

Different types of non-canonical basepairs, in addition to the Watson-Crick ones, are observed quite frequently in RNA. Their importance in the three dimensional structure is not fully understood, but their various roles have been proposed by different groups. We have analyzed the energetics and geometry of 32 most frequently observed basepairs in the functional RNA crystal structures using different popular empirical, semi-empirical and ab initio quantum chemical methods and compared their optimized geometry with the crystal data. These basepairs are classified into three categories: polar, non-polar and sugar-mediated, depending on the types of atoms involved in hydrogen bonding. In case of polar basepairs, most of the methods give rise to optimized structures close to their initial geometry. The interaction energies also follow similar trends, with the polar ones having more attractive interaction energies. Some of the C-H...O/N hydrogen bond mediated non-polar basepairs are also found to be significantly stable in terms of their interaction energy values. Few polar basepairs, having amino or carboxyl groups not hydrogen bonded to anything, such as G:G H:W C, show large flexibility. Most of the non-polar basepairs, except A:G s:s T and A:G w:s C, are found to be stable; indicating C-H...O/N interaction also plays a prominent role in stabilizing the basepairs. The sugar mediated basepairs show variability in their structures, due to the involvement of flexible ribose sugar. These presumably indicate that the most of the polar basepairs along with few non-polar ones act as seed for RNA folding while few may act as some conformational switch in the RNA.

CAPE suppresses migration and invasion of prostate cancer cells via activation of non-canonical Wnt signaling.

PubMed

Tseng, Jen-Chih; Lin, Ching-Yu; Su, Liang-Chen; Fu, Hsiao-Hui; Yang, Shiaw-Der; Chuu, Chih-Pin

2016-06-21

Prostate cancer (PCa) was the fifth most common cancer overall in the world. More than 80% of patients died from PCa developed bone metastases. Caffeic acid phenethyl ester (CAPE) is a main bioactive component of honeybee hive propolis. Transwell and wound healing assays demonstrated that CAPE treatment suppressed the migration and invasion of PC-3 and DU-145 PCa cells. Gelatin zymography and Western blotting indicated that CAPE treatment reduced the abundance and activity of MMP-9 and MMP-2. Analysis using Micro-Western Array (MWA), a high-throughput antibody-based proteomics platform with 264 antibodies detecting signaling proteins involved in important pathways indicated that CAPE treatment induced receptor tyrosine kinase-like orphan receptor 2 (ROR2) in non-canonical Wnt signaling pathway but suppressed abundance of β-catenin, NF-κB activity, PI3K-Akt signaling, and epithelial-mesenchymal transition (EMT). Overexpression or knockdown of ROR2 suppressed or enhanced cell migration of PC-3 cells, respectively. TCF-LEF promoter binding assay revealed that CAPE treatment reduced canonical Wnt signaling. Intraperitoneal injection of CAPE reduced the metastasis of PC-3 xenografts in tail vein injection nude mice model. Immunohistochemical staining demonstrated that CAPE treatment increased abundance of ROR2 and Wnt5a but decreased protein expression of Ki67, Frizzle 4, NF-κB p65, MMP-9, Snail, β-catenin, and phosphorylation of IκBα. Clinical evidences suggested that genes affected by CAPE treatment (CTNNB1, RELA, FZD5, DVL3, MAPK9, SNAl1, ROR2, SMAD4, NFKBIA, DUSP6, and PLCB3) correlate with the aggressiveness of PCa. Our study suggested that CAPE may be a potential therapeutic agent for patients with advanced PCa.

Random discrete linear canonical transform.

PubMed

Wei, Deyun; Wang, Ruikui; Li, Yuan-Min

2016-12-01

Linear canonical transforms (LCTs) are a family of integral transforms with wide applications in optical, acoustical, electromagnetic, and other wave propagation problems. In this paper, we propose the random discrete linear canonical transform (RDLCT) by randomizing the kernel transform matrix of the discrete linear canonical transform (DLCT). The RDLCT inherits excellent mathematical properties from the DLCT along with some fantastic features of its own. It has a greater degree of randomness because of the randomization in terms of both eigenvectors and eigenvalues. Numerical simulations demonstrate that the RDLCT has an important feature that the magnitude and phase of its output are both random. As an important application of the RDLCT, it can be used for image encryption. The simulation results demonstrate that the proposed encryption method is a security-enhanced image encryption scheme.

A canonical form of the equation of motion of linear dynamical systems

NASA Astrophysics Data System (ADS)

Kawano, Daniel T.; Salsa, Rubens Goncalves; Ma, Fai; Morzfeld, Matthias

2018-03-01

The equation of motion of a discrete linear system has the form of a second-order ordinary differential equation with three real and square coefficient matrices. It is shown that, for almost all linear systems, such an equation can always be converted by an invertible transformation into a canonical form specified by two diagonal coefficient matrices associated with the generalized acceleration and displacement. This canonical form of the equation of motion is unique up to an equivalence class for non-defective systems. As an important by-product, a damped linear system that possesses three symmetric and positive definite coefficients can always be recast as an undamped and decoupled system.

Evidence for possible non-canonical pathway(s) driven early-onset colorectal cancer in India

PubMed Central

Raman, Ratheesh; Kotapalli, Viswakalyan; Adduri, Raju; Gowrishankar, Swarnalata; Bashyam, Leena; Chaudhary, Ajay; Vamsy, Mohana; Patnaik, Sujith; Srinivasulu, Mukta; Sastry, Regulagadda; Rao, Subramanyeshwar; Vasala, Anjayneyulu; Kalidindi, NarasimhaRaju; Pollack, Jonathan; Murthy, Sudha; Bashyam, Murali

2012-01-01

Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for greater than 90% of late-onset colorectal cancer. Our understanding of early-onset sporadic CRC is however comparatively limited. In addition, most seminal studies have been performed in the western population and analyses of tumorigenesis pathway(s) causing CRC in developing nations have been rare. We performed a comparative analysis of early and late-onset CRC from India with respect to common genetic aberrations including Wnt, KRAS and p53 (constituting the classical CRC progression sequence) in addition to MSI. Our results revealed the absence of Wnt and MSI in a significant proportion of early-onset as against late-onset CRC in India. In addition, KRAS mutation frequency was significantly lower in early-onset CRC indicating that a significant proportion of CRC in India may follow tumorigenesis pathways distinct from the classical CRC progression sequence. Our study has therefore revealed the possible existence of non-canonical tumorigenesis pathways in early-onset CRC in India. PMID:23168910

Non-canonical mechanism for translational control in bacteria: synthesis of ribosomal protein S1

PubMed Central

Boni, Irina V.; Artamonova, Valentina S.; Tzareva, Nina V.; Dreyfus, Marc

2001-01-01

Translation initiation region (TIR) of the rpsA mRNA encoding ribosomal protein S1 is one of the most efficient in Escherichia coli despite the absence of a canonical Shine–Dalgarno-element. Its high efficiency is under strong negative autogenous control, a puzzling phenomenon as S1 has no strict sequence specificity. To define sequence and structural elements responsible for translational efficiency and autoregulation of the rpsA mRNA, a series of rpsA′–′lacZ chromosomal fusions bearing various mutations in the rpsA TIR was created and tested for β-galactosidase activity in the absence and presence of excess S1. These in vivo results, as well as data obtained by in vitro techniques and phylogenetic comparison, allow us to propose a model for the structural and functional organization of the rpsA TIR specific for proteobacteria related to E.coli. According to the model, the high efficiency of translation initiation is provided by a specific fold of the rpsA leader forming a non-contiguous ribosome entry site, which is destroyed upon binding of free S1 when it acts as an autogenous repressor. PMID:11483525

Non-Canonical G-quadruplexes cause the hCEB1 minisatellite instability in Saccharomyces cerevisiae

PubMed Central

Piazza, Aurèle; Cui, Xiaojie; Adrian, Michael; Samazan, Frédéric; Heddi, Brahim; Phan, Anh-Tuan; Nicolas, Alain G

2017-01-01

G-quadruplexes (G4) are polymorphic four-stranded structures formed by certain G-rich nucleic acids in vitro, but the sequence and structural features dictating their formation and function in vivo remains uncertain. Here we report a structure-function analysis of the complex hCEB1 G4-forming sequence. We isolated four G4 conformations in vitro, all of which bear unusual structural features: Form 1 bears a V-shaped loop and a snapback guanine; Form 2 contains a terminal G-triad; Form 3 bears a zero-nucleotide loop; and Form 4 is a zero-nucleotide loop monomer or an interlocked dimer. In vivo, Form 1 and Form 2 differently account for 2/3rd of the genomic instability of hCEB1 in two G4-stabilizing conditions. Form 3 and an unidentified form contribute to the remaining instability, while Form 4 has no detectable effect. This work underscores the structural polymorphisms originated from a single highly G-rich sequence and demonstrates the existence of non-canonical G4s in cells, thus broadening the definition of G4-forming sequences. DOI: http://dx.doi.org/10.7554/eLife.26884.001 PMID:28661396

The self-trapping transition in the non-half-filled strongly correlated extended Holstein-Hubbard model in two-dimensions

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

Sankar, I. V., E-mail: ivshankar27@gmail.com; Chatterjee, Ashok, E-mail: ivshankar27@gmail.com

2014-04-24

The two-dimensional extended Holstein-Hubbard model (EHH) has been considered at strong correlation regime in the non-half-filled band case to understand the self-trapping transition of electrons in strongly correlated electron system. We have used the method of optimized canonical transformations to transform an EHH model into an effective extended Hubbard (EEH) model. In the strong on-site correlation limit an EH model can be transformed into a t-J model which is finally solved using Hartree-Fock approximation (HFA). We found that, for non-half-filled band case, the transition is abrupt in the adiabatic region whereas it is continuous in the anti-adiabatic region.

Versions of the collocation and least squares method for solving biharmonic equations in non-canonical domains

NASA Astrophysics Data System (ADS)

Belyaev, V. A.; Shapeev, V. P.

2017-10-01

New versions of the collocations and least squares method of high-order accuracy are proposed and implemented for the numerical solution of the boundary value problems for the biharmonic equation in non-canonical domains. The solution of the biharmonic equation is used for simulating the stress-strain state of an isotropic plate under the action of transverse load. The differential problem is projected into a space of fourth-degree polynomials by the CLS method. The boundary conditions for the approximate solution are put down exactly on the boundary of the computational domain. The versions of the CLS method are implemented on the grids which are constructed in two different ways. It is shown that the approximate solution of problems converges with high order. Thus it matches with high accuracy with the analytical solution of the test problems in the case of known solution in the numerical experiments on the convergence of the solution of various problems on a sequence of grids.

A role for NRAGE in NF-κB activation through the non-canonical BMP pathway

PubMed Central

2010-01-01

Background Previous studies have linked neurotrophin receptor-interacting MAGE protein to the bone morphogenic protein signaling pathway and its effect on p38 mediated apoptosis of neural progenitor cells via the XIAP-Tak1-Tab1 complex. Its effect on NF-κB has yet to be explored. Results Herein we report that NRAGE, via the same XIAP-Tak1-Tab1 complex, is required for the phosphorylation of IKK -α/β and subsequent transcriptional activation of the p65 subunit of NF-κB. Ablation of endogenous NRAGE by siRNA inhibited NF-κB pathway activation, while ablation of Tak1 and Tab1 by morpholino inhibited overexpression of NRAGE from activating NF-κB. Finally, cytokine profiling of an NRAGE over-expressing stable line revealed the expression of macrophage migration inhibitory factor. Conclusion Modulation of NRAGE expression revealed novel roles in regulating NF-κB activity in the non-canonical bone morphogenic protein signaling pathway. The expression of macrophage migration inhibitory factor by bone morphogenic protein -4 reveals novel crosstalk between an immune cytokine and a developmental pathway. PMID:20100315

A model of individualized canonical microcircuits supporting cognitive operations

PubMed Central

Peterson, Andre D. H.; Haueisen, Jens; Knösche, Thomas R.

2017-01-01

Major cognitive functions such as language, memory, and decision-making are thought to rely on distributed networks of a large number of basic elements, called canonical microcircuits. In this theoretical study we propose a novel canonical microcircuit model and find that it supports two basic computational operations: a gating mechanism and working memory. By means of bifurcation analysis we systematically investigate the dynamical behavior of the canonical microcircuit with respect to parameters that govern the local network balance, that is, the relationship between excitation and inhibition, and key intrinsic feedback architectures of canonical microcircuits. We relate the local behavior of the canonical microcircuit to cognitive processing and demonstrate how a network of interacting canonical microcircuits enables the establishment of spatiotemporal sequences in the context of syntax parsing during sentence comprehension. This study provides a framework for using individualized canonical microcircuits for the construction of biologically realistic networks supporting cognitive operations. PMID:29200435

4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling

PubMed Central

Kim, Sang-Cheol; Kang, Jung-Il; Hyun, Jin-Won; Kang, Ji-Hoon; Koh, Young-Sang; Kim, Young-Heui; Kim, Ki-Ho; Ko, Ji-Hee; Yoo, Eun-Sook; Kang, Hee-Kyoung

2017-01-01

4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-β (TGF-β) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-β signal pathway has not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-β-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4-O-methylhonokiol, TGF-β1-induced G1/G0 phase arrest and TGF-β1-induced p21 expression were decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-β1-induced canonical pathway. We observed that ERK phosphorylation by TGF-β1 was significantly attenuated by treatment with 4-O-methylhonokiol. 4-O-methylhonokiol inhibited TGF-β1-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-β1-induced noncanonical pathway. These results indicate that 4-O-methylhonokiol could inhibit TGF-β1-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4-O-methylhonokiol might have protective action on TGF-β1-induced cell cycle arrest. PMID:28190316

4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling.

PubMed

Kim, Sang-Cheol; Kang, Jung-Il; Hyun, Jin-Won; Kang, Ji-Hoon; Koh, Young-Sang; Kim, Young-Heui; Kim, Ki-Ho; Ko, Ji-Hee; Yoo, Eun-Sook; Kang, Hee-Kyoung

2017-07-01

4- O -methylhonokiol, a neolignan compound from Magnolia Officinalis , has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-β (TGF-β) signal pathway has an essential role in the regression induction of hair growth, the effect of 4- O -methylhonokiol on the TGF-β signal pathway has not yet been elucidated. We thus examined the effect of 4- O -methylhonokiol on TGF-β-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4- O -methylhonokiol, TGF-β1-induced G1/G0 phase arrest and TGF-β1-induced p21 expression were decreased. Moreover, 4- O -methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-β1-induced canonical pathway. We observed that ERK phosphorylation by TGF-β1 was significantly attenuated by treatment with 4- O -methylhonokiol. 4- O -methylhonokiol inhibited TGF-β1-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-β1-induced noncanonical pathway. These results indicate that 4- O -methylhonokiol could inhibit TGF-β1-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4- O -methylhonokiol might have protective action on TGF-β1-induced cell cycle arrest.

Statistical field theory with constraints: Application to critical Casimir forces in the canonical ensemble.

PubMed

Gross, Markus; Gambassi, Andrea; Dietrich, S

2017-08-01

The effect of imposing a constraint on a fluctuating scalar order parameter field in a system of finite volume is studied within statistical field theory. The canonical ensemble, corresponding to a fixed total integrated order parameter (e.g., the total number of particles), is obtained as a special case of the theory. A perturbative expansion is developed which allows one to systematically determine the constraint-induced finite-volume corrections to the free energy and to correlation functions. In particular, we focus on the Landau-Ginzburg model in a film geometry (i.e., in a rectangular parallelepiped with a small aspect ratio) with periodic, Dirichlet, or Neumann boundary conditions in the transverse direction and periodic boundary conditions in the remaining, lateral directions. Within the expansion in terms of ε=4-d, where d is the spatial dimension of the bulk, the finite-size contribution to the free energy of the confined system and the associated critical Casimir force are calculated to leading order in ε and are compared to the corresponding expressions for an unconstrained (grand canonical) system. The constraint restricts the fluctuations within the system and it accordingly modifies the residual finite-size free energy. The resulting critical Casimir force is shown to depend on whether it is defined by assuming a fixed transverse area or a fixed total volume. In the former case, the constraint is typically found to significantly enhance the attractive character of the force as compared to the grand canonical case. In contrast to the grand canonical Casimir force, which, for supercritical temperatures, vanishes in the limit of thick films, in the canonical case with fixed transverse area the critical Casimir force attains for thick films a negative value for all boundary conditions studied here. Typically, the dependence of the critical Casimir force both on the temperaturelike and on the fieldlike scaling variables is different in the two ensembles.

Statistical field theory with constraints: Application to critical Casimir forces in the canonical ensemble

NASA Astrophysics Data System (ADS)

Gross, Markus; Gambassi, Andrea; Dietrich, S.

2017-08-01

The effect of imposing a constraint on a fluctuating scalar order parameter field in a system of finite volume is studied within statistical field theory. The canonical ensemble, corresponding to a fixed total integrated order parameter (e.g., the total number of particles), is obtained as a special case of the theory. A perturbative expansion is developed which allows one to systematically determine the constraint-induced finite-volume corrections to the free energy and to correlation functions. In particular, we focus on the Landau-Ginzburg model in a film geometry (i.e., in a rectangular parallelepiped with a small aspect ratio) with periodic, Dirichlet, or Neumann boundary conditions in the transverse direction and periodic boundary conditions in the remaining, lateral directions. Within the expansion in terms of ɛ =4 -d , where d is the spatial dimension of the bulk, the finite-size contribution to the free energy of the confined system and the associated critical Casimir force are calculated to leading order in ɛ and are compared to the corresponding expressions for an unconstrained (grand canonical) system. The constraint restricts the fluctuations within the system and it accordingly modifies the residual finite-size free energy. The resulting critical Casimir force is shown to depend on whether it is defined by assuming a fixed transverse area or a fixed total volume. In the former case, the constraint is typically found to significantly enhance the attractive character of the force as compared to the grand canonical case. In contrast to the grand canonical Casimir force, which, for supercritical temperatures, vanishes in the limit of thick films, in the canonical case with fixed transverse area the critical Casimir force attains for thick films a negative value for all boundary conditions studied here. Typically, the dependence of the critical Casimir force both on the temperaturelike and on the fieldlike scaling variables is different in the two

Restoring canonical partition functions from imaginary chemical potential

NASA Astrophysics Data System (ADS)

Bornyakov, V. G.; Boyda, D.; Goy, V.; Molochkov, A.; Nakamura, A.; Nikolaev, A.; Zakharov, V. I.

2018-03-01

Using GPGPU techniques and multi-precision calculation we developed the code to study QCD phase transition line in the canonical approach. The canonical approach is a powerful tool to investigate sign problem in Lattice QCD. The central part of the canonical approach is the fugacity expansion of the grand canonical partition functions. Canonical partition functions Zn(T) are coefficients of this expansion. Using various methods we study properties of Zn(T). At the last step we perform cubic spline for temperature dependence of Zn(T) at fixed n and compute baryon number susceptibility χB/T2 as function of temperature. After that we compute numerically ∂χ/∂T and restore crossover line in QCD phase diagram. We use improved Wilson fermions and Iwasaki gauge action on the 163 × 4 lattice with mπ/mρ = 0.8 as a sandbox to check the canonical approach. In this framework we obtain coefficient in parametrization of crossover line Tc(µ2B) = Tc(C-ĸµ2B/T2c) with ĸ = -0.0453 ± 0.0099.

Canonical Representations of the Simple Map

NASA Astrophysics Data System (ADS)

Kerwin, Olivia; Punjabi, Alkesh; Ali, Halima; Boozer, Allen

2007-11-01

The simple map is the simplest map that has the topology of a divertor tokamak. The simple map has three canonical representations: (i) toroidal flux and poloidal angle (ψ,θ) as canonical coordinates, (ii) the physical variables (R,Z) or (X,Y) as canonical coordinates, and (iii) the action-angle (J,ζ) or magnetic variables (ψ,θ) as canonical coordinates. We give the derivation of the simple map in the (X,Y) representation. The simple map in this representation has been studied extensively (Ref. 1 and references therein). We calculate the magnetic coordinates for the simple map, construct the simple map in magnetic coordinates, and calculate generic topological effects of magnetic perturbations in divertor tokamaks using the map. We also construct the simple map in (ψ,θ) representation. Preliminary results of these studies will be presented. This work is supported by US DOE OFES DE-FG02-01ER54624 and DE-FG02-04ER54793. [1] A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys Lett A 364 140--145 (2007).

El Escritor y las Normas del Canon Literario (The Writer and the Norms of the Literary Canon).

ERIC Educational Resources Information Center

Policarpo, Alcibiades

This paper speculates about whether a literary canon exists in contemporary Latin American literature, particularly in the prose genre. The paper points to Carlos Fuentes, Gabriel Garcia Marquez, and Mario Vargas Llosa as the three authors who might form this traditional and liberal canon with their works "La Muerte de Artemio Cruz"…

Non-canonical WNT6/WNT10A signal factor expression in EBV+ post-transplant smooth muscle tumors.

PubMed

Teiken, Kristin; Kuehnel, Mark; Rehkaemper, Jan; Kreipe, Hans; Laenger, Florian; Hussein, Kais; Jonigk, Danny

2018-01-01

Post-transplant smooth muscle tumors (PTSMTs) are rare mesenchymal neoplasms which occur after solid organ or haematopoietic stem cell transplantation. PTSMT typically consist of Epstein-Barr-virus (EBV)+ smooth muscle-like cells and show an intermediate malignancy. Their main occurrences are visceral organs, especially the liver, but intracranial appearances are described and associated with a poor prognosis. EBV drives the growth of PTSMT; however, the underlying molecular mechanisms still remain unclear. Gene expression analysis of a set of morphologically similar tumors (leiomyomas, leiomyosarcomas, angioleiomyomas and endothelial haemangiomas) from patients without immunosuppression or EBV-association was performed. Our findings indicate that PTSMT's growth is driven by two factors of the wingless-type protein family: WNT6 and WNT10A. We are first to report that in PTSMTs, a non-canonical activation of WNT, independent of beta-catenin, drives tumor cell proliferation via MTOR/AKT1, MYC and Cyclin D2.

Non-canonical Phototransduction Mediates Synchronization of the Drosophila melanogaster Circadian Clock and Retinal Light Responses.

PubMed

Ogueta, Maite; Hardie, Roger C; Stanewsky, Ralf

2018-06-04

The daily light-dark cycles represent a key signal for synchronizing circadian clocks. Both insects and mammals possess dedicated "circadian" photoreceptors but also utilize the visual system for clock resetting. In Drosophila, circadian clock resetting is achieved by the blue-light photoreceptor cryptochrome (CRY), which is expressed within subsets of the brain clock neurons. In addition, rhodopsin-expressing photoreceptor cells contribute to light synchronization. Light resets the molecular clock by CRY-dependent degradation of the clock protein Timeless (TIM), although in specific subsets of key circadian pacemaker neurons, including the small ventral lateral neurons (s-LNvs), TIM and Period (PER) oscillations can be synchronized by light independent of CRY and canonical visual Rhodopsin phototransduction. Here, we show that at least three of the seven Drosophila rhodopsins can utilize an alternative transduction mechanism involving the same α-subunit of the heterotrimeric G protein operating in canonical visual phototransduction (Gq). Surprisingly, in mutants lacking the canonical phospholipase C-β (PLC-β) encoded by the no receptor potential A (norpA) gene, we uncovered a novel transduction pathway using a different PLC-β encoded by the Plc21C gene. This novel pathway is important for behavioral clock resetting to semi-natural light-dark cycles and mediates light-dependent molecular synchronization within the s-LNv clock neurons. The same pathway appears to be responsible for norpA-independent light responses in the compound eye. We show that Rhodopsin 5 (Rh5) and Rh6, present in the R8 subset of retinal photoreceptor cells, drive both the long-term circadian and rapid light responses in the eye. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Length-independent structural similarities enrich the antibody CDR canonical class model.

PubMed

Nowak, Jaroslaw; Baker, Terry; Georges, Guy; Kelm, Sebastian; Klostermann, Stefan; Shi, Jiye; Sridharan, Sudharsan; Deane, Charlotte M

2016-01-01

Complementarity-determining regions (CDRs) are antibody loops that make up the antigen binding site. Here, we show that all CDR types have structurally similar loops of different lengths. Based on these findings, we created length-independent canonical classes for the non-H3 CDRs. Our length variable structural clusters show strong sequence patterns suggesting either that they evolved from the same original structure or result from some form of convergence. We find that our length-independent method not only clusters a larger number of CDRs, but also predicts canonical class from sequence better than the standard length-dependent approach. To demonstrate the usefulness of our findings, we predicted cluster membership of CDR-L3 sequences from 3 next-generation sequencing datasets of the antibody repertoire (over 1,000,000 sequences). Using the length-independent clusters, we can structurally classify an additional 135,000 sequences, which represents a ∼20% improvement over the standard approach. This suggests that our length-independent canonical classes might be a highly prevalent feature of antibody space, and could substantially improve our ability to accurately predict the structure of novel CDRs identified by next-generation sequencing.

Fourth order Douglas implicit scheme for solving three dimension reaction diffusion equation with non-linear source term

NASA Astrophysics Data System (ADS)

Hasnain, Shahid; Saqib, Muhammad; Mashat, Daoud Suleiman

2017-07-01

This research paper represents a numerical approximation to non-linear three dimension reaction diffusion equation with non-linear source term from population genetics. Since various initial and boundary value problems exist in three dimension reaction diffusion phenomena, which are studied numerically by different numerical methods, here we use finite difference schemes (Alternating Direction Implicit and Fourth Order Douglas Implicit) to approximate the solution. Accuracy is studied in term of L2, L∞ and relative error norms by random selected grids along time levels for comparison with analytical results. The test example demonstrates the accuracy, efficiency and versatility of the proposed schemes. Numerical results showed that Fourth Order Douglas Implicit scheme is very efficient and reliable for solving 3-D non-linear reaction diffusion equation.

Mutually unbiased bases in six dimensions: The four most distant bases

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

Raynal, Philippe; Lue Xin; Englert, Berthold-Georg

2011-06-15

We consider the average distance between four bases in six dimensions. The distance between two orthonormal bases vanishes when the bases are the same, and the distance reaches its maximal value of unity when the bases are unbiased. We perform a numerical search for the maximum average distance and find it to be strictly smaller than unity. This is strong evidence that no four mutually unbiased bases exist in six dimensions. We also provide a two-parameter family of three bases which, together with the canonical basis, reach the numerically found maximum of the average distance, and we conduct a detailedmore » study of the structure of the extremal set of bases.« less

Canonical fluid thermodynamics

NASA Technical Reports Server (NTRS)

Schmid, L. A.

1972-01-01

The space-time integral of the thermodynamic pressure plays the role of the thermodynamic potential for compressible, adiabatic flow in the sense that the pressure integral for stable flow is less than for all slightly different flows. This stability criterion can be converted into a variational minimum principle by requiring the molar free-enthalpy and the temperature, which are the arguments of the pressure function, to be generalized velocities, that is, the proper-time derivatives of scalar spare-time functions which are generalized coordinates in the canonical formalism. In a fluid context, proper-time differentiation must be expressed in terms of three independent quantities that specify the fluid velocity. This can be done in several ways, all of which lead to different variants (canonical transformations) of the same constraint-free action integral whose Euler-Lagrange equations are just the well-known equations of motion for adiabatic compressible flow.

New QCD sum rules based on canonical commutation relations

NASA Astrophysics Data System (ADS)

Hayata, Tomoya

2012-04-01

New derivation of QCD sum rules by canonical commutators is developed. It is the simple and straightforward generalization of Thomas-Reiche-Kuhn sum rule on the basis of Kugo-Ojima operator formalism of a non-abelian gauge theory and a suitable subtraction of UV divergences. By applying the method to the vector and axial vector current in QCD, the exact Weinberg’s sum rules are examined. Vector current sum rules and new fractional power sum rules are also discussed.

Thermal Non-Equilibrium Flows in Three Space Dimensions

NASA Astrophysics Data System (ADS)

Zeng, Yanni

2016-01-01

We study the equations describing the motion of a thermal non-equilibrium gas in three space dimensions. It is a hyperbolic system of six equations with a relaxation term. The dissipation mechanism induced by the relaxation is weak in the sense that the Shizuta-Kawashima criterion is violated. This implies that a perturbation of a constant equilibrium state consists of two parts: one decays in time while the other stays. In fact, the entropy wave grows weakly along the particle path as the process is irreversible. We study thermal properties related to the well-posedness of the nonlinear system. We also obtain a detailed pointwise estimate on the Green's function for the Cauchy problem when the system is linearized around an equilibrium constant state. The Green's function provides a complete picture of the wave pattern, with an exact and explicit leading term. Comparing with existing results for one dimensional flows, our results reveal a new feature of three dimensional flows: not only does the entropy wave not decay, but the velocity also contains a non-decaying part, strongly coupled with its decaying one. The new feature is supported by the second order approximation via the Chapman-Enskog expansions, which are the Navier-Stokes equations with vanished shear viscosity and heat conductivity.

Canonical considerations in corporate restructuring.

PubMed

Holland, S

1985-03-01

Religious institutes sponsoring Catholic health facilities face competitive economic pressures that impel them to seek corporate restructuring and joint ventures to fulfill their mission to the poor. They especially must look to the Church's Code of Canon Law to protect ecclesiastical goods and maintain their Catholic identity when entering such ventures. The U.S. bishops directives also assist in guaranteeing patient expectations that the health facility will observe the Church's ethical principles. Institutes first must ensure that subsidiaries will operate according to Catholic mission and philosophy. The canons delineate proper protection of assets and identify ends toward which the religious must apply temporal goods, such as supporting clergy and performing charitable works. Alienation, or conveyance of goods, is a critical consideration in such financial transactions; canons specify the institute's administrative limits and require superiors' written permission along with their councils' consent. All involved must be "thoroughly informed concerning the economic situation," show "just cause" for the transaction, and obtain expert estimates of property values. Religious administrators retain certain faith and executive obligations, such as amending the charter, appointing the board, and merging or dissolving the corporation. With the canons they help to ensure that collaborative efforts preserve the institute's corporate mission and allow religious to carry out their responsibility for ecclesiastical goods. Though alternatives to corporate ventures may be limited, options regarding how to structure and with whom to affiliate do exist. Sponsoring bodies dedicated to providing high-quality care must explore these options

Galilei group with multiple central extension, vorticity, and entropy generation: Exotic fluid in 3 +1 dimensions

NASA Astrophysics Data System (ADS)

Das, Praloy; Ghosh, Subir

2017-12-01

A noncommutative extension of an ideal (Hamiltonian) fluid model in 3 +1 dimensions is proposed. The model enjoys several interesting features: it allows a multiparameter central extension in Galilean boost algebra (which is significant being contrary to the existing belief that a similar feature can appear only in 2 +1 -dimensions); noncommutativity generates vorticity in a canonically irrotational fluid; it induces a nonbarotropic pressure leading to a nonisentropic system. (Barotropic fluids are entropy preserving as the pressure depends only on the matter density.) Our fluid model is termed "exotic" since it has a close resemblance with the extensively studied planar (2 +1 dimensions) exotic models and exotic (noncommutative) field theories.

MGA, L3MBTL2 and E2F6 determine genomic binding of the non-canonical Polycomb repressive complex PRC1.6

PubMed Central

Stielow, Bastian; Finkernagel, Florian; Stiewe, Thorsten

2018-01-01

Diverse Polycomb repressive complexes 1 (PRC1) play essential roles in gene regulation, differentiation and development. Six major groups of PRC1 complexes that differ in their subunit composition have been identified in mammals. How the different PRC1 complexes are recruited to specific genomic sites is poorly understood. The Polycomb Ring finger protein PCGF6, the transcription factors MGA and E2F6, and the histone-binding protein L3MBTL2 are specific components of the non-canonical PRC1.6 complex. In this study, we have investigated their role in genomic targeting of PRC1.6. ChIP-seq analysis revealed colocalization of MGA, L3MBTL2, E2F6 and PCGF6 genome-wide. Ablation of MGA in a human cell line by CRISPR/Cas resulted in complete loss of PRC1.6 binding. Rescue experiments revealed that MGA recruits PRC1.6 to specific loci both by DNA binding-dependent and by DNA binding-independent mechanisms. Depletion of L3MBTL2 and E2F6 but not of PCGF6 resulted in differential, locus-specific loss of PRC1.6 binding illustrating that different subunits mediate PRC1.6 loading to distinct sets of promoters. Mga, L3mbtl2 and Pcgf6 colocalize also in mouse embryonic stem cells, where PRC1.6 has been linked to repression of germ cell-related genes. Our findings unveil strikingly different genomic recruitment mechanisms of the non-canonical PRC1.6 complex, which specify its cell type- and context-specific regulatory functions. PMID:29381691

CaV channels and cancer: canonical functions indicate benefits of repurposed drugs as cancer therapeutics.

PubMed

Buchanan, Paul J; McCloskey, Karen D

2016-10-01

The importance of ion channels in the hallmarks of many cancers is increasingly recognised. This article reviews current knowledge of the expression of members of the voltage-gated calcium channel family (Ca V ) in cancer at the gene and protein level and discusses their potential functional roles. The ten members of the Ca V channel family are classified according to expression of their pore-forming α-subunit; moreover, co-expression of accessory α2δ, β and γ confers a spectrum of biophysical characteristics including voltage dependence of activation and inactivation, current amplitude and activation/inactivation kinetics. Ca V channels have traditionally been studied in excitable cells including neurones, smooth muscle, skeletal muscle and cardiac cells, and drugs targeting the channels are used in the treatment of hypertension and epilepsy. There is emerging evidence that several Ca V channels are differentially expressed in cancer cells compared to their normal counterparts. Interestingly, a number of Ca V channels also have non-canonical functions and are involved in transcriptional regulation of the expression of other proteins including potassium channels. Pharmacological studies show that Ca V canonical function contributes to the fundamental biology of proliferation, cell-cycle progression and apoptosis. This raises the intriguing possibility that calcium channel blockers, approved for the treatment of other conditions, could be repurposed to treat particular cancers. Further research will reveal the full extent of both the canonical and non-canonical functions of Ca V channels in cancer and whether calcium channel blockers are beneficial in cancer treatment.

Stable micron-scale holes are a general feature of canonical holins

PubMed Central

Savva, Christos G.; Dewey, Jill S.; Moussa, Samir H.; To, Kam H.; Holzenburg, Andreas; Young, Ry

2014-01-01

Summary At a programmed time in phage infection cycles, canonical holins suddenly trigger to cause lethal damage to the cytoplasmic membrane, resulting in the cessation of respiration and the non-specific release of pre-folded, fully active endolysins to the periplasm. For the paradigm holin S105 of lambda, triggering is correlated with the formation of micron-scale membrane holes, visible as interruptions in the bilayer in cryo-electron microscopic images and tomographic reconstructions. Here we report that the size distribution of the holes is stable for long periods after triggering. Moreover, early triggering caused by an early lysis allele of S105 formed approximately the same number of holes, but the lesions were significantly smaller. In contrast, early triggering prematurely induced by energy poisons resulted in many fewer visible holes, consistent with previous sizing studies. Importantly, the unrelated canonical holins P2 Y and T4 T were found to cause the formation of holes of approximately the same size and number as for lambda. In contrast, no such lesions were visible after triggering of the pinholin S2168. These results generalize the hole formation phenomenon for canonical holins. A model is presented suggesting the unprecedentedly large size of these holes is related to the timing mechanism. PMID:24164554

Stable micron-scale holes are a general feature of canonical holins.

PubMed

Savva, Christos G; Dewey, Jill S; Moussa, Samir H; To, Kam H; Holzenburg, Andreas; Young, Ry

2014-01-01

At a programmed time in phage infection cycles, canonical holins suddenly trigger to cause lethal damage to the cytoplasmic membrane, resulting in the cessation of respiration and the non-specific release of pre-folded, fully active endolysins to the periplasm. For the paradigm holin S105 of lambda, triggering is correlated with the formation of micron-scale membrane holes, visible as interruptions in the bilayer in cryo-electron microscopic images and tomographic reconstructions. Here we report that the size distribution of the holes is stable for long periods after triggering. Moreover, early triggering caused by an early lysis allele of S105 formed approximately the same number of holes, but the lesions were significantly smaller. In contrast, early triggering prematurely induced by energy poisons resulted in many fewer visible holes, consistent with previous sizing studies. Importantly, the unrelated canonical holins P2 Y and T4 T were found to cause the formation of holes of approximately the same size and number as for lambda. In contrast, no such lesions were visible after triggering of the pinholin S(21) 68. These results generalize the hole formation phenomenon for canonical holins. A model is presented suggesting the unprecedentedly large size of these holes is related to the timing mechanism. © 2013 John Wiley & Sons Ltd.

Simulation of gas adsorption on a surface and in slit pores with grand canonical and canonical kinetic Monte Carlo methods.

PubMed

Ustinov, E A; Do, D D

2012-08-21

We present for the first time in the literature a new scheme of kinetic Monte Carlo method applied on a grand canonical ensemble, which we call hereafter GC-kMC. It was shown recently that the kinetic Monte Carlo (kMC) scheme is a very effective tool for the analysis of equilibrium systems. It had been applied in a canonical ensemble to describe vapor-liquid equilibrium of argon over a wide range of temperatures, gas adsorption on a graphite open surface and in graphitic slit pores. However, in spite of the conformity of canonical and grand canonical ensembles, the latter is more relevant in the correct description of open systems; for example, the hysteresis loop observed in adsorption of gases in pores under sub-critical conditions can only be described with a grand canonical ensemble. Therefore, the present paper is aimed at an extension of the kMC to open systems. The developed GC-kMC was proved to be consistent with the results obtained with the canonical kMC (C-kMC) for argon adsorption on a graphite surface at 77 K and in graphitic slit pores at 87.3 K. We showed that in slit micropores the hexagonal packing in the layers adjacent to the pore walls is observed at high loadings even at temperatures above the triple point of the bulk phase. The potential and applicability of the GC-kMC are further shown with the correct description of the heat of adsorption and the pressure tensor of the adsorbed phase.

Contextuality in canonical systems of random variables

NASA Astrophysics Data System (ADS)

Dzhafarov, Ehtibar N.; Cervantes, Víctor H.; Kujala, Janne V.

2017-10-01

Random variables representing measurements, broadly understood to include any responses to any inputs, form a system in which each of them is uniquely identified by its content (that which it measures) and its context (the conditions under which it is recorded). Two random variables are jointly distributed if and only if they share a context. In a canonical representation of a system, all random variables are binary, and every content-sharing pair of random variables has a unique maximal coupling (the joint distribution imposed on them so that they coincide with maximal possible probability). The system is contextual if these maximal couplings are incompatible with the joint distributions of the context-sharing random variables. We propose to represent any system of measurements in a canonical form and to consider the system contextual if and only if its canonical representation is contextual. As an illustration, we establish a criterion for contextuality of the canonical system consisting of all dichotomizations of a single pair of content-sharing categorical random variables. This article is part of the themed issue `Second quantum revolution: foundational questions'.

THE TOPOLOGY OF CANONICAL FLUX TUBES IN FLARED JET GEOMETRY

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

Lavine, Eric Sander; You, Setthivoine, E-mail: Slavine2@uw.edu, E-mail: syou@aa.washington.edu

2017-01-20

Magnetized plasma jets are generally modeled as magnetic flux tubes filled with flowing plasma governed by magnetohydrodynamics (MHD). We outline here a more fundamental approach based on flux tubes of canonical vorticity, where canonical vorticity is defined as the circulation of the species’ canonical momentum. This approach extends the concept of magnetic flux tube evolution to include the effects of finite particle momentum and enables visualization of the topology of plasma jets in regimes beyond MHD. A flared, current-carrying magnetic flux tube in an ion-electron plasma with finite ion momentum is thus equivalent to either a pair of electron andmore » ion flow flux tubes, a pair of electron and ion canonical momentum flux tubes, or a pair of electron and ion canonical vorticity flux tubes. We examine the morphology of all these flux tubes for increasing electrical currents, different radial current profiles, different electron Mach numbers, and a fixed, flared, axisymmetric magnetic geometry. Calculations of gauge-invariant relative canonical helicities track the evolution of magnetic, cross, and kinetic helicities in the system, and show that ion flow fields can unwind to compensate for an increasing magnetic twist. The results demonstrate that including a species’ finite momentum can result in a very long collimated canonical vorticity flux tube even if the magnetic flux tube is flared. With finite momentum, particle density gradients must be normal to canonical vorticities, not to magnetic fields, so observations of collimated astrophysical jets could be images of canonical vorticity flux tubes instead of magnetic flux tubes.« less

Neoclassical canons of facial beauty: Do we see the deviations?

PubMed

Pavlic, Andrej; Trinajstic Zrinski, Magda; Katic, Visnja; Spalj, Stjepan

2017-05-01

To explore the presence of neoclassical canons of facial beauty among young people in Croatia and to question possible psychosocial repercussions occurring in those who demonstrate deviations in relation to canons. The study was cross-sectional and the sample included 249 subjects (60% female) aged 12-39 (median 20). Their en face and profile photographs were taken in Natural Head Position. Photogrammetry included analysis of nine neoclassical canons of facial beauty originating from the Renaissance. Psychosocial issues were assessed using the Self-Esteem Scale, Big Five Inventory and three domains of Orthognathic Quality of Life Questionnaire. Significant deviations from neoclassical facial beauty canons were observed in 55-65% of adolescents and young adults. Gender and age showed no relation to deviations. The deviations from canons that influenced the quality of life were mainly those related to vertical facial proportions and demonstrated increased facial aesthetics concern and social impact, and higher self-reported treatment need (p < 0.05). Deviations from canons were not related to self-esteem but a decrease in openness, agreeableness and neuroticism was observed. Neoclassical canons were not valid for the majority of adolescents and young adults in Croatia. Only deviations from some canons appear to provoke mild psychosocial repercussions. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Structure-based non-canonical amino acid design to covalently crosslink an antibody–antigen complex

PubMed Central

Xu, Jianqing; Tack, Drew; Hughes, Randall A.; Ellington, Andrew D.; Gray, Jeffrey J.

2014-01-01

Engineering antibodies to utilize non-canonical amino acids (NCAA) should greatly expand the utility of an already important biological reagent. In particular, introducing crosslinking reagents into antibody complementarity determining regions (CDRs) should provide a means to covalently crosslink residues at the antibody–antigen interface. Unfortunately, finding the optimum position for crosslinking two proteins is often a matter of iterative guessing, even when the interface is known in atomic detail. Computer-aided antibody design can potentially greatly restrict the number of variants that must be explored in order to identify successful crosslinking sites. We have therefore used Rosetta to guide the introduction of an oxidizable crosslinking NCAA, l-3,4-dihydroxyphenylalanine (l-DOPA), into the CDRs of the anti-protective antigen scFv antibody M18, and have measured crosslinking to its cognate antigen, domain 4 of the anthrax protective antigen. Computed crosslinking distance, solvent accessibility, and interface energetics were three factors considered that could impact the efficiency of l-DOPA-mediated crosslinking. In the end, 10 variants were synthesized, and crosslinking efficiencies were generally 10% or higher, with the best variant crosslinking to 52% of the available antigen. The results suggest that computational analysis can be used in a pipeline for engineering crosslinking antibodies. The rules learned from l-DOPA crosslinking of antibodies may also be generalizable to the formation of other crosslinked interfaces and complexes. PMID:23680795

The Current Canon in British Romantics Studies.

ERIC Educational Resources Information Center

Linkin, Harriet Kramer

1991-01-01

Describes and reports on a survey of 164 U.S. universities to ascertain what is taught as the current canon of British Romantic literature. Asserts that the canon may now include Mary Shelley with the former standard six major male Romantic poets, indicating a significant emergence of a feminist perspective on British Romanticism in the classroom.…

Relations of the Big-Five personality dimensions to autodestructive behavior in clinical and non-clinical adolescent populations.

PubMed

Kotrla Topic, Marina; Perkovic Kovacevic, Marina; Mlacic, Boris

2012-10-01

To examine the relationship between the Big-Five personality model and autodestructive behavior symptoms, namely Autodestructiveness and Suicidal Depression in two groups of participants: clinical and non-clinical adolescents. Two groups of participants, clinical (adolescents with diagnosis of psychiatric disorder based on clinical impression and according to valid diagnostic criteria, N=92) and non-clinical (high-school students, N=87), completed two sets of questionnaires: the Autodestructiveness Scale which provided data on Autodestructiveness and Suicidal Depression, and the International Personality Item Pool (IPIP), which provided data on the Big -Five personality dimensions. Clinical group showed significantly higher values on the Autodestructiveness scale in general, as well as on Suicidal Depression, Aggressiveness, and Borderline subscales than the non-clinical group. Some of the dimensions of the Big-Five personality model, ie, Emotional Stability, Conscientiousness, and Agreeableness showed significant relationship (hierarchical regression analyses, P values for β coefficients from 0.000 to 0.021) with Autodestructiveness and Suicidal Depression, even after controlling for the sex and group effects or, when analyzing Suicidal Depression, after controlling the effect of other subscales. The results indicate that dimensions of the Big-Five model are important when evaluating adolescent psychiatric patients and adolescents from general population at risk of self-destructive behavior.

Relations of the Big-Five personality dimensions to autodestructive behavior in clinical and non-clinical adolescent populations

PubMed Central

Kotrla Topić, Marina; Perković Kovačević, Marina; Mlačić, Boris

2012-01-01

Aim To examine the relationship between the Big-Five personality model and autodestructive behavior symptoms, namely Autodestructiveness and Suicidal Depression in two groups of participants: clinical and non-clinical adolescents. Methods Two groups of participants, clinical (adolescents with diagnosis of psychiatric disorder based on clinical impression and according to valid diagnostic criteria, N = 92) and non-clinical (high-school students, N = 87), completed two sets of questionnaires: the Autodestructiveness Scale which provided data on Autodestructiveness and Suicidal Depression, and the International Personality Item Pool (IPIP), which provided data on the Big -Five personality dimensions. Results Clinical group showed significantly higher values on the Autodestructiveness scale in general, as well as on Suicidal Depression, Aggressiveness, and Borderline subscales than the non-clinical group. Some of the dimensions of the Big-Five personality model, ie, Emotional Stability, Conscientiousness, and Agreeableness showed significant relationship (hierarchical regression analyses, P values for β coefficients from <0.001 to 0.021) with Autodestructivness and Suicidal Depression, even after controlling for the sex and group effects or, when analyzing Suicidal Depression, after controlling the effect of other subscales. Conclusion The results indicate that dimensions of the Big-Five model are important when evaluating adolescent psychiatric patients and adolescents from general population at risk of self-destructive behavior. PMID:23100207

Multicollinearity in canonical correlation analysis in maize.

PubMed

Alves, B M; Cargnelutti Filho, A; Burin, C

2017-03-30

The objective of this study was to evaluate the effects of multicollinearity under two methods of canonical correlation analysis (with and without elimination of variables) in maize (Zea mays L.) crop. Seventy-six maize genotypes were evaluated in three experiments, conducted in a randomized block design with three replications, during the 2009/2010 crop season. Eleven agronomic variables (number of days from sowing until female flowering, number of days from sowing until male flowering, plant height, ear insertion height, ear placement, number of plants, number of ears, ear index, ear weight, grain yield, and one thousand grain weight), 12 protein-nutritional variables (crude protein, lysine, methionine, cysteine, threonine, tryptophan, valine, isoleucine, leucine, phenylalanine, histidine, and arginine), and 6 energetic-nutritional variables (apparent metabolizable energy, apparent metabolizable energy corrected for nitrogen, ether extract, crude fiber, starch, and amylose) were measured. A phenotypic correlation matrix was first generated among the 29 variables for each of the experiments. A multicollinearity diagnosis was later performed within each group of variables using methodologies such as variance inflation factor and condition number. Canonical correlation analysis was then performed, with and without the elimination of variables, among groups of agronomic and protein-nutritional, and agronomic and energetic-nutritional variables. The canonical correlation analysis in the presence of multicollinearity (without elimination of variables) overestimates the variability of canonical coefficients. The elimination of variables is an efficient method to circumvent multicollinearity in canonical correlation analysis.

From Classical to Quantum: New Canonical Tools for the Dynamics of Gravity

NASA Astrophysics Data System (ADS)

Höhn, P. A.

2012-05-01

In a gravitational context, canonical methods offer an intuitive picture of the dynamics and simplify an identification of the degrees of freedom. Nevertheless, extracting dynamical information from background independent approaches to quantum gravity is a highly non-trivial challenge. In this thesis, the conundrum of (quantum) gravitational dynamics is approached from two different directions by means of new canonical tools. This thesis is accordingly divided into two parts: In the first part, a general canonical formalism for discrete systems featuring a variational action principle is developed which is equivalent to the covariant formulation following directly from the action. This formalism can handle evolving phase spaces and is thus appropriate for describing evolving lattices. Attention will be devoted to a characterization of the constraints, symmetries and degrees of freedom appearing in such discrete systems which, in the case of evolving phase spaces, is time step dependent. The advantage of this formalism is that it does not depend on the particular discretization and, hence, is suitable for coarse graining procedures. This formalism is applicable to discrete mechanics, lattice field theories and discrete gravity models---underlying some approaches to quantum gravity---and, furthermore, may prove useful for numerical imple mentations. For concreteness, these new tools are employed to formulate Regge Calculus canonically as a theory of the dynamics of discrete hypersurfaces in discrete spacetimes, thereby removing a longstanding obstacle to connecting covariant simplicial gravity models with canonical frameworks. This result is interesting in view of several background independent approaches to quantum gravity. In addition, perturbative expansions around symmetric background solutions of Regge Calculus are studied up to second order. Background gauge modes generically become propagating at second order as a consequence of a symmetry breaking. In the

Canon Fodder: Young Adult Literature as a Tool for Critiquing Canonicity

ERIC Educational Resources Information Center

Hateley, Erica

2013-01-01

Young adult literature is a tool of socialisation and acculturation for young readers. This extends to endowing "reading" with particular significance in terms of what literature should be read and why. This paper considers some recent young adult fiction with an eye to its engagement with canonical literature and its representations of…

Finite temperature grand canonical ensemble study of the minimum electrophilicity principle.

PubMed

Miranda-Quintana, Ramón Alain; Chattaraj, Pratim K; Ayers, Paul W

2017-09-28

We analyze the minimum electrophilicity principle of conceptual density functional theory using the framework of the finite temperature grand canonical ensemble. We provide support for this principle, both for the cases of systems evolving from a non-equilibrium to an equilibrium state and for the change from one equilibrium state to another. In doing so, we clearly delineate the cases where this principle can, or cannot, be used.

Myocardial pathology induced by aldosterone is dependent on non-canonical activities of G protein-coupled receptor kinases

PubMed Central

Cannavo, Alessandro; Liccardo, Daniela; Eguchi, Akito; Elliott, Katherine J.; Traynham, Christopher J.; Ibetti, Jessica; Eguchi, Satoru; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe; Koch, Walter J.

2016-01-01

Hyper-aldosteronism is associated with myocardial dysfunction including induction of cardiac fibrosis and maladaptive hypertrophy. Mechanisms of these cardiotoxicities are not fully understood. Here we show that mineralocorticoid receptor (MR) activation by aldosterone leads to pathological myocardial signalling mediated by mitochondrial G protein-coupled receptor kinase 2 (GRK2) pro-death activity and GRK5 pro-hypertrophic action. Moreover, these MR-dependent GRK2 and GRK5 non-canonical activities appear to involve cross-talk with the angiotensin II type-1 receptor (AT1R). Most importantly, we show that ventricular dysfunction caused by chronic hyper-aldosteronism in vivo is completely prevented in cardiac Grk2 knockout mice (KO) and to a lesser extent in Grk5 KO mice. However, aldosterone-induced cardiac hypertrophy is totally prevented in Grk5 KO mice. We also show human data consistent with MR activation status in heart failure influencing GRK2 levels. Therefore, our study uncovers GRKs as targets for ameliorating pathological cardiac effects associated with high-aldosterone levels. PMID:26932512

Interactions between TGF-β1, canonical WNT/β-catenin pathway and PPAR γ in radiation-induced fibrosis

PubMed Central

Vallée, Alexandre; Lecarpentier, Yves; Guillevin, Rémy; Vallée, Jean-Noël

2017-01-01

Radiation therapy induces DNA damage and inflammation leading to fibrosis. Fibrosis can occur 4 to 12 months after radiation therapy. This process worsens with time and years. Radiation-induced fibrosis is characterized by fibroblasts proliferation, myofibroblast differentiation, and synthesis of collagen, proteoglycans and extracellular matrix. Myofibroblasts are non-muscle cells that can contract and relax. Myofibroblasts evolve towards irreversible retraction during fibrosis process. In this review, we discussed the interplays between transforming growth factor-β1 (TGF-β1), canonical WNT/β-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR γ) in regulating the molecular mechanisms underlying the radiation-induced fibrosis, and the potential role of PPAR γ agonists. Overexpression of TGF-β and canonical WNT/β-catenin pathway stimulate fibroblasts accumulation and myofibroblast differentiation whereas PPAR γ expression decreases due to the opposite interplay of canonical WNT/β-catenin pathway. Both TGF-β1 and canonical WNT/β-catenin pathway stimulate each other through the Smad pathway and non-Smad pathways such as phosphatidylinositol 3-kinase/serine/threonine kinase (PI3K/Akt) signaling. WNT/β-catenin pathway and PPAR γ interact in an opposite manner. PPAR γ agonists decrease β-catenin levels through activation of inhibitors of the WNT pathway such as Smad7, glycogen synthase kinase-3 (GSK-3 β) and dickkopf-related protein 1 (DKK1). PPAR γ agonists also stimulate phosphatase and tensin homolog (PTEN) expression, which decreases both TGF-β1 and PI3K/Akt pathways. PPAR γ agonists by activating Smad7 decrease Smads pathway and then TGF-β signaling leading to decrease radiation-induced fibrosis. TGF-β1 and canonical WNT/β-catenin pathway promote radiation-induced fibrosis whereas PPAR γ agonists can prevent radiation-induced fibrosis. PMID:29163854

Correlations, soliton modes, and non-Hermitian linear mode transmutation in the one-dimensional noisy Burgers equation.

PubMed

Fogedby, Hans C

2003-08-01

Using the previously developed canonical phase space approach applied to the noisy Burgers equation in one dimension, we discuss in detail the growth morphology in terms of nonlinear soliton modes and superimposed linear modes. We moreover analyze the non-Hermitian character of the linear mode spectrum and the associated dynamical pinning, and mode transmutation from diffusive to propagating behavior induced by the solitons. We discuss the anomalous diffusion of growth modes, switching and pathways, correlations in the multisoliton sector, and in detail the correlations and scaling properties in the two-soliton sector.

Canonic FFT flow graphs for real-valued even/odd symmetric inputs

NASA Astrophysics Data System (ADS)

Lao, Yingjie; Parhi, Keshab K.

2017-12-01

Canonic real-valued fast Fourier transform (RFFT) has been proposed to reduce the arithmetic complexity by eliminating redundancies. In a canonic N-point RFFT, the number of signal values at each stage is canonic with respect to the number of signal values, i.e., N. The major advantage of the canonic RFFTs is that these require the least number of butterfly operations and only real datapaths when mapped to architectures. In this paper, we consider the FFT computation whose inputs are not only real but also even/odd symmetric, which indeed lead to the well-known discrete cosine and sine transforms (DCTs and DSTs). Novel algorithms for generating the flow graphs of canonic RFFTs with even/odd symmetric inputs are proposed. It is shown that the proposed algorithms lead to canonic structures with N/2 +1 signal values at each stage for an N-point real even symmetric FFT (REFFT) or N/2 -1 signal values at each stage for an N-point RFFT real odd symmetric FFT (ROFFT). In order to remove butterfly operations, several twiddle factor transformations are proposed in this paper. We also discuss the design of canonic REFFT for any composite length. Performances of the canonic REFFT/ROFFT are also discussed. It is shown that the flow graph of canonic REFFT/ROFFT has less number of interconnections, less butterfly operations, and less twiddle factor operations, compared to prior works.

Structure of multiphoton quantum optics. I. Canonical formalism and homodyne squeezed states

NASA Astrophysics Data System (ADS)

dell'Anno, Fabio; de Siena, Silvio; Illuminati, Fabrizio

2004-03-01

We introduce a formalism of nonlinear canonical transformations for general systems of multiphoton quantum optics. For single-mode systems the transformations depend on a tunable free parameter, the homodyne local-oscillator angle; for n -mode systems they depend on n heterodyne mixing angles. The canonical formalism realizes nontrivial mixing of pairs of conjugate quadratures of the electromagnetic field in terms of homodyne variables for single-mode systems, and in terms of heterodyne variables for multimode systems. In the first instance the transformations yield nonquadratic model Hamiltonians of degenerate multiphoton processes and define a class of non-Gaussian, nonclassical multiphoton states that exhibit properties of coherence and squeezing. We show that such homodyne multiphoton squeezed states are generated by unitary operators with a nonlinear time evolution that realizes the homodyne mixing of a pair of conjugate quadratures. Tuning of the local-oscillator angle allows us to vary at will the statistical properties of such states. We discuss the relevance of the formalism for the study of degenerate (up-)down-conversion processes. In a companion paper [

Dictionary-Based Tensor Canonical Polyadic Decomposition

NASA Astrophysics Data System (ADS)

Cohen, Jeremy Emile; Gillis, Nicolas

2018-04-01

To ensure interpretability of extracted sources in tensor decomposition, we introduce in this paper a dictionary-based tensor canonical polyadic decomposition which enforces one factor to belong exactly to a known dictionary. A new formulation of sparse coding is proposed which enables high dimensional tensors dictionary-based canonical polyadic decomposition. The benefits of using a dictionary in tensor decomposition models are explored both in terms of parameter identifiability and estimation accuracy. Performances of the proposed algorithms are evaluated on the decomposition of simulated data and the unmixing of hyperspectral images.

Extended canonical field theory of matter and space-time

NASA Astrophysics Data System (ADS)

Struckmeier, J.; Vasak, D.; matter, H. Stoecker Field theory of; space-time

2015-11-01

Any physical theory that follows from an action principle should be invariant in its form under mappings of the reference frame in order to comply with the general principle of relativity. The required form-invariance of the action principle implies that the mapping must constitute a particular extended canonical transformation. In the realm of the covariant Hamiltonian formulation of field theory, the term ``extended'' implies that not only the fields but also the space-time geometry is subject to transformation. A canonical transformation maintains the general form of the action principle by simultaneously defining the appropriate transformation rules for the fields, the conjugate momentum fields, and the transformation rule for the Hamiltonian. Provided that the given system of fields exhibits a particular global symmetry, the associated extended canonical transformation determines an amended Hamiltonian that is form-invariant under the corresponding local symmetry. This will be worked out for a Hamiltonian system of scalar and vector fields that is presupposed to be form-invariant under space-time transformations xμ\\mapsto Xμ with partial Xμ/partial xν=const., hence under global space-time transformations such as the Poincaré transformation. The corresponding amended system that is form-invariant under local space-time transformations partial Xμ/partial xν≠qconst. then describes the coupling of the fields to the space-time geometry and thus yields the dynamics of space-time that is associated with the given physical system. Non-zero spin matter determines thereby the space-time curvature via a well-defined source term in a covariant Poisson-type equation for the Riemann tensor.

A Canon, a Norm and an Attitude--Ideological Dimensions in Foreign Language Education in China.

ERIC Educational Resources Information Center

Feng, Anwei

An examination of China's policy, "making the ancient serve the present and foreign things serve China," introduced by Mao Ze-dong, is intended to provoke further discussion of the ideological dimension of foreign language education (FLE) in China. Some observers suggest that this has been an important guiding doctrine in FLE since 1949,…

BOOK REVIEW: Modern Canonical Quantum General Relativity

NASA Astrophysics Data System (ADS)

Kiefer, Claus

2008-06-01

The open problem of constructing a consistent and experimentally tested quantum theory of the gravitational field has its place at the heart of fundamental physics. The main approaches can be roughly divided into two classes: either one seeks a unified quantum framework of all interactions or one starts with a direct quantization of general relativity. In the first class, string theory (M-theory) is the only known example. In the second class, one can make an additional methodological distinction: while covariant approaches such as path-integral quantization use the four-dimensional metric as an essential ingredient of their formalism, canonical approaches start with a foliation of spacetime into spacelike hypersurfaces in order to arrive at a Hamiltonian formulation. The present book is devoted to one of the canonical approaches—loop quantum gravity. It is named modern canonical quantum general relativity by the author because it uses connections and holonomies as central variables, which are analogous to the variables used in Yang Mills theories. In fact, the canonically conjugate variables are a holonomy of a connection and the flux of a non-Abelian electric field. This has to be contrasted with the older geometrodynamical approach in which the metric of three-dimensional space and the second fundamental form are the fundamental entities, an approach which is still actively being pursued. It is the author's ambition to present loop quantum gravity in a way in which every step is formulated in a mathematically rigorous form. In his own words: 'loop quantum gravity is an attempt to construct a mathematically rigorous, background-independent, non-perturbative quantum field theory of Lorentzian general relativity and all known matter in four spacetime dimensions, not more and not less'. The formal Leitmotiv of loop quantum gravity is background independence. Non-gravitational theories are usually quantized on a given non-dynamical background. In contrast, due to

Nonuniform fluids in the grand canonical ensemble

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

Percus, J.K.

1982-01-01

Nonuniform simple classical fluids are considered quite generally. The grand canonical ensemble is particularly suitable, conceptually, in the leading approximation of local thermodynamics, which figuratively divides the system into approximately uniform spatial subsystems. The procedure is reviewed by which this approach is systematically corrected for slowly varying density profiles, and a model is suggested that carries the correction into the domain of local fluctuations. The latter is assessed for substrate bounded fluids, as well as for two-phase interfaces. The peculiarities of the grand ensemble in a two-phase region stem from the inherent very large number fluctuations. A primitive model showsmore » how these are quenched in the canonical ensemble. This is taken advantage of by applying the Kac-Siegert representation of the van der Waals decomposition with petit canonical corrections, to the two-phase regime.« less

Structuring Catholic Schools: Creative Imagination Meets Canon Law

ERIC Educational Resources Information Center

Brown, Phillip J.

2010-01-01

This paper will explore the underlying requirements of canon law for establishing and administering Catholic schools, with a view toward helping to arrive at creative solutions to the question of how best to structure these schools civilly and canonically in order to ensure their temporal, spiritual, and religious well-being, and to assure that…

Regulation of natural competence by the orphan two-component system sensor kinase ChiS involves a non-canonical transmembrane regulator in Vibrio cholerae.

PubMed

Yamamoto, Shouji; Mitobe, Jiro; Ishikawa, Takahiko; Wai, Sun Nyunt; Ohnishi, Makoto; Watanabe, Haruo; Izumiya, Hidemasa

2014-01-01

In Vibrio cholerae, 41 chitin-inducible genes, including the genes involved in natural competence for DNA uptake, are governed by the orphan two-component system (TCS) sensor kinase ChiS. However, the mechanism by which ChiS controls the expression of these genes is currently unknown. Here, we report the involvement of a novel transcription factor termed 'TfoS' in this process. TfoS is a transmembrane protein that contains a large periplasmic domain and a cytoplasmic AraC-type DNA-binding domain, but lacks TCS signature domains. Inactivation of tfoS abolished natural competence as well as transcription of the tfoR gene encoding a chitin-induced small RNA essential for competence gene expression. A TfoS fragment containing the DNA-binding domain specifically bound to and activated transcription from the tfoR promoter. Intracellular TfoS levels were unaffected by disruption of chiS and coexpression of TfoS and ChiS in Escherichia coli recovered transcription of the chromosomally integrated tfoR::lacZ gene, suggesting that TfoS is post-translationally modulated by ChiS during transcriptional activation; however, this regulation persisted when the canonical phosphorelay residues of ChiS were mutated. The results presented here suggest that ChiS operates a chitin-induced non-canonical signal transduction cascade through TfoS, leading to transcriptional activation of tfoR. © 2013 John Wiley & Sons Ltd.

Canonical microcircuits for predictive coding

PubMed Central

Bastos, Andre M.; Usrey, W. Martin; Adams, Rick A.; Mangun, George R.; Fries, Pascal; Friston, Karl J.

2013-01-01

Summary This review considers the influential notion of a canonical (cortical) microcircuit in light of recent theories about neuronal processing. Specifically, we conciliate quantitative studies of microcircuitry and the functional logic of neuronal computations. We revisit the established idea that message passing among hierarchical cortical areas implements a form of Bayesian inference – paying careful attention to the implications for intrinsic connections among neuronal populations. By deriving canonical forms for these computations, one can associate specific neuronal populations with specific computational roles. This analysis discloses a remarkable correspondence between the microcircuitry of the cortical column and the connectivity implied by predictive coding. Furthermore, it provides some intuitive insights into the functional asymmetries between feedforward and feedback connections and the characteristic frequencies over which they operate. PMID:23177956

Non-canonical Wnt signaling enhances differentiation of Sca1+/c-kit+ adipose-derived murine stromal vascular cells into spontaneously beating cardiac myocytes.

PubMed

Palpant, Nathan J; Yasuda, So-ichiro; MacDougald, Ormond; Metzger, Joseph M

2007-09-01

Recent reports have described a stem cell population termed stromal vascular cells (SVCs) derived from the stromal vascular fraction of adipose tissue, which are capable of intrinsic differentiation into spontaneously beating cardiomyocytes in vitro. The objective of this study was to further define the cardiac lineage differentiation potential of SVCs in vitro and to establish methods for enriching SVC-derived beating cardiac myocytes. SVCs were isolated from the stromal vascular fraction of murine adipose tissue. Cells were cultured in methylcellulose-based murine stem cell media. Analysis of SVC-derived beating myocytes included Western blot and calcium imaging. Enrichment of acutely isolated SVCs was carried out using antibody-tagged magnetic nanoparticles, and pharmacologic manipulation of Wnt and cytokine signaling. Under initial media conditions, spontaneously beating SVCs expressed both cardiac developmental and adult protein isoforms. Functionally, this specialized population can spontaneously contract and pace under field stimulation and shows the presence of coordinated calcium transients. Importantly, this study provides evidence for two independent mechanisms of enriching the cardiac differentiation of SVCs. First, this study shows that differentiation of SVCs into cardiac myocytes is augmented by non-canonical Wnt agonists, canonical Wnt antagonists, and cytokines. Second, SVCs capable of cardiac lineage differentiation can be enriched by selection for stem cell-specific membrane markers Sca1 and c-kit. Adipose-derived SVCs are a unique population of stem cells that show evidence of cardiac lineage development making them a potential source for stem cell-based cardiac regeneration studies.

Non-canonical Wnt Signaling Enhances differentiation of Sca1+/c-kit+ Adipose-derived Murine Stromal Vascular Cells into Spontaneously Beating Cardiac Myocytes

PubMed Central

Palpant, Nathan J.; Yasuda, So-ichiro; MacDougald, Ormond; Metzger, Joseph M.

2007-01-01

Recent reports have described a stem cell population termed stromal vascular cells (SVCs) derived from the stromal vascular fraction of adipose tissue, which are capable of intrinsic differentiation into spontaneously beating cardiomyocytes in vitro. The objective of this study was to further define the cardiac lineage differentiation potential of SVCs in vitro and to derive methods for enriching SVC-derived beating cardiac myocytes. SVCs were isolated from the stromal vascular fraction of murine adipose tissue. Cells were cultured in methylcellulose-based murine stem cell media. Analysis of SVC-derived beating myocytes included Western blot, and calcium imaging. Enrichment of acutely isolated SVCs was carried out using antibody tagged magnetic nanoparticles, and pharmacologic manipulation of Wnt and cytokine signaling. Under initial media conditions, spontaneously beating SVCs expressed both cardiac developmental and adult protein isoforms. Functionally, this specialized population can spontaneously contract and pace under field stimulation, and shows the presence of coordinated calcium transients. Importantly, this study provides evidence for two independent mechanisms of enriching the cardiac differentiation of SVCs. First, this study shows that differentiation of SVCs into cardiac myocytes is augmented by non-canonical Wnt agonists, canonical Wnt antagonists, and cytokines. Second, SVCs capable of cardiac lineage differentiation can be enriched by selection for stem cell-specific membrane markers Sca1 and c-kit. Adipose-derived SVCs are a unique population of stem cells that show evidence of cardiac lineage development making them a potential source for stem cell-based cardiac regeneration studies. PMID:17706246

Mesenchymal chemotaxis requires selective inactivation of Myosin II at the leading edge via a non-canonical PLCγ/PKCα pathway

PubMed Central

Asokan, Sreeja B.; Johnson, Heath E.; Rahman, Anisur; King, Samantha J.; Rotty, Jeremy D.; Lebedeva, Irina P.; Haugh, Jason M.; Bear, James E.

2014-01-01

Summary Chemotaxis, migration towards soluble chemical cues, is critical for processes such as wound healing and immune surveillance, and is exhibited by various cell types from rapidly-migrating leukocytes to slow-moving mesenchymal cells. To interrogate the mechanisms involved in mesenchymal chemotaxis, we observed cell migration in microfluidic chambers that generate stable gradients of the chemoattractant PDGF. Surprisingly, we found that pathways implicated in amoeboid chemotaxis, such as PI3K and mTOR signaling, are dispensable for chemotaxis to PDGF. Instead, we find that local inactivation of Myosin IIA, through a non-canonical Ser1/2 phosphorylation of the regulatory light chain, is essential. This site is phosphorylated by PKCα, which is activated by an intracellular gradient of diacylglycerol generated by PLCγ. Using a combination of TIRF imaging and gradients of activators/inhibitors in the microfluidic chambers, we demonstrate that this signaling pathway and subsequent inhibition of Myosin II activity at the leading edge is required for mesenchymal chemotaxis. PMID:25482883

Visual Search for Object Orientation Can Be Modulated by Canonical Orientation

ERIC Educational Resources Information Center

Ballaz, Cecile; Boutsen, Luc; Peyrin, Carole; Humphreys, Glyn W.; Marendaz, Christian

2005-01-01

The authors studied the influence of canonical orientation on visual search for object orientation. Displays consisted of pictures of animals whose axis of elongation was either vertical or tilted in their canonical orientation. Target orientation could be either congruent or incongruent with the object's canonical orientation. In Experiment 1,…

Critical Literature Pedagogy: Teaching Canonical Literature for Critical Literacy

ERIC Educational Resources Information Center

Borsheim-Black, Carlin; Macaluso, Michael; Petrone, Robert

2014-01-01

This article introduces Critical Literature Pedagogy (CLP), a pedagogical framework for applying goals of critical literacy within the context of teaching canonical literature. Critical literacies encompass skills and dispositions to understand, question, and critique ideological messages of texts; because canonical literature is often…

Canonical Formulation of Supermechanics

NASA Astrophysics Data System (ADS)

Matsumoto, S.

1990-07-01

The canonical formulation of a theory of dynamical systems with both Grassmann even and odd variables is investigated. The sufficient condition for the system being analytically solvable is given. The geodesic motion of a particle in the super Poincaré upper half plane is solved as an example.

Monitoring Replication Protein A (RPA) dynamics in homologous recombination through site-specific incorporation of non-canonical amino acids.

PubMed

Pokhrel, Nilisha; Origanti, Sofia; Davenport, Eric Parker; Gandhi, Disha; Kaniecki, Kyle; Mehl, Ryan A; Greene, Eric C; Dockendorff, Chris; Antony, Edwin

2017-09-19

An essential coordinator of all DNA metabolic processes is Replication Protein A (RPA). RPA orchestrates these processes by binding to single-stranded DNA (ssDNA) and interacting with several other DNA binding proteins. Determining the real-time kinetics of single players such as RPA in the presence of multiple DNA processors to better understand the associated mechanistic events is technically challenging. To overcome this hurdle, we utilized non-canonical amino acids and bio-orthogonal chemistry to site-specifically incorporate a chemical fluorophore onto a single subunit of heterotrimeric RPA. Upon binding to ssDNA, this fluorescent RPA (RPAf) generates a quantifiable change in fluorescence, thus serving as a reporter of its dynamics on DNA in the presence of multiple other DNA binding proteins. Using RPAf, we describe the kinetics of facilitated self-exchange and exchange by Rad51 and mediator proteins during various stages in homologous recombination. RPAf is widely applicable to investigate its mechanism of action in processes such as DNA replication, repair and telomere maintenance. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Monitoring Replication Protein A (RPA) dynamics in homologous recombination through site-specific incorporation of non-canonical amino acids

PubMed Central

Pokhrel, Nilisha; Origanti, Sofia; Davenport, Eric Parker; Gandhi, Disha; Kaniecki, Kyle; Mehl, Ryan A.; Greene, Eric C.; Dockendorff, Chris

2017-01-01

Abstract An essential coordinator of all DNA metabolic processes is Replication Protein A (RPA). RPA orchestrates these processes by binding to single-stranded DNA (ssDNA) and interacting with several other DNA binding proteins. Determining the real-time kinetics of single players such as RPA in the presence of multiple DNA processors to better understand the associated mechanistic events is technically challenging. To overcome this hurdle, we utilized non-canonical amino acids and bio-orthogonal chemistry to site-specifically incorporate a chemical fluorophore onto a single subunit of heterotrimeric RPA. Upon binding to ssDNA, this fluorescent RPA (RPAf) generates a quantifiable change in fluorescence, thus serving as a reporter of its dynamics on DNA in the presence of multiple other DNA binding proteins. Using RPAf, we describe the kinetics of facilitated self-exchange and exchange by Rad51 and mediator proteins during various stages in homologous recombination. RPAf is widely applicable to investigate its mechanism of action in processes such as DNA replication, repair and telomere maintenance. PMID:28934470

Late onset canonical babbling: a possible early marker of abnormal development.

PubMed

Oller, D K; Eilers, R E; Neal, A R; Cobo-Lewis, A B

1998-11-01

By their 10th month of life, typically developing infants produce canonical babbling, which includes the well-formed syllables required for meaningful speech. Research suggests that emerging speech or language-related disorders might be associated with late onset of canonical babbling. Onset of canonical babbling was investigated for 1,536 high-risk infants, at about 10-months corrected age. Parental report by open-ended questionnaire was found to be an efficient method for ascertaining babbling status. Although delays were infrequent, they were often associated with genetic, neurological, anatomical, and/or physiological abnormalities. Over half the cases of late canonical babbling were not, at the time they were discovered associated with prior significant medical diagnoses. Late canonical-babbling onset may be a predictor of later developmental disabilities, including problems in speech, language, and reading.

Texture segmentation of non-cooperative spacecrafts images based on wavelet and fractal dimension

NASA Astrophysics Data System (ADS)

Wu, Kanzhi; Yue, Xiaokui

2011-06-01

With the increase of on-orbit manipulations and space conflictions, missions such as tracking and capturing the target spacecrafts are aroused. Unlike cooperative spacecrafts, fixing beacons or any other marks on the targets is impossible. Due to the unknown shape and geometry features of non-cooperative spacecraft, in order to localize the target and obtain the latitude, we need to segment the target image and recognize the target from the background. The data and errors during the following procedures such as feature extraction and matching can also be reduced. Multi-resolution analysis of wavelet theory reflects human beings' recognition towards images from low resolution to high resolution. In addition, spacecraft is the only man-made object in the image compared to the natural background and the differences will be certainly observed between the fractal dimensions of target and background. Combined wavelet transform and fractal dimension, in this paper, we proposed a new segmentation algorithm for the images which contains complicated background such as the universe and planet surfaces. At first, Daubechies wavelet basis is applied to decompose the image in both x axis and y axis, thus obtain four sub-images. Then, calculate the fractal dimensions in four sub-images using different methods; after analyzed the results of fractal dimensions in sub-images, we choose Differential Box Counting in low resolution image as the principle to segment the texture which has the greatest divergences between different sub-images. This paper also presents the results of experiments by using the algorithm above. It is demonstrated that an accurate texture segmentation result can be obtained using the proposed technique.

Controlled levels of canonical Wnt signaling are required for neural crest migration.

PubMed

Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

2016-09-01

Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Structure of multiphoton quantum optics. I. Canonical formalism and homodyne squeezed states

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

Dell'Anno, Fabio; De Siena, Silvio; Illuminati, Fabrizio

2004-03-01

We introduce a formalism of nonlinear canonical transformations for general systems of multiphoton quantum optics. For single-mode systems the transformations depend on a tunable free parameter, the homodyne local-oscillator angle; for n-mode systems they depend on n heterodyne mixing angles. The canonical formalism realizes nontrivial mixing of pairs of conjugate quadratures of the electromagnetic field in terms of homodyne variables for single-mode systems, and in terms of heterodyne variables for multimode systems. In the first instance the transformations yield nonquadratic model Hamiltonians of degenerate multiphoton processes and define a class of non-Gaussian, nonclassical multiphoton states that exhibit properties of coherencemore » and squeezing. We show that such homodyne multiphoton squeezed states are generated by unitary operators with a nonlinear time evolution that realizes the homodyne mixing of a pair of conjugate quadratures. Tuning of the local-oscillator angle allows us to vary at will the statistical properties of such states. We discuss the relevance of the formalism for the study of degenerate (up-)down-conversion processes. In a companion paper [F. Dell'Anno, S. De Siena, and F. Illuminati, 69, 033813 (2004)], we provide the extension of the nonlinear canonical formalism to multimode systems, we introduce the associated heterodyne multiphoton squeezed states, and we discuss their possible experimental realization.« less

A Numerical-Analytical Approach Based on Canonical Transformations for Computing Optimal Low-Thrust Transfers

NASA Astrophysics Data System (ADS)

da Silva Fernandes, S.; das Chagas Carvalho, F.; Bateli Romão, J. V.

2018-04-01

A numerical-analytical procedure based on infinitesimal canonical transformations is developed for computing optimal time-fixed low-thrust limited power transfers (no rendezvous) between coplanar orbits with small eccentricities in an inverse-square force field. The optimization problem is formulated as a Mayer problem with a set of non-singular orbital elements as state variables. Second order terms in eccentricity are considered in the development of the maximum Hamiltonian describing the optimal trajectories. The two-point boundary value problem of going from an initial orbit to a final orbit is solved by means of a two-stage Newton-Raphson algorithm which uses an infinitesimal canonical transformation. Numerical results are presented for some transfers between circular orbits with moderate radius ratio, including a preliminary analysis of Earth-Mars and Earth-Venus missions.

Translation system engineering in Escherichia coli enhances non-canonical amino acid incorporation into proteins.

PubMed

Gan, Rui; Perez, Jessica G; Carlson, Erik D; Ntai, Ioanna; Isaacs, Farren J; Kelleher, Neil L; Jewett, Michael C

2017-05-01

The ability to site-specifically incorporate non-canonical amino acids (ncAAs) into proteins has made possible the study of protein structure and function in fundamentally new ways, as well as the bio synthesis of unnatural polymers. However, the task of site-specifically incorporating multiple ncAAs into proteins with high purity and yield continues to present a challenge. At the heart of this challenge lies the lower efficiency of engineered orthogonal translation system components compared to their natural counterparts (e.g., translation elements that specifically use a ncAA and do not interact with the cell's natural translation apparatus). Here, we show that evolving and tuning expression levels of multiple components of an engineered translation system together as a whole enhances ncAA incorporation efficiency. Specifically, we increase protein yield when incorporating multiple p-azido-phenylalanine(pAzF) residues into proteins by (i) evolving the Methanocaldococcus jannaschii p-azido-phenylalanyl-tRNA synthetase anti-codon binding domain, (ii) evolving the elongation factor Tu amino acid-binding pocket, and (iii) tuning the expression of evolved translation machinery components in a single vector. Use of the evolved translation machinery in a genomically recoded organism lacking release factor one enabled enhanced multi-site ncAA incorporation into proteins. We anticipate that our approach to orthogonal translation system development will accelerate and expand our ability to site-specifically incorporate multiple ncAAs into proteins and biopolymers, advancing new horizons for synthetic and chemical biotechnology. Biotechnol. Bioeng. 2017;114: 1074-1086. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Canonical structures for dispersive waves in shallow water

NASA Astrophysics Data System (ADS)

Neyzi, Fahrünisa; Nutku, Yavuz

1987-07-01

The canonical Hamiltonian structure of the equations of fluid dynamics obtained in the Boussinesq approximation are considered. New variational formulations of these equations are proposed and it is found that, as in the case of the KdV equation and the equations governing long waves in shallow water, they are degenerate Lagrangian systems. Therefore, in order to cast these equations into canonical form it is again necessary to use Dirac's theory of constraints. It is found that there are primary and secondary constraints which are second class and it is possible to construct the Hamiltonian in terms of canonical variables. Among the examples of Boussinesq equations that are discussed are the equations of Whitham-Broer-Kaup which Kupershmidt has recently expressed in symmetric form and shown to admit tri-Hamiltonian structure.

Data analytics using canonical correlation analysis and Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Rickman, Jeffrey M.; Wang, Yan; Rollett, Anthony D.; Harmer, Martin P.; Compson, Charles

2017-07-01

A canonical correlation analysis is a generic parametric model used in the statistical analysis of data involving interrelated or interdependent input and output variables. It is especially useful in data analytics as a dimensional reduction strategy that simplifies a complex, multidimensional parameter space by identifying a relatively few combinations of variables that are maximally correlated. One shortcoming of the canonical correlation analysis, however, is that it provides only a linear combination of variables that maximizes these correlations. With this in mind, we describe here a versatile, Monte-Carlo based methodology that is useful in identifying non-linear functions of the variables that lead to strong input/output correlations. We demonstrate that our approach leads to a substantial enhancement of correlations, as illustrated by two experimental applications of substantial interest to the materials science community, namely: (1) determining the interdependence of processing and microstructural variables associated with doped polycrystalline aluminas, and (2) relating microstructural decriptors to the electrical and optoelectronic properties of thin-film solar cells based on CuInSe2 absorbers. Finally, we describe how this approach facilitates experimental planning and process control.

A Phenotypic Screen in Zebrafish Identifies a Novel Small-Molecule Inducer of Ectopic Tail Formation Suggestive of Alterations in Non-Canonical Wnt/PCP Signaling

PubMed Central

Gebruers, Evelien; Cordero-Maldonado, María Lorena; Gray, Alexander I.; Clements, Carol; Harvey, Alan L.; Edrada-Ebel, Ruangelie; de Witte, Peter A. M.; Crawford, Alexander D.; Esguerra, Camila V.

2013-01-01

Zebrafish have recently emerged as an attractive model for the in vivo bioassay-guided isolation and characterization of pharmacologically active small molecules of natural origin. We carried out a zebrafish-based phenotypic screen of over 3000 plant-derived secondary metabolite extracts with the goal of identifying novel small-molecule modulators of the BMP and Wnt signaling pathways. One of the bioactive plant extracts identified in this screen – Jasminum gilgianum, an Oleaceae species native to Papua New Guinea – induced ectopic tails during zebrafish embryonic development. As ectopic tail formation occurs when BMP or non-canonical Wnt signaling is inhibited during the tail protrusion process, we suspected a constituent of this extract to act as a modulator of these pathways. A bioassay-guided isolation was carried out on the basis of this zebrafish phenotype, identifying para-coumaric acid methyl ester (pCAME) as the active compound. We then performed an in-depth phenotypic analysis of pCAME-treated zebrafish embryos, including a tissue-specific marker analysis of the secondary tails. We found pCAME to synergize with the BMP-inhibitors dorsomorphin and LDN-193189 in inducing ectopic tails, and causing convergence-extension defects in compound-treated embryos. These results indicate that pCAME may interfere with non-canonical Wnt signaling. Inhibition of Jnk, a downstream target of Wnt/PCP signaling (via morpholino antisense knockdown and pharmacological inhibition with the kinase inhibitor SP600125) phenocopied pCAME-treated embryos. However, immunoblotting experiments revealed pCAME to not directly inhibit Jnk-mediated phosphorylation of c-Jun, suggesting additional targets of SP600125, and/or other pathways, as possibly being involved in the ectopic tail formation activity of pCAME. Further investigation of pCAME’s mechanism of action will help determine this compound’s pharmacological utility. PMID:24349481

Canonical partition functions: ideal quantum gases, interacting classical gases, and interacting quantum gases

NASA Astrophysics Data System (ADS)

Zhou, Chi-Chun; Dai, Wu-Sheng

2018-02-01

In statistical mechanics, for a system with a fixed number of particles, e.g. a finite-size system, strictly speaking, the thermodynamic quantity needs to be calculated in the canonical ensemble. Nevertheless, the calculation of the canonical partition function is difficult. In this paper, based on the mathematical theory of the symmetric function, we suggest a method for the calculation of the canonical partition function of ideal quantum gases, including ideal Bose, Fermi, and Gentile gases. Moreover, we express the canonical partition functions of interacting classical and quantum gases given by the classical and quantum cluster expansion methods in terms of the Bell polynomial in mathematics. The virial coefficients of ideal Bose, Fermi, and Gentile gases are calculated from the exact canonical partition function. The virial coefficients of interacting classical and quantum gases are calculated from the canonical partition function by using the expansion of the Bell polynomial, rather than calculated from the grand canonical potential.

Hereditary non-polyposis colorectal cancer/Lynch syndrome in three dimensions.

PubMed

Kravochuck, Sara E; Church, James M

2017-12-01

Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing. Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry. There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC. Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance. © 2016 Royal Australasian College of Surgeons.

Association Study between Lead and Zinc Accumulation at Different Physiological Systems of Cattle by Canonical Correlation and Canonical Correspondence Analyses

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

Karmakar, Partha; Das, Pradip Kumar; Mondal, Seema Sarkar

2010-10-26

Pb pollution from automobile exhausts around highways is a persistent problem in India. Pb intoxication in mammalian body is a complex phenomenon which is influence by agonistic and antagonistic interactions of several other heavy metals and micronutrients. An attempt has been made to study the association between Pb and Zn accumulation in different physiological systems of cattles (n = 200) by application of both canonical correlation and canonical correspondence analyses. Pb was estimated from plasma, liver, bone, muscle, kidney, blood and milk where as Zn was measured from all these systems except bone, blood and milk. Both statistical techniques demonstratedmore » that there was a strong association among blood-Pb, liver-Zn, kidney-Zn and muscle-Zn. From observations, it can be assumed that Zn accumulation in cattles' muscle, liver and kidney directs Pb mobilization from those organs which in turn increases Pb pool in blood. It indicates antagonistic activity of Zn to the accumulation of Pb. Although there were some contradictions between the observations obtained from the two different statistical methods, the overall pattern of Pb accumulation in various organs as influenced by Zn were same. It is mainly due to the fact that canonical correlation is actually a special type of canonical correspondence analyses where linear relationship is followed between two groups of variables instead of Gaussian relationship.« less

Association Study between Lead and Zinc Accumulation at Different Physiological Systems of Cattle by Canonical Correlation and Canonical Correspondence Analyses

NASA Astrophysics Data System (ADS)

Karmakar, Partha; Das, Pradip Kumar; Mondal, Seema Sarkar; Karmakar, Sougata; Mazumdar, Debasis

2010-10-01

Pb pollution from automobile exhausts around highways is a persistent problem in India. Pb intoxication in mammalian body is a complex phenomenon which is influence by agonistic and antagonistic interactions of several other heavy metals and micronutrients. An attempt has been made to study the association between Pb and Zn accumulation in different physiological systems of cattles (n = 200) by application of both canonical correlation and canonical correspondence analyses. Pb was estimated from plasma, liver, bone, muscle, kidney, blood and milk where as Zn was measured from all these systems except bone, blood and milk. Both statistical techniques demonstrated that there was a strong association among blood-Pb, liver-Zn, kidney-Zn and muscle-Zn. From observations, it can be assumed that Zn accumulation in cattles' muscle, liver and kidney directs Pb mobilization from those organs which in turn increases Pb pool in blood. It indicates antagonistic activity of Zn to the accumulation of Pb. Although there were some contradictions between the observations obtained from the two different statistical methods, the overall pattern of Pb accumulation in various organs as influenced by Zn were same. It is mainly due to the fact that canonical correlation is actually a special type of canonical correspondence analyses where linear relationship is followed between two groups of variables instead of Gaussian relationship.

1/ r potential in higher dimensions

NASA Astrophysics Data System (ADS)

Chakraborty, Sumanta; Dadhich, Naresh

2018-01-01

In Einstein gravity, gravitational potential goes as 1/r^{d-3} in d non-compactified spacetime dimensions, which assumes the familiar 1 / r form in four dimensions. On the other hand, it goes as 1/r^{α }, with α =(d-2m-1)/m, in pure Lovelock gravity involving only one mth order term of the Lovelock polynomial in the gravitational action. The latter offers a novel possibility of having 1 / r potential for the non-compactified dimension spectrum given by d=3m+1. Thus it turns out that in the two prototype gravitational settings of isolated objects, like black holes and the universe as a whole - cosmological models, the Einstein gravity in four and mth order pure Lovelock gravity in 3m+1 dimensions behave in a similar fashion as far as gravitational interactions are considered. However propagation of gravitational waves (or the number of degrees of freedom) does indeed serve as a discriminator because it has two polarizations only in four dimensions.

Canonical single field slow-roll inflation with a non-monotonic tensor-to-scalar ratio

NASA Astrophysics Data System (ADS)

Germán, Gabriel; Herrera-Aguilar, Alfredo; Hidalgo, Juan Carlos; Sussman, Roberto A.

2016-05-01

We take a pragmatic, model independent approach to single field slow-roll canonical inflation by imposing conditions, not on the potential, but on the slow-roll parameter epsilon(phi) and its derivatives epsilon'(phi) and epsilon''(phi), thereby extracting general conditions on the tensor-to-scalar ratio r and the running nsk at phiH where the perturbations are produced, some 50-60 e-folds before the end of inflation. We find quite generally that for models where epsilon(phi) develops a maximum, a relatively large r is most likely accompanied by a positive running while a negligible tensor-to-scalar ratio implies negative running. The definitive answer, however, is given in terms of the slow-roll parameter ξ2(phi). To accommodate a large tensor-to-scalar ratio that meets the limiting values allowed by the Planck data, we study a non-monotonic epsilon(phi) decreasing during most part of inflation. Since at phiH the slow-roll parameter epsilon(phi) is increasing, we thus require that epsilon(phi) develops a maximum for phi > phiH after which epsilon(phi) decrease to small values where most e-folds are produced. The end of inflation might occur trough a hybrid mechanism and a small field excursion Δphie ≡ |phiH-phie| is obtained with a sufficiently thin profile for epsilon(phi) which, however, should not conflict with the second slow-roll parameter η(phi). As a consequence of this analysis we find bounds for Δphie, rH and for the scalar spectral index nsH. Finally we provide examples where these considerations are explicitly realised.

Tyrosine phosphorylation and proteolytic cleavage of Notch are required for non-canonical Notch/Abl signaling in Drosophila axon guidance.

PubMed

Kannan, Ramakrishnan; Cox, Eric; Wang, Lei; Kuzina, Irina; Gu, Qun; Giniger, Edward

2018-01-17

Notch signaling is required for the development and physiology of nearly every tissue in metazoans. Much of Notch signaling is mediated by transcriptional regulation of downstream target genes, but Notch controls axon patterning in Drosophila by local modulation of Abl tyrosine kinase signaling, via direct interactions with the Abl co-factors Disabled and Trio. Here, we show that Notch-Abl axonal signaling requires both of the proteolytic cleavage events that initiate canonical Notch signaling. We further show that some Notch protein is tyrosine phosphorylated in Drosophila , that this form of the protein is selectively associated with Disabled and Trio, and that relevant tyrosines are essential for Notch-dependent axon patterning but not for canonical Notch-dependent regulation of cell fate. Based on these data, we propose a model for the molecular mechanism by which Notch controls Abl signaling in Drosophila axons. © 2018. Published by The Company of Biologists Ltd.

A Canonical Analysis of Career Choice Crystallization and Vocational Maturity.

ERIC Educational Resources Information Center

Blustein, David L.

1988-01-01

Administered measures of vocational maturity and career choice crystallization to 158 community college students. Used canonical analysis to identify relationships between age, gender, career choice crystallization, and vocational maturity. Analysis yielded one significant canonical root, indicating most shared variance between variables was…

Accelerated Dimension-Independent Adaptive Metropolis

DOE PAGES

Chen, Yuxin; Keyes, David E.; Law, Kody J.; ...

2016-10-27

This work describes improvements from algorithmic and architectural means to black-box Bayesian inference over high-dimensional parameter spaces. The well-known adaptive Metropolis (AM) algorithm [33] is extended herein to scale asymptotically uniformly with respect to the underlying parameter dimension for Gaussian targets, by respecting the variance of the target. The resulting algorithm, referred to as the dimension-independent adaptive Metropolis (DIAM) algorithm, also shows improved performance with respect to adaptive Metropolis on non-Gaussian targets. This algorithm is further improved, and the possibility of probing high-dimensional (with dimension d 1000) targets is enabled, via GPU-accelerated numerical libraries and periodically synchronized concurrent chains (justimore » ed a posteriori). Asymptotically in dimension, this GPU implementation exhibits a factor of four improvement versus a competitive CPU-based Intel MKL parallel version alone. Strong scaling to concurrent chains is exhibited, through a combination of longer time per sample batch (weak scaling) and yet fewer necessary samples to convergence. The algorithm performance is illustrated on several Gaussian and non-Gaussian target examples, in which the dimension may be in excess of one thousand.« less

Accelerated Dimension-Independent Adaptive Metropolis

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

Chen, Yuxin; Keyes, David E.; Law, Kody J.

This work describes improvements from algorithmic and architectural means to black-box Bayesian inference over high-dimensional parameter spaces. The well-known adaptive Metropolis (AM) algorithm [33] is extended herein to scale asymptotically uniformly with respect to the underlying parameter dimension for Gaussian targets, by respecting the variance of the target. The resulting algorithm, referred to as the dimension-independent adaptive Metropolis (DIAM) algorithm, also shows improved performance with respect to adaptive Metropolis on non-Gaussian targets. This algorithm is further improved, and the possibility of probing high-dimensional (with dimension d 1000) targets is enabled, via GPU-accelerated numerical libraries and periodically synchronized concurrent chains (justimore » ed a posteriori). Asymptotically in dimension, this GPU implementation exhibits a factor of four improvement versus a competitive CPU-based Intel MKL parallel version alone. Strong scaling to concurrent chains is exhibited, through a combination of longer time per sample batch (weak scaling) and yet fewer necessary samples to convergence. The algorithm performance is illustrated on several Gaussian and non-Gaussian target examples, in which the dimension may be in excess of one thousand.« less

On partially massless theory in 3 dimensions

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

Alexandrov, Sergei; Laboratoire Charles Coulomb UMR 5221, CNRS, Place Eugène Bataillon, F-34095, Montpellier; Deffayet, Cédric

2015-03-24

We analyze the first-order formulation of the ghost-free bigravity model in three-dimensions known as zwei-dreibein gravity. For a special choice of parameters, it was argued to have an additional gauge symmetry and give rise to a partially massless theory. We provide a thorough canonical analysis and identify that whether the theory becomes partially massless depends on the form of the stability condition of the secondary constraint responsible for the absence of the ghost. Generically, it is found to be an equation for a Lagrange multiplier implying that partially massless zwei-dreibein gravity does not exist. However, for special backgrounds this conditionmore » is identically satisfied leading to the presence of additional symmetries, which however disappear at quadratic order in perturbations.« less

On partially massless theory in 3 dimensions

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

Alexandrov, Sergei; Deffayet, Cédric, E-mail: salexand@univ-montp2.fr, E-mail: deffayet@iap.fr

2015-03-01

We analyze the first-order formulation of the ghost-free bigravity model in three-dimensions known as zwei-dreibein gravity. For a special choice of parameters, it was argued to have an additional gauge symmetry and give rise to a partially massless theory. We provide a thorough canonical analysis and identify that whether the theory becomes partially massless depends on the form of the stability condition of the secondary constraint responsible for the absence of the ghost. Generically, it is found to be an equation for a Lagrange multiplier implying that partially massless zwei-dreibein gravity does not exist. However, for special backgrounds this conditionmore » is identically satisfied leading to the presence of additional symmetries, which however disappear at quadratic order in perturbations.« less

Non-canonical dynamic mechanisms of interaction between the p66Shc protein and Met receptor

PubMed Central

Landry, Mélissa; Pomerleau, Véronique; Saucier, Caroline

2016-01-01

Met receptor tyrosine kinase (RTK) is known to bind to the three distinct protein isoforms encoded by the ShcA (Shc) gene. Structure–function studies have unveiled critical roles for p52Shc-dependent signalling pathways in Met-regulated biological functions. The molecular basis of the interaction between the Met and p52Shc proteins is well-defined, but not for the longest protein isoform, p66Shc. In the present study, co-immunoprecipitation assays were performed in human embryonic kidney 293 (HEK293) cells, transiently co-transfected with Met and p66Shc mutants, in order to define the molecular determinants involved in mediating Met–p66Shc interaction. Our results show that p66Shc interacts constitutively with the receptor Met, and the Grb2 (growth factor receptor-bound protein-2) and Gab1 (Grb2-associated binder-1) adaptor proteins. Although its phosphotyrosine-binding domain (PTB) and Src homology 2 (SH2) domains co-ordinate p66Shc binding to non-activated Met receptor, these phosphotyrosine-binding modules, and its collagen homology domain 2 (CH2) region, exert negative constraints. In contrast, p66Shc interaction with the activated Met depends mainly on the integrity of its PTB domain, and to a lesser extent of its SH2 domain. Even though not required for the recruitment of p66Shc, tyrosine phosphorylation of p66Shc by activated Met enhances these interactions by mechanisms not reliant on the integrity of the Met multisubstrate-binding site. In turn, this increases phosphotyrosine-dependent p66Shc–Grb2–Gab1 complex formation away from the receptor, while blocking Grb2 and Gab1 recruitment to activated Met. In conclusion, we identify, for the first time, a novel non-canonical dynamic mode of interaction between Met and the p66 protein isoform of Shc and its effects on rewiring binding effector complexes according to the activation state of the receptor. PMID:27048591

Computation of canonical correlation and best predictable aspect of future for time series

NASA Technical Reports Server (NTRS)

Pourahmadi, Mohsen; Miamee, A. G.

1989-01-01

The canonical correlation between the (infinite) past and future of a stationary time series is shown to be the limit of the canonical correlation between the (infinite) past and (finite) future, and computation of the latter is reduced to a (generalized) eigenvalue problem involving (finite) matrices. This provides a convenient and essentially, finite-dimensional algorithm for computing canonical correlations and components of a time series. An upper bound is conjectured for the largest canonical correlation.

A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides.

PubMed

Calo, Silvia; Nicolás, Francisco E; Lee, Soo Chan; Vila, Ana; Cervantes, Maria; Torres-Martinez, Santiago; Ruiz-Vazquez, Rosa M; Cardenas, Maria E; Heitman, Joseph

2017-03-01

Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed to stressful compounds such as the antifungal drug FK506. To elucidate the molecular mechanism of this epimutation pathway, we performed a genetic analysis in Mucor circinelloides that revealed an inhibitory role for the non-canonical RdRP-dependent Dicer-independent silencing pathway, which is an RNAi-based mechanism involved in mRNA degradation that was recently identified. Thus, mutations that specifically block the mRNA degradation pathway, such as those in the genes r3b2 and rdrp3, enhance the production of drug resistant epimutants, similar to the phenotype previously described for mutation of the gene rdrp1. Our genetic analysis also revealed two new specific components of the epimutation pathway related to the quelling induced protein (qip) and a Sad-3-like helicase (rnhA), as mutations in these genes prevented formation of drug-resistant epimutants. Remarkably, drug-resistant epimutant production was notably increased in M. circinelloides f. circinelloides isolates from humans or other animal hosts. The host-pathogen interaction could be a stressful environment in which the phenotypic plasticity provided by the epimutant pathway might provide an advantage for these strains. These results evoke a model whereby balanced regulation of two different RNAi pathways is determined by the activation of the RNAi-dependent epimutant pathway under stress conditions, or its repression when the regular maintenance of the mRNA degradation pathway operates under non-stress conditions.

Canonical Wnt signaling in megakaryocytes regulates proplatelet formation

PubMed Central

Macaulay, Iain C.; Thon, Jonathan N.; Tijssen, Marloes R.; Steele, Brian M.; MacDonald, Bryan T.; Meade, Gerardene; Burns, Philippa; Rendon, Augusto; Salunkhe, Vishal; Murphy, Ronan P.; Bennett, Cavan; Watkins, Nicholas A.; He, Xi; Fitzgerald, Desmond J.; Italiano, Joseph E.

2013-01-01

Wnt signaling is involved in numerous aspects of vertebrate development and homeostasis, including the formation and function of blood cells. Here, we show that canonical and noncanonical Wnt signaling pathways are present and functional in megakaryocytes (MKs), with several Wnt effectors displaying MK-restricted expression. Using the CHRF288-11 cell line as a model for human MKs, the canonical Wnt3a signal was found to induce a time and dose-dependent increase in β-catenin expression. β-catenin accumulation was inhibited by the canonical antagonist dickkopf-1 (DKK1) and by the noncanonical agonist Wnt5a. Whole genome expression analysis demonstrated that Wnt3a and Wnt5a regulated distinct patterns of gene expression in MKs, and revealed a further interplay between canonical and noncanonical Wnt pathways. Fetal liver cells derived from low-density-lipoprotein receptor-related protein 6-deficient mice (LRP6−/−), generated dramatically reduced numbers of MKs in culture of lower ploidy (2N and 4N) than wild-type controls, implicating LRP6-dependent Wnt signaling in MK proliferation and maturation. Finally, in wild-type mature murine fetal liver-derived MKs, Wnt3a potently induced proplatelet formation, an effect that could be completely abrogated by DKK1. These data identify novel extrinsic regulators of proplatelet formation, and reveal a profound role for Wnt signaling in platelet production. PMID:23160460

Comparison of Blood Lipids, Blood Pressures and Left Ventricular Cavity Dimension between Soccer Players and Non-Athletes

ERIC Educational Resources Information Center

Gokhan, Ismail; Kurkcu, Recep; Cekin, Resul

2013-01-01

In this study, it was aimed to compare the investigate the effects of regular exercise on blood lipids, blood pressure and left ventricular cavity dimensions function between soccer players and non-athletes in football players. This study consisted included a total of 30 subjects, including an experimental group including 18 soccer players…

Loss of a membrane trafficking protein αSNAP induces non-canonical autophagy in human epithelia

PubMed Central

Naydenov, Nayden G.; Harris, Gianni; Morales, Victor; Ivanov, Andrei I.

2012-01-01

Autophagy is a catabolic process that sequesters intracellular proteins and organelles within membrane vesicles called autophagosomes with their subsequent delivery to lyzosomes for degradation. This process involves multiple fusions of autophagosomal membranes with different vesicular compartments; however, the role of vesicle fusion in autophagosomal biogenesis remains poorly understood. This study addresses the role of a key vesicle fusion regulator, soluble N-ethylmaleimide-sensitive factor attachment protein α (αSNAP), in autophagy. Small interfering RNA-mediated downregulation of αSNAP expression in cultured epithelial cells stimulated the autophagic flux, which was manifested by increased conjugation of microtubule-associated protein light chain 3 (LC3-II) and accumulation of LC3-positive autophagosomes. This enhanced autophagy developed via a non-canonical mechanism that did not require beclin1-p150-dependent nucleation, but involved Atg5 and Atg7-mediated elongation of autophagosomal membranes. Induction of autophagy in αSNAP-depleted cells was accompanied by decreased mTOR signaling but appeared to be independent of αSNAP-binding partners, N-ethylmaleimide-sensitive factor and BNIP1. Loss of αSNAP caused fragmentation of the Golgi and downregulation of the Golgi-specific GTP exchange factors, GBF1, BIG1 and BIG2. Pharmacological disruption of the Golgi and genetic inhibition of GBF1 recreated the effects of αSNAP depletion on the autophagic flux. Our study revealed a novel role for αSNAP as a negative regulator of autophagy that acts by enhancing mTOR signaling and regulating the integrity of the Golgi complex. PMID:23187805

BOOK REVIEW: Canonical Gravity and Applications: Cosmology, Black Holes, and Quantum Gravity Canonical Gravity and Applications: Cosmology, Black Holes, and Quantum Gravity

NASA Astrophysics Data System (ADS)

Husain, Viqar

2012-03-01

Research on quantum gravity from a non-perturbative 'quantization of geometry' perspective has been the focus of much research in the past two decades, due to the Ashtekar-Barbero Hamiltonian formulation of general relativity. This approach provides an SU(2) gauge field as the canonical configuration variable; the analogy with Yang-Mills theory at the kinematical level opened up some research space to reformulate the old Wheeler-DeWitt program into what is now known as loop quantum gravity (LQG). The author is known for his work in the LQG approach to cosmology, which was the first application of this formalism that provided the possibility of exploring physical questions. Therefore the flavour of the book is naturally informed by this history. The book is based on a set of graduate-level lectures designed to impart a working knowledge of the canonical approach to gravitation. It is more of a textbook than a treatise, unlike three other recent books in this area by Kiefer [1], Rovelli [2] and Thiemann [3]. The style and choice of topics of these authors are quite different; Kiefer's book provides a broad overview of the path integral and canonical quantization methods from a historical perspective, whereas Rovelli's book focuses on philosophical and formalistic aspects of the problems of time and observables, and gives a development of spin-foam ideas. Thiemann's is much more a mathematical physics book, focusing entirely on the theory of representing constraint operators on a Hilbert space and charting a mathematical trajectory toward a physical Hilbert space for quantum gravity. The significant difference from these books is that Bojowald covers mainly classical topics until the very last chapter, which contains the only discussion of quantization. In its coverage of classical gravity, the book has some content overlap with Poisson's book [4], and with Ryan and Shepley's older work on relativistic cosmology [5]; for instance the contents of chapter five of the

LCPT: a program for finding linear canonical transformations. [In MACSYMA

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

Char, B.W.; McNamara, B.

This article describes a MACSYMA program to compute symbolically a canonical linear transformation between coordinate systems. The difficulties in implementation of this canonical small physics problem are also discussed, along with the implications that may be drawn from such difficulties about widespread MACSYMA usage by the community of computational/theoretical physicists.

Canonical WNT signaling components in vascular development and barrier formation.

PubMed

Zhou, Yulian; Wang, Yanshu; Tischfield, Max; Williams, John; Smallwood, Philip M; Rattner, Amir; Taketo, Makoto M; Nathans, Jeremy

2014-09-01

Canonical WNT signaling is required for proper vascularization of the CNS during embryonic development. Here, we used mice with targeted mutations in genes encoding canonical WNT pathway members to evaluate the exact contribution of these components in CNS vascular development and in specification of the blood-brain barrier (BBB) and blood-retina barrier (BRB). We determined that vasculature in various CNS regions is differentially sensitive to perturbations in canonical WNT signaling. The closely related WNT signaling coreceptors LDL receptor-related protein 5 (LRP5) and LRP6 had redundant functions in brain vascular development and barrier maintenance; however, loss of LRP5 alone dramatically altered development of the retinal vasculature. The BBB in the cerebellum and pons/interpeduncular nuclei was highly sensitive to decrements in canonical WNT signaling, and WNT signaling was required to maintain plasticity of barrier properties in mature CNS vasculature. Brain and retinal vascular defects resulting from ablation of Norrin/Frizzled4 signaling were ameliorated by stabilizing β-catenin, while inhibition of β-catenin-dependent transcription recapitulated the vascular development and barrier defects associated with loss of receptor, coreceptor, or ligand, indicating that Norrin/Frizzled4 signaling acts predominantly through β-catenin-dependent transcriptional regulation. Together, these data strongly support a model in which identical or nearly identical canonical WNT signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB.

Romanticism, Sexuality, and the Canon.

ERIC Educational Resources Information Center

Rowe, Kathleen K.

1990-01-01

Traces the Romanticism in the work and persona of film director Jean-Luc Godard. Examines the contradictions posed by Godard's politics and representations of sexuality. Asserts, that by bringing an ironic distance to the works of such canonized directors, viewers can take pleasure in those works despite their contradictions. (MM)

Polydisperse sphere packing in high dimensions, a search for an upper critical dimension

NASA Astrophysics Data System (ADS)

Morse, Peter; Clusel, Maxime; Corwin, Eric

2012-02-01

The recently introduced granocentric model for polydisperse sphere packings has been shown to be in good agreement with experimental and simulational data in two and three dimensions. This model relies on two effective parameters that have to be estimated from experimental/simulational results. The non-trivial values obtained allow the model to take into account the essential effects of correlations in the packing. Once these parameters are set, the model provides a full statistical description of a sphere packing for a given polydispersity. We investigate the evolution of these effective parameters with the spatial dimension to see if, in analogy with the upper critical dimension in critical phenomena, there exists a dimension above which correlations become irrelevant and the model parameters can be fixed a priori as a function of polydispersity. This would turn the model into a proper theory of polydisperse sphere packings at that upper critical dimension. We perform infinite temperature quench simulations of frictionless polydisperse sphere packings in dimensions 2-8 using a parallel algorithm implemented on a GPGPU. We analyze the resulting packings by implementing an algorithm to calculate the additively weighted Voronoi diagram in arbitrary dimension.

The Western Canon: The Books and School of the Ages.

ERIC Educational Resources Information Center

Bloom, Harold

This book argues against the politicization of literature and presents a guide to the great works and essential writers of the ages, the "Western Canon." The book studies 26 writers and seeks to isolate the qualities that made these authors canonical, that is, authoritative in Western culture. Noting that although originally the…

[Study of correlation dimension on EEG].

PubMed

Yang, Hao; Fang, Liang; He, Wei

2004-02-01

The study of non-linear EEG is of great significance in clinical practice and research work. This paper has gone into the feasibility of calculating the correlation dimension and has developed some subjects with the characters of correlation dimension and the difference under four conditions: (1) passive eyes closed(PEC); (2) mental arithmetic with eyes closed(MAEC); (3) passive eyes open(PEO); (4) mental reasoning with eyes open (MRED). The results show it is feasible and meaningful to calculate correlation dimension and the correlation dimension can reflect the regular patterns of mental activity.

Rotating hairy black holes in arbitrary dimensions

NASA Astrophysics Data System (ADS)

Erices, Cristián; Martínez, Cristián

2018-01-01

A class of exact rotating black hole solutions of gravity nonminimally coupled to a self-interacting scalar field in arbitrary dimensions is presented. These spacetimes are asymptotically locally anti-de Sitter manifolds and have a Ricci-flat event horizon hiding a curvature singularity at the origin. The scalar field is real and regular everywhere, and its effective mass, coming from the nonminimal coupling with the scalar curvature, saturates the Breitenlohner-Freedman bound for the corresponding spacetime dimension. The rotating black hole is obtained by applying an improper coordinate transformation to the static one. Although both spacetimes are locally equivalent, they are globally different, as it is confirmed by the nonvanishing angular momentum of the rotating black hole. It is found that the mass is bounded from below by the angular momentum, in agreement with the existence of an event horizon. The thermodynamical analysis is carried out in the grand canonical ensemble. The first law is satisfied, and a Smarr formula is exhibited. The thermodynamical local stability of the rotating hairy black holes is established from their Gibbs free energy. However, the global stability analysis establishes that the vacuum spacetime is always preferred over the hairy black hole. Thus, the hairy black hole is likely to decay into the vacuum one for any temperature.

Memory, Literacy, and Invention: Reimagining the Canon of Memory for the Writing Classroom

ERIC Educational Resources Information Center

Ryan, Kathleen J.

2004-01-01

This article challenges the assumption that the canon of memory means memorization and transcription, and, as a result, has little relevance for the writing classroom. An examination of the canon's historical legacy and its relationships to literacy and invention open a space for redefining the canon of memory as "rememoried knowing." In brief,…

Fractal dimension analysis for robust ultrasonic non-destructive evaluation (NDE) of coarse grained materials

NASA Astrophysics Data System (ADS)

Li, Minghui; Hayward, Gordon

2018-04-01

Over the recent decades, there has been a growing demand on reliable and robust non-destructive evaluation (NDE) of structures and components made from coarse grained materials such as alloys, stainless steels, carbon-reinforced composites and concrete; however, when inspected using ultrasound, the flaw echoes are usually contaminated by high-level, time-invariant, and correlated grain noise originating from the microstructure and grain boundaries, leading to pretty low signal-to-noise ratio (SNR) and the flaw information being obscured or completely hidden by the grain noise. In this paper, the fractal dimension analysis of the A-scan echoes is investigated as a measure of complexity of the time series to distinguish the echoes originating from the real defects and the grain noise, and then the normalized fractal dimension coefficients are applied to the amplitudes as the weighting factor to enhance the SNR and defect detection. Experiments on industrial samples of the mild steel and the stainless steel are conducted and the results confirm the great benefits of the method.

Canonical Word Order of Japanese Ditransitive Sentences: A Preliminary Investigation through a Grammaticality Judgment Survey

ERIC Educational Resources Information Center

Shigenaga, Yasumasa

2014-01-01

There have been three competing analyses regarding the canonical word order of Japanese ditransitive sentences: a) "S-'ga' IO-'ni' DO-'o' V" is the canonical word order rather than "S-'ga' DO-'o' IO-'ni' V", b) both word orders are canonical, and c) the canonical word order depends on the type of the verb. The present study…

Bell - Kochen - Specker theorem for any finite dimension ?

NASA Astrophysics Data System (ADS)

Cabello, Adán; García-Alcaine, Guillermo

1996-03-01

The Bell - Kochen - Specker theorem against non-contextual hidden variables can be proved by constructing a finite set of `totally non-colourable' directions, as Kochen and Specker did in a Hilbert space of dimension n = 3. We generalize Kochen and Specker's set to Hilbert spaces of any finite dimension 0305-4470/29/5/016/img2, in a three-step process that shows the relationship between different kinds of proofs (`continuum', `probabilistic', `state-specific' and `state-independent') of the Bell - Kochen - Specker theorem. At the same time, this construction of a totally non-colourable set of directions in any dimension explicitly solves the question raised by Zimba and Penrose about the existence of such a set for n = 5.

TCDD Inhibition of Canonical Wnt Signaling Disrupts Prostatic Bud Formation in Mouse Urogenital Sinus

PubMed Central

Peterson, Richard E.

2013-01-01

In mice, in utero exposure to 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) reduces the number of dorsolateral prostatic buds resulting in a smaller dorsolateral prostate and prevents formation of ventral buds culminating in ventral prostate agenesis. The genes and signaling pathways affected by TCDD that are responsible for disrupting prostate development are largely unknown. Here we show that treatment of urogenital sinus (UGS) organ cultures with known inhibitors of canonical Wnt signaling also inhibits prostatic bud formation. In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of TCDD on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD. Thus, the TCDD-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway. This study focuses on determining whether treatment of TCDD-exposed UGS organ cultures with RSPO2 and/or RSPO3 is capable of rescuing the inhibitory effects of TCDD on canonical Wnt signaling and prostatic bud formation. We discovered that each RSPO alone or in combination partially rescues TCDD inhibition of both canonical Wnt signaling and prostatic bud formation. PMID:23429912

TCDD inhibition of canonical Wnt signaling disrupts prostatic bud formation in mouse urogenital sinus.

PubMed

Branam, Amanda M; Davis, Nicole M; Moore, Robert W; Schneider, Andrew J; Vezina, Chad M; Peterson, Richard E

2013-05-01

In mice, in utero exposure to 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) reduces the number of dorsolateral prostatic buds resulting in a smaller dorsolateral prostate and prevents formation of ventral buds culminating in ventral prostate agenesis. The genes and signaling pathways affected by TCDD that are responsible for disrupting prostate development are largely unknown. Here we show that treatment of urogenital sinus (UGS) organ cultures with known inhibitors of canonical Wnt signaling also inhibits prostatic bud formation. In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of TCDD on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD. Thus, the TCDD-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway. This study focuses on determining whether treatment of TCDD-exposed UGS organ cultures with RSPO2 and/or RSPO3 is capable of rescuing the inhibitory effects of TCDD on canonical Wnt signaling and prostatic bud formation. We discovered that each RSPO alone or in combination partially rescues TCDD inhibition of both canonical Wnt signaling and prostatic bud formation.

Critical non-Abelian vortex in four dimensions and little string theory

NASA Astrophysics Data System (ADS)

Shifman, M.; Yung, A.

2017-08-01

As was shown recently, non-Abelian vortex strings supported in four-dimensional N =2 supersymmetric QCD with the U(2) gauge group and Nf=4 quark multiplets (flavors) become critical superstrings. In addition to the translational moduli, non-Abelian strings under consideration carry six orientational and size moduli. Together, they form a ten-dimensional target space required for a superstring to be critical. The target space of the string sigma model is a product of the flat four-dimensional space and a Calabi-Yau noncompact threefold, namely, the conifold. We study closed string states which emerge in four dimensions and identify them with hadrons of four-dimensional N =2 QCD. One massless state was found previously; it emerges as a massless hypermultiplet associated with the deformation of the complex structure of the conifold. In this paper, we find a number of massive states. To this end, we exploit the approach used in LST little string theory, namely, the equivalence between the critical string on the conifold and noncritical c =1 string with the Liouville field and a compact scalar at the self-dual radius. The states we find carry "baryonic" charge (its definition differs from standard). We interpret them as "monopole necklaces" formed (at strong coupling) by the closed string with confined monopoles attached.

Non-Markovian quantum Brownian motion in one dimension in electric fields

NASA Astrophysics Data System (ADS)

Shen, H. Z.; Su, S. L.; Zhou, Y. H.; Yi, X. X.

2018-04-01

Quantum Brownian motion is the random motion of quantum particles suspended in a field (or an effective field) resulting from their collision with fast-moving modes in the field. It provides us with a fundamental model to understand various physical features concerning open systems in chemistry, condensed-matter physics, biophysics, and optomechanics. In this paper, without either the Born-Markovian or rotating-wave approximation, we derive a master equation for a charged-Brownian particle in one dimension coupled with a thermal reservoir in electric fields. The effect of the reservoir and the electric fields is manifested as time-dependent coefficients and coherent terms, respectively, in the master equation. The two-photon correlation between the Brownian particle and the reservoir can induce nontrivial squeezing dynamics to the particle. We derive a current equation including the source from the driving fields, transient current from the system flowing into the environment, and the two-photon current caused by the non-rotating-wave term. The presented results then are compared with that given by the rotating-wave approximation in the weak-coupling limit, and these results are extended to a more general quantum network involving an arbitrary number of coupled-Brownian particles. The presented formalism might open a way to better understand exactly the non-Markovian quantum network.

The MST/Hippo Pathway and Cell Death: A Non-Canonical Affair

PubMed Central

Fallahi, Emma; O’Driscoll, Niamh A.; Matallanas, David

2016-01-01

The MST/Hippo signalling pathway was first described over a decade ago in Drosophila melanogaster and the core of the pathway is evolutionary conserved in mammals. The mammalian MST/Hippo pathway regulates organ size, cell proliferation and cell death. In addition, it has been shown to play a central role in the regulation of cellular homeostasis and it is commonly deregulated in human tumours. The delineation of the canonical pathway resembles the behaviour of the Hippo pathway in the fly where the activation of the core kinases of the pathway prevents the proliferative signal mediated by the key effector of the pathway YAP. Nevertheless, several lines of evidence support the idea that the mammalian MST/Hippo pathway has acquired new features during evolution, including different regulators and effectors, crosstalk with other essential signalling pathways involved in cellular homeostasis and the ability to actively trigger cell death. Here we describe the current knowledge of the mechanisms that mediate MST/Hippo dependent cell death, especially apoptosis. We include evidence for the existence of complex signalling networks where the core proteins of the pathway play a central role in controlling the balance between survival and cell death. Finally, we discuss the possible involvement of these signalling networks in several human diseases such as cancer, diabetes and neurodegenerative disorders. PMID:27322327

Normalization as a canonical neural computation

PubMed Central

Carandini, Matteo; Heeger, David J.

2012-01-01

There is increasing evidence that the brain relies on a set of canonical neural computations, repeating them across brain regions and modalities to apply similar operations to different problems. A promising candidate for such a computation is normalization, in which the responses of neurons are divided by a common factor that typically includes the summed activity of a pool of neurons. Normalization was developed to explain responses in the primary visual cortex and is now thought to operate throughout the visual system, and in many other sensory modalities and brain regions. Normalization may underlie operations such as the representation of odours, the modulatory effects of visual attention, the encoding of value and the integration of multisensory information. Its presence in such a diversity of neural systems in multiple species, from invertebrates to mammals, suggests that it serves as a canonical neural computation. PMID:22108672

A Study on the Oral Disfluencies Developmental Traits of EFL Students--A Report Based on Canonical Correlation Analysis

ERIC Educational Resources Information Center

Gao, Ying; Du, Wanyi

2013-01-01

This paper traces 9 non-English major EFL students and collects their oral productions in 4 successive oral exams in 2 years. The canonical correlation analysis approach of SPSS is adopted to study the disfluencies developmental traits under the influence of language acquisition development. We find that as language acquisition develops, the total…

Paul Weiss and the genesis of canonical quantization

NASA Astrophysics Data System (ADS)

Rickles, Dean; Blum, Alexander

2015-12-01

This paper describes the life and work of a figure who, we argue, was of primary importance during the early years of field quantisation and (albeit more indirectly) quantum gravity. A student of Dirac and Born, he was interned in Canada during the second world war as an enemy alien and after his release never seemed to regain a good foothold in physics, identifying thereafter as a mathematician. He developed a general method of quantizing (linear and non-linear) field theories based on the parameters labelling an arbitrary hypersurface. This method (the `parameter formalism' often attributed to Dirac), though later discarded, was employed (and viewed at the time as an extremely important tool) by the leading figures associated with canonical quantum gravity: Dirac, Pirani and Schild, Bergmann, DeWitt, and others. We argue that he deserves wider recognition for this and other innovations.

Shannon Entropy of the Canonical Genetic Code

NASA Astrophysics Data System (ADS)

Nemzer, Louis

The probability that a non-synonymous point mutation in DNA will adversely affect the functionality of the resultant protein is greatly reduced if the substitution is conservative. In that case, the amino acid coded by the mutated codon has similar physico-chemical properties to the original. Many simplified alphabets, which group the 20 common amino acids into families, have been proposed. To evaluate these schema objectively, we introduce a novel, quantitative method based on the inherent redundancy in the canonical genetic code. By calculating the Shannon information entropy carried by 1- or 2-bit messages, groupings that best leverage the robustness of the code are identified. The relative importance of properties related to protein folding - like hydropathy and size - and function, including side-chain acidity, can also be estimated. In addition, this approach allows us to quantify the average information value of nucleotide codon positions, and explore the physiological basis for distinguishing between transition and transversion mutations. Supported by NSU PFRDG Grant #335347.

A canonical state-space representation for SISO systems using multipoint Jordan CFE. [Continued-Fraction Expansion

NASA Technical Reports Server (NTRS)

Hwang, Chyi; Guo, Tong-Yi; Shieh, Leang-San

1991-01-01

A canonical state-space realization based on the multipoint Jordan continued-fraction expansion (CFE) is presented for single-input-single-output (SISO) systems. The similarity transformation matrix which relates the new canonical form to the phase-variable canonical form is also derived. The presented canonical state-space representation is particularly attractive for the application of SISO system theory in which a reduced-dimensional time-domain model is necessary.

A canonical theory of dynamic decision-making.

PubMed

Fox, John; Cooper, Richard P; Glasspool, David W

2013-01-01

Decision-making behavior is studied in many very different fields, from medicine and economics to psychology and neuroscience, with major contributions from mathematics and statistics, computer science, AI, and other technical disciplines. However the conceptualization of what decision-making is and methods for studying it vary greatly and this has resulted in fragmentation of the field. A theory that can accommodate various perspectives may facilitate interdisciplinary working. We present such a theory in which decision-making is articulated as a set of canonical functions that are sufficiently general to accommodate diverse viewpoints, yet sufficiently precise that they can be instantiated in different ways for specific theoretical or practical purposes. The canons cover the whole decision cycle, from the framing of a decision based on the goals, beliefs, and background knowledge of the decision-maker to the formulation of decision options, establishing preferences over them, and making commitments. Commitments can lead to the initiation of new decisions and any step in the cycle can incorporate reasoning about previous decisions and the rationales for them, and lead to revising or abandoning existing commitments. The theory situates decision-making with respect to other high-level cognitive capabilities like problem solving, planning, and collaborative decision-making. The canonical approach is assessed in three domains: cognitive and neuropsychology, artificial intelligence, and decision engineering.

A Canonical Theory of Dynamic Decision-Making

PubMed Central

Fox, John; Cooper, Richard P.; Glasspool, David W.

2012-01-01

Decision-making behavior is studied in many very different fields, from medicine and economics to psychology and neuroscience, with major contributions from mathematics and statistics, computer science, AI, and other technical disciplines. However the conceptualization of what decision-making is and methods for studying it vary greatly and this has resulted in fragmentation of the field. A theory that can accommodate various perspectives may facilitate interdisciplinary working. We present such a theory in which decision-making is articulated as a set of canonical functions that are sufficiently general to accommodate diverse viewpoints, yet sufficiently precise that they can be instantiated in different ways for specific theoretical or practical purposes. The canons cover the whole decision cycle, from the framing of a decision based on the goals, beliefs, and background knowledge of the decision-maker to the formulation of decision options, establishing preferences over them, and making commitments. Commitments can lead to the initiation of new decisions and any step in the cycle can incorporate reasoning about previous decisions and the rationales for them, and lead to revising or abandoning existing commitments. The theory situates decision-making with respect to other high-level cognitive capabilities like problem solving, planning, and collaborative decision-making. The canonical approach is assessed in three domains: cognitive and neuropsychology, artificial intelligence, and decision engineering. PMID:23565100

Revisiting non-Gaussianity from non-attractor inflation models

NASA Astrophysics Data System (ADS)

Cai, Yi-Fu; Chen, Xingang; Namjoo, Mohammad Hossein; Sasaki, Misao; Wang, Dong-Gang; Wang, Ziwei

2018-05-01

Non-attractor inflation is known as the only single field inflationary scenario that can violate non-Gaussianity consistency relation with the Bunch-Davies vacuum state and generate large local non-Gaussianity. However, it is also known that the non-attractor inflation by itself is incomplete and should be followed by a phase of slow-roll attractor. Moreover, there is a transition process between these two phases. In the past literature, this transition was approximated as instant and the evolution of non-Gaussianity in this phase was not fully studied. In this paper, we follow the detailed evolution of the non-Gaussianity through the transition phase into the slow-roll attractor phase, considering different types of transition. We find that the transition process has important effect on the size of the local non-Gaussianity. We first compute the net contribution of the non-Gaussianities at the end of inflation in canonical non-attractor models. If the curvature perturbations keep evolving during the transition—such as in the case of smooth transition or some sharp transition scenarios—the Script O(1) local non-Gaussianity generated in the non-attractor phase can be completely erased by the subsequent evolution, although the consistency relation remains violated. In extremal cases of sharp transition where the super-horizon modes freeze immediately right after the end of the non-attractor phase, the original non-attractor result can be recovered. We also study models with non-canonical kinetic terms, and find that the transition can typically contribute a suppression factor in the squeezed bispectrum, but the final local non-Gaussianity can still be made parametrically large.

Issues in measure-preserving three dimensional flow integrators: Self-adjointness, reversibility, and non-uniform time stepping

DOE PAGES

Finn, John M.

2015-03-01

Properties of integration schemes for solenoidal fields in three dimensions are studied, with a focus on integrating magnetic field lines in a plasma using adaptive time stepping. It is shown that implicit midpoint (IM) and a scheme we call three-dimensional leapfrog (LF) can do a good job (in the sense of preserving KAM tori) of integrating fields that are reversible, or (for LF) have a 'special divergence-free' property. We review the notion of a self-adjoint scheme, showing that such schemes are at least second order accurate and can always be formed by composing an arbitrary scheme with its adjoint. Wemore » also review the concept of reversibility, showing that a reversible but not exactly volume-preserving scheme can lead to a fractal invariant measure in a chaotic region, although this property may not often be observable. We also show numerical results indicating that the IM and LF schemes can fail to preserve KAM tori when the reversibility property (and the SDF property for LF) of the field is broken. We discuss extensions to measure preserving flows, the integration of magnetic field lines in a plasma and the integration of rays for several plasma waves. The main new result of this paper relates to non-uniform time stepping for volume-preserving flows. We investigate two potential schemes, both based on the general method of Ref. [11], in which the flow is integrated in split time steps, each Hamiltonian in two dimensions. The first scheme is an extension of the method of extended phase space, a well-proven method of symplectic integration with non-uniform time steps. This method is found not to work, and an explanation is given. The second method investigated is a method based on transformation to canonical variables for the two split-step Hamiltonian systems. This method, which is related to the method of non-canonical generating functions of Ref. [35], appears to work very well.« less

Issues in measure-preserving three dimensional flow integrators: Self-adjointness, reversibility, and non-uniform time stepping

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

Finn, John M., E-mail: finn@lanl.gov

2015-03-15

Properties of integration schemes for solenoidal fields in three dimensions are studied, with a focus on integrating magnetic field lines in a plasma using adaptive time stepping. It is shown that implicit midpoint (IM) and a scheme we call three-dimensional leapfrog (LF) can do a good job (in the sense of preserving KAM tori) of integrating fields that are reversible, or (for LF) have a “special divergence-free” (SDF) property. We review the notion of a self-adjoint scheme, showing that such schemes are at least second order accurate and can always be formed by composing an arbitrary scheme with its adjoint.more » We also review the concept of reversibility, showing that a reversible but not exactly volume-preserving scheme can lead to a fractal invariant measure in a chaotic region, although this property may not often be observable. We also show numerical results indicating that the IM and LF schemes can fail to preserve KAM tori when the reversibility property (and the SDF property for LF) of the field is broken. We discuss extensions to measure preserving flows, the integration of magnetic field lines in a plasma and the integration of rays for several plasma waves. The main new result of this paper relates to non-uniform time stepping for volume-preserving flows. We investigate two potential schemes, both based on the general method of Feng and Shang [Numer. Math. 71, 451 (1995)], in which the flow is integrated in split time steps, each Hamiltonian in two dimensions. The first scheme is an extension of the method of extended phase space, a well-proven method of symplectic integration with non-uniform time steps. This method is found not to work, and an explanation is given. The second method investigated is a method based on transformation to canonical variables for the two split-step Hamiltonian systems. This method, which is related to the method of non-canonical generating functions of Richardson and Finn [Plasma Phys. Controlled Fusion 54, 014004

Canonical and Novel Non-Canonical Cholinergic Agonists Inhibit ATP-Induced Release of Monocytic Interleukin-1β via Different Combinations of Nicotinic Acetylcholine Receptor Subunits α7, α9 and α10

PubMed Central

Zakrzewicz, Anna; Richter, Katrin; Agné, Alisa; Wilker, Sigrid; Siebers, Kathrin; Fink, Bijan; Krasteva-Christ, Gabriela; Althaus, Mike; Padberg, Winfried; Hone, Arik J.; McIntosh, J. Michael; Grau, Veronika

2017-01-01

Recently, we discovered a cholinergic mechanism that inhibits the adenosine triphosphate (ATP)-dependent release of interleukin-1β (IL-1β) by human monocytes via nicotinic acetylcholine receptors (nAChRs) composed of α7, α9 and/or α10 subunits. Furthermore, we identified phosphocholine (PC) and dipalmitoylphosphatidylcholine (DPPC) as novel nicotinic agonists that elicit metabotropic activity at monocytic nAChR. Interestingly, PC does not provoke ion channel responses at conventional nAChRs composed of subunits α9 and α10. The purpose of this study is to determine the composition of nAChRs necessary for nicotinic signaling in monocytic cells and to test the hypothesis that common metabolites of phosphatidylcholines, lysophosphatidylcholine (LPC) and glycerophosphocholine (G-PC), function as nAChR agonists. In peripheral blood mononuclear cells from nAChR gene-deficient mice, we demonstrated that inhibition of ATP-dependent release of IL-1β by acetylcholine (ACh), nicotine and PC depends on subunits α7, α9 and α10. Using a panel of nAChR antagonists and siRNA technology, we confirmed the involvement of these subunits in the control of IL-1β release in the human monocytic cell line U937. Furthermore, we showed that LPC (C16:0) and G-PC efficiently inhibit ATP-dependent release of IL-1β. Of note, the inhibitory effects mediated by LPC and G-PC depend on nAChR subunits α9 and α10, but only to a small degree on α7. In Xenopus laevis oocytes heterologously expressing different combinations of human α7, α9 or α10 subunits, ACh induced canonical ion channel activity, whereas LPC, G-PC and PC did not. In conclusion, we demonstrate that canonical nicotinic agonists and PC elicit metabotropic nAChR activity in monocytes via interaction of nAChR subunits α7, α9 and α10. For the metabotropic signaling of LPC and G-PC, nAChR subunits α9 and α10 are needed, whereas α7 is virtually dispensable. Furthermore, molecules bearing a PC group in general seem to

Logical-rules and the classification of integral dimensions: individual differences in the processing of arbitrary dimensions

PubMed Central

Blunden, Anthea G.; Wang, Tony; Griffiths, David W.; Little, Daniel R.

2015-01-01

A variety of converging operations demonstrate key differences between separable dimensions, which can be analyzed independently, and integral dimensions, which are processed in a non-analytic fashion. A recent investigation of response time distributions, applying a set of logical rule-based models, demonstrated that integral dimensions are pooled into a single coactive processing channel, in contrast to separable dimensions, which are processed in multiple, independent processing channels. This paper examines the claim that arbitrary dimensions created by factorially morphing four faces are processed in an integral manner. In two experiments, 16 participants completed a categorization task in which either upright or inverted morph stimuli were classified in a speeded fashion. Analyses focused on contrasting different assumptions about the psychological representation of the stimuli, perceptual and decisional separability, and the processing architecture. We report consistent individual differences which demonstrate a mixture of some observers who demonstrate coactive processing with other observers who process the dimensions in a parallel self-terminating manner. PMID:25620941

37 CFR 10.21 - Canon 1.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canon 1. 10.21 Section 10.21 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

37 CFR 10.46 - Canon 3.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canon 3. 10.46 Section 10.46 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

37 CFR 10.21 - Canon 1.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canon 1. 10.21 Section 10.21 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

37 CFR 10.30 - Canon 2.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canon 2. 10.30 Section 10.30 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

37 CFR 10.56 - Canon 4.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canon 4. 10.56 Section 10.56 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

37 CFR 10.46 - Canon 3.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canon 3. 10.46 Section 10.46 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

37 CFR 10.30 - Canon 2.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canon 2. 10.30 Section 10.30 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

37 CFR 10.56 - Canon 4.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canon 4. 10.56 Section 10.56 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

37 CFR 10.61 - Canon 5.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canon 5. 10.61 Section 10.61 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark Office Code of Professional...

Traditional Herbal Remedies for Burn Wound Healing in Canon of Avicenna

PubMed Central

Aliasl, Jale; Khoshzaban, Fariba

2013-01-01

Burns are a worldwide problem. The incidence of severe burns has been higher than the combined incidence of tuberculosis and HIV infections. Throughout history there have been many different treatments prescribed for burns. The Canon is the masterpiece of Avicenna’s medical books. The Canon includes a description of 785 simple drugs. Avicenna believed in burn treatment, which follows two goals. The first goal is prevention of blistering and the second goal is treatment of the burn wound after it has created blisters, cold drugs are suitable for the first goal and dry drugs with moderate in cold and hot qualities are better for second goal, this study reviewed remedies for burn wounds in Canon.

Non-Abelian fractional quantum Hall states for hard-core bosons in one dimension

NASA Astrophysics Data System (ADS)

Paredes, Belén

2012-05-01

I present a family of one-dimensional bosonic liquids analogous to non-Abelian fractional quantum Hall states. A new quantum number is introduced to characterize these liquids, the chiral momentum, which differs from the usual angular or linear momentum in one dimension. As their two-dimensional counterparts, these liquids minimize a k-body hard-core interaction with the minimum total chiral momentum. They exhibit global order, with a hidden organization of the particles in k identical copies of a one-dimensional Laughlin state. For k=2 the state is a p-wave paired phase corresponding to the Pfaffian quantum Hall state. By imposing conservation of the total chiral momentum, an exact parent Hamiltonian is derived which involves long-range tunneling and interaction processes with an amplitude decaying with the chord distance. This family of non-Abelian liquids is shown to be in formal correspondence with a family of spin-(k)/(2) liquids which are total singlets made out of k indistinguishable resonating valence bond states. The corresponding spin Hamiltonians are obtained.

Neferine augments therapeutic efficacy of cisplatin through ROS- mediated non-canonical autophagy in human lung adenocarcinoma (A549 cells).

PubMed

Kalai Selvi, Sivalingam; Vinoth, Amirthalingam; Varadharajan, Thiyagarajan; Weng, Ching Feng; Vijaya Padma, Viswanadha

2017-05-01

Combination of dietary components with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses. Neferine, major bisbenzylisoquinoline alkaloid isolated from the seed embryo of Nelumbo nucifera (Lotus). In the present study, we investigated the efficacy of the combinatorial regimen of neferine and cisplatin compared to cisplatin high dose in human lung adenocarcinoma (A549) cells. Co-treatment with neferine enhanced cisplatin-induced autophagy in A549 cells was accompanied by Acidic vesicular accumulation (AVO), enhanced generation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH), down regulation of PI3K/AKT/mTOR pathway, conversion of LC3B-I to LC3B-II. This enhanced autophagy developed via a non-canonical mechanism that did not require Beclin-1, PI3KCIII. In conclusion, these results suggest that neferine enhances cisplatin -induced autophagic cancer cell death through downregulation of PI3K/Akt/mTOR signaling pro-survival pathway and ROS- mediated Beclin-1 and PI3K CIII independent autophagy in human lung adenocarcinoma (A549 cells). Copyright © 2017 Elsevier Ltd. All rights reserved.

Body Aesthetic Preference in Preschoolers and Attraction to Canons Violation: An Exploratory Study.

PubMed

Di Dio, Cinzia; Berchio, Cristina; Massaro, Davide; Lombardi, Elisabetta; Gilli, Gabriella; Marchetti, Antonella

2017-01-01

Sensitivity to canons of beauty as represented in the human body-and as typically defined in the Western Culture-has been poorly studied in children. Current literature shows that infants as young as about three months are sensitive to the human body structure and its parts. Using a sample of 54 three- to five-year-old children, the present study investigated preference for drawings representing the "canonical" body structure, contrasting these with drawings showing the same bodies, but where the relation between trunk and legs was modified. It was hypothesized that preference for the canonical body structures would emerge as early as three years, increasing with age. Results only partially supported the hypothesis: while three-year-olds showed a significant preference for the canonical body structures as predicted, a significant preference reversal was found for the four-year-olds, with a tendency to return to preferring the canonical body at five years. The results are discussed in light of research findings associated with developmental theories hallmarking visual art perception in children.

Creativity and Brain-Functioning in Product Development Engineers: A Canonical Correlation Analysis

ERIC Educational Resources Information Center

Travis, Frederick; Lagrosen, Yvonne

2014-01-01

This study used canonical correlation analysis to explore the relation among scores on the Torrance test of figural and verbal creativity and demographic, psychological and physiological measures in Swedish product-development engineers. The first canonical variate included figural and verbal flexibility and originality as dependent measures and…

Drinfeld-Sokolov reduction in quantum algebras: canonical form of generating matrices

NASA Astrophysics Data System (ADS)

Gurevich, Dimitri; Saponov, Pavel; Talalaev, Dmitry

2018-04-01

We define the second canonical forms for the generating matrices of the Reflection Equation algebras and the braided Yangians, associated with all even skew-invertible involutive and Hecke symmetries. By using the Cayley-Hamilton identities for these matrices, we show that they are similar to their canonical forms in the sense of Chervov and Talalaev (J Math Sci (NY) 158:904-911, 2008).

Histories approach to general relativity: I. The spacetime character of the canonical description

NASA Astrophysics Data System (ADS)

Savvidou, Ntina

2004-01-01

The problem of time in canonical quantum gravity is related to the fact that the canonical description is based on the prior choice of a spacelike foliation, hence making a reference to a spacetime metric. However, the metric is expected to be a dynamical, fluctuating quantity in quantum gravity. We show how this problem can be solved in the histories formulation of general relativity. We implement the 3 + 1 decomposition using metric-dependent foliations which remain spacelike with respect to all possible Lorentzian metrics. This allows us to find an explicit relation of covariant and canonical quantities which preserves the spacetime character of the canonical description. In this new construction, we also have the coexistence of the spacetime diffeomorphisms group, Diff(M), and the Dirac algebra of constraints.

Fibrin-Enhanced Canonical Wnt Signaling Directs Plasminogen Expression in Cementoblasts

PubMed Central

Rahman, Saeed Ur; Ryoo, Hyun-Mo

2017-01-01

Cementum is a mineralized layer on the tooth’s root surface and facilitates the biomechanical anchoring of fibrous connective tissues as a part of tooth-supportive complexes. Previously, we observed that OCCM30 cementoblasts cultured on fibrin matrices underwent apoptosis due to fibrin degradation through the expression of proteases. Here, we demonstrated that OCCM30 on fibrin matrices (OCCM30-fibrin) enhanced canonical Wnt signaling, which directed to plasminogen expression. The OCCM30-fibrin showed higher levels of Wnt3a expression, nuclear translocation of β-catenin, and T-cell factor (TCF) optimal motif (TOP) reporter activity than the cells on tissue culture dishes (OCCM30-TCD), indicating that the OCCM30-fibrin enhanced canonical Wnt/β-catenin signaling. Also, OCCM30-fibrin expressed biomineralization-associated markers at higher levels than OCCM30-TCD, of which levels were further increased with LiCl, a Wnt signaling activator. The OCCM30 cementoblasts simultaneously showed that high levels of plasminogen, a critical component of fibrinolysis, were expressed in the OCCM30-fibrin. Activation of canonical Wnt signaling with LiCl treatment or with forced lymphoid enhancer factor 1 (LEF1)-expression increased the expression of plasminogen. On the contrary, the inhibition of canonical Wnt signaling with siRNAs against Wnt3a or β-catenin abrogated fibrin-enhanced plasminogen expression. Furthermore, there are three conserved putative response elements for the LEF1/β-catenin complex in the plasminogen proximal promoter regions (−900 to +54). Site-directed mutations and chromatin immunoprecipitation indicated that canonical Wnt signaling directed plasminogen expression. Taken together, this study suggests that fibrin-based materials can modulate functional periodontal formations in controlling cementoblast differentiation and fibrin degradation. PMID:29120400

Algorithmic transformation of multi-loop master integrals to a canonical basis with CANONICA

NASA Astrophysics Data System (ADS)

Meyer, Christoph

2018-01-01

The integration of differential equations of Feynman integrals can be greatly facilitated by using a canonical basis. This paper presents the Mathematica package CANONICA, which implements a recently developed algorithm to automatize the transformation to a canonical basis. This represents the first publicly available implementation suitable for differential equations depending on multiple scales. In addition to the presentation of the package, this paper extends the description of some aspects of the algorithm, including a proof of the uniqueness of canonical forms up to constant transformations.

Kernel canonical-correlation Granger causality for multiple time series

NASA Astrophysics Data System (ADS)

Wu, Guorong; Duan, Xujun; Liao, Wei; Gao, Qing; Chen, Huafu

2011-04-01

Canonical-correlation analysis as a multivariate statistical technique has been applied to multivariate Granger causality analysis to infer information flow in complex systems. It shows unique appeal and great superiority over the traditional vector autoregressive method, due to the simplified procedure that detects causal interaction between multiple time series, and the avoidance of potential model estimation problems. However, it is limited to the linear case. Here, we extend the framework of canonical correlation to include the estimation of multivariate nonlinear Granger causality for drawing inference about directed interaction. Its feasibility and effectiveness are verified on simulated data.

Contraction of high eccentricity satellite orbits using uniformly regular KS canonical elements with oblate diurnally varying atmosphere.

NASA Astrophysics Data System (ADS)

Raj, Xavier James

2016-07-01

Accurate orbit prediction of an artificial satellite under the influence of air drag is one of the most difficult and untraceable problem in orbital dynamics. The orbital decay of these satellites is mainly controlled by the atmospheric drag effects. The effects of the atmosphere are difficult to determine, since the atmospheric density undergoes large fluctuations. The classical Newtonian equations of motion, which is non linear is not suitable for long-term integration. Many transformations have emerged in the literature to stabilize the equations of motion either to reduce the accumulation of local numerical errors or allowing the use of large integration step sizes, or both in the transformed space. One such transformation is known as KS transformation by Kustaanheimo and Stiefel, who regularized the nonlinear Kepler equations of motion and reduced it into linear differential equations of a harmonic oscillator of constant frequency. The method of KS total energy element equations has been found to be a very powerful method for obtaining numerical as well as analytical solution with respect to any type of perturbing forces, as the equations are less sensitive to round off and truncation errors. The uniformly regular KS canonical equations are a particular canonical form of the KS differential equations, where all the ten KS Canonical elements αi and βi are constant for unperturbed motion. These equations permit the uniform formulation of the basic laws of elliptic, parabolic and hyperbolic motion. Using these equations, developed analytical solution for short term orbit predictions with respect to Earth's zonal harmonic terms J2, J3, J4. Further, these equations were utilized to include the canonical forces and analytical theories with air drag were developed for low eccentricity orbits (e < 0.2) with different atmospheric models. Using uniformly regular KS canonical elements developed analytical theory for high eccentricity (e > 0.2) orbits by assuming the

Efficient replication, and evolution of Sindbis virus genomes with non-canonical 3'A/U-rich elements (NC3ARE) in neonatal mice.

PubMed

James, Frederick D; Hietala, Katie A; Eldar, Dganit; Guess, Tiffany E; Cone, Cecil; Mundell, Nathan A; Mundall, Nathan; Barnett, Joey V; Raju, Ramaswamy

2007-12-01

Sindbis virus (SIN) is a mosquito-transmitted animal RNA virus. We previously reported that SIN genomes lacking a canonical 19 nt 3'CSE undergo novel repair processes in BHK cells to generate a library of stable atypical SIN genomes with non-canonical 3'A/U-rich elements (NC3AREs) adjacent to the 3' poly(A) tail [1]. To determine the stability and evolutionary pressures on the SIN genomes with NC3AREs to regain a 3'CSE, five representative SIN isolates and a wild type SIN were tested in newborn mice. The key findings of this study are: (a) all six SIN isolates, including those that have extensive NC3AREs in the 3'NTRs, replicate well and produce high titer viremia in newborn mice; (b) 7-9 successive passages of these isolates in newborn mice produced comparable levels of viremia; (c) while all isolates produced only small-sized plaques during primary infection in animals, both small- and large-sized plaques were generated in all other passages; (d) polymerase stuttering occurs on select 3' oligo(U) motifs to add more U residues within the NC3AREs; (e) the S3-8 isolate with an internal UAUUU motif in the 3'poly(A) tail maintains this element even after 9 passages in animals; (f) despite differences in 3'NTRs and variable tissue distribution, all SIN isolates appear to produce similar tissue pathology in infected animals. Competition experiments with wt SIN and atypical SIN isolates in BHK cells show dominance of wt SIN. As shown for BHK cells in culture, the 3'CSE of the SIN genome is not required for virus replication and genome stability in live animals. Since the NC3AREs of atypical SIN genomes are not specific to SIN replicases, alternate RNA motifs of alphavirus genome must confer specificity in template selection. These studies fulfill the need to confirm the long-term viability of atypical SIN genomes in newborn mice and offer a basis for exploring the use of atypical SIN genomes in biotechnology.

Temperature extrapolation of multicomponent grand canonical free energy landscapes

NASA Astrophysics Data System (ADS)

Mahynski, Nathan A.; Errington, Jeffrey R.; Shen, Vincent K.

2017-08-01

We derive a method for extrapolating the grand canonical free energy landscape of a multicomponent fluid system from one temperature to another. Previously, we introduced this statistical mechanical framework for the case where kinetic energy contributions to the classical partition function were neglected for simplicity [N. A. Mahynski et al., J. Chem. Phys. 146, 074101 (2017)]. Here, we generalize the derivation to admit these contributions in order to explicitly illustrate the differences that result. Specifically, we show how factoring out kinetic energy effects a priori, in order to consider only the configurational partition function, leads to simpler mathematical expressions that tend to produce more accurate extrapolations than when these effects are included. We demonstrate this by comparing and contrasting these two approaches for the simple cases of an ideal gas and a non-ideal, square-well fluid.

PAPERCLIP identifies microRNA targets and a role of CstF64/64tau in promoting non-canonical poly(A) site usage

PubMed Central

Hwang, Hun-Way; Park, Christopher Y.; Goodarzi, Hani; Fak, John J.; Mele, Aldo; Moore, Michael J.; Saito, Yuhki; Darnell, Robert B.

2016-01-01

Accurate and precise annotation of the 3′ untranslated regions (3′ UTRs) is critical in understanding how mRNAs are regulated by microRNAs (miRNAs) and RNA-binding proteins (RBPs). Here we describe a method, PAPERCLIP (Poly(A) binding Protein-mediated mRNA 3′ End Retrieval by CrossLinking ImmunoPrecipitation), which shows high specificity for the mRNA 3′ ends and compares favorably to existing 3′ end mapping methods. PAPERCLIP uncovers a previously unrecognized role of CstF64/64tau in promoting the usage of a selected group of non-canonical poly(A) sites, the majority of them containing a downstream GUKKU motif. Furthermore, in mouse brain, PAPERCLIP discovers extended 3′ UTR sequences harboring functional miRNA binding sites and reveals developmentally regulated APA shifts including one in Atp2b2 that is evolutionarily conserved in human and results in a gain of a functional binding site of miR-137. PAPERCLIP provides a powerful tool to decipher post-transcriptional regulation of mRNAs through APA in vivo. PMID:27050522

Toddlers Default to Canonical Surface-to-Meaning Mapping When Learning Verbs

PubMed Central

Dautriche, Isabelle; Cristia, Alejandrina; Brusini, Perrine; Yuan, Sylvia; Fisher, Cynthia; Christophe, Anne

2013-01-01

Previous work has shown that toddlers readily encode each noun in the sentence as a distinct argument of the verb. However, languages allow multiple mappings between form and meaning which do not fit this canonical format. Two experiments examined French 28-month-olds’ interpretation of right-dislocated sentences (nouni-verb, nouni) where the presence of clear, language-specific cues should block such a canonical mapping. Toddlers (N = 96) interpreted novel verbs embedded in these sentences as transitive, disregarding prosodic cues to dislocation (Experiment 1) but correctly interpreted right-dislocated sentences containing well-known verbs (Experiment 2). These results suggest that toddlers can integrate multiple cues in ideal conditions, but default to canonical surface-to-meaning mapping when extracting structural information about novel verbs in semantically impoverished conditions. PMID:24117408

Stabilizing canonical-ensemble calculations in the auxiliary-field Monte Carlo method

NASA Astrophysics Data System (ADS)

Gilbreth, C. N.; Alhassid, Y.

2015-03-01

Quantum Monte Carlo methods are powerful techniques for studying strongly interacting Fermi systems. However, implementing these methods on computers with finite-precision arithmetic requires careful attention to numerical stability. In the auxiliary-field Monte Carlo (AFMC) method, low-temperature or large-model-space calculations require numerically stabilized matrix multiplication. When adapting methods used in the grand-canonical ensemble to the canonical ensemble of fixed particle number, the numerical stabilization increases the number of required floating-point operations for computing observables by a factor of the size of the single-particle model space, and thus can greatly limit the systems that can be studied. We describe an improved method for stabilizing canonical-ensemble calculations in AFMC that exhibits better scaling, and present numerical tests that demonstrate the accuracy and improved performance of the method.

What Is the Canon in American Politics? Analyses of Core Graduate Syllabi

ERIC Educational Resources Information Center

Diament, Sean M.; Howat, Adam J.; Lacombe, Matthew J.

2017-01-01

Many core graduate-level seminars claim to expose students to their discipline's "canon." The contents of this canon, however, can and do differ across departments and instructors. This project employs a survey of core American politics PhD seminar syllabi at highly ranked universities to construct a systematic account of the American…

Canonical wnt signaling regulates hematopoiesis in a dosage-dependent fashion.

PubMed

Luis, Tiago C; Naber, Brigitta A E; Roozen, Paul P C; Brugman, Martijn H; de Haas, Edwin F E; Ghazvini, Mehrnaz; Fibbe, Willem E; van Dongen, Jacques J M; Fodde, Riccardo; Staal, Frank J T

2011-10-04

Canonical Wnt signaling has been implicated in the regulation of hematopoiesis. By employing a Wnt-reporter mouse, we observed that Wnt signaling is differentially activated during hematopoiesis, suggesting an important regulatory role for specific Wnt signaling levels. To investigate whether canonical Wnt signaling regulates hematopoiesis in a dosage-dependent fashion, we analyzed the effect of different mutations in the Adenomatous polyposis coli gene (Apc), a negative modulator of the canonical Wnt pathway. By combining different targeted hypomorphic alleles and a conditional deletion allele of Apc, a gradient of five different Wnt signaling levels was obtained in vivo. We here show that different, lineage-specific Wnt dosages regulate hematopoietic stem cells (HSCs), myeloid precursors, and T lymphoid precursors during hematopoiesis. Differential, lineage-specific optimal Wnt dosages provide a unifying concept that explains the differences reported among inducible gain-of-function approaches, leading to either HSC expansion or depletion of the HSC pool. Copyright © 2011 Elsevier Inc. All rights reserved.

Reading Canonical Texts in Multicultural Classrooms

ERIC Educational Resources Information Center

Shah, Mehrunissa

2013-01-01

This essay explores the complexity of imposing texts that are considered part of the English literary canon on students from multicultural backgrounds. It considers the rhetoric of the coalition government, in the recent drive to emphasize the importance of the literary heritage and return to English culture and how its impact has been felt in the…

Canonical Visual Size for Real-World Objects

PubMed Central

Konkle, Talia; Oliva, Aude

2012-01-01

Real-world objects can be viewed at a range of distances and thus can be experienced at a range of visual angles within the visual field. Given the large amount of visual size variation possible when observing objects, we examined how internal object representations represent visual size information. In a series of experiments which required observers to access existing object knowledge, we observed that real-world objects have a consistent visual size at which they are drawn, imagined, and preferentially viewed. Importantly, this visual size is proportional to the logarithm of the assumed size of the object in the world, and is best characterized not as a fixed visual angle, but by the ratio of the object and the frame of space around it. Akin to the previous literature on canonical perspective, we term this consistent visual size information the canonical visual size. PMID:20822298

Canonical Descriptions of High Intensity Laser-Plasma Interaction

NASA Astrophysics Data System (ADS)

Le Cornu, B. J.

The problem of laser-plasma interaction has been studied extensively in the context of inertial confinement fusion (ICF). These studies have focussed on effects like the nonlinear force, self-focusing, Rayleigh- Taylor instabilities, stimulated Brillouin scattering and stimulated Raman scattering observed in ICF schemes. However, there remains a large discrepancy between theory and experiment in the context of nuclear fusion schemes. Several authors have attempted to gain greater understanding of the physics involved by the application of standard or 'canonical' methods used in Lagrangian and Hamiltonian mechanics to the problem of plasma physics. This thesis presents a new canonical description of laser-plasma interaction based on the Podolsky Lagrangian. Finite self-energy of charged particles, incroporation of high-frequency effects and an ability to quantise are the main advantages of this new model. The nature of the Podolsky constant is also analysed in the context of plasma physics, specifically in terms of the plasma dispersion relation. A new gauge invariant expression of the energy-momentum tensor for any gauge invariant Lagrangian dependent on second order derivatives is derived for the first time. Finally, the transient and nontransient expressions of the nonlinear ponderomotive force in laser-plasma interaction are discussed and shown to be closely approximated by a canonical derivation of the electromagnetic Lagrangian, a fact that seems to have been missed in the literature.

New variables for classical and quantum gravity in all dimensions: I. Hamiltonian analysis

NASA Astrophysics Data System (ADS)

Bodendorfer, N.; Thiemann, T.; Thurn, A.

2013-02-01

Loop quantum gravity (LQG) relies heavily on a connection formulation of general relativity such that (1) the connection Poisson commutes with itself and (2) the corresponding gauge group is compact. This can be achieved starting from the Palatini or Holst action when imposing the time gauge. Unfortunately, this method is restricted to D + 1 = 4 spacetime dimensions. However, interesting string theories and supergravity theories require higher dimensions and it would therefore be desirable to have higher dimensional supergravity loop quantizations at one’s disposal in order to compare these approaches. In this series of papers we take first steps toward this goal. The present first paper develops a classical canonical platform for a higher dimensional connection formulation of the purely gravitational sector. The new ingredient is a different extension of the ADM phase space than the one used in LQG which does not require the time gauge and which generalizes to any dimension D > 1. The result is a Yang-Mills theory phase space subject to Gauß, spatial diffeomorphism and Hamiltonian constraint as well as one additional constraint, called the simplicity constraint. The structure group can be chosen to be SO(1, D) or SO(D + 1) and the latter choice is preferred for purposes of quantization.

An amino acid depleted cell-free protein synthesis system for the incorporation of non-canonical amino acid analogs into proteins.

PubMed

Singh-Blom, Amrita; Hughes, Randall A; Ellington, Andrew D

2014-05-20

Residue-specific incorporation of non-canonical amino acids into proteins is usually performed in vivo using amino acid auxotrophic strains and replacing the natural amino acid with an unnatural amino acid analog. Herein, we present an efficient amino acid depleted cell-free protein synthesis system that can be used to study residue-specific replacement of a natural amino acid by an unnatural amino acid analog. This system combines a simple methodology and high protein expression titers with a high-efficiency analog substitution into a target protein. To demonstrate the productivity and efficacy of a cell-free synthesis system for residue-specific incorporation of unnatural amino acids in vitro, we use this system to show that 5-fluorotryptophan and 6-fluorotryptophan substituted streptavidin retain the ability to bind biotin despite protein-wide replacement of a natural amino acid for the amino acid analog. We envisage this amino acid depleted cell-free synthesis system being an economical and convenient format for the high-throughput screening of a myriad of amino acid analogs with a variety of protein targets for the study and functional characterization of proteins substituted with unnatural amino acids when compared to the currently employed in vivo methodologies. Copyright © 2014 Elsevier B.V. All rights reserved.

Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells.

PubMed

Scarlatti, F; Maffei, R; Beau, I; Codogno, P; Ghidoni, R

2008-08-01

Resveratrol, a polyphenol found in grapes and other fruit and vegetables, is a powerful chemopreventive and chemotherapeutic molecule potentially of interest for the treatment of breast cancer. The human breast cancer cell line MCF-7, which is devoid of caspase-3 activity, is refractory to apoptotic cell death after incubation with resveratrol. Here we show that resveratrol arrests cell proliferation, triggers death and decreases the number of colonies of cells that are sensitive to caspase-3-dependent apoptosis (MCF-7 casp-3) and also those that are unresponsive to it (MCF-7vc). We demonstrate that resveratrol (i) acts via multiple pathways to trigger cell death, (ii) induces caspase-dependent and caspase-independent cell death in MCF-7 casp-3 cells, (iii) induces only caspase-independent cell death in MCF-7vc cells and (iv) stimulates macroautophagy. Using BECN1 and hVPS34 (human vacuolar protein sorting 34) small interfering RNAs, we demonstrate that resveratrol activates Beclin 1-independent autophagy in both cell lines, whereas cell death via this uncommon form of autophagy occurs only in MCF-7vc cells. We also show that this variant form of autophagic cell death is blocked by the expression of caspase-3, but not by its enzymatic activity. In conclusion, this study reveals that non-canonical autophagy induced by resveratrol can act as a caspase-independent cell death mechanism in breast cancer cells.

Linear canonical transformations of coherent and squeezed states in the Wigner phase space

NASA Technical Reports Server (NTRS)

Han, D.; Kim, Y. S.; Noz, Marilyn E.

1988-01-01

It is shown that classical linear canonical transformations are possible in the Wigner phase space. Coherent and squeezed states are shown to be linear canonical transforms of the ground-state harmonic oscillator. It is therefore possible to evaluate the Wigner functions for coherent and squeezed states from that for the harmonic oscillator. Since the group of linear canonical transformations has a subgroup whose algebraic property is the same as that of the (2+1)-dimensional Lorentz group, it may be possible to test certain properties of the Lorentz group using optical devices. A possible experiment to measure the Wigner rotation angle is discussed.

Positioner with long travel in two dimensions

DOEpatents

Trumper, David L.; Williams, Mark E.

1997-12-23

A precision positioning system is provided which provides long travel in two of the linear dimensions, while using non-contact bearings for both a first subassembly which provides long travel in one of the linear dimension and a second subassembly which provides long travel in the second linear dimension. The first or upper subassembly is preferably a magnetic subassembly which, in addition to providing long travel, also compensates or positions in three rotary dimensions and in the third linear dimension. The second subassembly is preferably either an air bearing or magnetic subassembly and is normally used only to provide long travel. Angled surfaces may be provided for magnetic bearings and capacitive or other gap sensing probes may be mounted to the stage and ground flush with the bearing actuators to provide more precise gap measurements.

Measurements of the canonical helicity evolution of a gyrating kinked plasma column

NASA Astrophysics Data System (ADS)

von der Linden, Jens; Sears, Jason; Intrator, Thomas; You, Setthivoine

2017-10-01

Conversions between kinetic and magnetic energy occur over a wide range of plasma scales as exhibited in astrophysical and solar dynamos, and reconnection in the solar corona and laboratory experiments. Canonical flux tubes present the distinct advantage of reconciling all plasma regimes - e.g. kinetic, two-fluid, and MHD - with the topological concept of helicity: twists, writhes, and linkages. This poster presents the first visualization and analysis of the 3D dynamics of canonical flux tubes and their relative helicity evolution from experimental measurements. Ion and electron canonical flux tubes are visualized from Mach, triple, and Ḃ probe measurements at over 10,000 spatial locations of a gyrating kinked plasma column. The flux tubes co-gyrate with the peak density and electron temperature in and out of a measurement volume. The electron and ion canonical flux tubes twist with opposite handedness and the ion flux tube writhes around the electron flux tube. The relative cross helicity between the magnetic and ion flow vorticity flux tubes dominates the relative ion canonical helicity and is anticorrelated with the relative magnetic helicity. The 3D nature of the kink and a reverse eddy current affect the helicity evolution. This work is supported by DOE Grant DE-SC0010340 and the DOE Office of Science Graduate Student Research Program and prepared in part by LLNL under Contract DE-AC52-07NA27344. LLNL-ABS-734669.

Spatio-Chromatic Adaptation via Higher-Order Canonical Correlation Analysis of Natural Images

PubMed Central

Gutmann, Michael U.; Laparra, Valero; Hyvärinen, Aapo; Malo, Jesús

2014-01-01

Independent component and canonical correlation analysis are two general-purpose statistical methods with wide applicability. In neuroscience, independent component analysis of chromatic natural images explains the spatio-chromatic structure of primary cortical receptive fields in terms of properties of the visual environment. Canonical correlation analysis explains similarly chromatic adaptation to different illuminations. But, as we show in this paper, neither of the two methods generalizes well to explain both spatio-chromatic processing and adaptation at the same time. We propose a statistical method which combines the desirable properties of independent component and canonical correlation analysis: It finds independent components in each data set which, across the two data sets, are related to each other via linear or higher-order correlations. The new method is as widely applicable as canonical correlation analysis, and also to more than two data sets. We call it higher-order canonical correlation analysis. When applied to chromatic natural images, we found that it provides a single (unified) statistical framework which accounts for both spatio-chromatic processing and adaptation. Filters with spatio-chromatic tuning properties as in the primary visual cortex emerged and corresponding-colors psychophysics was reproduced reasonably well. We used the new method to make a theory-driven testable prediction on how the neural response to colored patterns should change when the illumination changes. We predict shifts in the responses which are comparable to the shifts reported for chromatic contrast habituation. PMID:24533049

Spatio-chromatic adaptation via higher-order canonical correlation analysis of natural images.

PubMed

Gutmann, Michael U; Laparra, Valero; Hyvärinen, Aapo; Malo, Jesús

2014-01-01

Independent component and canonical correlation analysis are two general-purpose statistical methods with wide applicability. In neuroscience, independent component analysis of chromatic natural images explains the spatio-chromatic structure of primary cortical receptive fields in terms of properties of the visual environment. Canonical correlation analysis explains similarly chromatic adaptation to different illuminations. But, as we show in this paper, neither of the two methods generalizes well to explain both spatio-chromatic processing and adaptation at the same time. We propose a statistical method which combines the desirable properties of independent component and canonical correlation analysis: It finds independent components in each data set which, across the two data sets, are related to each other via linear or higher-order correlations. The new method is as widely applicable as canonical correlation analysis, and also to more than two data sets. We call it higher-order canonical correlation analysis. When applied to chromatic natural images, we found that it provides a single (unified) statistical framework which accounts for both spatio-chromatic processing and adaptation. Filters with spatio-chromatic tuning properties as in the primary visual cortex emerged and corresponding-colors psychophysics was reproduced reasonably well. We used the new method to make a theory-driven testable prediction on how the neural response to colored patterns should change when the illumination changes. We predict shifts in the responses which are comparable to the shifts reported for chromatic contrast habituation.

Are Young Children's Drawings Canonically Biased?

ERIC Educational Resources Information Center

Picard, Delphine; Durand, Karine

2005-01-01

In a between-subjects design, 4-to 6-year-olds were asked to draw from three-dimensional (3D) models, two-and-a-half-dimensional (212D) models with or without depth cues, or two-dimensional (2D) models of a familiar object (a saucepan) in noncanonical orientations (handle at the back or at the front). Results showed that canonical errors were…

Dimension Reduction With Extreme Learning Machine.

PubMed

Kasun, Liyanaarachchi Lekamalage Chamara; Yang, Yan; Huang, Guang-Bin; Zhang, Zhengyou

2016-08-01

Data may often contain noise or irrelevant information, which negatively affect the generalization capability of machine learning algorithms. The objective of dimension reduction algorithms, such as principal component analysis (PCA), non-negative matrix factorization (NMF), random projection (RP), and auto-encoder (AE), is to reduce the noise or irrelevant information of the data. The features of PCA (eigenvectors) and linear AE are not able to represent data as parts (e.g. nose in a face image). On the other hand, NMF and non-linear AE are maimed by slow learning speed and RP only represents a subspace of original data. This paper introduces a dimension reduction framework which to some extend represents data as parts, has fast learning speed, and learns the between-class scatter subspace. To this end, this paper investigates a linear and non-linear dimension reduction framework referred to as extreme learning machine AE (ELM-AE) and sparse ELM-AE (SELM-AE). In contrast to tied weight AE, the hidden neurons in ELM-AE and SELM-AE need not be tuned, and their parameters (e.g, input weights in additive neurons) are initialized using orthogonal and sparse random weights, respectively. Experimental results on USPS handwritten digit recognition data set, CIFAR-10 object recognition, and NORB object recognition data set show the efficacy of linear and non-linear ELM-AE and SELM-AE in terms of discriminative capability, sparsity, training time, and normalized mean square error.

Categorical dimensions of human odor descriptor space revealed by non-negative matrix factorization

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

Chennubhotla, Chakra; Castro, Jason

2013-01-01

In contrast to most other sensory modalities, the basic perceptual dimensions of olfaction remain un- clear. Here, we use non-negative matrix factorization (NMF) - a dimensionality reduction technique - to uncover structure in a panel of odor profiles, with each odor defined as a point in multi-dimensional descriptor space. The properties of NMF are favorable for the analysis of such lexical and perceptual data, and lead to a high-dimensional account of odor space. We further provide evidence that odor di- mensions apply categorically. That is, odor space is not occupied homogenously, but rather in a discrete and intrinsically clustered manner.more » We discuss the potential implications of these results for the neural coding of odors, as well as for developing classifiers on larger datasets that may be useful for predicting perceptual qualities from chemical structures.« less

Development of Canonical Transformations from Hamilton's Principle.

ERIC Educational Resources Information Center

Quade, C. Richard

1979-01-01

The theory of canonical transformations and its development are discussed with regard to its application to Hutton's principle. Included are the derivation of the equations of motion and a lack of symmetry in the formulaion with respect to Lagrangian and the fundamental commutator relations of quantum mechanics. (Author/SA)

Generalized ensemble theory with non-extensive statistics

NASA Astrophysics Data System (ADS)

Shen, Ke-Ming; Zhang, Ben-Wei; Wang, En-Ke

2017-12-01

The non-extensive canonical ensemble theory is reconsidered with the method of Lagrange multipliers by maximizing Tsallis entropy, with the constraint that the normalized term of Tsallis' q -average of physical quantities, the sum ∑ pjq, is independent of the probability pi for Tsallis parameter q. The self-referential problem in the deduced probability and thermal quantities in non-extensive statistics is thus avoided, and thermodynamical relationships are obtained in a consistent and natural way. We also extend the study to the non-extensive grand canonical ensemble theory and obtain the q-deformed Bose-Einstein distribution as well as the q-deformed Fermi-Dirac distribution. The theory is further applied to the generalized Planck law to demonstrate the distinct behaviors of the various generalized q-distribution functions discussed in literature.

A Non-canonical Voltage-Sensing Mechanism Controls Gating in K2P K(+) Channels.

PubMed

Schewe, Marcus; Nematian-Ardestani, Ehsan; Sun, Han; Musinszki, Marianne; Cordeiro, Sönke; Bucci, Giovanna; de Groot, Bert L; Tucker, Stephen J; Rapedius, Markus; Baukrowitz, Thomas

2016-02-25

Two-pore domain (K2P) K(+) channels are major regulators of excitability that endow cells with an outwardly rectifying background "leak" conductance. In some K2P channels, strong voltage-dependent activation has been observed, but the mechanism remains unresolved because they lack a canonical voltage-sensing domain. Here, we show voltage-dependent gating is common to most K2P channels and that this voltage sensitivity originates from the movement of three to four ions into the high electric field of an inactive selectivity filter. Overall, this ion-flux gating mechanism generates a one-way "check valve" within the filter because outward movement of K(+) induces filter opening, whereas inward movement promotes inactivation. Furthermore, many physiological stimuli switch off this flux gating mode to convert K2P channels into a leak conductance. These findings provide insight into the functional plasticity of a K(+)-selective filter and also refine our understanding of K2P channels and the mechanisms by which ion channels can sense voltage. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Baryon number violation and novel canonical anti-commutation relations

NASA Astrophysics Data System (ADS)

Fujikawa, Kazuo; Tureanu, Anca

2018-02-01

The possible neutron-antineutron oscillation is described by an effective quadratic Lagrangian analogous to the BCS theory. It is shown that the conventional equal-time anti-commutation relations of the neutron variable n (t , x →) are modified by the baryon number violating terms. This is established by the Bjorken-Johnson-Low prescription and also by the canonical quantization combined with equations of motion. This novel canonical behavior can give rise to an important physical effect, which is illustrated by analyzing the Lagrangian that violates the baryon number but gives rise to the degenerate effective Majorana fermions and thus no neutron-antineutron oscillation. Technically, this model is neatly treated using a relativistic analogue of the Bogoliubov transformation.

Attenuation of the Squared Canonical Correlation Coefficient under Varying Estimates of Score Reliability

ERIC Educational Resources Information Center

Wilson, Celia M.

2010-01-01

Research pertaining to the distortion of the squared canonical correlation coefficient has traditionally been limited to the effects of sampling error and associated correction formulas. The purpose of this study was to compare the degree of attenuation of the squared canonical correlation coefficient under varying conditions of score reliability.…

SMAD4 feedback regulates the canonical TGF-β signaling pathway to control granulosa cell apoptosis.

PubMed

Du, Xing; Pan, Zengxiang; Li, Qiqi; Liu, Honglin; Li, Qifa

2018-02-02

Canonical TGF-β signals are transduced from the cell surface to the cytoplasm, and then translocated into the nucleus, a process that involves ligands (TGF-β1), receptors (TGFBR2/1), receptor-activated SMADs (SMAD2/3), and the common SMAD (SMAD4). Here we provide evidence that SMAD4, a core component of the canonical TGF-β signaling pathway, regulates the canonical TGF-β signaling pathway in porcine granulosa cells (GCs) through a feedback mechanism. Genome-wide analysis and qRT-PCR revealed that SMAD4 affected miRNA biogenesis in GCs. Interestingly, TGFBR2, the type II receptor of the canonical TGF-β signaling pathway, was downregulated in SMAD4-silenced GCs and found to be a common target of SMAD4-inhibited miRNAs. miR-425, the most significantly elevated miRNA in SMAD4-silenced GCs, mediated the SMAD4 feedback regulation of the TGF-β signaling pathway. This was accomplished through a direct interaction between the transcription factor SMAD4 and the miR-425 promoter, and a direct interaction between miR-425 and the TGFBR2 3'-UTR. Furthermore, miR-425 enhanced GC apoptosis by targeting TGFBR2 and the canonical TGF-β signaling pathway, which was rescued by SMAD4 and TGF-β1. Overall, our findings demonstrate that a positive feedback mechanism exists within the canonical TGF-β signaling pathway. This study also provides new insights into mechanism underlying the canonical TGF-β signaling pathway, which regulates GC function and follicular development.

Perceptual advantage for category-relevant perceptual dimensions: the case of shape and motion.

PubMed

Folstein, Jonathan R; Palmeri, Thomas J; Gauthier, Isabel

2014-01-01

Category learning facilitates perception along relevant stimulus dimensions, even when tested in a discrimination task that does not require categorization. While this general phenomenon has been demonstrated previously, perceptual facilitation along dimensions has been documented by measuring different specific phenomena in different studies using different kinds of objects. Across several object domains, there is support for acquired distinctiveness, the stretching of a perceptual dimension relevant to learned categories. Studies using faces and studies using simple separable visual dimensions have also found evidence of acquired equivalence, the shrinking of a perceptual dimension irrelevant to learned categories, and categorical perception, the local stretching across the category boundary. These later two effects are rarely observed with complex non-face objects. Failures to find these effects with complex non-face objects may have been because the dimensions tested previously were perceptually integrated. Here we tested effects of category learning with non-face objects categorized along dimensions that have been found to be processed by different areas of the brain, shape and motion. While we replicated acquired distinctiveness, we found no evidence for acquired equivalence or categorical perception.

Canonical decomposition of magnetotelluric responses: Experiment on 1D anisotropic structures

NASA Astrophysics Data System (ADS)

Guo, Ze-qiu; Wei, Wen-bo; Ye, Gao-feng; Jin, Sheng; Jing, Jian-en

2015-08-01

Horizontal electrical heterogeneity of subsurface earth is mostly originated from structural complexity and electrical anisotropy, and local near-surface electrical heterogeneity will severely distort regional electromagnetic responses. Conventional distortion analyses for magnetotelluric soundings are primarily physical decomposition methods with respect to isotropic models, which mostly presume that the geoelectric distribution of geological structures is of local and regional patterns represented by 3D/2D models. Due to the widespread anisotropy of earth media, the confusion between 1D anisotropic responses and 2D isotropic responses, and the defects of physical decomposition methods, we propose to conduct modeling experiments with canonical decomposition in terms of 1D layered anisotropic models, and the method is one of the mathematical decomposition methods based on eigenstate analyses differentiated from distortion analyses, which can be used to recover electrical information such as strike directions, and maximum and minimum conductivity. We tested this method with numerical simulation experiments on several 1D synthetic models, which turned out that canonical decomposition is quite effective to reveal geological anisotropic information. Finally, for the background of anisotropy from previous study by geological and seismological methods, canonical decomposition is applied to real data acquired in North China Craton for 1D anisotropy analyses, and the result shows that, with effective modeling and cautious interpretation, canonical decomposition could be another good method to detect anisotropy of geological media.

Carroll limit of non-BPS Dp-brane

NASA Astrophysics Data System (ADS)

Klusoň, J.

2017-05-01

We find Carroll non-BPS Dp-brane action by performing Carroll limit of a canonical form of unstable Dp-brane action. We analyze different Carroll limits and discuss solutions of the equations of motion of Carroll non-BPS Dp-brane at the tachyon vacuum.

Evaluation of macrozone dimensions by ultrasound and EBSD techniques

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

Moreau, Andre, E-mail: Andre.Moreau@cnrc-nrc.gc.ca; Toubal, Lotfi; Ecole de technologie superieure, 1100, rue Notre-Dame Ouest, Montreal, QC, Canada H3C 1K3

2013-01-15

Titanium alloys are known to have texture heterogeneities, i.e. regions much larger than the grain dimensions, where the local orientation distribution of the grains differs from one region to the next. The electron backscattering diffraction (EBSD) technique is the method of choice to characterize these macro regions, which are called macrozones. Qualitatively, the images obtained by EBSD show that these macrozones may be larger or smaller, elongated or equiaxed. However, often no well-defined boundaries are observed between the macrozones and it is very hard to obtain objective and quantitative estimates of the macrozone dimensions from these data. In the presentmore » work, we present a novel, non-destructive ultrasonic technique that provides objective and quantitative characteristic dimensions of the macrozones. The obtained dimensions are based on the spatial autocorrelation function of fluctuations in the sound velocity. Thus, a pragmatic definition of macrozone dimensions naturally arises from the ultrasonic measurement. This paper has three objectives: 1) to disclose the novel, non-destructive ultrasonic technique to measure macrozone dimensions, 2) to propose a quantitative and objective definition of macrozone dimensions adapted to and arising from the ultrasonic measurement, and which is also applicable to the orientation data obtained by EBSD, and 3) to compare the macrozone dimensions obtained using the two techniques on two samples of the near-alpha titanium alloy IMI834. In addition, it was observed that macrozones may present a semi-periodical arrangement. - Highlights: Black-Right-Pointing-Pointer Discloses a novel, ultrasonic NDT technique to measure macrozone dimensions Black-Right-Pointing-Pointer Proposes a quantitative and objective definition of macrozone dimensions Black-Right-Pointing-Pointer Compares macrozone dimensions obtained using EBSD and ultrasonics on 2 Ti samples Black-Right-Pointing-Pointer Observes that macrozones may have a

The landscape of the non-canonical RNA-binding site of Gemin5 unveils a feedback loop counteracting the negative effect on translation.

PubMed

Francisco-Velilla, Rosario; Fernandez-Chamorro, Javier; Dotu, Ivan; Martinez-Salas, Encarnación

2018-05-16

Gemin5 is a predominantly cytoplasmic protein that downregulates translation, beyond controlling snRNPs assembly. The C-terminal region harbors a non-canonical RNA-binding site consisting of two domains, RBS1 and RBS2, which differ in RNA-binding capacity and the ability to modulate translation. Here, we show that these domains recognize distinct RNA targets in living cells. Interestingly, the most abundant and exclusive RNA target of the RBS1 domain was Gemin5 mRNA. Biochemical and functional characterization of this target demonstrated that RBS1 polypeptide physically interacts with a predicted thermodynamically stable stem-loop upregulating mRNA translation, thereby counteracting the negative effect of Gemin5 protein on global protein synthesis. In support of this result, destabilization of the stem-loop impairs the stimulatory effect on translation. Moreover, RBS1 stimulates translation of the endogenous Gemin5 mRNA. Hence, although the RBS1 domain downregulates global translation, it positively enhances translation of RNA targets carrying thermodynamically stable secondary structure motifs. This mechanism allows fine-tuning the availability of Gemin5 to play its multiple roles in gene expression control.

An enquiry concerning the nature of conceptual categories: a case-study on the social dimension of human cognition

PubMed Central

Stewart, John

2014-01-01

Cognitive Science, in all its guises, has not yet accorded any fundamental importance to the social dimension of human cognition. In order to illustrate the possibilities that have not so far been developed, this article seeks to pursue the idea, first put forward by Durkheim, that the major categories which render conceptual thought possible may actually have a social origin. Durkheim illustrated his thesis, convincingly enough, by examining the societies of Australian aborigines. The aim here is to extend this idea to cover the case of the conceptual categories underpinning modern Western science, as they developed historically first in Ancient Greece, and then at the Renaissance. These major non-empirical concepts include those of abstract Space (Euclidean space, perfectly homogeneous in all its dimensions); abstract Time (conceived as spatially linearized, with the possibility of imaginatively going back and forth); and a number of canonical logical categories (equality, abstract quantity, essential versus accidental properties, the continuous and the discontinuous, the transcendental…). Sohn-Rethel (1978) has proposed that the heart of the conceptual categories in question is to be found in an analysis of the exchange abstraction. This hypothesis will be fleshed out by examining the co-emergence of new social structures and new forms of conceptual thought in the course of historical evolution. This includes the Renaissance, which saw the emergence of both Capitalism and Modern Science; and on the contemporary situation, where the form of social life is dominated by financial speculation which goes together with the advent of automation in the processes of production. It is concluded that Cognitive Science, and in particular the nascent paradigm of Enaction, would do well to broaden its transdisciplinary scope to include the dimensions of sociology and anthropology. PMID:25009526

An enquiry concerning the nature of conceptual categories: a case-study on the social dimension of human cognition.

PubMed

Stewart, John

2014-01-01

Cognitive Science, in all its guises, has not yet accorded any fundamental importance to the social dimension of human cognition. In order to illustrate the possibilities that have not so far been developed, this article seeks to pursue the idea, first put forward by Durkheim, that the major categories which render conceptual thought possible may actually have a social origin. Durkheim illustrated his thesis, convincingly enough, by examining the societies of Australian aborigines. The aim here is to extend this idea to cover the case of the conceptual categories underpinning modern Western science, as they developed historically first in Ancient Greece, and then at the Renaissance. These major non-empirical concepts include those of abstract Space (Euclidean space, perfectly homogeneous in all its dimensions); abstract Time (conceived as spatially linearized, with the possibility of imaginatively going back and forth); and a number of canonical logical categories (equality, abstract quantity, essential versus accidental properties, the continuous and the discontinuous, the transcendental…). Sohn-Rethel (1978) has proposed that the heart of the conceptual categories in question is to be found in an analysis of the exchange abstraction. This hypothesis will be fleshed out by examining the co-emergence of new social structures and new forms of conceptual thought in the course of historical evolution. This includes the Renaissance, which saw the emergence of both Capitalism and Modern Science; and on the contemporary situation, where the form of social life is dominated by financial speculation which goes together with the advent of automation in the processes of production. It is concluded that Cognitive Science, and in particular the nascent paradigm of Enaction, would do well to broaden its transdisciplinary scope to include the dimensions of sociology and anthropology.

Swarms with canonical active Brownian motion.

PubMed

Glück, Alexander; Hüffel, Helmuth; Ilijić, Saša

2011-05-01

We present a swarm model of Brownian particles with harmonic interactions, where the individuals undergo canonical active Brownian motion, i.e., each Brownian particle can convert internal energy to mechanical energy of motion. We assume the existence of a single global internal energy of the system. Numerical simulations show amorphous swarming behavior as well as static configurations. Analytic understanding of the system is provided by studying stability properties of equilibria.

Foundations of Education: Texts and the Canon.

ERIC Educational Resources Information Center

Gottlieb, Esther E.

This paper attempts to outline the textual canon of the foundations of education in U.S. teacher education programs. Background research for the project included a review of selected texts and samples of course syllabi. Analysis of the contents and prefaces of the two volumes of "Reading in the Foundations of Education" (published in…

Hmga2 is required for canonical WNT signaling during lung development

PubMed Central

2014-01-01

Background The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. HMG proteins are present at high levels in various undifferentiated tissues during embryonic development and their levels are strongly reduced in the corresponding adult tissues, where they have been implicated in maintaining and activating stem/progenitor cells. Here we deciphered the role of the high-mobility-group AT-hook protein 2 (HMGA2) during lung development by analyzing the lung of Hmga2-deficient mice (Hmga2 −/− ). Results We found that Hmga2 is expressed in the mouse embryonic lung at the distal airways. Analysis of Hmga2 −/− mice showed that Hmga2 is required for proper cell proliferation and distal epithelium differentiation during embryonic lung development. Hmga2 knockout led to enhanced canonical WNT signaling due to an increased expression of secreted WNT glycoproteins Wnt2b, Wnt7b and Wnt11 as well as a reduction of the WNT signaling antagonizing proteins GATA-binding protein 6 and frizzled homolog 2. Analysis of siRNA-mediated loss-of-function experiments in embryonic lung explant culture confirmed the role of Hmga2 as a key regulator of distal lung epithelium differentiation and supported the causal involvement of enhanced canonical WNT signaling in mediating the effect of Hmga2-loss-of-fuction. Finally, we found that HMGA2 directly regulates Gata6 and thereby modulates Fzd2 expression. Conclusions Our results support that Hmga2 regulates canonical WNT signaling at different points of the pathway. Increased expression of the secreted WNT glycoproteins might explain a paracrine effect by which Hmga2-knockout enhanced cell proliferation in the mesenchyme of the developing lung. In addition, HMGA2-mediated direct regulation of Gata6 is crucial for fine-tuning the activity of WNT signaling in the airway epithelium. Our results are the starting point for future studies investigating the relevance of Hmga2-mediated regulation of

Grand canonical ensemble Monte Carlo simulation of the dCpG/proflavine crystal hydrate.

PubMed

Resat, H; Mezei, M

1996-09-01

The grand canonical ensemble Monte Carlo molecular simulation method is used to investigate hydration patterns in the crystal hydrate structure of the dCpG/proflavine intercalated complex. The objective of this study is to show by example that the recently advocated grand canonical ensemble simulation is a computationally efficient method for determining the positions of the hydrating water molecules in protein and nucleic acid structures. A detailed molecular simulation convergence analysis and an analogous comparison of the theoretical results with experiments clearly show that the grand ensemble simulations can be far more advantageous than the comparable canonical ensemble simulations.

Leucine-Rich Repeat Kinase 2 Controls the Ca2+/Nuclear Factor of Activated T Cells/IL-2 Pathway during Aspergillus Non-Canonical Autophagy in Dendritic Cells.

PubMed

Wong, Alicia Yoke Wei; Oikonomou, Vasilis; Paolicelli, Giuseppe; De Luca, Antonella; Pariano, Marilena; Fric, Jan; Tay, Hock Soon; Ricciardi-Castagnoli, Paola; Zelante, Teresa

2018-01-01

The Parkinson's disease-associated protein, Leucine-rich repeat kinase 2 (LRRK2), a known negative regulator of nuclear factor of activated T cells (NFAT), is expressed in myeloid cells such as macrophages and dendritic cells (DCs) and is involved in the host immune response against pathogens. Since, the Ca 2+ /NFAT/IL-2 axis has been previously found to regulate DC response to the fungus Aspergillus , we have investigated the role played by the kinase LRRK2 during fungal infection. Mechanistically, we found that in the early stages of the non-canonical autophagic response of DCs to the germinated spores of Aspergillus , LRRK2 undergoes progressive degradation and regulates NFAT translocation from the cytoplasm to the nucleus. Our results shed new light on the complexity of the Ca 2+ /NFAT/IL-2 pathway, where LRRK2 plays a role in controlling the immune response of DCs to Aspergillus .

Evidence for a non-canonical role of HDAC5 in regulation of the cardiac Ncx1 and Bnp genes.

PubMed

Harris, Lillianne G; Wang, Sabina H; Mani, Santhosh K; Kasiganesan, Harinath; Chou, C James; Menick, Donald R

2016-05-05

Class IIa histone deacetylases (HDACs) are very important for tissue specific gene regulation in development and pathology. Because class IIa HDAC catalytic activity is low, their exact molecular roles have not been fully elucidated. Studies have suggested that class IIa HDACs may serve as a scaffold to recruit the catalytically active class I HDAC complexes to their substrate. Here we directly address whether the class IIa HDAC, HDAC5 may function as a scaffold to recruit co-repressor complexes to promoters. We examined two well-characterized cardiac promoters, the sodium calcium exchanger (Ncx1) and the brain natriuretic peptide (Bnp) whose hypertrophic upregulation is mediated by both class I and IIa HDACs. Selective inhibition of class IIa HDACs did not prevent adrenergic stimulated Ncx1 upregulation, however HDAC5 knockout prevented pressure overload induced Ncx1 upregulation. Using the HDAC5((-/-)) mouse we show that HDAC5 is required for the interaction of the HDAC1/2/Sin3a co-repressor complexes with the Nkx2.5 and YY1 transcription factors and critical for recruitment of the HDAC1/Sin3a co-repressor complex to either the Ncx1 or Bnp promoter. Our novel findings support a non-canonical role of class IIa HDACs in the scaffolding of transcriptional regulatory complexes, which may be relevant for therapeutic intervention for pathologies. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Clinical Trials With Large Numbers of Variables: Important Advantages of Canonical Analysis.

PubMed

Cleophas, Ton J

2016-01-01

Canonical analysis assesses the combined effects of a set of predictor variables on a set of outcome variables, but it is little used in clinical trials despite the omnipresence of multiple variables. The aim of this study was to assess the performance of canonical analysis as compared with traditional multivariate methods using multivariate analysis of covariance (MANCOVA). As an example, a simulated data file with 12 gene expression levels and 4 drug efficacy scores was used. The correlation coefficient between the 12 predictor and 4 outcome variables was 0.87 (P = 0.0001) meaning that 76% of the variability in the outcome variables was explained by the 12 covariates. Repeated testing after the removal of 5 unimportant predictor and 1 outcome variable produced virtually the same overall result. The MANCOVA identified identical unimportant variables, but it was unable to provide overall statistics. (1) Canonical analysis is remarkable, because it can handle many more variables than traditional multivariate methods such as MANCOVA can. (2) At the same time, it accounts for the relative importance of the separate variables, their interactions and differences in units. (3) Canonical analysis provides overall statistics of the effects of sets of variables, whereas traditional multivariate methods only provide the statistics of the separate variables. (4) Unlike other methods for combining the effects of multiple variables such as factor analysis/partial least squares, canonical analysis is scientifically entirely rigorous. (5) Limitations include that it is less flexible than factor analysis/partial least squares, because only 2 sets of variables are used and because multiple solutions instead of one is offered. We do hope that this article will stimulate clinical investigators to start using this remarkable method.

Measurements of the Canonical Helicity Evolution of a Gyrating Kinked Flux Rope

NASA Astrophysics Data System (ADS)

von der Linden, J.; Sears, J.; Intrator, T.; You, S.

2017-12-01

Magnetic structures in the solar corona and planetary magnetospheres are often modelled as magnetic flux ropes governed by magnetohydrodynamics (MHD); however, inside these structures, as exhibited in reconnection, conversions between magnetic and kinetic energies occur over a wide range of scales. Flux ropes based on the flux of canonical momentum circulation extend the flux rope concept to include effects of finite particle momentum and present the distinct advantage of reconciling all plasma regimes - e.g. kinetic, two-fluid, and MHD - with the topological concept of helicity: twists, writhes, and linkages. This presentation shows the first visualization and analysis of the 3D dynamics of canonical flux ropes and their relative helicity evolution from laboratory measurements. Ion and electron canonical flux ropes are visualized from a dataset of Mach, triple, and Ḃ probe measurements at over 10,000 spatial locations of a gyrating kinked flux rope. The flux ropes co-gyrate with the peak density and electron temperature in and out of a measurement volume. The electron and ion canonical flux ropes twist with opposite handedness and the ion flux ropes writhe around the electron flux ropes. The relative cross helicity between the magnetic and ion flow vorticity flux ropes dominates the relative ion canonical helicity and is anti-correlated with the relative magnetic helicity. The 3D nature of the kink and a reverse eddy current affect the helicity evolution. This work is supported by DOE Grant DE-SC0010340 and the DOE Office of Science Graduate Student Research Program and prepared in part by LLNL under Contract DE-AC52-07NA27344. LLNL-ABS-735426

Epithelial transformation by KLF4 requires Notch1 but not canonical Notch1 signaling

PubMed Central

Liu, Zhaoli; Teng, Lihong; Bailey, Sarah K.; Frost, Andra R.; Bland, Kirby I.; LoBuglio, Albert F.; Ruppert, J. Michael; Lobo-Ruppert, Susan M.

2009-01-01

The transcription factors Notch1 and KLF4 specify epithelial cell fates and confer stem cell properties. suggesting a functional relationship, each gene can act to promote or suppress tumorigenesis in a context-dependent manner, and alteration of KLF4 or Notch pathway genes in mice gives rise to similar phenotypes. Activation of a conditional allele of KLF4 in RK3E epithelial cells rapidly induces expression of Notch1 mRNA and the active, intracellular form of Notch1. KLF4-induced transformation was suppressed by knockdown of endogenous Notch1 using siRNA or an inhibitor of γ-secretase. Chromatin immunoprecipitation assay shows that KLF4 binds to the proximal Notch1 promoter in human mammary epithelial cells, and siRNA-mediated suppression of KLF4 in human mammary cancer cells results in reduced expression of Notch1. Furthermore, KLF4 and Notch1 expression are correlated in primary human breast tumors (N = 89; pearson analysis, r > 0.5, p < 0.0001). Like KLF4, Notch1 was previously shown to induce transformation of rat cells immortalized with adenovirus E1A, similar to RK3E cells. We therefore compared the signaling requirements for Notch1- or KLF4-induced malignant transformation of RK3E. As expected, transformation by Notch1 was suppressed by dominant-negative CSL or MaML1, inhibitors of canonical Notch1 signaling. However, these inhibitors did not suppress transformation by KLF4. Therefore, while KLF4-induced transformation requires Notch1, canonical Notch1 signaling is not required, and Notch1 may signal through a distinct pathway in cells with increased KLF4 activity. These results suggest that KLF4 could contribute to breast tumor progression by activating synthesis of Notch1 and by promoting signaling through a non-canonical Notch1 pathway. PMID:19717984

Relationship between organisational commitment and burnout syndrome: a canonical correlation approach.

PubMed

Enginyurt, Ozgur; Cankaya, Soner; Aksay, Kadir; Tunc, Taner; Koc, Bozkurt; Bas, Orhan; Ozer, Erdal

2016-04-01

Objective Burnout syndrome can significantly reduce the performance of health workers. Although many factors have been identified as antecedents of burnout, few studies have investigated the role of organisational commitment in its development. The purpose of the present study was to examine the relationships between subdimensions of burnout syndrome (emotional exhaustion, depersonalisation and personal accomplishment) and subdimensions of organisational commitment (affective commitment, continuance commitment and normative commitment). Methods The present study was a cross-sectional survey of physicians and other healthcare employees working in the Ministry of Health Ordu University Education and Research Hospital. The sample consisted of 486 healthcare workers. Data were collected using the Maslach Burnout Inventory and the Organisation Commitment Scale, and were analysed using the canonical correlation approach. Results The first of three canonical correlation coefficients between pairs of canonical variables (Ui , burnout syndrome and Vi, organisational commitment) was found to be statistically significant. Emotional exhaustion was found to contribute most towards the explanatory capacity of canonical variables estimated from the subdimensions of burnout syndrome, whereas affective commitment provided the largest contribution towards the explanatory capacity of canonical variables estimated from the subdimensions of organisational commitment. Conclusions The results of the present study indicate that affective commitment is the primary determinant of burnout syndrome in healthcare professionals. What is known about the topic? Organisational commitment and burnout syndrome are the most important criteria in predicting health workforce performance. An increasing number of studies in recent years have clearly indicated the field's continued relevance and importance. Conversely, canonical correlation analysis (CCA) is a technique for describing the relationship

A general transformation to canonical form for potentials in pairwise interatomic interactions.

PubMed

Walton, Jay R; Rivera-Rivera, Luis A; Lucchese, Robert R; Bevan, John W

2015-06-14

A generalized formulation of explicit force-based transformations is introduced to investigate the concept of a canonical potential in both fundamental chemical and intermolecular bonding. Different classes of representative ground electronic state pairwise interatomic interactions are referenced to a chosen canonical potential illustrating application of such transformations. Specifically, accurately determined potentials of the diatomic molecules H2, H2(+), HF, LiH, argon dimer, and one-dimensional dissociative coordinates in Ar-HBr, OC-HF, and OC-Cl2 are investigated throughout their bound potentials. Advantages of the current formulation for accurately evaluating equilibrium dissociation energies and a fundamentally different unified perspective on nature of intermolecular interactions will be emphasized. In particular, this canonical approach has significance to previous assertions that there is no very fundamental distinction between van der Waals bonding and covalent bonding or for that matter hydrogen and halogen bonds.

Multiset canonical correlations analysis and multispectral, truly multitemporal remote sensing data.

PubMed

Nielsen, Allan Aasbjerg

2002-01-01

This paper describes two- and multiset canonical correlations analysis (CCA) for data fusion, multisource, multiset, or multitemporal exploratory data analysis. These techniques transform multivariate multiset data into new orthogonal variables called canonical variates (CVs) which, when applied in remote sensing, exhibit ever-decreasing similarity (as expressed by correlation measures) over sets consisting of 1) spectral variables at fixed points in time (R-mode analysis), or 2) temporal variables with fixed wavelengths (T-mode analysis). The CVs are invariant to linear and affine transformations of the original variables within sets which means, for example, that the R-mode CVs are insensitive to changes over time in offset and gain in a measuring device. In a case study, CVs are calculated from Landsat Thematic Mapper (TM) data with six spectral bands over six consecutive years. Both Rand T-mode CVs clearly exhibit the desired characteristic: they show maximum similarity for the low-order canonical variates and minimum similarity for the high-order canonical variates. These characteristics are seen both visually and in objective measures. The results from the multiset CCA R- and T-mode analyses are very different. This difference is ascribed to the noise structure in the data. The CCA methods are related to partial least squares (PLS) methods. This paper very briefly describes multiset CCA-based multiset PLS. Also, the CCA methods can be applied as multivariate extensions to empirical orthogonal functions (EOF) techniques. Multiset CCA is well-suited for inclusion in geographical information systems (GIS).

Non-perturbative methodologies for low-dimensional strongly-correlated systems: From non-Abelian bosonization to truncated spectrum methods

DOE PAGES

James, Andrew J. A.; Konik, Robert M.; Lecheminant, Philippe; ...

2018-02-26

We review two important non-perturbative approaches for extracting the physics of low-dimensional strongly correlated quantum systems. Firstly, we start by providing a comprehensive review of non-Abelian bosonization. This includes an introduction to the basic elements of conformal field theory as applied to systems with a current algebra, and we orient the reader by presenting a number of applications of non-Abelian bosonization to models with large symmetries. We then tie this technique into recent advances in the ability of cold atomic systems to realize complex symme-tries. Secondly, we discuss truncated spectrum methods for the numerical study of systems in one andmore » two dimensions. For one-dimensional systems we provide the reader with considerable insight into the methodology by reviewing canonical applications of the technique to the Ising model (and its variants) and the sine-Gordon model. Following this we review recent work on the development of renormalization groups, both numerical and analytical, that alleviate the effects of truncating the spectrum. Using these technologies, we consider a number of applications to one-dimensional systems: properties of carbon nanotubes, quenches in the Lieb-Liniger model, 1+1D quantum chro-modynamics, as well as Landau-Ginzburg theories. In the final part we move our attention to consider truncated spectrum methods applied to two-dimensional systems. This involves combining truncated spectrum methods with matrix product state algorithms. Lastly, we describe applications of this method to two-dimensional systems of free fermions and the quantum Ising model, including their non-equilibrium dynamics.« less

Non-perturbative methodologies for low-dimensional strongly-correlated systems: From non-Abelian bosonization to truncated spectrum methods

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

James, Andrew J. A.; Konik, Robert M.; Lecheminant, Philippe

We review two important non-perturbative approaches for extracting the physics of low-dimensional strongly correlated quantum systems. Firstly, we start by providing a comprehensive review of non-Abelian bosonization. This includes an introduction to the basic elements of conformal field theory as applied to systems with a current algebra, and we orient the reader by presenting a number of applications of non-Abelian bosonization to models with large symmetries. We then tie this technique into recent advances in the ability of cold atomic systems to realize complex symme-tries. Secondly, we discuss truncated spectrum methods for the numerical study of systems in one andmore » two dimensions. For one-dimensional systems we provide the reader with considerable insight into the methodology by reviewing canonical applications of the technique to the Ising model (and its variants) and the sine-Gordon model. Following this we review recent work on the development of renormalization groups, both numerical and analytical, that alleviate the effects of truncating the spectrum. Using these technologies, we consider a number of applications to one-dimensional systems: properties of carbon nanotubes, quenches in the Lieb-Liniger model, 1+1D quantum chro-modynamics, as well as Landau-Ginzburg theories. In the final part we move our attention to consider truncated spectrum methods applied to two-dimensional systems. This involves combining truncated spectrum methods with matrix product state algorithms. Lastly, we describe applications of this method to two-dimensional systems of free fermions and the quantum Ising model, including their non-equilibrium dynamics.« less

Non-perturbative methodologies for low-dimensional strongly-correlated systems: From non-Abelian bosonization to truncated spectrum methods

NASA Astrophysics Data System (ADS)

James, Andrew J. A.; Konik, Robert M.; Lecheminant, Philippe; Robinson, Neil J.; Tsvelik, Alexei M.

2018-04-01

We review two important non-perturbative approaches for extracting the physics of low-dimensional strongly correlated quantum systems. Firstly, we start by providing a comprehensive review of non-Abelian bosonization. This includes an introduction to the basic elements of conformal field theory as applied to systems with a current algebra, and we orient the reader by presenting a number of applications of non-Abelian bosonization to models with large symmetries. We then tie this technique into recent advances in the ability of cold atomic systems to realize complex symmetries. Secondly, we discuss truncated spectrum methods for the numerical study of systems in one and two dimensions. For one-dimensional systems we provide the reader with considerable insight into the methodology by reviewing canonical applications of the technique to the Ising model (and its variants) and the sine-Gordon model. Following this we review recent work on the development of renormalization groups, both numerical and analytical, that alleviate the effects of truncating the spectrum. Using these technologies, we consider a number of applications to one-dimensional systems: properties of carbon nanotubes, quenches in the Lieb–Liniger model, 1  +  1D quantum chromodynamics, as well as Landau–Ginzburg theories. In the final part we move our attention to consider truncated spectrum methods applied to two-dimensional systems. This involves combining truncated spectrum methods with matrix product state algorithms. We describe applications of this method to two-dimensional systems of free fermions and the quantum Ising model, including their non-equilibrium dynamics.

Non-perturbative methodologies for low-dimensional strongly-correlated systems: From non-Abelian bosonization to truncated spectrum methods.

PubMed

James, Andrew J A; Konik, Robert M; Lecheminant, Philippe; Robinson, Neil J; Tsvelik, Alexei M

2018-02-26

We review two important non-perturbative approaches for extracting the physics of low-dimensional strongly correlated quantum systems. Firstly, we start by providing a comprehensive review of non-Abelian bosonization. This includes an introduction to the basic elements of conformal field theory as applied to systems with a current algebra, and we orient the reader by presenting a number of applications of non-Abelian bosonization to models with large symmetries. We then tie this technique into recent advances in the ability of cold atomic systems to realize complex symmetries. Secondly, we discuss truncated spectrum methods for the numerical study of systems in one and two dimensions. For one-dimensional systems we provide the reader with considerable insight into the methodology by reviewing canonical applications of the technique to the Ising model (and its variants) and the sine-Gordon model. Following this we review recent work on the development of renormalization groups, both numerical and analytical, that alleviate the effects of truncating the spectrum. Using these technologies, we consider a number of applications to one-dimensional systems: properties of carbon nanotubes, quenches in the Lieb-Liniger model, 1  +  1D quantum chromodynamics, as well as Landau-Ginzburg theories. In the final part we move our attention to consider truncated spectrum methods applied to two-dimensional systems. This involves combining truncated spectrum methods with matrix product state algorithms. We describe applications of this method to two-dimensional systems of free fermions and the quantum Ising model, including their non-equilibrium dynamics.

Canonical ensemble ground state and correlation entropy of Bose-Einstein condensate

NASA Astrophysics Data System (ADS)

Svidzinsky, Anatoly; Kim, Moochan; Agarwal, Girish; Scully, Marlan O.

2018-01-01

Constraint of a fixed total number of particles yields a correlation between the fluctuation of particles in different states in the canonical ensemble. Here we show that, below the temperature of Bose-Einstein condensation (BEC), the correlation part of the entropy of an ideal Bose gas is cancelled by the ground-state contribution. Thus, in the BEC region, the thermodynamic properties of the gas in the canonical ensemble can be described accurately in a simplified model which excludes the ground state and assumes no correlation between excited levels.

A residue in helical conformation in the native state adopts a β-strand conformation in the folding transition state despite its high and canonical Φ-value.

PubMed

Zarrine-Afsar, Arash; Dahesh, Samira; Davidson, Alan R

2012-05-01

Delineating structures of the transition states in protein folding reactions has provided great insight into the mechanisms by which proteins fold. The most common method for obtaining this information is Φ-value analysis, which is carried out by measuring the changes in the folding and unfolding rates caused by single amino acid substitutions at various positions within a given protein. Canonical Φ-values range between 0 and 1, and residues displaying high values within this range are interpreted to be important in stabilizing the transition state structure, and to elicit this stabilization through native-like interactions. Although very successful in defining the general features of transition state structures, Φ-value analysis can be confounded when non-native interactions stabilize this state. In addition, direct information on backbone conformation within the transition state is not provided. In the work described here, we have investigated structure formation at a conserved β-bulge (with helical conformation) in the Fyn SH3 domain by characterizing the effects of substituting all natural amino acids at one position within this structural motif. By comparing the effects on folding rates of these substitutions with database-derived local structure propensity values, we have determined that this position adopts a non-native backbone conformation in the folding transition state. This result is surprising because this position displays a high and canonical Φ-value of 0.7. This work emphasizes the potential role of non-native conformations in folding pathways and demonstrates that even positions displaying high and canonical Φ-values may, nevertheless, adopt a non-native conformation in the transition state. Copyright © 2012 Wiley Periodicals, Inc.

Interrelationship of canonical and non-canonical Wnt signalling pathways in chronic metabolic diseases.

PubMed

Ackers, Ian; Malgor, Ramiro

2018-01-01

Chronic diseases account for approximately 45% of all deaths in developed countries and are particularly prevalent in countries with the most sophisticated and robust public health systems. Chronic metabolic diseases, specifically lifestyle-related diseases pertaining to diet and exercise, continue to be difficult to treat clinically. The most prevalent of these chronic metabolic diseases include obesity, diabetes, non-alcoholic fatty liver disease, chronic kidney disease and cardiovascular disease and will be the focus of this review. Wnt proteins are highly conserved glycoproteins best known for their role in development and homeostasis of tissues. Given the importance of Wnt signalling in homeostasis, aberrant Wnt signalling likely regulates metabolic processes and may contribute to the development of chronic metabolic diseases. Expression of Wnt proteins and dysfunctional Wnt signalling has been reported in multiple chronic diseases. It is interesting to speculate about an interrelationship between the Wnt signalling pathways as a potential pathological mechanism in chronic metabolic diseases. The aim of this review is to summarize reported findings on the contrasting roles of Wnt signalling in lifestyle-related chronic metabolic diseases; specifically, the contribution of Wnt signalling to lipid accumulation, fibrosis and chronic low-grade inflammation.

Non-canonical Smads phosphorylation induced by the glutamate release inhibitor, riluzole, through GSK3 activation in melanoma.

PubMed

Abushahba, Walid; Olabisi, Oyenike O; Jeong, Byeong-Seon; Boregowda, Rajeev K; Wen, Yu; Liu, Fang; Goydos, James S; Lasfar, Ahmed; Cohen-Solal, Karine A

2012-01-01

Riluzole, an inhibitor of glutamate release, has shown the ability to inhibit melanoma cell xenograft growth. A phase 0 clinical trial of riluzole as a single agent in patients with melanoma resulted in involution of tumors associated with inhibition of both the mitogen-activated protein kinase (MAPK) and phophoinositide-3-kinase/AKT (PI3K/AKT) pathways in 34% of patients. In the present study, we demonstrate that riluzole inhibits AKT-mediated glycogen synthase kinase 3 (GSK3) phosphorylation in melanoma cell lines. Because we have demonstrated that GSK3 is involved in the phosphorylation of two downstream effectors of transforming growth factor beta (TGFβ), Smad2 and Smad3, at their linker domain, our aim was to determine whether riluzole could induce GSK3β-mediated linker phosphorylation of Smad2 and Smad3. We present evidence that riluzole increases Smad2 and Smad3 linker phosphorylation at the cluster of serines 245/250/255 and serine 204 respectively. Using GSK3 inhibitors and siRNA knock-down, we demonstrate that the mechanism of riluzole-induced Smad phosphorylation involved GSK3β. In addition, GSK3β could phosphorylate the same linker sites in vitro. The riluzole-induced Smad linker phosphorylation is mechanistically different from the Smad linker phosphorylation induced by TGFβ. We also demonstrate that riluzole-induced Smad linker phosphorylation is independent of the expression of the metabotropic glutamate receptor 1 (GRM1), which is one of the glutamate receptors whose involvement in human melanoma has been documented. We further show that riluzole upregulates the expression of INHBB and PLAU, two genes associated with the TGFβ signaling pathway. The non-canonical increase in Smad linker phosphorylation induced by riluzole could contribute to the modulation of the pro-oncogenic functions of Smads in late stage melanomas.

Non-Canonical Smads Phosphorylation Induced by the Glutamate Release Inhibitor, Riluzole, through GSK3 Activation in Melanoma

PubMed Central

Jeong, Byeong-Seon; Boregowda, Rajeev K.; Wen, Yu; Liu, Fang; Goydos, James S.; Lasfar, Ahmed; Cohen-Solal, Karine A.

2012-01-01

Riluzole, an inhibitor of glutamate release, has shown the ability to inhibit melanoma cell xenograft growth. A phase 0 clinical trial of riluzole as a single agent in patients with melanoma resulted in involution of tumors associated with inhibition of both the mitogen-activated protein kinase (MAPK) and phophoinositide-3-kinase/AKT (PI3K/AKT) pathways in 34% of patients. In the present study, we demonstrate that riluzole inhibits AKT-mediated glycogen synthase kinase 3 (GSK3) phosphorylation in melanoma cell lines. Because we have demonstrated that GSK3 is involved in the phosphorylation of two downstream effectors of transforming growth factor beta (TGFβ), Smad2 and Smad3, at their linker domain, our aim was to determine whether riluzole could induce GSK3β-mediated linker phosphorylation of Smad2 and Smad3. We present evidence that riluzole increases Smad2 and Smad3 linker phosphorylation at the cluster of serines 245/250/255 and serine 204 respectively. Using GSK3 inhibitors and siRNA knock-down, we demonstrate that the mechanism of riluzole-induced Smad phosphorylation involved GSK3β. In addition, GSK3β could phosphorylate the same linker sites in vitro. The riluzole-induced Smad linker phosphorylation is mechanistically different from the Smad linker phosphorylation induced by TGFβ. We also demonstrate that riluzole-induced Smad linker phosphorylation is independent of the expression of the metabotropic glutamate receptor 1 (GRM1), which is one of the glutamate receptors whose involvement in human melanoma has been documented. We further show that riluzole upregulates the expression of INHBB and PLAU, two genes associated with the TGFβ signaling pathway. The non-canonical increase in Smad linker phosphorylation induced by riluzole could contribute to the modulation of the pro-oncogenic functions of Smads in late stage melanomas. PMID:23077590

Metabolic engineering of monoterpene biosynthesis in tomato fruits via introduction of the non-canonical substrate neryl diphosphate.

PubMed

Gutensohn, Michael; Nguyen, Thuong T H; McMahon, Richard D; Kaplan, Ian; Pichersky, Eran; Dudareva, Natalia

2014-07-01

Recently it was shown that monoterpenes in tomato trichomes (Solanum lycopersicum) are synthesized by phellandrene synthase 1 (PHS1) from the non-canonical substrate neryl diphosphate (NPP), the cis-isomer of geranyl diphosphate (GPP). As PHS1 accepts both NPP and GPP substrates forming different monoterpenes, it was overexpressed in tomato fruits to test if NPP is also available in a tissue highly active in carotenoid production. However, transgenic fruits overexpressing PHS1 produced only small amounts of GPP-derived PHS1 monoterpene products, indicating the absence of endogenous NPP. Therefore, NPP formation was achieved by diverting the metabolic flux from carotenoids via expression of tomato neryl diphosphate synthase 1 (NDPS1). NDPS1 transgenic fruits produced NPP-derived monoterpenes, including nerol, neral and geranial, while displaying reduced lycopene content. NDPS1 co-expression with PHS1 resulted in a monoterpene blend, including β-phellandrene, similar to that produced from NPP by PHS1 in vitro and in trichomes. Unexpectedly, PHS1×NDPS1 fruits showed recovery of lycopene levels compared to NDPS1 fruits, suggesting that redirection of metabolic flux is only partially responsible for the reduction in carotenoids. In vitro assays demonstrated that NPP serves as an inhibitor of geranylgeranyl diphosphate synthase, thus its consumption by PHS1 leads to recovery of lycopene levels. Monoterpenes produced in PHS1×NDPS1 fruits contributed to direct plant defense negatively affecting feeding behavior of the herbivore Helicoverpa zea and displaying antifungal activity against Botrytis cinerea. These results show that NPP-derived terpenoids can be produced in plant tissues; however, NPP has to be consumed to avoid negative impacts on plant metabolism. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Building a Science of Animal Minds: Lloyd Morgan, Experimentation, and Morgan's Canon.

PubMed

Fitzpatrick, Simon; Goodrich, Grant

2017-08-01

Conwy Lloyd Morgan (1852-1936) is widely regarded as the father of modern comparative psychology. Yet, Morgan initially had significant doubts about whether a genuine science of comparative psychology was even possible, only later becoming more optimistic about our ability to make reliable inferences about the mental capacities of non-human animals. There has been a fair amount of disagreement amongst scholars of Morgan's work about the nature, timing, and causes of this shift in Morgan's thinking. We argue that Morgan underwent two quite different shifts of attitude towards the proper practice of comparative psychology. The first was a qualified acceptance of the Romanesian approach to comparative psychology that he had initially criticized. The second was a shift away from Romanes' reliance on systematizing anecdotal evidence of animal intelligence towards an experimental approach, focused on studying the development of behaviour. We emphasize the role of Morgan's evolving epistemological views in bringing about the first shift - in particular, his philosophy of science. We emphasize the role of an intriguing but overlooked figure in the history of comparative psychology in explaining the second shift, T. Mann Jones, whose correspondence with Morgan provided an important catalyst for Morgan's experimental turn, particularly the special focus on development. We also shed light on the intended function of Morgan's Canon, the methodological principle for which Morgan is now mostly known. The Canon can only be properly understood by seeing it in the context of Morgan's own unique experimental vision for comparative psychology.

Grand canonical ensemble Monte Carlo simulation of the dCpG/proflavine crystal hydrate.

PubMed Central

Resat, H; Mezei, M

1996-01-01

The grand canonical ensemble Monte Carlo molecular simulation method is used to investigate hydration patterns in the crystal hydrate structure of the dCpG/proflavine intercalated complex. The objective of this study is to show by example that the recently advocated grand canonical ensemble simulation is a computationally efficient method for determining the positions of the hydrating water molecules in protein and nucleic acid structures. A detailed molecular simulation convergence analysis and an analogous comparison of the theoretical results with experiments clearly show that the grand ensemble simulations can be far more advantageous than the comparable canonical ensemble simulations. Images FIGURE 5 FIGURE 7 PMID:8873992

Deviations from Newton's law in supersymmetric large extra dimensions

NASA Astrophysics Data System (ADS)

Callin, P.; Burgess, C. P.

2006-09-01

Deviations from Newton's inverse-squared law at the micron length scale are smoking-gun signals for models containing supersymmetric large extra dimensions (SLEDs), which have been proposed as approaches for resolving the cosmological constant problem. Just like their non-supersymmetric counterparts, SLED models predict gravity to deviate from the inverse-square law because of the advent of new dimensions at sub-millimeter scales. However SLED models differ from their non-supersymmetric counterparts in three important ways: (i) the size of the extra dimensions is fixed by the observed value of the dark energy density, making it impossible to shorten the range over which new deviations from Newton's law must be seen; (ii) supersymmetry predicts there to be more fields in the extra dimensions than just gravity, implying different types of couplings to matter and the possibility of repulsive as well as attractive interactions; and (iii) the same mechanism which is purported to keep the cosmological constant naturally small also keeps the extra-dimensional moduli effectively massless, leading to deviations from general relativity in the far infrared of the scalar-tensor form. We here explore the deviations from Newton's law which are predicted over micron distances, and show the ways in which they differ and resemble those in the non-supersymmetric case.

Bach, Beethoven, Bourdieu: "Cultural Capital" and the Scholastic Canon in England's A-Level Examinations

ERIC Educational Resources Information Center

Legg, Robert

2012-01-01

This article applies Bourdieu's notion of "cultural capital" to historical, documentary research which investigates the construction of a scholastic canon within England's A-level music examinations. A digest of the ways in which this canon evolved between 1951 and 1986 is presented in support of the idea that examiners' responses to…

Representations of spacetime diffeomorphisms. I. Canonical parametrized field theories

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

Isham, C.J.; Kuchar, K.V.

The super-Hamiltonian and supermomentum in canonical geometrodynamics or in a parametried field theory on a given Riemannian background have Poisson brackets which obey the Dirac relations. By smearing the supermomentum with vector fields VepsilonL Diff..sigma.. on the space manifold ..sigma.., the Lie algebra L Diff ..sigma.. of the spatial diffeomorphism group Diff ..sigma.. can be mapped antihomomorphically into the Poisson bracket algebra on the phase space of the system. The explicit dependence of the Poisson brackets between two super-Hamiltonians on canonical coordinates (spatial metrics in geometrodynamics and embedding variables in parametrized theories) is usually regarded as an indication that themore » Dirac relations cannot be connected with a representation of the complete Lie algebra L Diff M of spacetime diffeomorphisms.« less

The structure of common psychiatric symptoms: how many dimensions of neurosis?

PubMed

Ormel, J; Oldehinkel, A J; Goldberg, D P; Hodiamont, P P; Wilmink, F W; Bridges, K

1995-05-01

In order to replicate and elaborate the two-dimensional model of depression and anxiety underlying the structure of common psychiatric symptoms proposed by Goldberg et al. (1987), we carried out latent trait analyses on PSE symptom data of the original Manchester study and two recent Dutch studies. We used the same analytical strategy as Goldberg et al. to facilitate comparison with the earlier work. It was found that a more comprehensive set of common psychiatric symptoms caused an extra, third dimension to emerge, so that the earlier anxiety dimension became split between a specific anxiety axis characterized by situational and phobic anxiety and avoidance, and a non-specific anxiety axis characterized by free-floating anxiety, various symptoms relating to tension, irritability and restlessness. It is argued that three dimensions are sufficient to account for the covariance between common psychiatric symptoms. A fairly consistent correlation between the non-specific anxiety and the depression dimension was found across sites, as well as independence of the specific anxiety dimension from the other two dimensions. Furthermore, the depression dimension was robust with similar symptom profiles across samples, but there appeared to be local differences in the structure of anxiety symptoms.

37 CFR 10.20 - Canons and Disciplinary Rules.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Canons and Disciplinary Rules. 10.20 Section 10.20 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark...

37 CFR 10.20 - Canons and Disciplinary Rules.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canons and Disciplinary Rules. 10.20 Section 10.20 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and Trademark...

Avicenna's Canon of Medicine and modern urology: part II: bladder calculi.

PubMed

Madineh, Sayed Mohammad Ali

2009-01-01

In the previous issue of the Urology Journal, a comparison of Avicenna's Canon of Medicine with modern urologic findings was done in part I of this article, addressing bladder anatomy and physiology and bladder calculi. In part II of this review, the remaining chapters of the Canon of Medicine on bladder calculi are reviewed. Avicenna points to perineal urethrostomy (perineostomy), which is today performed as the last therapeutic line or as a temporary remedy before surgical treatment. He also describes surgery via transperineal route and warns the surgeon of the proximity of vasa deferentia, prostate gland, and neurovascular bundle and their exposure in this position. Usage of grasping forceps for removal of bladder calculus and emphasis on removing all calculus fragments are the interesting points of this chapter. Avicenna explains a technique similar to the use of a Babcock forceps for prevention of calculus migration. Complications of bladder calculus surgery and cystostomy are also addressed with scientific precision in the Canon. It is noteworthy that 8 centuries before Fournier described necrotizing fasciitis in male genitalia, Avicenna had described Fournier gangrene in his book.

Retro-dimension-cue benefit in visual working memory.

PubMed

Ye, Chaoxiong; Hu, Zhonghua; Ristaniemi, Tapani; Gendron, Maria; Liu, Qiang

2016-10-24

In visual working memory (VWM) tasks, participants' performance can be improved by a retro-object-cue. However, previous studies have not investigated whether participants' performance can also be improved by a retro-dimension-cue. Three experiments investigated this issue. We used a recall task with a retro-dimension-cue in all experiments. In Experiment 1, we found benefits from retro-dimension-cues compared to neutral cues. This retro-dimension-cue benefit is reflected in an increased probability of reporting the target, but not in the probability of reporting the non-target, as well as increased precision with which this item is remembered. Experiment 2 replicated the retro-dimension-cue benefit and showed that the length of the blank interval after the cue disappeared did not influence recall performance. Experiment 3 replicated the results of Experiment 2 with a lower memory load. Our studies provide evidence that there is a robust retro-dimension-cue benefit in VWM. Participants can use internal attention to flexibly allocate cognitive resources to a particular dimension of memory representations. The results also support the feature-based storing hypothesis.

Enabling grand-canonical Monte Carlo: extending the flexibility of GROMACS through the GromPy python interface module.

PubMed

Pool, René; Heringa, Jaap; Hoefling, Martin; Schulz, Roland; Smith, Jeremy C; Feenstra, K Anton

2012-05-05

We report on a python interface to the GROMACS molecular simulation package, GromPy (available at https://github.com/GromPy). This application programming interface (API) uses the ctypes python module that allows function calls to shared libraries, for example, written in C. To the best of our knowledge, this is the first reported interface to the GROMACS library that uses direct library calls. GromPy can be used for extending the current GROMACS simulation and analysis modes. In this work, we demonstrate that the interface enables hybrid Monte-Carlo/molecular dynamics (MD) simulations in the grand-canonical ensemble, a simulation mode that is currently not implemented in GROMACS. For this application, the interplay between GromPy and GROMACS requires only minor modifications of the GROMACS source code, not affecting the operation, efficiency, and performance of the GROMACS applications. We validate the grand-canonical application against MD in the canonical ensemble by comparison of equations of state. The results of the grand-canonical simulations are in complete agreement with MD in the canonical ensemble. The python overhead of the grand-canonical scheme is only minimal. Copyright © 2012 Wiley Periodicals, Inc.

A Problem-Centered Approach to Canonical Matrix Forms

ERIC Educational Resources Information Center

Sylvestre, Jeremy

2014-01-01

This article outlines a problem-centered approach to the topic of canonical matrix forms in a second linear algebra course. In this approach, abstract theory, including such topics as eigenvalues, generalized eigenspaces, invariant subspaces, independent subspaces, nilpotency, and cyclic spaces, is developed in response to the patterns discovered…

The Dimensions of Residential Segregation.

ERIC Educational Resources Information Center

Massey, Douglas S.; Denton, Nancy A.

1988-01-01

Evaluates 20 potential indicators of residential segregation using census data on Hispanics, Blacks, Asians, and non-Hispanic Whites in 60 U.S. metropolitan areas. Factor-analyzes the results to select a single best indicator for each of five dimensions of residential segregation. Contains 69 references and 22 statistical formulas. (SV)

New approach to canonical partition functions computation in Nf=2 lattice QCD at finite baryon density

NASA Astrophysics Data System (ADS)

Bornyakov, V. G.; Boyda, D. L.; Goy, V. A.; Molochkov, A. V.; Nakamura, Atsushi; Nikolaev, A. A.; Zakharov, V. I.

2017-05-01

We propose and test a new approach to computation of canonical partition functions in lattice QCD at finite density. We suggest a few steps procedure. We first compute numerically the quark number density for imaginary chemical potential i μq I . Then we restore the grand canonical partition function for imaginary chemical potential using the fitting procedure for the quark number density. Finally we compute the canonical partition functions using high precision numerical Fourier transformation. Additionally we compute the canonical partition functions using the known method of the hopping parameter expansion and compare results obtained by two methods in the deconfining as well as in the confining phases. The agreement between two methods indicates the validity of the new method. Our numerical results are obtained in two flavor lattice QCD with clover improved Wilson fermions.

Effects of Environmental Stimulation on Infant Vocalizations and Orofacial Dynamics at the Onset of Canonical Babbling

PubMed Central

Harold, Meredith Poore; Barlow, Steven M.

2012-01-01

The vocalizations and jaw kinematics of 30 infants aged 6–8 months were recorded using a Motion Analysis System and audiovisual technologies. This study represents the first attempt to determine the effect of play environment on infants’ rate of vocalization and jaw movement. Four play conditions were compared: watching videos, social contingent reinforcement and vocal modeling with an adult, playing alone with small toys, and playing alone with large toys. The fewest vocalizations and spontaneous movement were observed when infants were watching videos or interacting with an adult. Infants vocalized most when playing with large toys. The small toys, which naturally elicited gross motor movement (e.g., waving, banging, shaking), educed fewer vocalizations. This study was also the first to quantify the kinematics of vocalized and non-vocalized jaw movements of 6–8 month-old infants. Jaw kinematics did not differentiate infants who produced canonical syllables from those who did not. All infants produced many jaw movements without vocalization. However, during vocalization, infants were unlikely to move their jaw. This contradicts current theories that infant protophonic vocalizations are jaw dominant. Results of the current study can inform socio-linguistic and kinematic theories of canonical babbling. PMID:23261792

Systemic combinatorial peptide selection yields a non-canonical iron-mimicry mechanism for targeting tumors in a mouse model of human glioblastoma

PubMed Central

Staquicini, Fernanda I.; Ozawa, Michael G.; Moya, Catherine A.; Driessen, Wouter H.P.; Barbu, E. Magda; Nishimori, Hiroyuki; Soghomonyan, Suren; Flores, Leo G.; Liang, Xiaowen; Paolillo, Vincenzo; Alauddin, Mian M.; Basilion, James P.; Furnari, Frank B.; Bogler, Oliver; Lang, Frederick F.; Aldape, Kenneth D.; Fuller, Gregory N.; Höök, Magnus; Gelovani, Juri G.; Sidman, Richard L.; Cavenee, Webster K.; Pasqualini, Renata; Arap, Wadih

2010-01-01

The management of CNS tumors is limited by the blood-brain barrier (BBB), a vascular interface that restricts the passage of most molecules from the blood into the brain. Here we show that phage particles targeted with certain ligand motifs selected in vivo from a combinatorial peptide library can cross the BBB under normal and pathological conditions. Specifically, we demonstrated that phage clones displaying an iron-mimic peptide were able to target a protein complex of transferrin and transferrin receptor (TfR) through a non-canonical allosteric binding mechanism and that this functional protein complex mediated transport of the corresponding viral particles into the normal mouse brain. We also showed that, in an orthotopic mouse model of human glioblastoma, a combination of TfR overexpression plus extended vascular permeability and ligand retention resulted in remarkable brain tumor targeting of chimeric adeno-associated virus/phage particles displaying the iron-mimic peptide and carrying a gene of interest. As a proof of concept, we delivered the HSV thymidine kinase gene for molecular-genetic imaging and targeted therapy of intracranial xenografted tumors. Finally, we established that these experimental findings might be clinically relevant by determining through human tissue microarrays that many primary astrocytic tumors strongly express TfR. Together, our combinatorial selection system and results may provide a translational avenue for the targeted detection and treatment of brain tumors. PMID:21183793

Connecting the Canon to Current Young Adult Literature

ERIC Educational Resources Information Center

Rybakova, Katie; Roccanti, Rikki

2016-01-01

In this article we discuss the respective roles of young adult literature and literary texts in the secondary level English Language Arts classroom and explore the connections that can be made between popular young adult books and the traditional canon. We provide examples showing how young adult literature bestsellers such as "The Book…

The Canon, the Web, and the Long Tail

ERIC Educational Resources Information Center

Sanderhoff, Merete

2017-01-01

This article argues that releasing images of artworks into the public domain creates a new possibility for the public to challenge the canon or create their own, based on access to previously inaccessible images. Through the dissemination of openly licensed artworks across the Internet, museums can support the public in expanding their engagement…

'Non-hypotensive' hypovolaemia reduces ascending aortic dimensions in humans

NASA Technical Reports Server (NTRS)

Taylor, J. A.; Halliwill, J. R.; Brown, T. E.; Hayano, J.; Eckberg, D. L.

1995-01-01

1. The notion that small, 'non-hypotensive' reductions of effective blood volume alter neither arterial pressure nor arterial baroreceptor activity is pervasive in the experimental literature. We tested two hypotheses: (a) that minute arterial pressure and cardiac autonomic outflow changes during hypovolaemia induced by lower body suction in humans are masked by alterations in breathing, and (b) that evidence for arterial baroreflex engagement might be obtained from measurements of thoracic aorta dimensions. 2. In two studies, responses to graded lower body suction at 0 (control), 5, 10, 15, 20 and 40 mmHg were examined in twelve and ten healthy young men, respectively. In the first, arterial pressure (photoplethysmograph), R-R interval, and respiratory sinus arrhythmia amplitude (complex demodulation) were measured during uncontrolled and controlled breathing (constant breathing frequency and tidal volume). In the second, cross-sectional areas of the ascending thoracic aorta were calculated from nuclear magnetic resonance images. 3. Lower body suction with controlled breathing resulted in an increased arterial pulse pressure at mild levels (5-20 mmHg; ANOVA, P < 0.05) and a decreased arterial pulse pressure at moderate levels (40 mmHg; ANOVA, P < 0.05). Both R-R intervals and respiratory sinus arrhythmia were negatively related to lower body suction level, whether group averages (general linear regression, r > 0.92) or individual subjects (orthogonal polynomials, 12 of 12 subjects) were assessed. 4. Aortic pulse area decreased progressively and significantly during mild lower body suction, with 47% of the total decline occurring by 5 mmHg. 5. These results suggest that small reductions of effective blood volume reduce aortic baroreceptive areas and trigger haemodynamic adjustments which are so efficient that alterations in arterial pressure escape detection by conventional means.

The canonical way to make a heart: β-catenin and plakoglobin in heart development and remodeling.

PubMed

Piven, Oksana O; Winata, Cecilia L

2017-12-01

The main mediator of the canonical Wnt pathway, β-catenin, is a major effector of embryonic development, postnatal tissue homeostasis, and adult tissue regeneration. The requirement for β-catenin in cardiogenesis and embryogenesis has been well established. However, many questions regarding the molecular mechanisms by which β-catenin and canonical Wnt signaling regulate these developmental processes remain unanswered. An interesting question that emerged from our studies concerns how β-catenin signaling is modulated through interaction with other factors. Recent experimental data implicate new players in canonical Wnt signaling, particularly those which modulate β-catenin function in many its biological processes, including cardiogenesis. One of the interesting candidates is plakoglobin, a little-studied member of the catenin family which shares several mechanistic and functional features with its close relative, β-catenin. Here we have focused on the function of β-catenin in cardiogenesis. We also summarize findings on plakoglobin signaling function and discuss possible interplays between β-catenin and plakoglobin in the regulation of embryonic heart development. Impact statement Heart development, function, and remodeling are complex processes orchestrated by multiple signaling networks. This review examines our current knowledge of the role of canonical Wnt signaling in cardiogenesis and heart remodeling, focusing primarily on the mechanistic action of its effector β-catenin. We summarize the generally accepted understanding of the field based on experimental in vitro and in vivo data, and address unresolved questions in the field, specifically relating to the role of canonical Wnt signaling in heart maturation and regeneration. What are the modulators of canonical Wnt, and particularly what are the potential roles of plakoglobin, a close relative of β-catenin, in regulating Wnt signaling?Answers to these questions will enhance our understanding of the

WNT16 antagonises excessive canonical WNT activation and protects cartilage in osteoarthritis.

PubMed

Nalesso, Giovanna; Thomas, Bethan Lynne; Sherwood, Joanna Claire; Yu, Jing; Addimanda, Olga; Eldridge, Suzanne Elizabeth; Thorup, Anne-Sophie; Dale, Leslie; Schett, Georg; Zwerina, Jochen; Eltawil, Noha; Pitzalis, Costantino; Dell'Accio, Francesco

2017-01-01

Both excessive and insufficient activation of WNT signalling results in cartilage breakdown and osteoarthritis. WNT16 is upregulated in the articular cartilage following injury and in osteoarthritis. Here, we investigate the function of WNT16 in osteoarthritis and the downstream molecular mechanisms. Osteoarthritis was induced by destabilisation of the medial meniscus in wild-type and WNT16-deficient mice. Molecular mechanisms and downstream effects were studied in vitro and in vivo in primary cartilage progenitor cells and primary chondrocytes. The pathway downstream of WNT16 was studied in primary chondrocytes and using the axis duplication assay in Xenopus. WNT16-deficient mice developed more severe osteoarthritis with reduced expression of lubricin and increased chondrocyte apoptosis. WNT16 supported the phenotype of cartilage superficial-zone progenitor cells and lubricin expression. Increased osteoarthritis in WNT16-deficient mice was associated with excessive activation of canonical WNT signalling. In vitro, high doses of WNT16 weakly activated canonical WNT signalling, but, in co-stimulation experiments, WNT16 reduced the capacity of WNT3a to activate the canonical WNT pathway. In vivo, WNT16 rescued the WNT8-induced primary axis duplication in Xenopus embryos. In osteoarthritis, WNT16 maintains a balanced canonical WNT signalling and prevents detrimental excessive activation, thereby supporting the homeostasis of progenitor cells. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Retro-dimension-cue benefit in visual working memory

PubMed Central

Ye, Chaoxiong; Hu, Zhonghua; Ristaniemi, Tapani; Gendron, Maria; Liu, Qiang

2016-01-01

In visual working memory (VWM) tasks, participants’ performance can be improved by a retro-object-cue. However, previous studies have not investigated whether participants’ performance can also be improved by a retro-dimension-cue. Three experiments investigated this issue. We used a recall task with a retro-dimension-cue in all experiments. In Experiment 1, we found benefits from retro-dimension-cues compared to neutral cues. This retro-dimension-cue benefit is reflected in an increased probability of reporting the target, but not in the probability of reporting the non-target, as well as increased precision with which this item is remembered. Experiment 2 replicated the retro-dimension-cue benefit and showed that the length of the blank interval after the cue disappeared did not influence recall performance. Experiment 3 replicated the results of Experiment 2 with a lower memory load. Our studies provide evidence that there is a robust retro-dimension-cue benefit in VWM. Participants can use internal attention to flexibly allocate cognitive resources to a particular dimension of memory representations. The results also support the feature-based storing hypothesis. PMID:27774983

Grand canonical electronic density-functional theory: Algorithms and applications to electrochemistry.

PubMed

Sundararaman, Ravishankar; Goddard, William A; Arias, Tomas A

2017-03-21

First-principles calculations combining density-functional theory and continuum solvation models enable realistic theoretical modeling and design of electrochemical systems. When a reaction proceeds in such systems, the number of electrons in the portion of the system treated quantum mechanically changes continuously, with a balancing charge appearing in the continuum electrolyte. A grand-canonical ensemble of electrons at a chemical potential set by the electrode potential is therefore the ideal description of such systems that directly mimics the experimental condition. We present two distinct algorithms: a self-consistent field method and a direct variational free energy minimization method using auxiliary Hamiltonians (GC-AuxH), to solve the Kohn-Sham equations of electronic density-functional theory directly in the grand canonical ensemble at fixed potential. Both methods substantially improve performance compared to a sequence of conventional fixed-number calculations targeting the desired potential, with the GC-AuxH method additionally exhibiting reliable and smooth exponential convergence of the grand free energy. Finally, we apply grand-canonical density-functional theory to the under-potential deposition of copper on platinum from chloride-containing electrolytes and show that chloride desorption, not partial copper monolayer formation, is responsible for the second voltammetric peak.

Vocal patterns in infants with autism spectrum disorder: canonical babbling status and vocalization frequency.

PubMed

Patten, Elena; Belardi, Katie; Baranek, Grace T; Watson, Linda R; Labban, Jeffrey D; Oller, D Kimbrough

2014-10-01

Canonical babbling is a critical milestone for speech development and is usually well in place by 10 months. The possibility that infants with autism spectrum disorder (ASD) show late onset of canonical babbling has so far eluded evaluation. Rate of vocalization or "volubility" has also been suggested as possibly aberrant in infants with ASD. We conducted a retrospective video study examining vocalizations of 37 infants at 9-12 and 15-18 months. Twenty-three of the 37 infants were later diagnosed with ASD and indeed produced low rates of canonical babbling and low volubility by comparison with the 14 typically developing infants. The study thus supports suggestions that very early vocal patterns may prove to be a useful component of early screening and diagnosis of ASD.

Canonical transformation path to gauge theories of gravity

NASA Astrophysics Data System (ADS)

Struckmeier, J.; Muench, J.; Vasak, D.; Kirsch, J.; Hanauske, M.; Stoecker, H.

2017-06-01

In this paper, the generic part of the gauge theory of gravity is derived, based merely on the action principle and on the general principle of relativity. We apply the canonical transformation framework to formulate geometrodynamics as a gauge theory. The starting point of our paper is constituted by the general De Donder-Weyl Hamiltonian of a system of scalar and vector fields, which is supposed to be form-invariant under (global) Lorentz transformations. Following the reasoning of gauge theories, the corresponding locally form-invariant system is worked out by means of canonical transformations. The canonical transformation approach ensures by construction that the form of the action functional is maintained. We thus encounter amended Hamiltonian systems which are form-invariant under arbitrary spacetime transformations. This amended system complies with the general principle of relativity and describes both, the dynamics of the given physical system's fields and their coupling to those quantities which describe the dynamics of the spacetime geometry. In this way, it is unambiguously determined how spin-0 and spin-1 fields couple to the dynamics of spacetime. A term that describes the dynamics of the "free" gauge fields must finally be added to the amended Hamiltonian, as common to all gauge theories, to allow for a dynamic spacetime geometry. The choice of this "dynamics" Hamiltonian is outside of the scope of gauge theory as presented in this paper. It accounts for the remaining indefiniteness of any gauge theory of gravity and must be chosen "by hand" on the basis of physical reasoning. The final Hamiltonian of the gauge theory of gravity is shown to be at least quadratic in the conjugate momenta of the gauge fields—this is beyond the Einstein-Hilbert theory of general relativity.

Sequence dependency of canonical base pair opening in the DNA double helix

PubMed Central

Villa, Alessandra

2017-01-01

The flipping-out of a DNA base from the double helical structure is a key step of many cellular processes, such as DNA replication, modification and repair. Base pair opening is the first step of base flipping and the exact mechanism is still not well understood. We investigate sequence effects on base pair opening using extensive classical molecular dynamics simulations targeting the opening of 11 different canonical base pairs in two DNA sequences. Two popular biomolecular force fields are applied. To enhance sampling and calculate free energies, we bias the simulation along a simple distance coordinate using a newly developed adaptive sampling algorithm. The simulation is guided back and forth along the coordinate, allowing for multiple opening pathways. We compare the calculated free energies with those from an NMR study and check assumptions of the model used for interpreting the NMR data. Our results further show that the neighboring sequence is an important factor for the opening free energy, but also indicates that other sequence effects may play a role. All base pairs are observed to have a propensity for opening toward the major groove. The preferred opening base is cytosine for GC base pairs, while for AT there is sequence dependent competition between the two bases. For AT opening, we identify two non-canonical base pair interactions contributing to a local minimum in the free energy profile. For both AT and CG we observe long-lived interactions with water and with sodium ions at specific sites on the open base pair. PMID:28369121

Quantized vortices in arbitrary dimensions and the normal-to-superfluid phase transition

NASA Astrophysics Data System (ADS)

Bora, Florin

The structure and energetics of superflow around quantized vortices, and the motion inherited by these vortices from this superflow, are explored in the general setting of a superfluid in arbitrary dimensions. The vortices may be idealized as objects of co-dimension two, such as one-dimensional loops and two-dimensional closed surfaces, respectively, in the cases of three- and four-dimensional superfluidity. By using the analogy between vortical superflow and Ampere-Maxwell magnetostatics, the equilibrium superflow containing any specified collection of vortices is constructed. The energy of the superflow is found to take on a simple form for vortices that are smooth and asymptotically large, compared with the vortex core size. The motion of vortices is analyzed in general, as well as for the special cases of hyper-spherical and weakly distorted hyper-planar vortices. In all dimensions, vortex motion reflects vortex geometry. In dimension four and higher, this includes not only extrinsic but also intrinsic aspects of the vortex shape, which enter via the first and second fundamental forms of classical geometry. For hyper-spherical vortices, which generalize the vortex rings of three dimensional superfluidity, the energy-momentum relation is determined. Simple scaling arguments recover the essential features of these results, up to numerical and logarithmic factors. Extending these results to systems containing multiple vortices is elementary due to the linearity of the theory. The energy for multiple vortices is thus a sum of self-energies and power-law interaction terms. The statistical mechanics of a system containing vortices is addressed via the grand canonical partition function. A renormalization-group analysis in which the low energy excitations are integrated approximately, is used to compute certain critical coefficients. The exponents obtained via this approximate procedure are compared with values obtained previously by other means. For dimensions higher

Renal hypodysplasia associates with a WNT4 variant that causes aberrant canonical WNT signaling.

PubMed

Vivante, Asaf; Mark-Danieli, Michal; Davidovits, Miriam; Harari-Steinberg, Orit; Omer, Dorit; Gnatek, Yehudit; Cleper, Roxana; Landau, Daniel; Kovalski, Yael; Weissman, Irit; Eisenstein, Israel; Soudack, Michalle; Wolf, Haike Reznik; Issler, Naomi; Lotan, Danny; Anikster, Yair; Dekel, Benjamin

2013-03-01

Abnormal differentiation of the renal stem/progenitor pool into kidney tissue can lead to renal hypodysplasia (RHD), but the underlying causes of RHD are not well understood. In this multicenter study, we identified 20 Israeli pedigrees with isolated familial, nonsyndromic RHD and screened for mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1. In addition to previously reported RHD-causing genes, we found that two affected brothers were heterozygous for a missense variant in the WNT4 gene. Functional analysis of this variant revealed both antagonistic and agonistic canonical WNT stimuli, dependent on cell type. In HEK293 cells, WNT4 inhibited WNT3A induced canonical activation, and the WNT4 variant significantly enhanced this inhibition of the canonical WNT pathway. In contrast, in primary cultures of human fetal kidney cells, which maintain WNT activation and more closely represent WNT signaling in renal progenitors during nephrogenesis, this mutation caused significant loss of function, resulting in diminished canonical WNT/β-catenin signaling. In conclusion, heterozygous WNT4 variants are likely to play a causative role in renal hypodysplasia.

Renal Hypodysplasia Associates with a Wnt4 Variant that Causes Aberrant Canonical Wnt Signaling

PubMed Central

Vivante, Asaf; Mark-Danieli, Michal; Davidovits, Miriam; Harari-Steinberg, Orit; Omer, Dorit; Gnatek, Yehudit; Cleper, Roxana; Landau, Daniel; Kovalski, Yael; Weissman, Irit; Eisenstein, Israel; Soudack, Michalle; Wolf, Haike Reznik; Issler, Naomi; Lotan, Danny; Anikster, Yair

2013-01-01

Abnormal differentiation of the renal stem/progenitor pool into kidney tissue can lead to renal hypodysplasia (RHD), but the underlying causes of RHD are not well understood. In this multicenter study, we identified 20 Israeli pedigrees with isolated familial, nonsyndromic RHD and screened for mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1. In addition to previously reported RHD-causing genes, we found that two affected brothers were heterozygous for a missense variant in the WNT4 gene. Functional analysis of this variant revealed both antagonistic and agonistic canonical WNT stimuli, dependent on cell type. In HEK293 cells, WNT4 inhibited WNT3A induced canonical activation, and the WNT4 variant significantly enhanced this inhibition of the canonical WNT pathway. In contrast, in primary cultures of human fetal kidney cells, which maintain WNT activation and more closely represent WNT signaling in renal progenitors during nephrogenesis, this mutation caused significant loss of function, resulting in diminished canonical WNT/β-catenin signaling. In conclusion, heterozygous WNT4 variants are likely to play a causative role in renal hypodysplasia. PMID:23520208

Spleen dimensions are inversely associated with lysosomal acid lipase activity in patients with non-alcoholic fatty liver disease.

PubMed

Polimeni, Licia; Pastori, Daniele; Baratta, Francesco; Tozzi, Giulia; Novo, Marta; Vicinanza, Roberto; Troisi, Giovanni; Pannitteri, Gaetano; Ceci, Fabrizio; Scardella, Laura; Violi, Francesco; Angelico, Francesco; Del Ben, Maria

2017-12-01

Fatty liver and splenomegaly are typical features of genetic lysosomal acid lipase (LAL) deficiency. No data in adult patients with non-genetic reduction of LAL activity are available. We investigate the association between spleen dimensions and LAL activity in non-alcoholic fatty liver disease (NAFLD) patients, in whom a reduced LAL activity has been reported. We include 425 consecutive patients who underwent abdominal ultrasound to evaluate hepatic steatosis and spleen dimensions. LAL activity was measured with dried blood spot method (Lalistat2). NAFLD was present in 74.1% of screened patients. Higher median spleen longitudinal diameter (10.6 vs. 9.9 cm; p < 0.001) and spleen area (SA) (32.7 vs. 27.7 cm 2 ; p < 0.001), together with a higher and proportion of splenomegaly (17.8 vs. 5.5%, p = 0.001), are present in patients with NAFLD compared to those without. In NAFLD patients, median LAL activity is 0.9 nmol/spot/h. LAL activity is lower in 56 patients with splenomegaly, as compared to those without (p = 0.009). At multivariable logistic regression analysis, age (above median, OR 0.344; p = 0.003), LAL activity (below median, OR 2.206, p = 0.028), and platelets (OR 0.101, p = 0.002) are significantly associated with splenomegaly. NAFLD patients disclose a relatively high prevalence of spleen enlargement and splenomegaly, which are significantly associated with a reduced LAL activity, suggesting that LAL may contribute to spleen enlargement in this setting.

Vocal patterns in infants with Autism Spectrum Disorder: Canonical babbling status and vocalization frequency

PubMed Central

Patten, Elena; Belardi, Katie; Baranek, Grace T.; Watson, Linda R.; Labban, Jeffrey D.; Oller, D. Kimbrough

2014-01-01

Canonical babbling is a critical milestone for speech development and is usually well in place by 10 months. The possibility that infants with ASD show late onset of canonical babbling has so far eluded evaluation. Rate of vocalization or “volubility” has also been suggested as possibly aberrant in infants with ASD. We conducted a retrospective video study examining vocalizations of 37 infants at 9–12 and 15–18 months. Twenty-three of the 37 infants were later diagnosed with ASD and indeed produced low rates of canonical babbling and low volubility by comparison with the 14 typically developing infants. The study thus supports suggestions that very early vocal patterns may prove to be a useful component of early screening and diagnosis of ASD. PMID:24482292

Cable Connected Spinning Spacecraft, 1. the Canonical Equations, 2. Urban Mass Transportation, 3

NASA Technical Reports Server (NTRS)

Sitchin, A.

1972-01-01

Work on the dynamics of cable-connected spinning spacecraft was completed by formulating the equations of motion by both the canonical equations and Lagrange's equations and programming them for numerical solution on a digital computer. These energy-based formulations will permit future addition of the effect of cable mass. Comparative runs indicate that the canonical formulation requires less computer time. Available literature on urban mass transportation was surveyed. Areas of the private rapid transit concept of urban transportation are also studied.

Selective Attention to Perceptual Dimensions and Switching between Dimensions

ERIC Educational Resources Information Center

Meiran, Nachshon; Dimov, Eduard; Ganel, Tzvi

2013-01-01

In the present experiments, the question being addressed was whether switching attention between perceptual dimensions and selective attention to dimensions are processes that compete over a common resource? Attention to perceptual dimensions is usually studied by requiring participants to ignore a never-relevant dimension. Selection failure…

Incidence Rate of Canonical vs. Derived Medical Terminology in Natural Language.

PubMed

Topac, Vasile; Jurcau, Daniel-Alexandru; Stoicu-Tivadar, Vasile

2015-01-01

Medical terminology appears in the natural language in multiple forms: canonical, derived or inflected form. This research presents an analysis of the form in which medical terminology appears in Romanian and English language. The sources of medical language used for the study are web pages presenting medical information for patients and other lay users. The results show that, in English, medical terminology tends to appear more in canonical form while, in the case of Romanian, it is the opposite. This paper also presents the service that was created to perform this analysis. This tool is available for the general public, and it is designed to be easily extensible, allowing the addition of other languages.

Bidimensional nano-optomechanics and topological backaction in a non-conservative radiation force field.

PubMed

Gloppe, A; Verlot, P; Dupont-Ferrier, E; Siria, A; Poncharal, P; Bachelier, G; Vincent, P; Arcizet, O

2014-11-01

Optomechanics, which explores the fundamental coupling between light and mechanical motion, has made important advances in manipulating macroscopic mechanical oscillators down to the quantum level. However, dynamical effects related to the vectorial nature of the optomechanical interaction remain to be investigated. Here we study a nanowire with subwavelength dimensions coupled strongly to a tightly focused beam of light, enabling an ultrasensitive readout of the nanoresonator dynamics. We determine experimentally the vectorial structure of the optomechanical interaction and demonstrate that a bidimensional dynamical backaction governs the nanowire dynamics. Moreover, the spatial topology of the optomechanical interaction is responsible for novel canonical signatures of strong coupling between mechanical modes, which leads to a topological instability that underlies the non-conservative nature of the optomechanical interaction. These results have a universal character and illustrate the increased sensitivity of nanomechanical devices towards spatially varying interactions, opening fundamental perspectives in nanomechanics, optomechanics, ultrasensitive scanning force microscopy and nano-optics.

A non-canonical role for Rgnef in promoting integrin-stimulated focal adhesion kinase activation

PubMed Central

Miller, Nichol L. G.; Lawson, Christine; Kleinschmidt, Elizabeth G.; Tancioni, Isabelle; Uryu, Sean; Schlaepfer, David D.

2013-01-01

Summary Rgnef (also known as p190RhoGEF or ARHGEF28) is a Rho guanine-nucleotide-exchange factor (GEF) that binds focal adhesion kinase (FAK). FAK is recruited to adhesions and activated by integrin receptors binding to matrix proteins, such as fibronectin (FN). Canonical models place Rgnef downstream of integrin–FAK signaling in regulating Rho GTPase activity and cell movement. Herein, we establish a new, upstream role for Rgnef in enhancing FAK localization to early peripheral adhesions and promoting FAK activation upon FN binding. Rgnef-null mouse embryo fibroblasts (MEFs) exhibit defects in adhesion formation, levels of FAK phosphotyrosine (pY)-397 and FAK localization to peripheral adhesions upon re-plating on FN. Rgnef re-expression rescues these defects, but requires Rgnef–FAK binding. A mutation in the Rgnef pleckstrin homology (PH) domain inhibits adhesion formation, FAK localization, and FAK-Y397 and paxillin-Y118 phosphorylation without disrupting the Rgnef–FAK interaction. A GEF-inactive Rgnef mutant rescues FAK-Y397 phosphorylation and early adhesion localization, but not paxillin-Y118 phosphorylation. This suggests that, downstream of FN binding, paxillin-pY118 requires Rgnef GEF activity through a mechanism distinct from adhesion formation and FAK activation. These results support a scaffolding role for Rgnef in FAK localization and activation at early adhesions in a PH-domain-dependent but GEF-activity-independent manner. PMID:24006257

Non-minimally coupled tachyon field in teleparallel gravity

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

Fazlpour, Behnaz; Banijamali, Ali, E-mail: b.fazlpour@umz.ac.ir, E-mail: a.banijamali@nit.ac.ir

2015-04-01

We perform a full investigation on dynamics of a new dark energy model in which the four-derivative of a non-canonical scalar field (tachyon) is non-minimally coupled to the vector torsion. Our analysis is done in the framework of teleparallel equivalent of general relativity which is based on torsion instead of curvature. We show that in our model there exists a late-time scaling attractor (point P{sub 4}), corresponding to an accelerating universe with the property that dark energy and dark matter densities are of the same order. Such a point can help to alleviate the cosmological coincidence problem. Existence of thismore » point is the most significant difference between our model and another model in which a canonical scalar field (quintessence) is used instead of tachyon field.« less

Grand canonical electronic density-functional theory: Algorithms and applications to electrochemistry

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

Sundararaman, Ravishankar; Goddard, III, William A.; Arias, Tomas A.

First-principles calculations combining density-functional theory and continuum solvation models enable realistic theoretical modeling and design of electrochemical systems. When a reaction proceeds in such systems, the number of electrons in the portion of the system treated quantum mechanically changes continuously, with a balancing charge appearing in the continuum electrolyte. A grand-canonical ensemble of electrons at a chemical potential set by the electrode potential is therefore the ideal description of such systems that directly mimics the experimental condition. We present two distinct algorithms: a self-consistent field method and a direct variational free energy minimization method using auxiliary Hamiltonians (GC-AuxH), to solvemore » the Kohn-Sham equations of electronic density-functional theory directly in the grand canonical ensemble at fixed potential. Both methods substantially improve performance compared to a sequence of conventional fixed-number calculations targeting the desired potential, with the GC-AuxH method additionally exhibiting reliable and smooth exponential convergence of the grand free energy. Lastly, we apply grand-canonical density-functional theory to the under-potential deposition of copper on platinum from chloride-containing electrolytes and show that chloride desorption, not partial copper monolayer formation, is responsible for the second voltammetric peak.« less

Grand canonical electronic density-functional theory: Algorithms and applications to electrochemistry

DOE PAGES

Sundararaman, Ravishankar; Goddard, III, William A.; Arias, Tomas A.

2017-03-16

First-principles calculations combining density-functional theory and continuum solvation models enable realistic theoretical modeling and design of electrochemical systems. When a reaction proceeds in such systems, the number of electrons in the portion of the system treated quantum mechanically changes continuously, with a balancing charge appearing in the continuum electrolyte. A grand-canonical ensemble of electrons at a chemical potential set by the electrode potential is therefore the ideal description of such systems that directly mimics the experimental condition. We present two distinct algorithms: a self-consistent field method and a direct variational free energy minimization method using auxiliary Hamiltonians (GC-AuxH), to solvemore » the Kohn-Sham equations of electronic density-functional theory directly in the grand canonical ensemble at fixed potential. Both methods substantially improve performance compared to a sequence of conventional fixed-number calculations targeting the desired potential, with the GC-AuxH method additionally exhibiting reliable and smooth exponential convergence of the grand free energy. Lastly, we apply grand-canonical density-functional theory to the under-potential deposition of copper on platinum from chloride-containing electrolytes and show that chloride desorption, not partial copper monolayer formation, is responsible for the second voltammetric peak.« less

The effect of hand dimensions, hand shape and some anthropometric characteristics on handgrip strength in male grip athletes and non-athletes.

PubMed

Fallahi, Ali Asghar; Jadidian, Ali Akbar

2011-09-01

It has been suggested that athletes with longer fingers and larger hand surfaces enjoy stronger grip power. Therefore, some researchers have examined a number of factors and anthropometric variables that explain this issue. To our knowledge, the data is scarce. Thus, the aim of this study was to investigate the effect of hand dimensions, hand shape and some anthropometric characteristics on handgrip strength in male grip athletes and non-athletes. 80 subjects aged between 19 and 29 participated in this study in two groups including: national and collegian grip athletes (n=40), and non-athletes (n=40). Body height and mass were measured to calculate body mass index. The shape of the dominant hand was drawn on a piece of paper with a thin marker so that finger spans, finger lengths, and perimeters of the hand could be measured. The hand shape was estimated as the ratio of the hand width to hand length. Handgrip strength was measured in the dominant and non-dominant hand using a standard dynamometer. Descriptive statistics were used for each variable and independent t test was used to analyze the differences between the two groups. The Pearson correlation coefficient test was used to evaluate the correlation between studied variables. Also, to predict important variables in handgrip strength, the linear trend was assessed using a linear regression analysis. There was a significant difference between the two groups in absolute handgrip strength (p<0.001) and handgrip/height ratio (p<0.001). The indices of body height, body mass, lean body mass and body fat content (p<0.001) were significantly greater in grip athletes. All hand variables except FS1-4 (p>0.05) were significantly different between the groups (p<0.001). After controlling body mass all hand anthropometric characteristics except thumb length (r=0.240, p= 0.135), hand shape (r=-0.029, p=0.858), middle finger length (r=0.305, p=0.056) and forearm circumference (r=0.162, p=0.319) significantly correlated with

The Effect of Hand Dimensions, Hand Shape and Some Anthropometric Characteristics on Handgrip Strength in Male Grip Athletes and Non-Athletes

PubMed Central

Fallahi, Ali Asghar; Jadidian, Ali Akbar

2011-01-01

It has been suggested that athletes with longer fingers and larger hand surfaces enjoy stronger grip power. Therefore, some researchers have examined a number of factors and anthropometric variables that explain this issue. To our knowledge, the data is scarce. Thus, the aim of this study was to investigate the effect of hand dimensions, hand shape and some anthropometric characteristics on handgrip strength in male grip athletes and non-athletes. 80 subjects aged between 19 and 29 participated in this study in two groups including: national and collegian grip athletes (n=40), and non-athletes (n=40). Body height and mass were measured to calculate body mass index. The shape of the dominant hand was drawn on a piece of paper with a thin marker so that finger spans, finger lengths, and perimeters of the hand could be measured. The hand shape was estimated as the ratio of the hand width to hand length. Handgrip strength was measured in the dominant and non-dominant hand using a standard dynamometer. Descriptive statistics were used for each variable and independent t test was used to analyze the differences between the two groups. The Pearson correlation coefficient test was used to evaluate the correlation between studied variables. Also, to predict important variables in handgrip strength, the linear trend was assessed using a linear regression analysis. There was a significant difference between the two groups in absolute handgrip strength (p<0.001) and handgrip/height ratio (p<0.001). The indices of body height, body mass, lean body mass and body fat content (p<0.001) were significantly greater in grip athletes. All hand variables except FS1-4 (p>0.05) were significantly different between the groups (p<0.001). After controlling body mass all hand anthropometric characteristics except thumb length (r=0.240, p= 0.135), hand shape (r=−0.029, p=0.858), middle finger length (r=0.305, p=0.056) and forearm circumference (r=0.162, p=0.319) significantly correlated with

Effects of environmental stimulation on infant vocalizations and orofacial dynamics at the onset of canonical babbling.

PubMed

Harold, Meredith Poore; Barlow, Steven M

2013-02-01

The vocalizations and jaw kinematics of 30 infants aged 6-8 months were recorded using a Motion Analysis System and audiovisual technologies. This study represents the first attempt to determine the effect of play environment on infants' rate of vocalization and jaw movement. Four play conditions were compared: watching videos, social contingent reinforcement and vocal modeling with an adult, playing alone with small toys, and playing alone with large toys. The fewest vocalizations and spontaneous movement were observed when infants were watching videos or interacting with an adult. Infants vocalized most when playing with large toys. The small toys, which naturally elicited gross motor movement (e.g., waving, banging, shaking), educed fewer vocalizations. This study was also the first to quantify the kinematics of vocalized and non-vocalized jaw movements of 6-8 month-old infants. Jaw kinematics did not differentiate infants who produced canonical syllables from those who did not. All infants produced many jaw movements without vocalization. However, during vocalization, infants were unlikely to move their jaw. This contradicts current theories that infant protophonic vocalizations are jaw-dominant. Results of the current study can inform socio-linguistic and kinematic theories of canonical babbling. Copyright © 2012 Elsevier Inc. All rights reserved.

Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling.

PubMed

Zhou, Yulian; Nathans, Jeremy

2014-10-27

Canonical Wnt signaling in endothelial cells (ECs) is required for vascularization of the central nervous system (CNS) and for formation and maintenance of barrier properties unique to CNS vasculature. Gpr124 is an orphan member of the adhesion G protein-coupled receptor family that is expressed in ECs and is essential for CNS angiogenesis and barrier formation via an unknown mechanism. Using canonical Wnt signaling assays in cell culture and genetic loss- and gain-of-function experiments in mice, we show that Gpr124 functions as a coactivator of Wnt7a- and Wnt7b-stimulated canonical Wnt signaling via a Frizzled receptor and Lrp coreceptor and that Gpr124-stimulated signaling functions in concert with Norrin/Frizzled4 signaling to control CNS vascular development. These experiments identify Gpr124 as a ligand-specific coactivator of canonical Wnt signaling.

Selective attention to perceptual dimensions and switching between dimensions.

PubMed

Meiran, Nachshon; Dimov, Eduard; Ganel, Tzvi

2013-02-01

In the present experiments, the question being addressed was whether switching attention between perceptual dimensions and selective attention to dimensions are processes that compete over a common resource? Attention to perceptual dimensions is usually studied by requiring participants to ignore a never-relevant dimension. Selection failure (Garner's Interference, GI) is indicated by poorer performance in the filtering condition (when this dimension varies) as compared with baseline (when it is fixed). Switching between perceptual dimensions is usually studied with the task switching paradigm. In the present experiments, attention switching was manipulated by using single-task blocks and blocks in which participants switched between tasks or dimensions in reaction to task cues, and attention to dimensions was assessed by including a third, never-relevant dimension that was either fixed or varied randomly. In Experiments 1 (long cue-target interval, CTI) and 2 (short CTI), the tasks involved shape and color and the never-relevant dimension (texture) was chosen to be separable from them. In Experiments 3 (long CTI) and 4 (short CTI), the tasks involved shape and brightness and the never-relevant dimension, saturation, was chosen to be separable from shape and integral with brightness. Task switching did not generate GI but a short CTI did. Thus, switching and filtering generally do not compete over central limited resources unless under tight time pressure. Experiment 3 shows GI in the brightness task but not in the shape task, suggesting that participants switched their attention between brightness and shape when they switched tasks. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Induction of Canonical Wnt Signaling by the Alarmins S100A8/A9 in Murine Knee Joints: Implications for Osteoarthritis.

PubMed

van den Bosch, Martijn H; Blom, Arjen B; Schelbergen, Rik F P; Vogl, Thomas; Roth, Johannes P; Slöetjes, Annet W; van den Berg, Wim B; van der Kraan, Peter M; van Lent, Peter L E M

2016-01-01

Both alarmins S100A8/A9 and canonical Wnt signaling have been found to play active roles in the development of experimental osteoarthritis (OA). However, what activates canonical Wnt signaling remains unknown. This study was undertaken to investigate whether S100A8 induces canonical Wnt signaling and whether S100 proteins exert their effects via activation of Wnt signaling. Expression of the genes for S100A8/A9 and Wnt signaling pathway members was measured in an experimental OA model. Selected Wnt signaling pathway members were overexpressed, and levels of S100A8/A9 were measured. Activation of canonical Wnt signaling was determined after injection of S100A8 into naive joints and induction of collagenase-induced OA in S100A9-deficient mice. Expression of Wnt signaling pathway members was tested in macrophages and fibroblasts after S100A8 stimulation. Canonical Wnt signaling was inhibited in vivo to determine if the effects of S100A8 injections were dependent on Wnt signaling. The alarmins S100A8/A9 and members of the Wnt signaling pathway showed coinciding expression in synovial tissue in an experimental OA model. Synovial overexpression of selected Wnt signaling pathway members did not result in increased expression of S100 proteins. In contrast, intraarticular injection of S100A8 increased canonical Wnt signaling, whereas canonical Wnt signaling was decreased after induction of experimental OA in S100A9-deficient mice. S100A8 stimulation of macrophages, but not fibroblasts, resulted in increased expression of canonical Wnt signaling members. Overexpression of Dkk-1 to inhibit canonical Wnt signaling decreased the induction of matrix metalloproteinase 3, interleukin-6, and macrophage inflammatory protein 1α after injection of S100A8. Our findings indicate that the alarmin S100A8 induces canonical Wnt signaling in macrophages and murine knee joints. The effects of S100A8 are partially dependent on activation of canonical Wnt signaling. © 2016, American College

On the use and computation of the Jordan canonical form in system theory

NASA Technical Reports Server (NTRS)

Sridhar, B.; Jordan, D.

1974-01-01

This paper investigates various aspects of the application of the Jordan canonical form of a matrix in system theory and develops a computational approach to determining the Jordan form for a given matrix. Applications include pole placement, controllability and observability studies, serving as an intermediate step in yielding other canonical forms, and theorem proving. The computational method developed in this paper is both simple and efficient. The method is based on the definition of a generalized eigenvector and a natural extension of Gauss elimination techniques. Examples are included for demonstration purposes.

Servo-hydraulic actuator in controllable canonical form: Identification and experimental validation

NASA Astrophysics Data System (ADS)

Maghareh, Amin; Silva, Christian E.; Dyke, Shirley J.

2018-02-01

Hydraulic actuators have been widely used to experimentally examine structural behavior at multiple scales. Real-time hybrid simulation (RTHS) is one innovative testing method that largely relies on such servo-hydraulic actuators. In RTHS, interface conditions must be enforced in real time, and controllers are often used to achieve tracking of the desired displacements. Thus, neglecting the dynamics of hydraulic transfer system may result either in system instability or sub-optimal performance. Herein, we propose a nonlinear dynamical model for a servo-hydraulic actuator (a.k.a. hydraulic transfer system) coupled with a nonlinear physical specimen. The nonlinear dynamical model is transformed into controllable canonical form for further tracking control design purposes. Through a number of experiments, the controllable canonical model is validated.

Feedback linearization of singularly perturbed systems based on canonical similarity transformations

NASA Astrophysics Data System (ADS)

Kabanov, A. A.

2018-05-01

This paper discusses the problem of feedback linearization of a singularly perturbed system in a state-dependent coefficient form. The result is based on the introduction of a canonical similarity transformation. The transformation matrix is constructed from separate blocks for fast and slow part of an original singularly perturbed system. The transformed singular perturbed system has a linear canonical form that significantly simplifies a control design problem. Proposed similarity transformation allows accomplishing linearization of the system without considering the virtual output (as it is needed for normal form method), a technique of a transition from phase coordinates of the transformed system to state variables of the original system is simpler. The application of the proposed approach is illustrated through example.

A curvilinear, fully implicit, conservative electromagnetic PIC algorithm in multiple dimensions

NASA Astrophysics Data System (ADS)

Chacón, L.; Chen, G.

2016-07-01

We extend a recently proposed fully implicit PIC algorithm for the Vlasov-Darwin model in multiple dimensions (Chen and Chacón (2015) [1]) to curvilinear geometry. As in the Cartesian case, the approach is based on a potential formulation (ϕ, A), and overcomes many difficulties of traditional semi-implicit Darwin PIC algorithms. Conservation theorems for local charge and global energy are derived in curvilinear representation, and then enforced discretely by a careful choice of the discretization of field and particle equations. Additionally, the algorithm conserves canonical-momentum in any ignorable direction, and preserves the Coulomb gauge ∇ ṡ A = 0 exactly. An asymptotically well-posed fluid preconditioner allows efficient use of large cell sizes, which are determined by accuracy considerations, not stability, and can be orders of magnitude larger than required in a standard explicit electromagnetic PIC simulation. We demonstrate the accuracy and efficiency properties of the algorithm with numerical experiments in mapped meshes in 1D-3V and 2D-3V.

Electron cryo-microscopy structure of the canonical TRPC4 ion channel

PubMed Central

Vinayagam, Deivanayagabarathy; Mager, Thomas; Apelbaum, Amir; Bothe, Arne; Merino, Felipe; Hofnagel, Oliver; Gatsogiannis, Christos

2018-01-01

Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca2+ signaling and have been proposed to act as store-operated channels (SOC). Their malfunction is related to cardiomyopathies and their modulation by small molecules has been shown to be effective against renal cancer cells. The molecular mechanism underlying the complex activation and regulation is poorly understood. Here, we report the electron cryo-microscopy structure of zebrafish TRPC4 in its unliganded (apo), closed state at an overall resolution of 3.6 Å. The structure reveals the molecular architecture of the cation conducting pore, including the selectivity filter and lower gate. The cytoplasmic domain contains two key hubs that have been shown to interact with modulating proteins. Structural comparisons with other TRP channels give novel insights into the general architecture and domain organization of this superfamily of channels and help to understand their function and pharmacology. PMID:29717981

The Problematics of Postmodernism: The Double-Voiced Honors Canon.

ERIC Educational Resources Information Center

McCracken, Tim

Honors education is not immune from the current controversy concerning the role of the literary canon. Indeed, the problem seems especially crucial for honors programs, for their curriculums are often multi-disciplinary in their approaches to culture and history. The solution may lie in what Linda Hutcheon calls the "poetics of the…

Joint Blind Source Separation by Multi-set Canonical Correlation Analysis

PubMed Central

Li, Yi-Ou; Adalı, Tülay; Wang, Wei; Calhoun, Vince D

2009-01-01

In this work, we introduce a simple and effective scheme to achieve joint blind source separation (BSS) of multiple datasets using multi-set canonical correlation analysis (M-CCA) [1]. We first propose a generative model of joint BSS based on the correlation of latent sources within and between datasets. We specify source separability conditions, and show that, when the conditions are satisfied, the group of corresponding sources from each dataset can be jointly extracted by M-CCA through maximization of correlation among the extracted sources. We compare source separation performance of the M-CCA scheme with other joint BSS methods and demonstrate the superior performance of the M-CCA scheme in achieving joint BSS for a large number of datasets, group of corresponding sources with heterogeneous correlation values, and complex-valued sources with circular and non-circular distributions. We apply M-CCA to analysis of functional magnetic resonance imaging (fMRI) data from multiple subjects and show its utility in estimating meaningful brain activations from a visuomotor task. PMID:20221319

Region 8: Colorado Canon City Adequate Letter (8/17/2011)

EPA Pesticide Factsheets

This May 4, 2011 letter from EPA to Chistopher E. Urbina M.D., MPH, Colorado Department of Public Health and Environment states that EPA has found that the Canon City PM10 maintenance plan and the 2020 motor vehicle emissions budget (MVEB) adequate

Toward canonical ensemble distribution from self-guided Langevin dynamics simulation

NASA Astrophysics Data System (ADS)

Wu, Xiongwu; Brooks, Bernard R.

2011-04-01

This work derives a quantitative description of the conformational distribution in self-guided Langevin dynamics (SGLD) simulations. SGLD simulations employ guiding forces calculated from local average momentums to enhance low-frequency motion. This enhancement in low-frequency motion dramatically accelerates conformational search efficiency, but also induces certain perturbations in conformational distribution. Through the local averaging, we separate properties of molecular systems into low-frequency and high-frequency portions. The guiding force effect on the conformational distribution is quantitatively described using these low-frequency and high-frequency properties. This quantitative relation provides a way to convert between a canonical ensemble and a self-guided ensemble. Using example systems, we demonstrated how to utilize the relation to obtain canonical ensemble properties and conformational distributions from SGLD simulations. This development makes SGLD not only an efficient approach for conformational searching, but also an accurate means for conformational sampling.

Ethnic Rhinoplasty in Female Patients: The Neoclassical Canons Revisited.

PubMed

Saad, Ahmad; Hewett, Sierra; Nolte, Megan; Delaunay, Flore; Saad, Mariam; Cohen, Steven R

2018-04-01

Despite the substantial amount of research devoted to objectively defining facial attractiveness, the canons have remained a paradigm of aesthetic facial analysis, yet their omnipresence in clinical assessments revealed their limitations outside of a subset of North American Caucasians, leading to criticism about their validity as a standard of facial beauty. In an effort to introduce more objective treatment planning into ethnic rhinoplasty, we compared neoclassical canons and other current standards pertaining to nasal proportions to anatomic proportions of attractive individuals from seven different ethnic backgrounds. Beauty pageant winners (Miss Universe and Miss World nominees) between 2005 and 2015 were selected and assigned to one of seven regionally defined ethnic groups. Anteroposterior and lateral images were obtained through Google, Wikipedia, Miss Universe, and Miss World Web sites. Anthropometry of facial features was performed via Adobe Photoshop TM. Individual facial measurements were then standardized to proportions and compared to the neoclassical canons. Our data reflected an ethnic-dependent preference for the multiple fitness model. Wide-set eyes, larger mouth widths, and smaller noses were significantly relevant in Eastern Mediterranean and European ethnic groups. Exceptions lied within East African and Asian groups. As in the attractive face, the concept of the ideal nasal anatomy varies between different ethnicities. Using objective criteria and proportions of beauty to plan and execute rhinoplasty in different ethnicities can help the surgeon plan and deliver results that are in harmony with patients' individual background and facial anatomy. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Arjunolic acid, a peroxisome proliferator-activated receptor α agonist, regresses cardiac fibrosis by inhibiting non-canonical TGF-β signaling.

PubMed

Bansal, Trisha; Chatterjee, Emeli; Singh, Jasdeep; Ray, Arjun; Kundu, Bishwajit; Thankamani, V; Sengupta, Shantanu; Sarkar, Sagartirtha

2017-10-06

Cardiac hypertrophy and associated heart fibrosis remain a major cause of death worldwide. Phytochemicals have gained attention as alternative therapeutics for managing cardiovascular diseases. These include the extract from the plant Terminalia arjuna, which is a popular cardioprotectant and may prevent or slow progression of pathological hypertrophy to heart failure. Here, we investigated the mode of action of a principal bioactive T. arjuna compound, arjunolic acid (AA), in ameliorating hemodynamic load-induced cardiac fibrosis and identified its intracellular target. Our data revealed that AA significantly represses collagen expression and improves cardiac function during hypertrophy. We found that AA binds to and stabilizes the ligand-binding domain of peroxisome proliferator-activated receptor α (PPARα) and increases its expression during cardiac hypertrophy. PPARα knockdown during AA treatment in hypertrophy samples, including angiotensin II-treated adult cardiac fibroblasts and renal artery-ligated rat heart, suggests that AA-driven cardioprotection primarily arises from PPARα agonism. Moreover, AA-induced PPARα up-regulation leads to repression of TGF-β signaling, specifically by inhibiting TGF-β-activated kinase1 (TAK1) phosphorylation. We observed that PPARα directly interacts with TAK1, predominantly via PPARα N-terminal transactivation domain (AF-1) thereby masking the TAK1 kinase domain. The AA-induced PPARα-bound TAK1 level thereby shows inverse correlation with the phosphorylation level of TAK1 and subsequent reduction in p38 MAPK and NF-κBp65 activation, ultimately culminating in amelioration of excess collagen synthesis in cardiac hypertrophy. In conclusion, our findings unravel the mechanism of AA action in regressing hypertrophy-associated cardiac fibrosis by assigning a role of AA as a PPARα agonist that inactivates non-canonical TGF-β signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Anomalous dimensions of spinning operators from conformal symmetry

NASA Astrophysics Data System (ADS)

Gliozzi, Ferdinando

2018-01-01

We compute, to the first non-trivial order in the ɛ-expansion of a perturbed scalar field theory, the anomalous dimensions of an infinite class of primary operators with arbitrary spin ℓ = 0, 1, . . . , including as a particular case the weakly broken higher-spin currents, using only constraints from conformal symmetry. Following the bootstrap philosophy, no reference is made to any Lagrangian, equations of motion or coupling constants. Even the space dimensions d are left free. The interaction is implicitly turned on through the local operators by letting them acquire anomalous dimensions. When matching certain four-point and five-point functions with the corresponding quantities of the free field theory in the ɛ → 0 limit, no free parameter remains. It turns out that only the expected discrete d values are permitted and the ensuing anomalous dimensions reproduce known results for the weakly broken higher-spin currents and provide new results for the other spinning operators.

Self-forces on static bodies in arbitrary dimensions

NASA Astrophysics Data System (ADS)

Taylor, Peter

2016-03-01

I will present exact expressions for the scalar and electromagnetic self-forces and self-torques acting on arbitrary static extended bodies in arbitrary static spacetimes with any number of dimensions. Non-perturbatively, these results are identical in all dimensions. Meaningful point particle limits are quite different, however. I will discuss how such limits are defined and evaluated, resulting in simple ``regularization algorithms'' which can be used in concrete calculations. In them, self-interaction is shown to be progressively less important in higher numbers of dimensions, generically competing in magnitude with increasingly high-order extended-body effects. Conversely, self-interaction effects can be relatively large in 1 + 1 and 2 + 1 dimensions. It will further be shown that there is considerable freedom to use different ``effective fields'' in the laws of motion. Different choices give rise to different inertias, gravitational forces, and electromagnetic or scalar self-forces. However, the particular combinations of these quantities which are observable remain invariant under all possible field redefinitions.

Comparison of Penalty Functions for Sparse Canonical Correlation Analysis

PubMed Central

Chalise, Prabhakar; Fridley, Brooke L.

2011-01-01

Canonical correlation analysis (CCA) is a widely used multivariate method for assessing the association between two sets of variables. However, when the number of variables far exceeds the number of subjects, such in the case of large-scale genomic studies, the traditional CCA method is not appropriate. In addition, when the variables are highly correlated the sample covariance matrices become unstable or undefined. To overcome these two issues, sparse canonical correlation analysis (SCCA) for multiple data sets has been proposed using a Lasso type of penalty. However, these methods do not have direct control over sparsity of solution. An additional step that uses Bayesian Information Criterion (BIC) has also been suggested to further filter out unimportant features. In this paper, a comparison of four penalty functions (Lasso, Elastic-net, SCAD and Hard-threshold) for SCCA with and without the BIC filtering step have been carried out using both real and simulated genotypic and mRNA expression data. This study indicates that the SCAD penalty with BIC filter would be a preferable penalty function for application of SCCA to genomic data. PMID:21984855

Establishing the Canon: George Ripley and his alchemical sources.

PubMed

Rampling, Jennifer M

2008-11-01

George Ripley, Canon of Bridlington (ca. 1415 to ca. 1490) was one of England's most famous alchemists, whose alchemical opera attracted study and commentary throughout the sixteenth and seventeenth centuries, and were printed and translated both in England and abroad. Yet Ripley's frequently baffling texts have proved resistant to scholarly interpretation. This paper attempts to unravel some of Ripley's alchemical theories and practice, firstly by identifying his major sources, and secondly by gauging his response to these texts. For instance, although Ripley's interest in the corpus of alchemical texts pseudonymously attributed to Ramon Lull is well documented, it transpires that his best known work, the Compound of Alchemy, or Twelve Gates, is actually based not on a Lullian work, but on a Latin treatise that Ripley attributed to the little-known alchemist, Guido de Montanor. Further clues to Ripley's alchemical thought can be obtained by considering his handling of a potential conflict between his two authorities, Lull and Guido. The resulting insights into Ripley's alchemy provide an instrument for assessing which of Ripley's pseudoepigraphic works can be truly called "canonical".

Canonical Structure and Orthogonality of Forces and Currents in Irreversible Markov Chains

NASA Astrophysics Data System (ADS)

Kaiser, Marcus; Jack, Robert L.; Zimmer, Johannes

2018-03-01

We discuss a canonical structure that provides a unifying description of dynamical large deviations for irreversible finite state Markov chains (continuous time), Onsager theory, and Macroscopic Fluctuation Theory (MFT). For Markov chains, this theory involves a non-linear relation between probability currents and their conjugate forces. Within this framework, we show how the forces can be split into two components, which are orthogonal to each other, in a generalised sense. This splitting allows a decomposition of the pathwise rate function into three terms, which have physical interpretations in terms of dissipation and convergence to equilibrium. Similar decompositions hold for rate functions at level 2 and level 2.5. These results clarify how bounds on entropy production and fluctuation theorems emerge from the underlying dynamical rules. We discuss how these results for Markov chains are related to similar structures within MFT, which describes hydrodynamic limits of such microscopic models.

BOOK REVIEW: Black Holes, Cosmology and Extra Dimensions Black Holes, Cosmology and Extra Dimensions

NASA Astrophysics Data System (ADS)

Frolov, Valeri P.

2013-10-01

The book Black holes, Cosmology and Extra Dimensions written by Kirill A Bronnikov and Sergey G Rubin has been published recently by World Scientific Publishing Company. The authors are well known experts in gravity and cosmology. The book is a monograph, a considerable part of which is based on the original work of the authors. Their original point of view on some of the problems makes the book quite interesting, covering a variety of important topics of the modern theory of gravity, astrophysics and cosmology. It consists of 11 chapters which are organized in three parts. The book starts with an introduction, where the authors briefly discuss the main ideas of General Relativity, giving some historical remarks on its development and application to cosmology, and mentioning some more recent subjects such as brane worlds, f(R)-theories and gravity in higher dimensions. Part I of the book is called 'Gravity'. Chapters two and three are devoted to the Einstein equations and their spherical symmetric black hole solutions. This material is quite standard and can be found in practically any book on General Relativity. A brief summary of the Kerr metric and black hole thermodynamics are given in chapter four. The main part of this chapter is devoted to spherically symmetric black holes in non-Einstein gravity (with scalar and phantom fields), black holes with regular interior, and black holes in brane worlds. Chapters five and six are mainly dedicated to wormholes and the problem of their stability. Part II (Cosmology) starts with discussion of the Friedmann-Robertson-Walker and de Sitter solutions of the Einstein equations and their properties. It follows by describing a `big picture' of the modern cosmology (inflation, post-inflationary reheating, the radiation-dominated and matter-dominated states, and modern stage of the (secondary) inflation). The authors explain how the inflation models allow one to solve many of the long-standing problems of cosmology, such as

Kirkwood-Buff Approach Rescues Overcollapse of a Disordered Protein in Canonical Protein Force Fields.

PubMed

Mercadante, Davide; Milles, Sigrid; Fuertes, Gustavo; Svergun, Dmitri I; Lemke, Edward A; Gräter, Frauke

2015-06-25

Understanding the function of intrinsically disordered proteins is intimately related to our capacity to correctly sample their conformational dynamics. So far, a gap between experimentally and computationally derived ensembles exists, as simulations show overcompacted conformers. Increasing evidence suggests that the solvent plays a crucial role in shaping the ensembles of intrinsically disordered proteins and has led to several attempts to modify water parameters and thereby favor protein-water over protein-protein interactions. This study tackles the problem from a different perspective, which is the use of the Kirkwood-Buff theory of solutions to reproduce the correct conformational ensemble of intrinsically disordered proteins (IDPs). A protein force field recently developed on such a basis was found to be highly effective in reproducing ensembles for a fragment from the FG-rich nucleoporin 153, with dimensions matching experimental values obtained from small-angle X-ray scattering and single molecule FRET experiments. Kirkwood-Buff theory presents a complementary and fundamentally different approach to the recently developed four-site TIP4P-D water model, both of which can rescue the overcollapse observed in IDPs with canonical protein force fields. As such, our study provides a new route for tackling the deficiencies of current protein force fields in describing protein solvation.

Gender and the Contemporary Educational Canon in the UK

ERIC Educational Resources Information Center

Elliott, Victoria

2017-01-01

This paper presents an analysis of the gender of the authors and the main characters of the set texts for English examinations taken at age 16 in England, Northern Ireland, Scotland and Wales. It presents an argument for why representation within the canon is important and places this within the context of recent educational reform in England and…

Flying under the radar: The non-canonical biochemistry and molecular biology of petrobactin from Bacillus anthracis.

PubMed

Hagan, A K; Carlson, P E; Hanna, P C

2016-10-01

The dramatic, rapid growth of Bacillus anthracis that occurs during systemic anthrax implies a crucial requirement for the efficient acquisition of iron. While recent advances in our understanding of B. anthracis iron acquisition systems indicate the use of strategies similar to other pathogens, this review focuses on unique features of the major siderophore system, petrobactin. Ways that petrobactin differs from other siderophores include: A. unique ferric iron binding moieties that allow petrobactin to evade host immune proteins; B. a biosynthetic operon that encodes enzymes from both major siderophore biosynthesis classes; C. redundancy in membrane transport systems for acquisition of Fe-petrobactin holo-complexes; and, D. regulation that appears to be controlled predominately by sensing the host-like environmental signals of temperature, CO 2 levels and oxidative stress, as opposed to canonical sensing of intracellular iron levels. We argue that these differences contribute in meaningful ways to B. anthracis pathogenesis. This review will also outline current major gaps in our understanding of the petrobactin iron acquisition system, some projected means for exploiting current knowledge, and potential future research directions. © 2016 John Wiley & Sons Ltd.

A Synthetic Alternative to Canonical One-Carbon Metabolism.

PubMed

Bouzon, Madeleine; Perret, Alain; Loreau, Olivier; Delmas, Valérie; Perchat, Nadia; Weissenbach, Jean; Taran, Frédéric; Marlière, Philippe

2017-08-18

One-carbon metabolism is an ubiquitous metabolic pathway that encompasses the reactions transferring formyl-, hydroxymethyl- and methyl-groups bound to tetrahydrofolate for the synthesis of purine nucleotides, thymidylate, methionine and dehydropantoate, the precursor of coenzyme A. An alternative cyclic pathway was designed that substitutes 4-hydroxy-2-oxobutanoic acid (HOB), a compound absent from known metabolism, for the amino acids serine and glycine as one-carbon donors. It involves two novel reactions, the transamination of l-homoserine and the transfer of a one-carbon unit from HOB to tetrahydrofolate releasing pyruvate as coproduct. Since canonical reactions regenerate l-homoserine from pyruvate by carboxylation and subsequent reduction, every one-carbon moiety made available for anabolic reactions originates from CO 2 . The HOB-dependent pathway was established in an Escherichia coli auxotroph selected for prototrophy using long-term cultivation protocols. Genetic, metabolic and biochemical evidence support the emergence of a functional HOB-dependent one-carbon pathway achieved with the recruitment of the two enzymes l-homoserine transaminase and HOB-hydroxymethyltransferase and of HOB as an essential metabolic intermediate. Escherichia coli biochemical reprogramming was achieved by minimally altering canonical metabolism and leveraging on natural selection mechanisms, thereby launching the resulting strain on an evolutionary trajectory diverging from all known extant species.

Multivariable extrapolation of grand canonical free energy landscapes

NASA Astrophysics Data System (ADS)

Mahynski, Nathan A.; Errington, Jeffrey R.; Shen, Vincent K.

2017-12-01

We derive an approach for extrapolating the free energy landscape of multicomponent systems in the grand canonical ensemble, obtained from flat-histogram Monte Carlo simulations, from one set of temperature and chemical potentials to another. This is accomplished by expanding the landscape in a Taylor series at each value of the order parameter which defines its macrostate phase space. The coefficients in each Taylor polynomial are known exactly from fluctuation formulas, which may be computed by measuring the appropriate moments of extensive variables that fluctuate in this ensemble. Here we derive the expressions necessary to define these coefficients up to arbitrary order. In principle, this enables a single flat-histogram simulation to provide complete thermodynamic information over a broad range of temperatures and chemical potentials. Using this, we also show how to combine a small number of simulations, each performed at different conditions, in a thermodynamically consistent fashion to accurately compute properties at arbitrary temperatures and chemical potentials. This method may significantly increase the computational efficiency of biased grand canonical Monte Carlo simulations, especially for multicomponent mixtures. Although approximate, this approach is amenable to high-throughput and data-intensive investigations where it is preferable to have a large quantity of reasonably accurate simulation data, rather than a smaller amount with a higher accuracy.

Shannon information entropy in the canonical genetic code.

PubMed

Nemzer, Louis R

2017-02-21

The Shannon entropy measures the expected information value of messages. As with thermodynamic entropy, the Shannon entropy is only defined within a system that identifies at the outset the collections of possible messages, analogous to microstates, that will be considered indistinguishable macrostates. This fundamental insight is applied here for the first time to amino acid alphabets, which group the twenty common amino acids into families based on chemical and physical similarities. To evaluate these schemas objectively, a novel quantitative method is introduced based the inherent redundancy in the canonical genetic code. Each alphabet is taken as a separate system that partitions the 64 possible RNA codons, the microstates, into families, the macrostates. By calculating the normalized mutual information, which measures the reduction in Shannon entropy, conveyed by single nucleotide messages, groupings that best leverage this aspect of fault tolerance in the code are identified. The relative importance of properties related to protein folding - like hydropathy and size - and function, including side-chain acidity, can also be estimated. This approach allows the quantification of the average information value of nucleotide positions, which can shed light on the coevolution of the canonical genetic code with the tRNA-protein translation mechanism. Copyright © 2016 Elsevier Ltd. All rights reserved.

The influence of arene-ring size on stacking interaction with canonical base pairs

NASA Astrophysics Data System (ADS)

Formánek, Martin; Burda, Jaroslav V.

2014-04-01

Stacking interactions between aromatic molecules (benzene, p-cymene, biphenyl, and di- and tetra-hydrogen anthracene) and G.C and A.T canonical Watson-Crick (WC) base pairs are explored. Two functionals with dispersion corrections: ω-B97XD and B3LYP-D3 are used. For a comparison also the MP2 and B3LYP-D3/PCM methods were used for the most stable p-cymene…WC geometries. It was found that the stacking interaction increases with the size of π-conjugation system. Its extent is in agreement with experimental finding on anticancer activity of Ru(II) piano-stool complexes where intercalation of these aromatic molecules should play an important role. The explored structures are considered as ternary system so that decomposition of the interaction energy to pairwise and non-additivity contributions is also examined.

Catechistic Teaching, National Canons, and the Regimentation of Students' Voice

ERIC Educational Resources Information Center

Kroon, Sjaak

2013-01-01

Drawing on key incident analysis of classroom transcripts from Bashkortostan, France, North Korea, and Suriname, this article discusses the relationship between an increasingly canonical content of education and the discursive organization of teaching processes at the expense of both teachers' and students' voice. It argues that canonical…

Detection of pup odors by non-canonical adult vomeronasal neurons expressing an odorant receptor gene is influenced by sex and parenting status.

PubMed

Nakahara, Thiago S; Cardozo, Leonardo M; Ibarra-Soria, Ximena; Bard, Andrew D; Carvalho, Vinicius M A; Trintinalia, Guilherme Z; Logan, Darren W; Papes, Fabio

2016-02-15

Olfaction is a fundamental sense through which most animals perceive the external world. The olfactory system detects odors via specialized sensory organs such as the main olfactory epithelium and the vomeronasal organ. Sensory neurons in these organs use G-protein coupled receptors to detect chemosensory stimuli. The odorant receptor (OR) family is expressed in sensory neurons of the main olfactory epithelium, while the adult vomeronasal organ is thought to express other types of receptors. Here, we describe Olfr692, a member of the OR gene family identified by next-generation RNA sequencing, which is highly upregulated and non-canonically expressed in the vomeronasal organ. We show that neurons expressing this gene are activated by odors emanating from pups. Surprisingly, activity in Olfr692-positive cells is sexually dimorphic, being very low in females. Our results also show that juvenile odors activate a large number of Olfr692 vomeronasal neurons in virgin males, which is correlated with the display of infanticide behavior. . In contrast, activity substantially decreases in parenting males (fathers), where infanticidal aggressive behavior is not frequently observed. Our results describe, for the first time, a sensory neural population with a specific molecular identity involved in the detection of pup odors. Moreover, it is one of the first reports of a group of sensory neurons the activity of which is sexually dimorphic and depends on social status. Our data suggest that the Olfr692 population is involved in mediating pup-oriented behaviors in mice.

A distinguishing gravitational property for gravitational equation in higher dimensions

NASA Astrophysics Data System (ADS)

Dadhich, Naresh

2016-03-01

It is well known that Einstein gravity is kinematic (meaning that there is no non-trivial vacuum solution; i.e. the Riemann tensor vanishes whenever the Ricci tensor does so) in 3 dimension because the Riemann tensor is entirely given in terms of the Ricci tensor. Could this property be universalized for all odd dimensions in a generalized theory? The answer is yes, and this property uniquely singles out pure Lovelock (it has only one Nth order term in the action) gravity for which the Nth order Lovelock-Riemann tensor is indeed given in terms of the corresponding Ricci tensor for all odd, d=2N+1, dimensions. This feature of gravity is realized only in higher dimensions and it uniquely picks out pure Lovelock gravity from all other generalizations of Einstein gravity. It serves as a good distinguishing and guiding criterion for the gravitational equation in higher dimensions.

Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts

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

Ohnaka, Keizo; Tanabe, Mizuho; Kawate, Hisaya

2005-04-01

To explore the mechanism of glucocorticoid-induced osteoporosis, we investigated the effect of glucocorticoid on canonical Wnt signaling that emerged as a novel key pathway for promoting bone formation. Wnt3a increased the T-cell factor (Tcf)/lymphoid enhancer factor (Lef)-dependent transcriptional activity in primary cultured human osteoblasts. Dexamethasone suppressed this transcriptional activity in a dose-dependent manner, while 1,25-dihydroxyvitamin D3 increased this transcriptional activity. LiCl, an inhibitor of glycogen synthase kinase-3{beta}, also enhanced the Tcf/Lef-dependent transcriptional activity, which was, however, not inhibited by dexamethasone. The addition of anti-dickkopf-1 antibody partially restored the transcriptional activity suppressed by dexamethasone. Dexamethasone decreased the cytosolic amount of {beta}-cateninmore » accumulated by Wnt3a and also inhibited the nuclear translocation of {beta}-catenin induced by Wnt3a. These data suggest that glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts, partially through the enhancement of the dickkopf-1 production.« less

A canonical correlation neural network for multicollinearity and functional data.

PubMed

Gou, Zhenkun; Fyfe, Colin

2004-03-01

We review a recent neural implementation of Canonical Correlation Analysis and show, using ideas suggested by Ridge Regression, how to make the algorithm robust. The network is shown to operate on data sets which exhibit multicollinearity. We develop a second model which not only performs as well on multicollinear data but also on general data sets. This model allows us to vary a single parameter so that the network is capable of performing Partial Least Squares regression (at one extreme) to Canonical Correlation Analysis (at the other)and every intermediate operation between the two. On multicollinear data, the parameter setting is shown to be important but on more general data no particular parameter setting is required. Finally, we develop a second penalty term which acts on such data as a smoother in that the resulting weight vectors are much smoother and more interpretable than the weights without the robustification term. We illustrate our algorithms on both artificial and real data.

From grand-canonical density functional theory towards rational compound design

NASA Astrophysics Data System (ADS)

von Lilienfeld, Anatole

2008-03-01

The fundamental challenge of rational compound design, ie the reverse engineering of chemical compounds with predefined specific properties, originates in the high-dimensional combinatorial nature of chemical space. Chemical space is the hyper-space of a given set of molecular observables that is spanned by the grand-canonical variables (particle densities of electrons and nuclei) which define chemical composition. A brief but rigorous description of chemical space within the molecular grand-canonical ensemble multi-component density functional theory framework will be given [1]. Numerical results will be presented for intermolecular energies as a continuous function of alchemical variations within a neutral and isoelectronic 10 proton system, including CH4, NH3, H2O, and HF, interacting with formic acid [2]. Furthermore, engineering the Fermi level through alchemical generation of boron-nitrogen doped mutants of benzene shall be discussed [3].[1] von Lilienfeld and Tuckerman JCP 125 154104 (2006)[2] von Lilienfeld and Tuckerman JCTC 3 1083 (2007)[3] Marcon et al. JCP 127 064305 (2007)

Chaos in non-diagonal spatially homogeneous cosmological models in spacetime dimensions <=10

NASA Astrophysics Data System (ADS)

Demaret, Jacques; de Rop, Yves; Henneaux, Marc

1988-08-01

It is shown that the chaotic oscillatory behaviour, absent in diagonal homogeneous cosmological models in spacetime dimensions between 5 and 10, can be reestablished when off-diagonal terms are included. Also at Centro de Estudios Cientificos de Santiago, Casilla 16443, Santiago 9, Chile

Electromagnetic field computation at fractal dimensions

NASA Astrophysics Data System (ADS)

Zubair, M.; Ang, Y. S.; Ang, L. K.

According to Mandelbrot's work on fractals, many objects are in fractional dimensions that the traditional calculus or differential equations are not sufficient. Thus fractional models solving the relevant differential equations are critical to understand the physical dynamics of such objects. In this work, we develop computational electromagnetics or Maxwell equations in fractional dimensions. For a given degree of imperfection, impurity, roughness, anisotropy or inhomogeneity, we consider the complicated object can be formulated into a fractional dimensional continuous object characterized by an effective fractional dimension D, which can be calculated from a self-developed algorithm. With this non-integer value of D, we develop the computational methods to design and analyze the EM scattering problems involving rough surfaces or irregularities in an efficient framework. The fractional electromagnetic based model can be extended to other key differential equations such as Schrodinger or Dirac equations, which will be useful for design of novel 2D materials stacked up in complicated device configuration for applications in electronics and photonics. This work is supported by Singapore Temasek Laboratories (TL) Seed Grant (IGDS S16 02 05 1).

Kato expansion in quantum canonical perturbation theory

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

Nikolaev, Andrey, E-mail: Andrey.Nikolaev@rdtex.ru

2016-06-15

This work establishes a connection between canonical perturbation series in quantum mechanics and a Kato expansion for the resolvent of the Liouville superoperator. Our approach leads to an explicit expression for a generator of a block-diagonalizing Dyson’s ordered exponential in arbitrary perturbation order. Unitary intertwining of perturbed and unperturbed averaging superprojectors allows for a description of ambiguities in the generator and block-diagonalized Hamiltonian. We compare the efficiency of the corresponding computational algorithm with the efficiencies of the Van Vleck and Magnus methods for high perturbative orders.

Cognitive Consequences of Participation in a "Fifth Dimension" After-School Computer Club.

ERIC Educational Resources Information Center

Mayer, Richard E.; Quilici, Jill; Moreno, Roxana; Duran, Richard; Woodbridge, Scott; Simon, Rebecca; Sanchez, David; Lavezzo, Amy

1997-01-01

Children who attended the Fifth Dimension after-school computer club at least 10 times during the 1994-95 school year performed better on word problem comprehension tests than did non-participating children. Results support the hypothesis that experience in using computer software in the Fifth Dimension club produces measurable, resilient, and…

The issue of gauge choice in the Landau problem and the physics of canonical and mechanical orbital angular momenta

NASA Astrophysics Data System (ADS)

Wakamatsu, M.; Kitadono, Y.; Zhang, P.-M.

2018-05-01

One intriguing issue in the nucleon spin decomposition problem is the existence of two types of decompositions, which are representably characterized by two different orbital angular momenta (OAMs) of quarks. The one is the mechanical OAM, while the other is the so-called gauge-invariant canonical (g.i.c.) OAM, the concept of which was introduced by Chen et al. An especially delicate quantity is the g.i.c. OAM, which must be distinguished from the ordinary (gauge-variant) canonical OAM. We find that, owing to its analytically solvable nature, the famous Landau problem offers an ideal tool to understand the difference and the physical meaning of the above three OAMs, i.e. the standard canonical OAM, g.i.c. OAM, and the mechanical OAM. We analyze these three OAMs in two different formulations of the Landau problem, first in the standard (gauge-fixed) formulation and second in the gauge-invariant (but path-dependent) formulation of DeWitt. Especially interesting is the latter formalism. It is shown that the choice of path has an intimate connection with the choice of gauge, but they are not necessarily equivalent. Then, we answer the question about what is the consequence of a particular choice of path in DeWitt's formalism. This analysis also clarifies the implication of the gauge symmetry hidden in the concept of g.i.c. OAM. Finally, we show that the finding above offers a clear understanding about the uniqueness or non-uniqueness problem of the nucleon spin decomposition, which arises from the arbitrariness in the definition of the so-called physical component of the gauge field.

A Conserved Non-Canonical Docking Mechanism Regulates the Binding of Dual Specificity Phosphatases to Cell Integrity Mitogen-Activated Protein Kinases (MAPKs) in Budding and Fission Yeasts

PubMed Central

Sacristán-Reviriego, Almudena; Madrid, Marisa; Cansado, José; Martín, Humberto; Molina, María

2014-01-01

Dual-specificity MAPK phosphatases (MKPs) are essential for the negative regulation of MAPK pathways. Similar to other MAPK-interacting proteins, most MKPs bind MAPKs through specific docking domains known as D-motifs. However, we found that the Saccharomyces cerevisiae MKP Msg5 binds the MAPK Slt2 within the cell wall integrity (CWI) pathway through a distinct motif (IYT). Here, we demonstrate that the IYT motif mediates binding of the Msg5 paralogue Sdp1 to Slt2 as well as of the MKP Pmp1 to its CWI MAPK counterpart Pmk1 in the evolutionarily distant yeast Schizosaccharomyces pombe. As a consequence, removal of the IYT site in Msg5, Sdp1 and Pmp1 reduces MAPK trapping caused by the overexpression of catalytically inactive versions of these phosphatases. Accordingly, an intact IYT site is necessary for inactive Sdp1 to prevent nuclear accumulation of Slt2. We also show that both Ile and Tyr but not Thr are essential for the functionality of the IYT motif. These results provide mechanistic insight into MKP-MAPK interplay and stress the relevance of this conserved non-canonical docking site in the regulation of the CWI pathway in fungi. PMID:24465549

Long-term forecasting of meteorological time series using Nonlinear Canonical Correlation Analysis (NLCCA)

NASA Astrophysics Data System (ADS)

Woldesellasse, H. T.; Marpu, P. R.; Ouarda, T.

2016-12-01

Wind is one of the crucial renewable energy sources which is expected to bring solutions to the challenges of clean energy and the global issue of climate change. A number of linear and nonlinear multivariate techniques has been used to predict the stochastic character of wind speed. A wind forecast with good accuracy has a positive impact on the reduction of electricity system cost and is essential for the effective grid management. Over the past years, few studies have been done on the assessment of teleconnections and its possible effects on the long-term wind speed variability in the UAE region. In this study Nonlinear Canonical Correlation Analysis (NLCCA) method is applied to study the relationship between global climate oscillation indices and meteorological variables, with a major emphasis on wind speed and wind direction, of Abu Dhabi, UAE. The wind dataset was obtained from six ground stations. The first mode of NLCCA is capable of capturing the nonlinear mode of the climate indices at different seasons, showing the symmetry between the warm states and the cool states. The strength of the nonlinear canonical correlation between the two sets of variables varies with the lead/lag time. The performance of the models is assessed by calculating error indices such as the root mean square error (RMSE) and Mean absolute error (MAE). The results indicated that NLCCA models provide more accurate information about the nonlinear intrinsic behaviour of the dataset of variables than linear CCA model in terms of the correlation and root mean square error. Key words: Nonlinear Canonical Correlation Analysis (NLCCA), Canonical Correlation Analysis, Neural Network, Climate Indices, wind speed, wind direction

The D-dimensional non-relativistic particle in the Scarf Trigonometry plus Non-Central Rosen-Morse Potentials

NASA Astrophysics Data System (ADS)

Deta, U. A.; Lestari, N. A.; Yantidewi, M.; Suparmi, A.; Cari, C.

2018-03-01

The D-Dimensional Non-Relativistic Particle Properties in the Scarf Trigonometry plus Non-Central Rosen-Morse Potentials was investigated using an analytical method. The bound state energy is given approximately in the closed form. The approximate wave function for arbitrary l-state in D-dimensions are expressed in the form of generalised Jacobi Polynomials. The energy spectra of the particle are increased when the dimensions are higher. The relationship between the orbital number in each dimension is recursive. The special case in 3 dimensions is given to the ground state.

Hierarchical Type Stability Criteria for Delayed Neural Networks via Canonical Bessel-Legendre Inequalities.

PubMed

Zhang, Xian-Ming; Han, Qing-Long; Zeng, Zhigang

2018-05-01

This paper is concerned with global asymptotic stability of delayed neural networks. Notice that a Bessel-Legendre inequality plays a key role in deriving less conservative stability criteria for delayed neural networks. However, this inequality is in the form of Legendre polynomials and the integral interval is fixed on . As a result, the application scope of the Bessel-Legendre inequality is limited. This paper aims to develop the Bessel-Legendre inequality method so that less conservative stability criteria are expected. First, by introducing a canonical orthogonal polynomial sequel, a canonical Bessel-Legendre inequality and its affine version are established, which are not explicitly in the form of Legendre polynomials. Moreover, the integral interval is shifted to a general one . Second, by introducing a proper augmented Lyapunov-Krasovskii functional, which is tailored for the canonical Bessel-Legendre inequality, some sufficient conditions on global asymptotic stability are formulated for neural networks with constant delays and neural networks with time-varying delays, respectively. These conditions are proven to have a hierarchical feature: the higher level of hierarchy, the less conservatism of the stability criterion. Finally, three numerical examples are given to illustrate the efficiency of the proposed stability criteria.

Quantitative Profiling of Peptides from RNAs classified as non-coding

PubMed Central

Prabakaran, Sudhakaran; Hemberg, Martin; Chauhan, Ruchi; Winter, Dominic; Tweedie-Cullen, Ry Y.; Dittrich, Christian; Hong, Elizabeth; Gunawardena, Jeremy; Steen, Hanno; Kreiman, Gabriel; Steen, Judith A.

2014-01-01

Only a small fraction of the mammalian genome codes for messenger RNAs destined to be translated into proteins, and it is generally assumed that a large portion of transcribed sequences - including introns and several classes of non-coding RNAs (ncRNAs) do not give rise to peptide products. A systematic examination of translation and physiological regulation of ncRNAs has not been conducted. Here, we use computational methods to identify the products of non-canonical translation in mouse neurons by analyzing unannotated transcripts in combination with proteomic data. This study supports the existence of non-canonical translation products from both intragenic and extragenic genomic regions, including peptides derived from anti-sense transcripts and introns. Moreover, the studied novel translation products exhibit temporal regulation similar to that of proteins known to be involved in neuronal activity processes. These observations highlight a potentially large and complex set of biologically regulated translational events from transcripts formerly thought to lack coding potential. PMID:25403355

The Quality of Life of Hemodialysis Patients Is Affected Not Only by Medical but also Psychosocial Factors: a Canonical Correlation Study.

PubMed

Kim, Kyungmin; Kang, Gun Woo; Woo, Jungmin

2018-04-02

The quality of life (QoL) of patients with end-stage renal disease (ESRD) is very poor, plausibly due to both psychosocial and medical factors. This study aimed to determine the relationship among psychosocial factors, medical factors, and QoL in patients with ESRD undergoing hemodialysis (HD). In total, 55 male and 47 female patients were evaluated (mean age, 57.1 ± 12.0 years). The QoL was evaluated using the Korean version of World Health Organization Quality of Life Scale-Abbreviated Version. The psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, Pittsburgh Sleep Quality Index, and Zarit Burden Interview. The medical factors were assessed using laboratory examinations. Correlation and canonical correlation analyses were performed to investigate the association patterns. The QoL was significantly correlated with the psychosocial factors, and to a lesser extent with the medical factors. The medical and psychosocial factors were also correlated. The canonical correlation analysis indicated a correlation between QoL and psychosocial factors (1st canonical correlation = 0.696, P < 0.001; 2nd canonical correlation = 0.421, P = 0.191), but not medical factors (1st canonical correlation = 0.478, P = 0.475; 2nd canonical correlation = 0.419, P = 0.751). The medical and psychosocial factors were also correlated (1st canonical correlation = 0.689, P < 0.001; 2nd canonical correlation = 0.603, P = 0.009). Psychosocial factors influence QoL in patients with ESRD, and should thus be carefully considered when caring for these patients in clinical practice. © 2018 The Korean Academy of Medical Sciences.

Gender Differences in and the Relationships Between Social Anxiety and Problematic Internet Use: Canonical Analysis

PubMed Central

Özteke Kozan, Hatice İrem; Kesici, Şahin

2018-01-01

Background The cognitive-behavioral model of problematic Internet use (PIU) proposes that psychological well-being is associated with specific thoughts and behaviors on the Internet. Hence, there is growing concern that PIU is associated with psychological impairments. Objective Given the proposal of gender schema theory and social role theory, men and women are predisposed to experience social anxiety and engage in Internet use differently. Thus, an investigation of gender differences in these areas is warranted. According to the cognitive-behavioral model of PIU, social anxiety is associated with specific cognitions and behaviors on the Internet. Thus, an investigation of the association between social anxiety and PIU is essential. In addition, research that takes into account the multidimensional nature of social anxiety and PIU is lacking. Therefore, this study aimed to explore multivariate gender differences in and the relationships between social anxiety and PIU. Methods Participants included 505 college students, of whom 241 (47.7%) were women and 264 (52.3%) were men. Participants’ ages ranged from 18 to 22 years, with a mean age of 20.34 (SD=1.16). The Social Anxiety Scale and Problematic Internet Use Scale were used in data collection. Multivariate analysis of variance (MANOVA) and canonical correlation analysis were used. Results Mean differences between men and women were not statistically significant in social anxiety (λ=.02, F3,501=2.47, P=.06). In all three PIU dimensions, men scored higher than women, and MANOVA shows that multivariate difference was statistically significant (λ=.94, F3,501=10.69, P<.001). Of the canonical correlation functions computed for men, only the first was significant (Rc=.43, λ=.78, χ29=64.7, P<.001) and accounted for 19% of the overlapping variance. Similarly, only the first canonical function was significant for women (Rc=.36, λ=.87, χ29=33.9, P<.001), which accounted for 13% of the overlapping variance

Effect of explicit dimension instruction on speech category learning

PubMed Central

Chandrasekaran, Bharath; Yi, Han-Gyol; Smayda, Kirsten E.; Maddox, W. Todd

2015-01-01

Learning non-native speech categories is often considered a challenging task in adulthood. This difficulty is driven by cross-language differences in weighting critical auditory dimensions that differentiate speech categories. For example, previous studies have shown that differentiating Mandarin tonal categories requires attending to dimensions related to pitch height and direction. Relative to native speakers of Mandarin, the pitch direction dimension is under-weighted by native English speakers. In the current study, we examined the effect of explicit instructions (dimension instruction) on native English speakers' Mandarin tone category learning within the framework of a dual-learning systems (DLS) model. This model predicts that successful speech category learning is initially mediated by an explicit, reflective learning system that frequently utilizes unidimensional rules, with an eventual switch to a more implicit, reflexive learning system that utilizes multidimensional rules. Participants were explicitly instructed to focus and/or ignore the pitch height dimension, the pitch direction dimension, or were given no explicit prime. Our results show that instruction instructing participants to focus on pitch direction, and instruction diverting attention away from pitch height resulted in enhanced tone categorization. Computational modeling of participant responses suggested that instruction related to pitch direction led to faster and more frequent use of multidimensional reflexive strategies, and enhanced perceptual selectivity along the previously underweighted pitch direction dimension. PMID:26542400

Dependence of ripple dimensions on cohesive and non-cohesive bed properties in the intertidal Dee Estuary

NASA Astrophysics Data System (ADS)

Lichtman, Ian; Thorne, Peter; Baas, Jacobus; O'Boyle, Louise; Cooke, Richard; Amoudry, Laurent; Bell, Paul; Aspden, Rebecca; Bass, Sarah; Davies, Alan; Hope, Julie; Malarkey, Jonathan; Manning, Andrew; Parsons, Daniel; Paterson, David; Peakall, Jeffrey; Schindler, Robert; Ye, Leiping

2014-05-01

There is a need to better understand the effects of cohesive and mixed sediments on coastal processes, to improve sediment transport models for the management of coastal erosion, siltation of navigation channels and habitat change. Although reasonable sediment transport predictors are available for pure sands, it still is not the case for mixed cohesive and non-cohesive sediments. Existing predictors mostly relate ripple dimensions to hydrodynamic conditions and median sediment grain diameter, assuming a narrow unimodal particle size distribution. Properties typical of mixed conditions, such as composition and cohesion for example, are not usually taken into account. This presents severe shortcomings to predictors' abilities. Indeed, laboratory experiments using mixed cohesive sediments have shown that bedform dimensions decrease with increasing bed mud content. In the field, one may expect current predictors to match data for well-sorted sands closely, but poorly for mixed sediments. Our work is part of the COHBED project and aims to: (1) examine, in field conditions, if ripple dimensions are significantly different for mixed cohesive sediment beds compared to beds with pure sand; (2) compare the field data with laboratory results that showed reduced ripple length due to cohesive mud content; and (3) assess the performance of a selection of ripple predictors for mixed sediment data. The COHBED project was set up to undertake laboratory experiments and fieldwork to study how physical and biological processes influence bedform development in a mixed cohesive-cohesionless sediment environment. As part of COHBED, a suite of instruments was deployed on tidal flats in the Dee Estuary (on the NW coast of England), collecting co-located measurements of the hydrodynamics, suspended sediment properties and bed morphology. The instruments occupied three sites collecting data over different bed compositions during a two week period (21 May to 4 June 2013). One site was

Coding principles of the canonical cortical microcircuit in the avian brain

PubMed Central

Calabrese, Ana; Woolley, Sarah M. N.

2015-01-01

Mammalian neocortex is characterized by a layered architecture and a common or “canonical” microcircuit governing information flow among layers. This microcircuit is thought to underlie the computations required for complex behavior. Despite the absence of a six-layered cortex, birds are capable of complex cognition and behavior. In addition, the avian auditory pallium is composed of adjacent information-processing regions with genetically identified neuron types and projections among regions comparable with those found in the neocortex. Here, we show that the avian auditory pallium exhibits the same information-processing principles that define the canonical cortical microcircuit, long thought to have evolved only in mammals. These results suggest that the canonical cortical microcircuit evolved in a common ancestor of mammals and birds and provide a physiological explanation for the evolution of neural processes that give rise to complex behavior in the absence of cortical lamination. PMID:25691736

Relationship between climatic variables and the variation in bulk tank milk composition using canonical correlation analysis.

PubMed

Stürmer, Morgana; Busanello, Marcos; Velho, João Pedro; Heck, Vanessa Isabel; Haygert-Velho, Ione Maria Pereira

2018-06-04

A number of studies have addressed the relations between climatic variables and milk composition, but these works used univariate statistical approaches. In our study, we used a multivariate approach (canonical correlation) to study the impact of climatic variables on milk composition, price, and monthly milk production at a dairy farm using bulk tank milk data. Data on milk composition, price, and monthly milk production were obtained from a dairy company that purchased the milk from the farm, while climatic variable data were obtained from the National Institute of Meteorology (INMET). The data are from January 2014 to December 2016. Univariate correlation analysis and canonical correlation analysis were performed. Few correlations between the climatic variables and milk composition were found using a univariate approach. However, using canonical correlation analysis, we found a strong and significant correlation (r c  = 0.95, p value = 0.0029). Lactose, ambient temperature measures (mean, minimum, and maximum), and temperature-humidity index (THI) were found to be the most important variables for the canonical correlation. Our study indicated that 10.2% of the variation in milk composition, pricing, and monthly milk production can be explained by climatic variables. Ambient temperature variables, together with THI, seem to have the most influence on variation in milk composition.

Zwitterionic versus canonical amino acids over the various defects in zeolites: A two-layer ONIOM calculation

PubMed Central

Yang, Gang; Zhou, Lijun

2014-01-01

Defects are often considered as the active sites for chemical reactions. Here a variety of defects in zeolites are used to stabilize zwitterionic glycine that is not self-stable in gas phase; in addition, effects of acidic strengths and zeolite channels on zwitterionic stabilization are demonstrated. Glycine zwitterions can be stabilized by all these defects and energetically prefer to canonical structures over Al and Ga Lewis acidic sites rather than Ti Lewis acidic site, silanol and titanol hydroxyls. For titanol (Ti-OH), glycine interacts with framework Ti and hydroxyl sites competitively, and the former with Lewis acidity predominates. The transformations from canonical to zwitterionic glycine are obviously more facile over Al and Ga Lewis acidic sites than over Ti Lewis acidic site, titanol and silanol hydroxyls. Charge transfers that generally increase with adsorption energies are found to largely decide the zwitterionic stabilization effects. Zeolite channels play a significant role during the stabilization process. In absence of zeolite channels, canonical structures predominate for all defects; glycine zwitterions remain stable over Al and Ga Lewis acidic sites and only with synergy of H-bonding interactions can exist over Ti Lewis acidic site, while automatically transform to canonical structures over silanol and titanol hydroxyls. PMID:25307449

Relationship between climatic variables and the variation in bulk tank milk composition using canonical correlation analysis

NASA Astrophysics Data System (ADS)

Stürmer, Morgana; Busanello, Marcos; Velho, João Pedro; Heck, Vanessa Isabel; Haygert-Velho, Ione Maria Pereira

2018-06-01

A number of studies have addressed the relations between climatic variables and milk composition, but these works used univariate statistical approaches. In our study, we used a multivariate approach (canonical correlation) to study the impact of climatic variables on milk composition, price, and monthly milk production at a dairy farm using bulk tank milk data. Data on milk composition, price, and monthly milk production were obtained from a dairy company that purchased the milk from the farm, while climatic variable data were obtained from the National Institute of Meteorology (INMET). The data are from January 2014 to December 2016. Univariate correlation analysis and canonical correlation analysis were performed. Few correlations between the climatic variables and milk composition were found using a univariate approach. However, using canonical correlation analysis, we found a strong and significant correlation (r c = 0.95, p value = 0.0029). Lactose, ambient temperature measures (mean, minimum, and maximum), and temperature-humidity index (THI) were found to be the most important variables for the canonical correlation. Our study indicated that 10.2% of the variation in milk composition, pricing, and monthly milk production can be explained by climatic variables. Ambient temperature variables, together with THI, seem to have the most influence on variation in milk composition.

Canonical Wnt Signaling as a Specific Marker for Normal and Tumorigenic Mammary Stem Cells

DTIC Science & Technology

2012-02-01

These cells were identified by  flow   cytometry  to detect cells that were positive for CD24 and CD49f.   2. We have established that activation of Wnt...09-1-0072 TITLE: Canonical Wnt Signaling as a Specific marker for Normal and Tumorigenic Mammary Stem Cells PRINCIPAL...activation of canonical Wnt signaling may be a very specific marker for mammary stem cells and be a target for transformation that results in the

Interglomerular Connectivity within the Canonical and GC-D/Necklace Olfactory Subsystems

PubMed Central

Puche, Adam C.; Munger, Steven D.

2016-01-01

The mammalian main olfactory system contains several subsystems that differ not only in the receptors they express and the glomerular targets they innervate within the main olfactory bulb (MOB), but also in the strategies they use to process odor information. The canonical main olfactory system employs a combinatorial coding strategy that represents odorant identity as a pattern of glomerular activity. By contrast, the "GC-D/necklace" olfactory subsystem—formed by olfactory sensory neurons expressing the receptor guanylyl cyclase GC-D and their target necklace glomeruli (NGs) encircling the caudal MOB—is critical for the detection of a small number of semiochemicals that promote the acquisition of food preferences. The formation of these socially-transmitted food preferences requires the animal to integrate information about two types of olfactory stimuli: these specialized social chemosignals and the food odors themselves. However, the neural mechanisms with which the GC-D/necklace subsystem processes this information are unclear. We used stimulus-induced increases in intrinsic fluorescence signals to map functional circuitry associated with NGs and canonical glomeruli (CGs) in the MOB. As expected, CG-associated activity spread laterally through both the glomerular and external plexiform layers associated with activated glomeruli. Activation of CGs or NGs resulted in activity spread between the two types of glomeruli; there was no evidence of preferential connectivity between individual necklace glomeruli. These results support previous anatomical findings that suggest the canonical and GC-D/necklace subsystems are functionally connected and may integrate general odor and semiochemical information in the MOB. PMID:27902696

Study of high-performance canonical molecular orbitals calculation for proteins

NASA Astrophysics Data System (ADS)

Hirano, Toshiyuki; Sato, Fumitoshi

2017-11-01

The canonical molecular orbital (CMO) calculation can help to understand chemical properties and reactions in proteins. However, it is difficult to perform the CMO calculation of proteins because of its self-consistent field (SCF) convergence problem and expensive computational cost. To certainly obtain the CMO of proteins, we work in research and development of high-performance CMO applications and perform experimental studies. We have proposed the third-generation density-functional calculation method of calculating the SCF, which is more advanced than the FILE and direct method. Our method is based on Cholesky decomposition for two-electron integrals calculation and the modified grid-free method for the pure-XC term evaluation. By using the third-generation density-functional calculation method, the Coulomb, the Fock-exchange, and the pure-XC terms can be given by simple linear algebraic procedure in the SCF loop. Therefore, we can expect to get a good parallel performance in solving the SCF problem by using a well-optimized linear algebra library such as BLAS on the distributed memory parallel computers. The third-generation density-functional calculation method is implemented to our program, ProteinDF. To achieve computing electronic structure of the large molecule, not only overcoming expensive computation cost and also good initial guess for safe SCF convergence are required. In order to prepare a precise initial guess for the macromolecular system, we have developed the quasi-canonical localized orbital (QCLO) method. The QCLO has the characteristics of both localized and canonical orbital in a certain region of the molecule. We have succeeded in the CMO calculations of proteins by using the QCLO method. For simplified and semi-automated calculation of the QCLO method, we have also developed a Python-based program, QCLObot.

A curvilinear, fully implicit, conservative electromagnetic PIC algorithm in multiple dimensions

DOE PAGES

Chacon, L.; Chen, G.

2016-04-19

Here, we extend a recently proposed fully implicit PIC algorithm for the Vlasov–Darwin model in multiple dimensions (Chen and Chacón (2015) [1]) to curvilinear geometry. As in the Cartesian case, the approach is based on a potential formulation (Φ, A), and overcomes many difficulties of traditional semi-implicit Darwin PIC algorithms. Conservation theorems for local charge and global energy are derived in curvilinear representation, and then enforced discretely by a careful choice of the discretization of field and particle equations. Additionally, the algorithm conserves canonical-momentum in any ignorable direction, and preserves the Coulomb gauge ∇ • A = 0 exactly. Anmore » asymptotically well-posed fluid preconditioner allows efficient use of large cell sizes, which are determined by accuracy considerations, not stability, and can be orders of magnitude larger than required in a standard explicit electromagnetic PIC simulation. We demonstrate the accuracy and efficiency properties of the algorithm with numerical experiments in mapped meshes in 1D-3V and 2D-3V.« less

A curvilinear, fully implicit, conservative electromagnetic PIC algorithm in multiple dimensions

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

Chacon, L.; Chen, G.

Here, we extend a recently proposed fully implicit PIC algorithm for the Vlasov–Darwin model in multiple dimensions (Chen and Chacón (2015) [1]) to curvilinear geometry. As in the Cartesian case, the approach is based on a potential formulation (Φ, A), and overcomes many difficulties of traditional semi-implicit Darwin PIC algorithms. Conservation theorems for local charge and global energy are derived in curvilinear representation, and then enforced discretely by a careful choice of the discretization of field and particle equations. Additionally, the algorithm conserves canonical-momentum in any ignorable direction, and preserves the Coulomb gauge ∇ • A = 0 exactly. Anmore » asymptotically well-posed fluid preconditioner allows efficient use of large cell sizes, which are determined by accuracy considerations, not stability, and can be orders of magnitude larger than required in a standard explicit electromagnetic PIC simulation. We demonstrate the accuracy and efficiency properties of the algorithm with numerical experiments in mapped meshes in 1D-3V and 2D-3V.« less

General relativity in two dimensions: A Hamilton-Jacobi analysis

NASA Astrophysics Data System (ADS)

Bertin, M. C.; Pimentel, B. M.; Pompeia, P. J.

2010-11-01

We analyzed the constraint structure of the Einstein-Hilbert first-order action in two dimensions using the Hamilton-Jacobi approach. We were able to find a set of involutive, as well as a set of non-involutive constraints. Using generalized brackets we showed how to assure integrability of the theory, to eliminate the set of non-involutive constraints and how to build the field equations.

Arsenic Induces Polyadenylation of Canonical Histone mRNA by Down-regulating Stem-Loop-binding Protein Gene Expression*

PubMed Central

Brocato, Jason; Fang, Lei; Chervona, Yana; Chen, Danqi; Kiok, Kathrin; Sun, Hong; Tseng, Hsiang-Chi; Xu, Dazhong; Shamy, Magdy; Jin, Chunyuan; Costa, Max

2014-01-01

The replication-dependent histone genes are the only metazoan genes whose messenger RNA (mRNA) does not terminate with a poly(A) tail at the 3′-end. Instead, the histone mRNAs display a stem-loop structure at their 3′-end. Stem-loop-binding protein (SLBP) binds the stem-loop and regulates canonical histone mRNA metabolism. Here we report that exposure to arsenic, a carcinogenic metal, decreased cellular levels of SLBP by inducing its proteasomal degradation and inhibiting SLBP transcription via epigenetic mechanisms. Notably, arsenic exposure dramatically increased polyadenylation of canonical histone H3.1 mRNA possibly through down-regulation of SLBP expression. The polyadenylated H3.1 mRNA induced by arsenic was not susceptible to normal degradation that occurs at the end of S phase, resulting in continued presence into mitosis, increased total H3.1 mRNA, and increased H3 protein levels. Excess expression of canonical histones have been shown to increase sensitivity to DNA damage as well as increase the frequency of missing chromosomes and induce genomic instability. Thus, polyadenylation of canonical histone mRNA following arsenic exposure may contribute to arsenic-induced carcinogenesis. PMID:25266719

Identification of non-visual photomotor response cells in the vertebrate hindbrain

PubMed Central

Kokel, David; Dunn, Timothy W.; Ahrens, Misha B.; Alshut, Rüdiger; Cheung, Chung Yan J.; Saint-Amant, Louis; Bruni, Giancarlo; Mateus, Rita; van Ham, Tjakko J.; Shiraki, Tomoya; Fukada, Yoshitaka; Kojima, Daisuke; Yeh, Jing-Ruey J.; Mikut, Ralf; von Lintig, Johannes; Engert, Florian; Peterson, Randall T.

2013-01-01

Non-visual photosensation enables animals to sense light without sight. However, the cellular and molecular mechanisms of non-visual photobehaviors are poorly understood, especially in vertebrate animals. Here, we describe the photomotor response (PMR), a robust and reproducible series of motor behaviors in zebrafish that is elicited by visual wavelengths of light, but does not require the eyes, pineal gland or other canonical deep-brain photoreceptive organs. Unlike the relatively slow effects of canonical non-visual pathways, motor circuits are strongly and quickly (seconds) recruited during the PMR behavior. We find that the hindbrain is both necessary and sufficient to drive these behaviors. Using in vivo calcium imaging, we identify a discrete set of neurons within the hindbrain whose responses to light mirror the PMR behavior. Pharmacological inhibition of the visual cycle blocks PMR behaviors, suggesting that opsin-based photoreceptors control this behavior. These data represent the first known light-sensing circuit in the vertebrate hindbrain. PMID:23447595

Anomaly-free cosmological perturbations in effective canonical quantum gravity

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

Barrau, Aurelien; Bojowald, Martin; Kagan, Mikhail

2015-05-01

This article lays out a complete framework for an effective theory of cosmological perturbations with corrections from canonical quantum gravity. Since several examples exist for quantum-gravity effects that change the structure of space-time, the classical perturbative treatment must be rethought carefully. The present discussion provides a unified picture of several previous works, together with new treatments of higher-order perturbations and the specification of initial states.

AdS/CFT in Fractional Dimension and Higher-Spins at One Loop

NASA Astrophysics Data System (ADS)

Skvortsov, Evgeny; Tran, Tung

2017-08-01

Large-$N$, $\\epsilon$-expansion or the conformal bootstrap allow one to make sense of some of conformal field theories in non-integer dimension, which suggests that AdS/CFT may also extend to fractional dimensions. It was shown recently that the sphere free energy and the $a$-anomaly coefficient of the free scalar field can be reproduced as a one-loop effect in the dual higher-spin theory in a number of integer dimensions. We extend this result to all integer and also to fractional dimensions. Upon changing the boundary conditions in the higher-spin theory the sphere free energy of the large-$N$ Wilson-Fisher CFT can also be reproduced from the higher-spin side.

A non-canonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia (AML)

PubMed Central

Shanmugam, Rajasubramaniam; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A.; Baghdadi, Tareq Al; Sargent, Katie J.; Cripe, Larry D.; Kalvakolanu, Dhananjaya V.; Boswell, H. Scott

2014-01-01

Purpose DAPK1, a tumor suppressor, is a rate-limiting effector in an ER stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of AML with poor prognosis, which lacked ER stress-induced apoptosis. Experimental Design Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB- and c- jun-responsive genes, was studied. RNAi knockdown studies were performed in Flt3ITD+ve cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were performed to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. Results AMLs characterized by normal karyotype with Flt3ITD were found to have 10-100-fold lower DAPK1 transcripts normalized to the expression of c-jun, a transcriptional activator of DAPK1, as compared to a heterogeneous cytogenetic category. Meis1, a c-jun-responsive adverse AML prognostic gene signature was also measured as control. These Flt3ITD+ve AMLs over-express relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter along with HDAC2 and HDAC6 in the Flt3ITD+ve human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NIK, de-repressed DAPK1. DAPK1-repressed primary Flt3ITD+ve AMLs had selective nuclear activation of p52NF-κB. Conclusions Flt3ITD promotes a non-canonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD+ve AML. PMID:22096027

Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease

PubMed Central

Mitchelson, Keith Richard; Qin, Wen-Yan

2015-01-01

MicroRNAs are small non-coding RNAs that participate in different biological processes, providing subtle combinational regulation of cellular pathways, often by regulating components of signalling pathways. Aberrant expression of miRNAs is an important factor in the development and progression of disease. The canonical myomiRs (miR-1, -133 and -206) are central to the development and health of mammalian skeletal and cardiac muscles, but new findings show they have regulatory roles in the development of other mammalian non-muscle tissues, including nerve, brain structures, adipose and some specialised immunological cells. Moreover, the deregulation of myomiR expression is associated with a variety of different cancers, where typically they have tumor suppressor functions, although examples of an oncogenic role illustrate their diverse function in different cell environments. This review examines the involvement of the related myomiRs at the crossroads between cell development/tissue regeneration/tissue inflammation responses, and cancer development. PMID:26322174

Dimensions of care for dementia sufferers in long-term care institutions: are they related to outcomes?

PubMed

Chappell, N L; Reid, R C

2000-07-01

This study empirically examined whether dimensions of care cluster in special care units (SCUs) compared with non-SCUs. The relationship between SCU status plus separate measures of the dimensions of care and outcomes for dementia sufferers was then investigated. Data were drawn from the Intermediate Care Facility Project. The sample (N = 510) included residents with dementia, aged 65 and older, in intermediate care facilities throughout the province of British Columbia. Canada. Longitudinal data included 6 outcomes: cognitive function, behavioral problems of agitation and social skills, physical functioning, and quality of life measured through affect and expressive language skills. Separate multiple linear regression equations were estimated, relating each of these outcomes to 5 dimensions of care: preadmission and admission procedures. staff training and education, nonuse of physical and chemical restraints, flexible care routines and resident-relevant activities, and the environment. The results showed there is virtually no clustering of dimensions along SCU/non-SCU lines. Neither SCU status nor the individual dimensions were highly predictive of outcomes. Residents' affect at t1 emerged as a characteristic that was significantly correlated with other outcomes. This Canadian research can be added to the few but growing number of rigorous studies that suggest SCUs are not homogeneous and do not necessarily provide better care than non-SCUs. Moreover, it raises questions about the benefits of "best practice" dimensions of care, regardless of SCU status.

Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling: implications for therapeutic targeting.

PubMed

Hankey, William; Frankel, Wendy L; Groden, Joanna

2018-03-01

The acquisition of biallelic mutations in the APC gene is a rate-limiting step in the development of most colorectal cancers and occurs in the earliest lesions. APC encodes a 312-kDa protein that localizes to multiple subcellular compartments and performs diverse functions. APC participates in a cytoplasmic complex that promotes the destruction of the transcriptional licensing factor β-catenin; APC mutations that abolish this function trigger constitutive activation of the canonical WNT signaling pathway, a characteristic found in almost all colorectal cancers. By negatively regulating canonical WNT signaling, APC counteracts proliferation, promotes differentiation, facilitates apoptosis, and suppresses invasion and tumor progression. APC further antagonizes canonical WNT signaling by interacting with and counteracting β-catenin in the nucleus. APC also suppresses tumor initiation and progression in the colorectal epithelium through functions that are independent of canonical WNT signaling. APC regulates the mitotic spindle to facilitate proper chromosome segregation, localizes to the cell periphery and cell protrusions to establish cell polarity and appropriate directional migration, and inhibits DNA replication by interacting directly with DNA. Mutations in APC are often frameshifts, insertions, or deletions that introduce premature stop codons and lead to the production of truncated APC proteins that lack its normal functions and possess tumorigenic properties. Therapeutic approaches in development for the treatment of APC-deficient tumors are focused on the inhibition of canonical WNT signaling, especially through targets downstream of APC in the pathway, or on the restoration of wild-type APC expression.

Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling: Implications for therapeutic targeting

PubMed Central

Hankey, William; Frankel, Wendy L.

2018-01-01

The acquisition of biallelic mutations in the APC gene is a rate-limiting step in the development of most colorectal cancers and occurs in the earliest lesions. APC encodes a 312-kDa protein that localizes to multiple subcellular compartments and performs diverse functions. APC participates in a cytoplasmic complex that promotes the destruction of the transcriptional licensing factor β-catenin; APC mutations that abolish this function trigger constitutive activation of the canonical WNT signaling pathway, a characteristic found in almost all colorectal cancers. By negatively regulating canonical WNT signaling, APC counteracts proliferation, promotes differentiation, facilitates apoptosis and suppresses invasion and tumor progression. APC further antagonizes canonical WNT signaling by interacting with and counteracting β-catenin in the nucleus. APC also suppresses tumor initiation and progression in the colorectal epithelium through functions that are independent of canonical WNT signaling. APC regulates the mitotic spindle to facilitate proper chromosome segregation, localizes to the cell periphery and cell protrusions to establish cell polarity and appropriate directional migration, and inhibits DNA replication by interacting directly with DNA. Mutations in APC are often frameshifts, insertions or deletions that introduce premature stop codons and lead to the production of truncated APC proteins that lack its normal functions and possess tumorigenic properties. Therapeutic approaches in development for the treatment of APC-deficient tumors are focused on the inhibition of canonical WNT signaling, especially through targets downstream of APC in the pathway, or on the restoration of wild-type APC expression. PMID:29318445

Generalized prolate spheroidal wave functions for optical finite fractional Fourier and linear canonical transforms.

PubMed

Pei, Soo-Chang; Ding, Jian-Jiun

2005-03-01

Prolate spheroidal wave functions (PSWFs) are known to be useful for analyzing the properties of the finite-extension Fourier transform (fi-FT). We extend the theory of PSWFs for the finite-extension fractional Fourier transform, the finite-extension linear canonical transform, and the finite-extension offset linear canonical transform. These finite transforms are more flexible than the fi-FT and can model much more generalized optical systems. We also illustrate how to use the generalized prolate spheroidal functions we derive to analyze the energy-preservation ratio, the self-imaging phenomenon, and the resonance phenomenon of the finite-sized one-stage or multiple-stage optical systems.

Inter-correlations between Cloninger's temperament dimensions-- a meta-analysis.

PubMed

Miettunen, Jouko; Lauronen, Erika; Kantojärvi, Liisa; Veijola, Juha; Joukamaa, Matti

2008-07-15

The Temperament and Character Inventory (TCI) was developed to measure the following temperament dimensions: novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (P). These four dimensions of temperament were originally proposed to be independent of one another. In this study the inter-relationships between the dimensions were studied with meta-analytic techniques. We also studied the effects of sociodemographic factors (location of the study, mean age and gender distribution) on correlations between temperament dimensions. We searched studies on healthy (non-clinical) populations that used the TCI (version 9), and that had a required sample size of at least 100. The search resulted in 16 articles. The resulted pooled correlation coefficient was medium level between NS and HA (-0.27). Correlations were small for HA-P (-0.20), NS-P (-0.14), NS-RD (0.10), RD-P (0.05) and HA-RD (0.04). In meta-regression, the correlation NS-P was significantly affected by the location of the study (Asian/other) and by the gender distribution of the sample. In the HA-P correlation, the mean age of the sample affected the correlation. In conclusion, we found a medium level negative correlation between NS and HA; other correlations between the dimensions were small. These findings mainly support Cloninger's theory of independent dimensions.

The Canon and Cultural Studies: Culture and Anarchy in Gotham City.

ERIC Educational Resources Information Center

DeBona, Guerric

1997-01-01

Finds that including media studies at the end of a traditional literature course is an effective pedagogical instrument for instigating discussion regarding the literary canon, since students recognize and address the important contribution of popular culture when it is in dialogue with more traditional material. Selects the film…

GRB 060614 in the canonical fireshell model

NASA Astrophysics Data System (ADS)

Caito, L.; Bernardini, M. G.; Bianco, C. L.; Dainotti, M. G.; Guida, R.; Ruffini, R.

2008-10-01

Gamma-Ray Burst (GRB) 060614 is the first nearby long duration GRB clearly not associated to any bright Ib/c Supernova. The explosion of this burst undermines one of the fundamental assumptions of the standard scenario and opens new horizons and hints of investigation. GRB 060614, hardly classifiable as a short GRB, is not either a ``typical'' long GRB since it occurs in a low star forming region. Moreover, it presents deep similarities with GRB 970228, which is the prototype of the ``fake'' short bursts, or better canonical GRBs disguised as short ones. Within the ``fireshell'' model ([1]), we test if this ``anomalous'' source can be a disguised short GRB([2]).

Uncertainty relations, zero point energy and the linear canonical group

NASA Technical Reports Server (NTRS)

Sudarshan, E. C. G.

1993-01-01

The close relationship between the zero point energy, the uncertainty relations, coherent states, squeezed states, and correlated states for one mode is investigated. This group-theoretic perspective enables the parametrization and identification of their multimode generalization. In particular the generalized Schroedinger-Robertson uncertainty relations are analyzed. An elementary method of determining the canonical structure of the generalized correlated states is presented.

On non-exponential cosmological solutions with two factor spaces of dimensions m and 1 in the Einstein-Gauss-Bonnet model with a Λ-term

NASA Astrophysics Data System (ADS)

Ernazarov, K. K.

2017-12-01

We consider a (m + 2)-dimensional Einstein-Gauss-Bonnet (EGB) model with the cosmological Λ-term. We restrict the metrics to be diagonal ones and find for certain Λ = Λ(m) class of cosmological solutions with non-exponential time dependence of two scale factors of dimensions m > 2 and 1. Any solution from this class describes an accelerated expansion of m-dimensional subspace and tends asymptotically to isotropic solution with exponential dependence of scale factors.

Phase transition and thermodynamic geometry of f (R ) AdS black holes in the grand canonical ensemble

NASA Astrophysics Data System (ADS)

Li, Gu-Qiang; Mo, Jie-Xiong

2016-06-01

The phase transition of a four-dimensional charged AdS black hole solution in the R +f (R ) gravity with constant curvature is investigated in the grand canonical ensemble, where we find novel characteristics quite different from that in the canonical ensemble. There exists no critical point for T -S curve while in former research critical point was found for both the T -S curve and T -r+ curve when the electric charge of f (R ) black holes is kept fixed. Moreover, we derive the explicit expression for the specific heat, the analog of volume expansion coefficient and isothermal compressibility coefficient when the electric potential of f (R ) AdS black hole is fixed. The specific heat CΦ encounters a divergence when 0 <Φ b . This finding also differs from the result in the canonical ensemble, where there may be two, one or no divergence points for the specific heat CQ . To examine the phase structure newly found in the grand canonical ensemble, we appeal to the well-known thermodynamic geometry tools and derive the analytic expressions for both the Weinhold scalar curvature and Ruppeiner scalar curvature. It is shown that they diverge exactly where the specific heat CΦ diverges.