WorldWideScience

Sample records for superstring-inspired e6 unification

  1. Dark matter, mirror world, and E6 unification

    International Nuclear Information System (INIS)

    Das, Ch. R.; Laperashvili, L. V.

    2009-01-01

    The idea that the ordinary (O) and mirror (M) worlds exist simultaneously is developed. It is shown that, in the case of a violated mirror parity (MP), the renormalization-group evolution of the coupling constants, which is represented in the O world by the dependence α i -1 (μ) (μ is an energy variable), is not identical to the evolution of the coupling constants α' i -1 (μ) in the M world. Here, the index i labels the symmetry group under consideration, while a dash labels quantities defined in the M world. It is assumed that E 6 unification predicted by superstring theory restores MP at the unification scale M SGUT ∼ 10 18 GeV, this inevitably leading to the difference in the violation of E 6 unification in the O and M worlds at lower energies: E 6 → SO(10) x U(1) Z and E' 6 → SU(6)' x SU(2)' Z . Considering only asymptotically free theories, we present the evolution of all the inverse coupling constants α i -1 (μ) in the one-loop approximation. In dealing with the M world involving MP violation, we then arrive at the model of the accelerating expansion of our Universe, where the axion ('acceleron') belongs to the SU(2)' Z group of the M world. The coupling constant g' Z , which grows indefinitely at the scale Λ' Z ∼ 10 -3 eV, is associated with this group. Within this theory, our Universe is in the false vacuum of the M world, in agreement with the phenomenologically observed cosmological constant of about (3 x 10 -3 eV) 4 .

  2. Preon Model and Family Replicated E_6 Unification

    Directory of Open Access Journals (Sweden)

    Larisa V. Laperashvili

    2008-02-01

    Full Text Available Previously we suggested a new preon model of composite quark-leptons and bosons with the 'flipped' $E_6imes widetilde{E_6}$ gauge symmetry group. We assumed that preons are dyons having both hyper-electric $g$ and hyper-magnetic $ilde g$ charges, and these preons-dyons are confined by hyper-magnetic strings which are an ${f N}=1$ supersymmetric non-Abelian flux tubes created by the condensation of spreons near the Planck scale. In the present paper we show that the existence of the three types of strings with tensions $T_k=k T_0$ $(k = 1,2,3$ producing three (and only three generations of composite quark-leptons, also provides three generations of composite gauge bosons ('hyper-gluons' and, as a consequence, predicts the family replicated $[E_6]^3$ unification at the scale $sim 10^{17}$ GeV. This group of unification has the possibility of breaking to the group of symmetry: $ [SU(3_C]^3imes [SU(2_L]^3imes [U(1_Y]^3 imes [U(1_{(B-L}]^3$ which undergoes the breakdown to the Standard Model at lower energies. Some predictive advantages of the family replicated gauge groups of symmetry are briefly discussed.

  3. Superstring-inspired SO(10) GUT model with intermediate scale

    Science.gov (United States)

    Sasaki, Ken

    1987-12-01

    A new mechanism is proposed for the mixing of Weinberg-Salam Higgs fields in superstring-inspired SO(10) models with no SO(10) singlet fields. The higher-dimensional terms in the superpotential can generate both Higgs field mixing and a small mass for the physical neutrino. I would like to thank Professor C. Iso for hospitality extended to me at the Tokyo Institute of Technology.

  4. Low-energy consequences of superstring-inspired models with intermediate-mass scales

    International Nuclear Information System (INIS)

    Gabbiani, F.

    1987-01-01

    The phenomenological consequences of implementing intermediate-mass scales in E 6 superstring-inspired models are discussed. Starting from a suitable Calabi-Yau compactification with b 1,1 >1, one gets, after Hosotani breaking, the rank r=5 gauge group SU(3) C x SU(2) L x U(1) Y x U(1) E , that is broken at an intermediate-mass scale down to the standard-model group. The analysis of both the intermediate and the electroweak breaking is performed in the two cases Λ c = M x and Λ c x , where Λ c is the scale at which the hidden sector gauginos condensate. It is performed quantitatively the minimization of the low-energy effective potential and the renormalization group analysis, yielding a viable set of mass spectra and confirming the reliability of the intermediate-breaking scheme

  5. E6 unification model building. III. Clebsch-Gordan coefficients in E6 tensor products of the 27 with higher dimensional representations

    International Nuclear Information System (INIS)

    Anderson, Gregory W.; Blazek, Tomas

    2005-01-01

    E 6 is an attractive group for unification model building. However, the complexity of a rank 6 group makes it nontrivial to write down the structure of higher dimensional operators in an E 6 theory in terms of the states labeled by quantum numbers of the standard model gauge group. In this paper, we show the results of our computation of the Clebsch-Gordan coefficients for the products of the 27 with irreducible representations of higher dimensionality: 78, 351, 351 ' , 351, and 351 ' . Application of these results to E 6 model building involving higher dimensional operators is straightforward

  6. Vectorlike particles, Z′ and Yukawa unification in F-theory inspired E6

    Directory of Open Access Journals (Sweden)

    Athanasios Karozas

    2018-03-01

    Full Text Available We explore the low energy implications of an F-theory inspired E6 model whose breaking yields, in addition to the MSSM gauge symmetry, a Z′ gauge boson associated with a U(1 symmetry broken at the TeV scale. The zero mode spectrum of the effective low energy theory is derived from the decomposition of the 27 and 27‾ representations of E6 and we parametrise their multiplicities in terms of a minimum number of flux parameters. We perform a two-loop renormalisation group analysis of the gauge and Yukawa couplings of the effective theory model and estimate lower bounds on the new vectorlike particles predicted in the model. We compute the third generation Yukawa couplings in an F-theory context assuming an E8 point of enhancement and express our results in terms of the local flux densities associated with the gauge symmetry breaking. We find that their values are compatible with the ones computed by the renormalisation group equations, and we identify points in the parameter space of the flux densities where the t−b−τ Yukawa couplings unify.

  7. Vectorlike particles, Z‧ and Yukawa unification in F-theory inspired E6

    Science.gov (United States)

    Karozas, Athanasios; Leontaris, George K.; Shafi, Qaisar

    2018-03-01

    We explore the low energy implications of an F-theory inspired E6 model whose breaking yields, in addition to the MSSM gauge symmetry, a Z‧ gauge boson associated with a U (1) symmetry broken at the TeV scale. The zero mode spectrum of the effective low energy theory is derived from the decomposition of the 27 and 27 ‾ representations of E6 and we parametrise their multiplicities in terms of a minimum number of flux parameters. We perform a two-loop renormalisation group analysis of the gauge and Yukawa couplings of the effective theory model and estimate lower bounds on the new vectorlike particles predicted in the model. We compute the third generation Yukawa couplings in an F-theory context assuming an E8 point of enhancement and express our results in terms of the local flux densities associated with the gauge symmetry breaking. We find that their values are compatible with the ones computed by the renormalisation group equations, and we identify points in the parameter space of the flux densities where the t - b - τ Yukawa couplings unify.

  8. Unification

    International Nuclear Information System (INIS)

    Iliopoulos, J.

    1983-01-01

    This chapter describes the weak and electromagnetic interactions by a gauge theory based on the group U(1)xSU(2). Discusses SO(10), E 6 , beyond gauge theories, Grassmann algebras, graded superalgebras, Majorana and Weyl spinors; particle representations; all possible supersymmetries of the S-matrix; representations in terms of fields; a simple field theory model; supersymmetry and gauge invariance; the breaking of supersymmetry; the supersymmetric extension of the standard model; and supersymmetry and grand-unified theories. Finds that the rate of approach to the symmetric, which is logarithmic for dimensionless couplings, is too slow to account for the high accuracy with which symmetries are observed in nature. Shows that scalar Q.E.D. in perturbation theory is not an I.R. attractor when one attempts to approach it via a class of theories with negative metric

  9. Superstring inspired phenomenology

    International Nuclear Information System (INIS)

    Binetruy, P.

    1988-01-01

    Recent progress in superstring model building is reviewed with an emphasis on the general features of the models obtained. The problems associated with supersymmetry breaking and intermediate gauge symmetry breaking (M W I GUT ) are described. Finally, the phenomenology of these models is summarized, with a discussion of the role that new experimental results could play to help clearing up the above difficulties

  10. Superstring-inspired models

    International Nuclear Information System (INIS)

    Aguila, F. del; Blair, G.; Daniel, M.; Ross, G.G.

    1986-01-01

    We discuss the structure of low-energy groups arising from compactified models based on the heterotic string. Particular regard is paid to the possibility of intermediate scale breaking which may change the low-energy gauge structure and may naturally lead to doublet-triplet splitting and the suppression of proton decay. We present an illustrative example of such a model with a low-energy gauge group structure SU 3 sup(c)xSU 2 sup(L)xSU 2 sup(R)xU 1 sup(B-L) which may be compatible with low-energy phenomena including limits on neutrino masses and sin 2 thetasub(W). Mechanisms leading to the minimal SU 3 sup(c)xSU 2 sup(L)xU 1 sup(Y) low-energy gauge group are also presented. (orig.)

  11. Superstring inspired models and phenomenology

    International Nuclear Information System (INIS)

    Ross, G.G.

    1987-01-01

    An investigation of the effective low-energy theory resulting from the superstring is given. The possible light gauge and chiral super-multiplet structure is considered and a specific model leading to a SU(3)xSU(2)xU(1) gauge group is presented. Phenomenological implications for such models are briefly discussed

  12. Unification predictions

    International Nuclear Information System (INIS)

    Ghilencea, D.; Ross, G.G.; Lanzagorta, M.

    1997-07-01

    The unification of gauge couplings suggests that there is an underlying (supersymmetric) unification of the strong, electromagnetic and weak interactions. The prediction of the unification scale may be the first quantitative indication that this unification may extend to unification with gravity. We make a precise determination of these predictions for a class of models which extend the multiplet structure of the Minimal Supersymmetric Standard Model to include the heavy states expected in many Grand Unified and/or superstring theories. We show that there is a strong cancellation between the 2-loop and threshold effects. As a result the net effect is smaller than previously thought, giving a small increase in both the unification scale and the value of the strong coupling at low energies. (author). 15 refs, 5 figs

  13. Identification of E6-generated Z' from combined CHARM II, LEP 1, SLC high-precision measurements

    International Nuclear Information System (INIS)

    Lynn, B.W.; Renard, F.M.; Verzegnassi, C.

    1988-01-01

    We show that a combined analysis of three specific longitudinal polarization asymmetries in electron-positron annihilation on Z 0 resonance, of the mass ratio M w /M z and of the neutrino-electron neutral cross-section ratio, which could be measured in the near future at SLC, LEP, ACOL and CHARM II, would lead to a well-defined identification of a single new E 6 -generated Z'. In particular, it might be possible to disentangle a superstring-inspired model from other currently considered possibilities down to values of the mixing angle vertical strokeθ η vertical stroke = 0.02 and, at the same time, to fix the mass ratio ε = M Z 2 /Msub(Z') 2 with known accuracy. (orig.)

  14. Simple unification

    International Nuclear Information System (INIS)

    Ponce, W.A.; Zepeda, A.

    1987-08-01

    We present the results obtained from our systematic search of a simple Lie group that unifies weak and electromagnetic interactions in a single truly unified theory. We work with fractionally charged quarks, and allow for particles and antiparticles to belong to the same irreducible representation. We found that models based on SU(6), SU(7), SU(8) and SU(10) are viable candidates for simple unification. (author). 23 refs

  15. Grand unification: status report

    International Nuclear Information System (INIS)

    Georgi, H.

    1983-01-01

    Grand unification is reviewed with regard to the flavor puzzle and the hierarchy puzzle. Progress in CP and the PQWWKDFS axion is reviewed. The neutrino mass and B-L research, the understanding and assimilation of the language of effective theories (which divide the momentum scale up into regions), with focus on the models, are surveyed. Various unified models are organized according to whether they address the hierarchy puzzle or the flavor puzzle. SU(5), SO(10), E6, and Higgs are considered simple and explicit models. Global symmetry addresses hierarchy puzzle, but the rules are unclear. In SO (18), with regard to hierarchy, perturbation theory breaks down. SO (14) fails for hierarchy because of GIM, b and t problems. Supersymmetry and technicolor with regard to flavor puzzle are questioned. The CP solution of ETC and Composite C models (addressing both flavor and hierarchy) is a minus. Composite A model has no evident virtues, and the basic idea of ETC model needs checking

  16. Functional Pearls : Polytypic Unification

    NARCIS (Netherlands)

    Jansson, P.; Jeuring, J.T.

    1998-01-01

    Unification, or two-way pattern matching, is the process of solving an equation involving two first-order terms with variables. Unification is used in type inference in many programming languages and in the execution of logic programs. This means that unification algorithms have to be written over

  17. Can the superstring inspire the standard model

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, J.; Enqvist, K.; Nanopoulos, D.V.; Olive, K.A.

    1988-02-01

    We discuss general features of models in which the E/sub 8/xE'/sub 8/ heterotic superstring is compactified on a specific Calabi-Yau manifold. The gauge group of rank-6 in four dimensions is supposed to be broken down at an intermediate scale m/sub I/ to the standard model group SU(3)/sub C/ x SU(2)/sub L/ x U(1)/sub Y/, as a result of two neutral scalar fields acquiring large vacuum expectations (vev's) in one of many flat directions of the effective potential. We find that it is difficult to generate such an intermediate scale by radiative symmetry breaking, whilst such models have prima facie problems with baryon decay mediated by massive particles and with non-perturbative behaviour of the gauge couplings, unless m/sub I/ > or approx. 10/sup 16/ GeV. Rapid baryon decay mediated by light particles, large neutrino masses, other ..delta..L not = 0 processes and flavour-changing neutral currents are generic features of these models. We illustrate these observations with explicit calculations in a number of different models given by vev's in different flat directions.

  18. Can the superstring inspire the standard model?

    International Nuclear Information System (INIS)

    Ellis, J.; Enqvist, K.; Nanopoulos, D.V.; Olive, K.A.

    1988-01-01

    We discuss general features of models in which the E 8 xE' 8 heterotic superstring is compactified on a specific Calabi-Yau manifold. The gauge group of rank-6 in four dimensions is supposed to be broken down at an intermediate scale m I to the standard model group SU(3) C x SU(2) L x U(1) Y , as a result of two neutral scalar fields acquiring large vacuum expectations (vev's) in one of many flat directions of the effective potential. We find that it is difficult to generate such an intermediate scale by radiative symmetry breaking, whilst such models have prima facie problems with baryon decay mediated by massive particles and with non-perturbative behaviour of the gauge couplings, unless m I > or approx. 10 16 GeV. Rapid baryon decay mediated by light particles, large neutrino masses, other ΔL ≠ 0 processes and flavour-changing neutral currents are generic features of these models. We illustrate these observations with explicit calculations in a number of different models given by vev's in different flat directions. (orig.)

  19. Papillomavirus E6 proteins

    International Nuclear Information System (INIS)

    Howie, Heather L.; Katzenellenbogen, Rachel A.; Galloway, Denise A.

    2009-01-01

    The papillomaviruses are small DNA viruses that encode approximately eight genes, and require the host cell DNA replication machinery for their viral DNA replication. Thus papillomaviruses have evolved strategies to induce host cell DNA synthesis balanced with strategies to protect the cell from unscheduled replication. While the papillomavirus E1 and E2 genes are directly involved in viral replication by binding to and unwinding the origin of replication, the E6 and E7 proteins have auxillary functions that promote proliferation. As a consequence of disrupting the normal checkpoints that regulate cell cycle entry and progression, the E6 and E7 proteins play a key role in the oncogenic properties of human papillomaviruses with a high risk of causing anogenital cancers (HR HPVs). As a consequence, E6 and E7 of HR HPVs are invariably expressed in cervical cancers. This article will focus on the E6 protein and its numerous activities including inactivating p53, blocking apoptosis, activating telomerase, disrupting cell adhesion, polarity and epithelial differentiation, altering transcription and reducing immune recognition

  20. Unification beyond GUT's: Gauge-Yukawa unification

    International Nuclear Information System (INIS)

    Kubo, J.; Mondragon, M.; Zoupanos, G.

    1996-01-01

    Gauge-Yukawa Unification (GYU) is a renormalization group invariant functional relation among gauge and Yukawa couplings which holds beyond the unification point in Grand Unified Theories (GUTs). We present here various models where GYU is obtained by requiring the principles of finiteness and reduction of couplings. We examine the consequences of these requirements for the low energy parameters, especially for the top quark mass. The predictions are such that they clearly distinguish already GYU from ordinary GUTs. It is expected that it will be possible to discriminate among the various GYUs when more accurate measurements of the top quark mass are available. (author)

  1. SU(5) unification revisited

    International Nuclear Information System (INIS)

    Giveon, A.; Sarid, U.; Hall, L.J.; California Univ., Berkeley, CA

    1991-01-01

    Model-independent criteria for unification in the SU(5) framework are studied. These are applied to the minimal supersymmetric standard model and to the standard model with a split 45 Higgs representation. Although the former is consistent with SU(5) unification, the superpartner masses can vary over a wide range, and may even all lie well beyond the reach of planned colliders. Adding a split 45 to the standard model can also satisfy the unification criteria, so supersymmetric SU(5) is far from unique. Furthermore, we learn that separate Higgs doublets must couple to the top and bottom quarks in order to give a correct m b /m τ prediction. (orig.)

  2. Prospects for further unification

    International Nuclear Information System (INIS)

    Ne'eman, Y.

    1983-07-01

    We review the unification of weak and electromagnetic interactions (QAD), the prevalent color gauge theory of the strong interactions (QCD) and attempts to embed both these theories in a further Unified Gauge Theory. We discuss the related advances in cosmology and touch upon other approaches to the understanding of particles and fields. 44 references

  3. Dark matter from unification

    DEFF Research Database (Denmark)

    Kainulainen, Kimmo; Tuominen, Kimmo; Virkajärvi, Jussi Tuomas

    2013-01-01

    We consider a minimal extension of the Standard Model (SM), which leads to unification of the SM coupling constants, breaks electroweak symmetry dynamically by a new strongly coupled sector and leads to novel dark matter candidates. In this model, the coupling constant unification requires...... eigenstates of this sector and determine the resulting relic density. The results are constrained by available data from colliders and direct and indirect dark matter experiments. We find the model viable and outline briefly future research directions....... the existence of electroweak triplet and doublet fermions singlet under QCD and new strong dynamics underlying the Higgs sector. Among these new matter fields and a new right handed neutrino, we consider the mass and mixing patterns of the neutral states. We argue for a symmetry stabilizing the lightest mass...

  4. Direct mediation, duality and unification

    International Nuclear Information System (INIS)

    Abel, Steven; Khoze, Valentin V.

    2008-01-01

    It is well-known that in scenarios with direct gauge mediation of supersymmetry breaking the messenger fields significantly affect the running of Standard Model couplings and introduce Landau poles which are difficult to avoid. Among other things, this appears to remove any possibility of a meaningful unification prediction and is often viewed as a strong argument against direct mediation. We propose two ways that Seiberg duality can circumvent this problem. In the first, which we call 'deflected-unification', the SUSY-breaking hidden sector is a magnetic theory which undergoes a Seiberg duality to an electric phase. Importantly, the electric version has fewer fundamental degrees of freedom coupled to the MSSM compared to the magnetic formulation. This changes the β-functions of the MSSM gauge couplings so as to push their Landau poles above the unification scale. We show that this scenario is realised for recently suggested models of gauge mediation based on a metastable SCQD-type hidden sector directly coupled to MSSM. The second possibility for avoiding Landau poles, which we call 'dual-unification', begins with the observation that, if the mediating fields fall into complete SU(5) multiplets, then the MSSM+messengers exhibits a fake unification at unphysical values of the gauge couplings. We show that, in known examples of electric/magnetic duals, such a fake unification in the magnetic theory reflects a real unification in the electric theory. We therefore propose that the Standard Model could itself be a magnetic dual of some unknown electric theory in which the true unification takes place. This scenario maintains the unification prediction (and unification scale) even in the presence of Landau poles in the magnetic theory below the GUT scale. We further note that this dual realization of grand unification can explain why Nature appears to unify, but the proton does not decay.

  5. Unification and supersymmetry

    International Nuclear Information System (INIS)

    Mohapatra, R.N.

    1991-01-01

    This book deals with some of the latest developments in our attempts to construct a unified theory of the fundamental interactions of nature. Among the topics covered are spontaneous symmetry breaking, grand unified theories, supersymmetry, and supergravity. The book starts with a quick review of elementary particle theory and continues with a discussion of composite quarks, leptons, Higgs bosons, and CP violation; it concludes with consideration of supersymmetric unification schemes, in which bosons and leptons are considered in some sense equivalent. The second edition is updated and corrected and contains new chapters on recent developments

  6. Grand unification theory and technicolor

    International Nuclear Information System (INIS)

    Rubakov, V.A.; Shaposhnikov, M.E.

    1983-01-01

    The lecture course can be considered as introduction to the problems concerning grand unification models. The course is incomplete. Such problems as CP-violations in strong interactions and the problem of gravitational interaction inclusion in the scheme of grand unification theory are not touched upon. Models of early unification, in which strong, weak and electromagnetic interactions are compared according to the ''strength'' at energies of about 10 5 -10 6 GeV, are not discussed. Models with horizontal symmetry, considering different generations of quarks and leptons from one viewpoint, are not analyzed. Cosmological applications of supersymmetric unified theories are not considered. Certain problems of standard elementary particle theory, philosophy of the great unification, general properties of the grand unification models and the main principles of the construction of models: the SU(5) model, models on the SO(10) groups, have been considered. The problem of supersymmetric unification hierarchies, supersymmetric generalization of the minimum SU(5) model, supersymmetry violation and the problem of hierarchies, phenomenology of the o.rand unification models, cosmological application and technicolour, are discussed

  7. Supersymmetry, supergravity, and unification

    CERN Document Server

    Nath, Pran

    2017-01-01

    This unique book gives a modern account of particle physics and gravity based on supersymmetry and supergravity, two of the most significant developments in theoretical physics since general relativity. The book begins with a brief overview of the history of unification and then goes into a detailed exposition of both fundamental and phenomenological topics. The topics in fundamental physics include Einstein gravity, Yang-Mills theory, anomalies, the standard model, supersymmetry and supergravity, and the construction of supergravity couplings with matter and gauge fields, as well as computational techniques for SO(10) couplings. The topics of phenomenological interest include implications of supergravity models at colliders, CP violation, and proton stability, as well as topics in cosmology such as inflation, leptogenesis, baryogenesis, and dark matter. The book is intended for graduate students and researchers seeking to master the techniques for building grand unified models.

  8. The string unification of gauge couplings and gauge kinetic mixings

    International Nuclear Information System (INIS)

    Hattori, Chuichiro; Matsuda, Masahisa; Matsuoka, Takeo; Mochinaga, Daizo.

    1993-01-01

    In the superstring models we have not only the complete 27 multiplets of E 6 but also extra incomplete (27+27-bar) chiral supermultiplets being alive at low energies. Associated with these additional multiplets, when the gauge symmetry contains more than one U(1) gauge group, there may exist gauge kinetic mixings among these U(1) gauge groups. In such cases the effect of gauge kinetic mixings should be incorporated into the study of unification of gauge couplings. We study these interesting effects systematically in these models. The string threshold effect is also taken into account. It is found that in the four-generation models we do not have an advisable solution of string unification of gauge couplings consistent with experimental values at the electroweak scale. We also discuss the possible scenarios to solve this problem. (author)

  9. Selected topics in grand unification

    International Nuclear Information System (INIS)

    Seckel, D.

    1983-01-01

    This dissertation is a collection of four pieces of research dealing with grand unification. The topics are neutron oscillation, CP violation, magnetic monopole abundance and distribution in neutron stars, and a proposal for an inflationary cosmology driven by stress-energy in domain walls

  10. Problems in unification and supergravity

    Energy Technology Data Exchange (ETDEWEB)

    Farrar, G.; Henyey, F. (eds.)

    1984-01-01

    Problems in unification of the various gauge groups, quantum gravity, supersymmetry and supergravity, compact dimensions of space-time, and conditions at the beginning of the universe are discussed. Separate entries were prepared for the data base for the 15 papers presented. (WHK)

  11. Problems in unification and supergravity

    International Nuclear Information System (INIS)

    Farrar, G.; Henyey, F.

    1984-01-01

    Problems in unification of the various gauge groups, quantum gravity, supersymmetry and supergravity, compact dimensions of space-time, and conditions at the beginning of the universe are discussed. Separate entries were prepared for the data base for the 15 papers presented

  12. Gauge unification of fundamental forces

    International Nuclear Information System (INIS)

    Salam, A.

    1980-02-01

    After having reviewed briefly the last twenty years' progress in the theory of unification, with the twin aspects of development of a gauge theory of basic interactions linked with internal symmetry and the spontaneous breaking of these symmetries, the Nobel prize winners have summarized the present situation and the immediate problems. At the end, an extrapolation of the future is also given

  13. Introduction to grand unification theories

    International Nuclear Information System (INIS)

    Kang, Kyungsik

    1980-01-01

    We introduce the Georgi-Glashow model based on the minimal gauge group SU(5) as a prototype grand unification theory of the electroweak and strong interactions. Simple estimation of sin 2 thetasub(W) in the symmetry limit and the renormalization corrections at the energy scale of Msub(W) are given along wich other successes of the SU(5) model

  14. Unification, small and large

    Energy Technology Data Exchange (ETDEWEB)

    Fritzsch, Harald

    1993-04-15

    Full text: Fruitful exchanges between particle physics, astrophysics and cosmology have become a common feature in the last decade. In January, Coral Gables near Miami was the stage for a 'Unified Symmetry in the Small and the Large' meeting. Coral Gables is a famous physics venue. In January 1964, the year that the quark model of hadrons emerged, Behram Kursunoglu initiated a series of particle physics meetings that continued for 20 years and formed a regular focus for this development. The final such meeting was in 1983, coinciding with both the 80th birthday of field theory pioneer Paul Dirac, who worked in Florida towards the end of his career, and the discovery of the W bosons at CERN. The resurrected Coral Gables meeting began with historical accounts of the emergence of Big Bang cosmology, by Robert Ralph and Herman Alpher, while Andrei Linde proposed our expanding universe as a small part of a stationary system, infinite both in space and in time. The observational status of Big Bang cosmology was reviewed by Bruce Partridge, John Mather and Martin Harwit, emphasizing the cosmic background radiation, where temperature is now measured by the COBE satellite detectors to 2.726 ± 0.01 OK. The tiny fluctuations observed by COBE pose problems for standard cold dark matter models. Edward ('Rocky') Kolb reported on new studies on the electroweak phase transition, based on an analogy with the physics of liquid crystals. Richard Holman discussed the fate of global symmetries at energies near the Planck (grand unification) energy, and Paul Steinhardt talked about tensorial and scalar metric fluctuations in the light of the COBE results. Anthony Tyson gave an impressive description of dark matter studies using gravitational lensing, now emerging as a unique tool for indirectly observing intervening dark matter. A neutrino mass of 10 electronvolts could account for observed dark matter distributions, but fails to provide the necessary seeds for galaxy formation. A

  15. Unification, small and large

    International Nuclear Information System (INIS)

    Fritzsch, Harald

    1993-01-01

    Full text: Fruitful exchanges between particle physics, astrophysics and cosmology have become a common feature in the last decade. In January, Coral Gables near Miami was the stage for a 'Unified Symmetry in the Small and the Large' meeting. Coral Gables is a famous physics venue. In January 1964, the year that the quark model of hadrons emerged, Behram Kursunoglu initiated a series of particle physics meetings that continued for 20 years and formed a regular focus for this development. The final such meeting was in 1983, coinciding with both the 80th birthday of field theory pioneer Paul Dirac, who worked in Florida towards the end of his career, and the discovery of the W bosons at CERN. The resurrected Coral Gables meeting began with historical accounts of the emergence of Big Bang cosmology, by Robert Ralph and Herman Alpher, while Andrei Linde proposed our expanding universe as a small part of a stationary system, infinite both in space and in time. The observational status of Big Bang cosmology was reviewed by Bruce Partridge, John Mather and Martin Harwit, emphasizing the cosmic background radiation, where temperature is now measured by the COBE satellite detectors to 2.726 ± 0.01 OK. The tiny fluctuations observed by COBE pose problems for standard cold dark matter models. Edward ('Rocky') Kolb reported on new studies on the electroweak phase transition, based on an analogy with the physics of liquid crystals. Richard Holman discussed the fate of global symmetries at energies near the Planck (grand unification) energy, and Paul Steinhardt talked about tensorial and scalar metric fluctuations in the light of the COBE results. Anthony Tyson gave an impressive description of dark matter studies using gravitational lensing, now emerging as a unique tool for indirectly observing intervening dark matter. A neutrino mass of 10 electronvolts could account for observed dark matter distributions, but fails to provide the necessary seeds for

  16. Gauge coupling unification and nonequilibrium thermal dark matter.

    Science.gov (United States)

    Mambrini, Yann; Olive, Keith A; Quevillon, Jérémie; Zaldívar, Bryan

    2013-06-14

    We study a new mechanism for the production of dark matter in the Universe which does not rely on thermal equilibrium. Dark matter is populated from the thermal bath subsequent to inflationary reheating via a massive mediator whose mass is above the reheating scale T(RH). To this end, we consider models with an extra U(1) gauge symmetry broken at some intermediate scale (M(int) ≃ 10(10)-10(12) GeV). We show that not only does the model allow for gauge coupling unification (at a higher scale associated with grand unification) but it can provide a dark matter candidate which is a standard model singlet but charged under the extra U(1). The intermediate scale gauge boson(s) which are predicted in several E6/SO(10) constructions can be a natural mediator between dark matter and the thermal bath. We show that the dark matter abundance, while never having achieved thermal equilibrium, is fixed shortly after the reheating epoch by the relation T(RH)(3)/M(int)(4). As a consequence, we show that the unification of gauge couplings which determines M(int) also fixes the reheating temperature, which can be as high as T(RH) ≃ 10(11) GeV.

  17. An Ordering Linear Unification Algorithm

    Institute of Scientific and Technical Information of China (English)

    胡运发

    1989-01-01

    In this paper,we present an ordering linear unification algorithm(OLU).A new idea on substituteion of the binding terms is introduced to the algorithm,which is able to overcome some drawbacks of other algorithms,e.g.,MM algorithm[1],RG1 and RG2 algorithms[2],Particularly,if we use the directed eyclie graphs,the algoritm needs not check the binding order,then the OLU algorithm can also be aplied to the infinite tree data struceture,and a higher efficiency can be expected.The paper focuses upon the discussion of OLU algorithm and a partial order structure with respect to the unification algorithm.This algorithm has been implemented in the GKD-PROLOG/VAX 780 interpreting system.Experimental results have shown that the algorithm is very simple and efficient.

  18. Macroscopic constraints on string unification

    International Nuclear Information System (INIS)

    Taylor, T.R.

    1989-03-01

    The comparison of sting theory with experiment requires a huge extrapolation from the microscopic distances, of order of the Planck length, up to the macroscopic laboratory distances. The quantum effects give rise to large corrections to the macroscopic predictions of sting unification. I discus the model-independent constraints on the gravitational sector of string theory due to the inevitable existence of universal Fradkin-Tseytlin dilatons. 9 refs

  19. Flavour Democracy in Strong Unification

    CERN Document Server

    Abel, S A; Abel, Steven; King, Steven

    1998-01-01

    We show that the fermion mass spectrum may naturally be understood in terms of flavour democratic fixed points in supersymmetric theories which have a large domain of attraction in the presence of "strong unification". Our approach provides an alternative to the approximate Yukawa texture zeroes of the Froggatt-Nielsen mechanism. We discuss a particular model based on a broken gauged $SU(3)_L\\times SU(3)_R$ family symmetry which illustrates our approach.

  20. Psychotherapy Integration via Theoretical Unification

    Directory of Open Access Journals (Sweden)

    Warren W. Tryon

    2017-01-01

    Full Text Available Meaningful psychotherapy integration requires theoretical unification because psychotherapists can only be expected to treat patients with the same diagnoses similarly if they understand these disorders similarly and if they agree on the mechanisms by which effective treatments work. Tryon (in press has proposed a transtheoretic transdiagnostic psychotherapy based on an Applied Psychological Science (APS clinical orientation, founded on a BioPsychology Network explanatory system that provides sufficient theoretical unification to support meaningful psychotherapy integration. That proposal focused mainly on making a neuroscience argument. This article makes a different argument for theoretical unification and consequently psychotherapy integration. The strength of theories of psychotherapy, like all theory, is to focus on certain topics, goals, and methods. But this strength is also a weakness because it can blind one to alternative perspectives and thereby promote unnecessary competition among therapies. This article provides a broader perspective based on learning and memory that is consistent with the behavioral, cognitive, cognitive-behavioral, psychodynamic, pharmacologic, and Existential/Humanistic/Experiential clinical orientations. It thereby provides a basis for meaningful psychotherapy integration.

  1. Family unification in five and six dimensions

    International Nuclear Information System (INIS)

    Babu, K.S.; Barr, S.M.; Kyae, Bumseok

    2002-01-01

    In family unification models, all three families of quarks and leptons are grouped together into an irreducible representation of a simple gauge group, thus unifying the standard model gauge symmetries and a gauged family symmetry. Large orthogonal groups, and the exceptional groups E 7 and E 8 , have been much studied for family unification. The main theoretical difficulty of family unification is the existence of mirror families at the weak scale. It is shown here that family unification without mirror families can be realized in simple five-dimensional and six-dimensional orbifold models similar to those recently proposed for SU(5) and SO(10) grand unification. It is noted that a family unification group that survived to near the weak scale and whose coupling extrapolated to high scales unified with those of the standard model would be evidence, accessible in principle at low energy, of the existence of small (Planckian or GUT-scale) extra dimensions

  2. SAT Encoding of Unification in EL

    Science.gov (United States)

    Baader, Franz; Morawska, Barbara

    Unification in Description Logics has been proposed as a novel inference service that can, for example, be used to detect redundancies in ontologies. In a recent paper, we have shown that unification in EL is NP-complete, and thus of a complexity that is considerably lower than in other Description Logics of comparably restricted expressive power. In this paper, we introduce a new NP-algorithm for solving unification problems in EL, which is based on a reduction to satisfiability in propositional logic (SAT). The advantage of this new algorithm is, on the one hand, that it allows us to employ highly optimized state-of-the-art SAT solvers when implementing an EL-unification algorithm. On the other hand, this reduction provides us with a proof of the fact that EL-unification is in NP that is much simpler than the one given in our previous paper on EL-unification.

  3. HPV16 E6 and E6AP differentially cooperate to stimulate or augment Wnt signaling

    International Nuclear Information System (INIS)

    Sominsky, Sophia; Kuslansky, Yael; Shapiro, Beny; Jackman, Anna; Haupt, Ygal; Rosin-Arbesfeld, Rina; Sherman, Levana

    2014-01-01

    The present study investigated the roles of E6 and E6AP in the Wnt pathway. We showed that E6 levels are markedly reduced in cells in which Wnt signaling is activated. Coexpression of wild-type or mutant E6AP (C820A) in Wnt-activated cells stabilized E6 and enhanced Wnt/β-catenin/TCF transcription. Expression of E6AP alone in nonstimulated cells elevated β-catenin level, promoted its nuclear accumulation, and activated β-catenin/TCF transcription. A knockdown of E6AP lowered β-catenin levels. Coexpression with E6 intensified the activities of E6AP. Further experiments proved that E6AP/E6 stabilize β-catenin by protecting it from proteasomal degradation. This function was dependent on the catalytic activity of E6AP, the kinase activity of GSK3β and the susceptibility of β-catenin to GSK3β phosphorylation. Thus, this study identified E6AP as a novel regulator of the Wnt signaling pathway, capable of cooperating with E6 in stimulating or augmenting Wnt/β-catenin signaling, thereby possibly contributing to HPV carcinogenesis. - Highlights: • The roles of E6 and E6AP in the Wnt pathway were investigated. • E6AP stabilizes E6 and enhances E6 activity in augmentation of Wnt signaling. • E6AP cooperates with E6 to stabilize β-catenin and stimulate Wnt/β-catenin signaling. • E6AP and E6 act through different mechanisms to augment or stimulate Wnt signaling

  4. HPV16 E6 and E6AP differentially cooperate to stimulate or augment Wnt signaling

    Energy Technology Data Exchange (ETDEWEB)

    Sominsky, Sophia, E-mail: sophia.tab@gmail.com [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978 (Israel); Kuslansky, Yael, E-mail: ykuslansky@gmail.com [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978 (Israel); Shapiro, Beny, E-mail: benyshap@gmail.com [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978 (Israel); Jackman, Anna, E-mail: jackman@post.tau.ac.il [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978 (Israel); Haupt, Ygal, E-mail: ygal.haupt@petermac.org [Research Division, The Peter MacCallum Cancer Centre, East Melbourne (Australia); Rosin-Arbesfeld, Rina, E-mail: arina@post.tau.ac.il [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978 (Israel); Sherman, Levana, E-mail: lsherman@post.tau.ac.il [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978 (Israel)

    2014-11-15

    The present study investigated the roles of E6 and E6AP in the Wnt pathway. We showed that E6 levels are markedly reduced in cells in which Wnt signaling is activated. Coexpression of wild-type or mutant E6AP (C820A) in Wnt-activated cells stabilized E6 and enhanced Wnt/β-catenin/TCF transcription. Expression of E6AP alone in nonstimulated cells elevated β-catenin level, promoted its nuclear accumulation, and activated β-catenin/TCF transcription. A knockdown of E6AP lowered β-catenin levels. Coexpression with E6 intensified the activities of E6AP. Further experiments proved that E6AP/E6 stabilize β-catenin by protecting it from proteasomal degradation. This function was dependent on the catalytic activity of E6AP, the kinase activity of GSK3β and the susceptibility of β-catenin to GSK3β phosphorylation. Thus, this study identified E6AP as a novel regulator of the Wnt signaling pathway, capable of cooperating with E6 in stimulating or augmenting Wnt/β-catenin signaling, thereby possibly contributing to HPV carcinogenesis. - Highlights: • The roles of E6 and E6AP in the Wnt pathway were investigated. • E6AP stabilizes E6 and enhances E6 activity in augmentation of Wnt signaling. • E6AP cooperates with E6 to stabilize β-catenin and stimulate Wnt/β-catenin signaling. • E6AP and E6 act through different mechanisms to augment or stimulate Wnt signaling.

  5. Grand unification: quo vadis domine

    International Nuclear Information System (INIS)

    Senjanovic, G.

    1985-01-01

    The present theoretical and experimental situation with grand unification is summarized. The issues of proton decay and the Weinberg angle are addressed, going through the predictions of both the standard SU(5) theory and its supersymmetric extension. The SO(10) theory, which provides a minimal one family model, is then studied. The gravitational characteristics of domain walls and strings are then discussed. It is argued that there is a need to go beyond SO(10) in order to incorporate a unified picture of families. This leads to the prediction of mirror fermions, whose physics is analyzed. 31 refs

  6. Family unification within SO(15)

    International Nuclear Information System (INIS)

    Enqvist, K.; Maalampi, J.

    1981-01-01

    We present a model for the unification of fermion families based on the gauge symmetry SO(15). It is a minimal SO(n) model which can accommodate the known fermions within a single irreducible representation. The model predicts four ordinary fermion families and four families of mirror fermions. The latter have V + A weak interactions, and their mass scale is predicted to be 10 2 GeV/c 2 . We argue that radiative corrections to the fermion masses can cause non-negligible mixing between ordinary and mirror fermions. The implications of these mixings for the weak interaction phenomenology and solar neutrinos are discussed. (orig.)

  7. Proton hexality in local grand unification

    Energy Technology Data Exchange (ETDEWEB)

    Foerste, Stefan; Nilles, Hans Peter [Bonn Univ. (Germany). Bethe Center for Theoretical Physics and Physikalisches Institut; Ramos-Sanchez, Saul [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Vaudrevange, Patrick K.S. [Muenchen Univ. (Germany). Arnold Sommerfeld Center for Theoretical Physics

    2010-07-15

    Proton hexality is a discrete symmetry that avoids the problem of too fast proton decay in the supersymmetric extension of the standard model. Unfortunately it is inconsistent with conventional grand unification. We show that proton hexality can be incorporated in the scheme of ''Local Grand Unification'' discussed in the framework of model building in (heterotic) string theory. (orig.)

  8. Alternative Z ' bosons in E 6

    Science.gov (United States)

    Rojas, Eduardo; Erler, Jens

    2015-10-01

    We classify the quantum numbers of the extra U(1)' symmetries contained in E 6. In particular, we categorize the cases with rational charges and present the full list of models which arise from the chains of the maximal subgroups of E 6. As an application, the classification allows us to determine all embeddings of the Standard Model fermions in all possible decompositions of the fundamental representation of E 6 under its maximal subgroups. From this we find alternative chains of subgroups for Grand Unified Theories. We show how many of the known models including some new ones appear in alternative breaking patterns. We also use low energy constraints coming from parity-violating asymmetry measurements and atomic parity non-conservation to set limits on the E 6 motivated parameter space for a Z ' boson mass of 1.2 TeV. We include projected limits for the present and upcoming QWEAK, MOLLER and SOLID experiments.

  9. Effective Higgs theories in supersymmetric grand unification

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Sibo [Chongqing University, Department of Physics, Chongqing (China)

    2017-09-15

    The effective Higgs theories at the TeV scale in supersymmetric SU(5) grand unification models are systematically derived. Restricted to extensions on 5{sub H} containing the Higgs sector we show that only two types of real (vector-like) models and one type of chiral model are found to be consistent with perturbative grand unification. While the chiral model has been excluded by the LHC data, the fate of perturbative unification will be uniquely determined by the two classes of vector-like models. (orig.)

  10. Low-scale gaugino mass unification

    International Nuclear Information System (INIS)

    Endo, M.; Yoshioka, K.

    2008-04-01

    We present a new class of scenarios with the gaugino mass unification at the weak scale. The unification conditions are generally classified and then, the mirage gauge mediation is explored where gaugino masses are naturally unified and scalar partners of quarks and leptons have no mass hierarchy. The low-energy mass spectrum is governed by the mirage of unified gauge coupling which is seen by low-energy observers. We also study several explicit models for dynamically realizing the TeV-scale unification. (orig.)

  11. Low-scale gaugino mass unification

    Energy Technology Data Exchange (ETDEWEB)

    Endo, M [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Yoshioka, K [Kyoto Univ. (Japan). Dept. of Physics

    2008-04-15

    We present a new class of scenarios with the gaugino mass unification at the weak scale. The unification conditions are generally classified and then, the mirage gauge mediation is explored where gaugino masses are naturally unified and scalar partners of quarks and leptons have no mass hierarchy. The low-energy mass spectrum is governed by the mirage of unified gauge coupling which is seen by low-energy observers. We also study several explicit models for dynamically realizing the TeV-scale unification. (orig.)

  12. The Economic Implications of Korean Unification

    National Research Council Canada - National Science Library

    Schmitz, Jonathan

    2002-01-01

    .... To lessen this burden, South Korea will need to initiate policy reforms that can ease the financial stress and repercussions of unification and create an integrated economic community with North Korea...

  13. Higher-derivative Lee-Wick unification

    International Nuclear Information System (INIS)

    Carone, Christopher D.

    2009-01-01

    We consider gauge coupling unification in Lee-Wick extensions of the Standard Model that include higher-derivative quadratic terms beyond the minimally required set. We determine how the beta functions are modified when some Standard Model particles have two Lee-Wick partners. We show that gauge coupling unification can be achieved in such models without requiring the introduction of additional fields in the higher-derivative theory and we comment on possible ultraviolet completions.

  14. Grand unification and gravity - selected topics

    International Nuclear Information System (INIS)

    Zee, A.

    1981-09-01

    The material given here was presented in lectures delivered at the 4th Kyoto Summer Institute on Grand Unification and Related Topics. It consists of six sections. The sections are: the family problem, fermion mass hierarchy, maximal local symmetry, operator analysis of new physics, dynamically generated gravity, and Kaluza theory and grand unification. The last section contains a (hopefully) pedagogical introduction to Kaluza theory. For pedagogical completeness, several appendices reviewing some elementary notions of differential geometry have been added

  15. The economic implications of Korean unification

    OpenAIRE

    Schmitz, Jonathan L.

    2002-01-01

    Approved for public release; distribution unlimited A major area of concern for Korean unification is the immense cost it will impose on South Korea. To lessen this burden, South Korea will need to initiate policy reforms that can ease the financial stress and repercussions of unification and create an integrated economic community with North Korea. At the same time, North Korea will need to create an environment that is conducive to economic integration by accepting and adopting reform me...

  16. Hidden SUSY from precision gauge unification

    Energy Technology Data Exchange (ETDEWEB)

    Krippendorf, Sven; Nilles, Hans Peter [Bonn Univ. (Germany). Bethe Center for Theoretical Physics; Bonn Univ. (Germany). Physikalisches Inst.; Ratz, Michael [Technische Univ. Muenchen, Garching (Germany). Physik-Department; Winkler, Martin Wolfgang [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2013-06-15

    We revisit the implications of naturalness and gauge unification in the MSSM. We find that precision unification of the couplings in connection with a small {mu} parameter requires a highly compressed gaugino pattern as it is realized in mirage mediation. Due to the small mass difference between gluino and LSP, collider limits on the gluino mass are drastically relaxed. Without further assumptions, the relic density of the LSP is very close to the observed dark matter density due to coannihilation effects.

  17. Hidden SUSY from precision gauge unification

    International Nuclear Information System (INIS)

    Krippendorf, Sven; Nilles, Hans Peter

    2013-06-01

    We revisit the implications of naturalness and gauge unification in the MSSM. We find that precision unification of the couplings in connection with a small μ parameter requires a highly compressed gaugino pattern as it is realized in mirage mediation. Due to the small mass difference between gluino and LSP, collider limits on the gluino mass are drastically relaxed. Without further assumptions, the relic density of the LSP is very close to the observed dark matter density due to coannihilation effects.

  18. Association of papillomavirus E6 proteins with either MAML1 or E6AP clusters E6 proteins by structure, function, and evolutionary relatedness.

    Directory of Open Access Journals (Sweden)

    Nicole Brimer

    2017-12-01

    Full Text Available Papillomavirus E6 proteins bind to LXXLL peptide motifs displayed on targeted cellular proteins. Alpha genus HPV E6 proteins associate with the cellular ubiquitin ligase E6AP (UBE3A, by binding to an LXXLL peptide (ELTLQELLGEE displayed by E6AP, thereby stimulating E6AP ubiquitin ligase activity. Beta, Gamma, and Delta genera E6 proteins bind a similar LXXLL peptide (WMSDLDDLLGS on the cellular transcriptional co-activator MAML1 and thereby repress Notch signaling. We expressed 45 different animal and human E6 proteins from diverse papillomavirus genera to ascertain the overall preference of E6 proteins for E6AP or MAML1. E6 proteins from all HPV genera except Alpha preferentially interacted with MAML1 over E6AP. Among animal papillomaviruses, E6 proteins from certain ungulate (SsPV1 from pigs and cetacean (porpoises and dolphins hosts functionally resembled Alpha genus HPV by binding and targeting the degradation of E6AP. Beta genus HPV E6 proteins functionally clustered with Delta, Pi, Tau, Gamma, Chi, Mu, Lambda, Iota, Dyokappa, Rho, and Dyolambda E6 proteins to bind and repress MAML1. None of the tested E6 proteins physically and functionally interacted with both MAML1 and E6AP, indicating an evolutionary split. Further, interaction of an E6 protein was insufficient to activate degradation of E6AP, indicating that E6 proteins that target E6AP co-evolved to separately acquire both binding and triggering of ubiquitin ligase activation. E6 proteins with similar biological function clustered together in phylogenetic trees and shared structural features. This suggests that the divergence of E6 proteins from either MAML1 or E6AP binding preference is a major event in papillomavirus evolution.

  19. Electroweak unification and tree unitarity

    International Nuclear Information System (INIS)

    Horejsi, J.

    1993-01-01

    The monograph is an unconventional introduction into the theory of unification of weak and electromagnetic interactions, which is conceptually different from the exposition presented in standard textbooks. A detailed explanation is given of the way to the standard model of electroweak interactions which is based on a straightforward application of the requirement of renormalizability of the perturbation series expansion. The procedure to derive the model is interesting as it demonstrates the necessity of introducing vector bosons and Yang-Mills type interactions and at least one elementary scalar boson to obtain a renormalizable theory of weak and electromagnetic interactions. The book is divided into 5 chapters: introduction, problems encountered in a Fermi type theory, the intermediate vector boson, electrodynamics of vector bosons, tree unitarity, and electroweak interactions. Each chapter is completed with exercise problems to be solved by the reader. The text is supplemented with a number of appendices. The monograph is aimed at undergraduate and postgraduate students as well as at physicists interested in the theory of elementary particles. (Z.J.)

  20. E6 signatures in atomic physics

    International Nuclear Information System (INIS)

    Bordes, J.

    1987-02-01

    The effect of neutral massive gauge bosons in atoms is considered in the framework of models inspired by superstring theories with low energy group E 6 . Significant deviations from the prediction of the standard model are found in non-spinless light atoms. In models with two massive neutral gauge bosons the deviations are particularly important in Hydrogen if the ratio between the physical boson masses is < or approx., 3. (author)

  1. Flavor structure of E6 GUT models

    International Nuclear Information System (INIS)

    Kawase, Hidetoshi; Maekawa, Nobuhiro

    2010-01-01

    In E 6 grand unified theory with SU(2) H family symmetry, the spontaneous CP violation can solve the supersymmetric CP problem. The scenario predicts V ub -O(λ 4 ) instead of O(λ 3 ), which is the naively expected value, because of cancellation at the leading order. Since the experimental value of V ub is O(λ 4 ), it is important to consider the reason and the conditions for the cancellation. In this paper, we provide a simple reason for the cancellation and show that in some E 6 models, such cancellation requires that the vacuum expectation value (VEV) of the adjoint Higgs does not break U(1) B-L . Note that the direction of the VEV plays an important role in solving the doublet-triplet splitting problem by the Dimopoulos-Wilczek mechanism. In this E 6 model, the direction of the adjoint Higgs VEV can be measured experimentally by measuring the size of V ub -O(λ 4 ). (author)

  2. Minimal SUSY SO(10) and Yukawa unification

    International Nuclear Information System (INIS)

    Okada, Nobuchika

    2013-01-01

    The minimal supersymmetric (SUSY) SO(10) model, where only two Higgs multiplets {10⊕126-bar} are utilized for Yukawa couplings with matter fields, can nicely fit the neutrino oscillation parameters as well as charged fermion masses and mixing angles. In the fitting of the fermion mass matrix data, the largest element in the Yukawa coupling with the 126-bar -plet Higgs (Y 126 ) is found to be of order one, so that the right see-saw scale should be provided by Higgs vacuum expectation values (VEVs) of β(10 14 GeV). This fact causes a serious problem, namely, the gauge coupling unification is spoiled because of the presence of many exotic Higgs multiples emerging at the see-saw scale. In order to solve this problem, we consider a unification between bottom-quark and tau Yukawa couplings (b - τ Yukawa coupling unification) at the grand unified theory (GUT) scale, due to threshold corrections of superpartners to the Yukawa couplings at the 1 TeV scale. When the b - τ Yukawa coupling unification is very accurate, the largest element in Y 126 can become β(0.01), so that the right see-saw scale is realized by the GUT scale VEV and the usual gauge coupling unification is maintained. Since the b - τ Yukawa unification alters the Yukawa coupling data at the GUT scale, we re-analyze the fitting of the fermion mass matrix data by taking all the relevant free parameters into account. Unfortunately, we find that no parameter region shows up to give a nice fit for the current neutrino oscillation data and therefore, the usual picture of the gauge coupling unification cannot accommodate the fermion mass matrix data fitting in our procedure.

  3. Low energy implications of minimal superstring unification

    International Nuclear Information System (INIS)

    Khalil, S.; Vissani, F.; Masiero, A.

    1995-11-01

    We study the phenomenological implications of effective supergravities based on string vacua with spontaneously broken N =1 supersymmetry by dilation and moduli F-terms. We further require Minimal String Unification, namely that large string threshold corrections ensure the correct unification of the gauge couplings at the grand unification scale. The whole supersymmetric mass spectrum turns out to be determined in terms of only two independent parameters, the dilaton-moduli mixing angle and the gravitino mass. In particular we discuss the region of the parameter space where at least one superpartner is ''visible'' at LEPII. We find that the most likely candidates are the scalar partner of the right-handed electron and the lightest chargino, with interesting correlations between their masses and with the mass of the lightest higgs. We show how discovering SUSY particles at LEPII might rather sharply discriminate between scenarios with pure dilaton SUSY breaking and mixed dilaton-moduli breaking. (author). 10 refs, 7 figs

  4. Dirac gauginos, gauge mediation and unification

    International Nuclear Information System (INIS)

    Benakli, K.

    2010-03-01

    We investigate the building of models with Dirac gauginos and perturbative gauge coupling unification. Here, in contrast to the MSSM, additional fields are required for unification, and these can naturally play the role of the messengers of supersymmetry breaking. We present a framework within which such models can be constructed, including the constraints that the messenger sector must satisfy; and the renormalisation group equations for the soft parameters, which differ from those of the MSSM. For illustration, we provide the spectrum at the electroweak scale for explicit models whose gauge couplings unify at the scale predicted by heterotic strings. (orig.)

  5. Unification of Patrimonial Laws Governing International Trade

    DEFF Research Database (Denmark)

    Lando, Ole

    2016-01-01

    Should the laws of the world dealing with cross-border transactions be unified? Such unification presupposes an agreement on what we understand by ‘law’ and what its sources are. The drafters of uniform laws and lawyers who are preoccupied with comparative law often ask themselves: Is there, among...... the nations, a common core of legal values? If there is, this will facilitate legal unification. It will also make the international law-making easier if, in exceptional cases, a court is permitted to disregard a legal rule....

  6. Dirac gauginos, gauge mediation and unification

    Energy Technology Data Exchange (ETDEWEB)

    Benakli, K. [UPMC Univ. Paris 06 (France). Laboratoire de Physique Theorique et Hautes Energies, CNRS; Goodsell, M.D. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2010-03-15

    We investigate the building of models with Dirac gauginos and perturbative gauge coupling unification. Here, in contrast to the MSSM, additional fields are required for unification, and these can naturally play the role of the messengers of supersymmetry breaking. We present a framework within which such models can be constructed, including the constraints that the messenger sector must satisfy; and the renormalisation group equations for the soft parameters, which differ from those of the MSSM. For illustration, we provide the spectrum at the electroweak scale for explicit models whose gauge couplings unify at the scale predicted by heterotic strings. (orig.)

  7. Dirac Gauginos, Gauge Mediation and Unification

    CERN Document Server

    Benakli, K

    2010-01-01

    We investigate the building of models with Dirac gauginos and perturbative gauge coupling unification. Here, in contrast to the MSSM, additional fields are required for unification, and these can naturally play the role of the messengers of supersymmetry breaking. We present a framework within which such models can be constructed, including the constraints that the messenger sector must satisfy; and the renormalisation group equations for the soft parameters, which differ from those of the MSSM. For illustration, we provide the spectrum at the electroweak scale for explicit models whose gauge couplings unify at the scale predicted by heterotic strings.

  8. Elementary particles and physics interaction unification

    International Nuclear Information System (INIS)

    Leite-Lopes, J.

    1985-01-01

    Quantum theory and relativity theory are fundamental of relativistic quantum mechanics, quantum field theory, which is the base of elementary particle physics, gauge field theory and basic force unification models. After a short introduction of relativistic equations of the main fields, the free scalar field, the free vector field, the free electromagnetic field and the free spinor field, and of elementary particles and basic interactions, gauge invariance and electromagnetic gauge field are detailed. Then the presentation of internal degrees of freedom, especially isospin, introduces gauge field theory of Yang-Mills. At last weak interactions and strong interactions are presented and lead to grand unification theory in conclusion [fr

  9. China’s unification: Myth or reality?

    Directory of Open Access Journals (Sweden)

    Estrada Mario Arturo Ruiz

    2014-01-01

    Full Text Available This paper evaluates the prospect of a possible unification between People’s Republic of China (Mainland China and Republic of China (Taiwan from a multi-dimensional perspective which encompasses the political, social, economic, and technological dimensions. The underlying idea is to evaluate the possibility of a partial or total reunification between the two countries in a more comprehensive way than just assessing the economic costs and benefits. Our evaluation is based on the application of the GDRI-Model, which looks at unification and regional integration simultaneously from the political, economic, social and technological perspectives.

  10. Gauge Coupling Unification with Partly Composite Matter

    International Nuclear Information System (INIS)

    Gherghetta, Tony

    2005-01-01

    It is shown how gauge coupling unification can occur in models with partly composite matter. The particle states which are composite only contribute small logarithmns to the running of gauge couplings, while the elementary states contribute the usual large logarithmns. This introduces a new differential running contribution to the gauge couplings from partly composite SU(5) matter multiplets. In particular, for partly supersymmetric models, the incomplete SU(5) elementary matter multiplets restore gauge coupling unification even though the usual elementary gaugino and Higgsino contributions need not be present

  11. Unification types of housing during Sochi Olympics

    Directory of Open Access Journals (Sweden)

    Aleksandr A. Babaev

    2011-05-01

    Full Text Available In the article the statement of the unification problem of housing accommodation of participants, spectators, staff, committee during the Winter Olympics in Sochi. We give a mathematical formalization of the problem, where the unknown variables are theelements of the combination of types of accommodation sorted by the level of comfortand representation.

  12. Unification of Forces: The Road to Jointness?

    Science.gov (United States)

    1991-05-15

    tend to resist large change--or innovation. Because organizations value "predictability, stability, and certainty," incremental change is the...preferred mode of behavior for organizations.29 Unification of the forces would be a large, rather than an incremental , change; thus, the services would...coordinating planning and bidgeting , providing unified direction, accounting and controlling weapons and equipment acquisition, eliminating duplication of

  13. Principles of the Unification of Our Agency

    Science.gov (United States)

    Roth, Klas

    2011-01-01

    Do we need principles of the unification of our agency, our mode of acting? Immanuel Kant and Christine Korsgaard argue that the reflective structure of our mind forces us to have some conception of ourselves, others and the world--including our agency--and that it is through will and reason, and in particular principles of our agency, that we…

  14. Explanatory Unification by Proofs in School Mathematics

    Science.gov (United States)

    Komatsu, Kotaro; Fujita, Taro; Jones, Keith; Naoki, Sue

    2018-01-01

    Kitcher's idea of 'explanatory unification', while originally proposed in the philosophy of science, may also be relevant to mathematics education, as a way of enhancing student thinking and achieving classroom activity that is closer to authentic mathematical practice. There is, however, no mathematics education research treating explanatory…

  15. Authenticity and Unification in Quechua Language Planning.

    Science.gov (United States)

    Hornberger, Nancy H.; King, Kendall

    1998-01-01

    Examines the potentially problematic tension between the goals of authenticity and unification in Quechua-language planning. One case study examines the orthographic debate that arose in Peru, and the second case study concerns two indigenous communities in Saraguro in the Southern Ecuadorian highlands where Spanish predominates but two Quichua…

  16. Families in the nonperturbative unification scheme

    Energy Technology Data Exchange (ETDEWEB)

    Kapetanakis, D. (National Research Centre for the Physical Sciences Democritos, Athens (Greece)); Theisen, S. (European Organization for Nuclear Research, Geneva (Switzerland)); Zoupanos, G. (Ethnikon Metsovion Polytechneion, Athens (Greece). Dept. of Physics)

    1989-10-12

    Within the nonperturbative unification framework of Maiani, Parisi and Petronzio, we examine the influence of the number of fermion and Higgs families, when they are grouped in representations of horizontal family groups, on the low energy couplings of the standard model. In this way we find a number of new phenomenologically acceptable solutions for the standard model's low energy couplings. (orig.).

  17. Families in the nonperturbative unification scheme

    International Nuclear Information System (INIS)

    Kapetanakis, D.; Theisen, S.; Zoupanos, G.

    1989-01-01

    Within the nonperturbative unification framework of Maiani, Parisi and Petronzio, we examine the influence of the number of fermion and Higgs families, when they are grouped in representations of horizontal family groups, on the low energy couplings of the standard model. In this way we find a number of new phenomenologically acceptable solutions for the standard model's low energy couplings. (orig.)

  18. Unification and new particles at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Arkani-Hamed, Nima; D’Agnolo, Raffaele Tito; Low, Matthew [School of Natural Sciences, Institute for Advanced Study,Einstein Drive, Princeton, NJ 08540 (United States); Pinner, David [Princeton Center for Theoretical Physics, Princeton University,Jadwin Hall, Princeton, NJ 08544 (United States)

    2016-11-14

    Precision gauge coupling unification is one of the primary quantitative successes of low energy or split supersymmetry. Preserving this success puts severe restrictions on possible matter and gauge sectors that might appear at collider-accessible energies. In this work we enumerate new gauge sectors which are compatible with unification, consisting of horizontal gauge groups acting on vector-like matter charged under the Standard Model. Interestingly, almost all of these theories are in the supersymmetric conformal window at high energies and confine quickly after the superpartners are decoupled. For a range of scalar masses compatible with both moderately tuned and minimally split supersymmetry, the confining dynamics happen at the multi-TeV scale, leading to a spectrum of multiple spin-0 and spin-1 resonances accessible to the LHC, with unusual quantum numbers and striking decay patterns.

  19. The Unification of Private International Law

    Directory of Open Access Journals (Sweden)

    Emira Kazazi

    2015-07-01

    Full Text Available Civil and the common law approaching Europe is no longer a “future project”, but more and more rather a present attempt (Kötz, 2003 – 2004. In this prism, concentrating on the European International Private Law within the space of mixed jurisdictions, it may seem surprising in light of the attempts to create a new European ius commune. But is it possible that a unification of the material law may sign the start of the end of the European conflicts of laws? Last but not the least private international law is not just a choice of law. The unification of the private law, in its definition as a concept, does not influence two of the three pillars of the private international law: respectively, that of the jurisdiction and recognition as well as implementation of foreign decisions.

  20. Unification and new particles at the LHC

    International Nuclear Information System (INIS)

    Arkani-Hamed, Nima; D’Agnolo, Raffaele Tito; Low, Matthew; Pinner, David

    2016-01-01

    Precision gauge coupling unification is one of the primary quantitative successes of low energy or split supersymmetry. Preserving this success puts severe restrictions on possible matter and gauge sectors that might appear at collider-accessible energies. In this work we enumerate new gauge sectors which are compatible with unification, consisting of horizontal gauge groups acting on vector-like matter charged under the Standard Model. Interestingly, almost all of these theories are in the supersymmetric conformal window at high energies and confine quickly after the superpartners are decoupled. For a range of scalar masses compatible with both moderately tuned and minimally split supersymmetry, the confining dynamics happen at the multi-TeV scale, leading to a spectrum of multiple spin-0 and spin-1 resonances accessible to the LHC, with unusual quantum numbers and striking decay patterns.

  1. Gauge coupling unification in six dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Lee, H.M. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)]|[Carnegie-Mellon Univ., Pittsburgh, PA (United States). Dept. of Physics

    2006-11-15

    We compute the one-loop gauge couplings in six-dimensional non-Abelian gauge theories on the T{sup 2}/Z{sub 2} orbifold with general GUT breaking boundary conditions. For concreteness, we apply the obtained general formulae to the gauge coupling running in a 6D SO(10) orbifold GUT where the GUT group is broken down to the standard model gauge group up to an extra U(1). We find that the one-loop corrections depend on the parity matrices encoding the orbifold boundary conditions as well as the volume and shape moduli of extra dimensions. When the U(1) is broken by the VEV of bulk singlets, the accompanying extra color triplets also affect the unification of the gauge couplings. In this case, the B-L breaking scale is closely linked to the compactification scales for maintaining a success of the gauge coupling unification. (orig.)

  2. Deductive Synthesis of the Unification Algorithm,

    Science.gov (United States)

    1981-06-01

    DEDUCTIVE SYNTHESIS OF THE I - UNIFICATION ALGORITHM Zohar Manna Richard Waldinger I F? Computer Science Department Artificial Intelligence Center...theorem proving," Artificial Intelligence Journal, Vol. 9, No. 1, pp. 1-35. Boyer, R. S. and J S. Moore [Jan. 19751, "Proving theorems about LISP...d’Intelligence Artificielle , U.E.R. de Luminy, Universit6 d’ Aix-Marseille II. Green, C. C. [May 1969], "Application of theorem proving to problem

  3. E6AP is Required for Human Papillomavirus type 16 E6 to Cause Cervical Cancer in Mice

    Science.gov (United States)

    Shai, Anny; Pitot, Henry C.; Lambert, Paul F.

    2010-01-01

    High-risk human papillomaviruses cause certain anogenital and head and neck cancers. E6, one of three potent HPV oncogenes that contribute to the development of these malignancies, is a multifunctional protein with many biochemical activities. Among these activities are its ability to bind and inactivate the cellular tumor suppressor p53, induce expression of telomerase, and bind to various other proteins including Bak, E6BP1, E6TP1, and proteins that contain PDZ domains such as hScrib and hDlg. Many of these activities are thought to contribute to E6’s role in carcinogenesis. E6’s interaction with many of these cellular proteins, including p53, leads to their destabilization. This property is mediated at least in part through E6’s ability to recruit the ubiquitin ligase, E6AP into complexes with these cellular proteins resulting in their ubiquitin–mediated degradation by the proteasome. In this study, we address the requirement for E6AP in mediating E6's acute and oncogenic phenotypes, including induction of epithelial hyperplasia, abrogation of DNA damage response and induction of cervical cancer. Loss of E6AP had no discernable effect on E6's ability to induce hyperplasia or abrogate DNA damage responses, akin to what we had earlier observed in the mouse epidermis. Nevertheless, in cervical carcinogenesis studies, there was a complete loss of E6’s oncogenic potential in mice nulligenic for E6AP. Thus, E6AP is absolutely required for E6 to cause cervical cancer. PMID:20530688

  4. Quark-lepton unification and proton decay

    International Nuclear Information System (INIS)

    Pati, J.C.; Salam, A.

    1980-05-01

    Complexions for proton decay arising within a maximal symmetry for quark-lepton unification, which leads to spontaneous rather than intrinsic violations of B, L and F are considered. Four major modes satisfying δB=-1 and δF=0, -2, -4 and -6 are noted. It is stressed that some of these modes can coexist in accord with allowed solutions for renormalization group equations for coupling constants for a class of unifying symmetries. None of these remarks is dependent on the nature of quark charges. It is noted that if quarks and leptons are made of constituent preons, the preon binding is likely to be magnetic. (author)

  5. MUC (Memory, Unification, Control and beyond

    Directory of Open Access Journals (Sweden)

    Peter eHagoort

    2013-07-01

    Full Text Available A neurobiological model of language is discussed that overcomes the shortcomings of the classical Wernicke-Lichtheim-Geschwind model. It is based on a subdivision of language processing into three components: Memory, Unification, and Control. The functional components as well as the neurobiological underpinnings of the model are discussed. In addition, the need for extension of the model beyond the classical core regions for language is shown. Attentional networks as well as networks for inferential processing are crucial to realize language comprehension beyond single word processing and beyond decoding propositional content. It is shown that this requires the dynamic interaction between multiple brain regions.

  6. Unification of fuel elements for research reactors

    International Nuclear Information System (INIS)

    Vatulyn, A.V.; Stetskyi, Y.A.; Dobrikova, I.V.

    1997-01-01

    To the purpose of fuel elements unification the possibility of rod fuel assembly (FA) using in the cores of research reactors have been considered in this paper. The calculation results of geometric, hydraulic and thermotechnical parameters of rod assembly are submitted. Several designs of finned square fuel element and fuel assembly are proposed on base of analysis of rod FA characteristics in compare of tube ones. The fuel elements specimens and the model assembly are manufactured. The developed designs are the basis for further optimization after neutron-physical calculations of cores. (author)

  7. Unification of electromagnetic, strong and weak interaction

    International Nuclear Information System (INIS)

    Duong Van Phi; Duong Anh Duc

    1993-09-01

    The Unification of Electromagnetic, Strong and Weak Interactions is realized in the framework of the Quantum Field Theory, established in an 8-dimensional Unified Space. Two fundamental, spinor and vector field equations are considered. The first of the matter particles and the second is of the gauge particles. Interaction Lagrangians are formed from the external and internal currents and the external and internal vector field operators. Generators of the local gauge transformations are the combinations of the matrices of the first field equation. (author). 15 refs

  8. Genesis of Electroweak Unification and the Higgs

    CERN Multimedia

    CERN. Geneva

    2014-01-01

    I will give a historical account of the developments leading up to the unification of weak and electromagnetic interactions, as I saw them from my standpoint in Imperial College London. I will describe the state of physics in the 1950s, the aim of finding a unified theory of various interactions, the obstacles encountered in trying to unify the weak and electromagnetic interactions, and their eventual resolution, with a brief discussion of the later history culminating in the discovery of the Higgs boson in 2012.

  9. Astrophysical Probes of Varying Constants and Unification

    International Nuclear Information System (INIS)

    Martins, C J A P

    2016-01-01

    The observational evidence for the acceleration of the universe demonstrates that canonical theories of gravitation and particle physics are incomplete, if not incorrect. A new generation of astronomical facilities will soon carry out precision consistency tests of the standard cosmological model and search for evidence of new physics beyond it. I describe recent work of CAUP's Dark Side team on some of these tests, focusing on the stability of nature's fundamental couplings and tests of unification scenarios. (paper)

  10. Supersymmetry and supergravity: Phenomenology and grand unification

    International Nuclear Information System (INIS)

    Arnowitt, R.; Nath, P.

    1993-01-01

    A survey is given of supersymmetry and supergravity and their phenomenology. Some of the topics discussed are the basic ideas of global supersymmetry, the minimal supersymmetric Standard Model (MSSM) and its phenomenology, the basic ideas of local supersymmetry (supergravity), grand unification, supersymmetry breaking in supergravity grand unified models, radiative breaking of SU(2) x U(1), proton decay, cosmological constraints, and predictions of supergravity grand unified models. While the number of detailed derivations are necessarily limited, a sufficient number of results are given so that a reader can get a working knowledge of this field

  11. Structural convergence under reversible and irreversible monetary unification

    NARCIS (Netherlands)

    Beetsma, R.M.W.J.; Jensen, H.

    2003-01-01

    We explore endogenous monetary unification in the context of a model in which a country with serious structural distortions (and, hence, high inflation) is admitted into a monetary union once its economic structure has converged sufficiently towards that of the existing participants. If unification

  12. Structural convergence under reversible and irreversible monetary unification

    NARCIS (Netherlands)

    Beetsma, R.M.W.J.; Jensen, H.

    1999-01-01

    We explore endogenous monetary unification in the context of a model in which a country with serious structural distortions (and, hence, high inflation) is admitted into a monetary union once its economic structure has converged sufficiently towards that of the existing participants. If unification

  13. Unification and geometrization of physics in the cosmological context

    International Nuclear Information System (INIS)

    Heller, M.; Watykanskie Obserwatorium Astronomiczne, Vatican

    1991-01-01

    Einstein belived that a good physical theory should posses an ''inner perfection''. Trace the inner perfection of the present gauge theories by contemplating their geometric structures (in terms of fibre bundles). The search for the ultimate symmetry of the unification of physics unavoidably leads to the unification of physics and cosmology. 4 figs., 23 refs. (author)

  14. Gauge coupling unification in superstring derived standard-like models

    International Nuclear Information System (INIS)

    Faraggi, A.E.

    1992-11-01

    I discuss gauge coupling unification in a class of superstring standard-like models, which are derived in the free fermionic formulation. Recent calculations indicate that the superstring unification scale is at O(10 18 GeV) while the minimal supersymmetric standard model is consistent with LEP data if the unification scale is at O(10 16 )GeV. A generic feature of the superstring standard-like models is the appearance of extra color triplets (D,D), and electroweak doublets (l,l), in vector-like representations, beyond the supersymmetric standard model. I show that the gauge coupling unification at O(10 18 GeV) in the superstring standard-like models can be consistent with LEP data. I present an explicit standard-like model that can realize superstring gauge coupling unification. (author)

  15. Gauge unification in highly anisotropic string compactifications

    International Nuclear Information System (INIS)

    Hebecker, A.; Trapletti, M.

    2005-01-01

    It is well known that heterotic string compactifications have, in spite of their conceptual simplicity and aesthetic appeal, a serious problem with precision gauge coupling unification in the perturbative regime of string theory. Using both a duality-based and a field-theoretic definition of the boundary of the perturbative regime, we reevaluate the situation in a quantitative manner. We conclude that the simplest and most promising situations are those where some of the compactification radii are exceptionally large, corresponding to highly anisotropic orbifold models. Thus, one is led to consider constructions which are known to the effective field-theorist as higher-dimensional or orbifold grand unified theories (orbifold GUTs). In particular, if the discrete symmetry used to break the GUT group acts freely, a non-local breaking in the larger compact dimensions can be realized, leading to a precise gauge coupling unification as expected on the basis of the MSSM particle spectrum. Furthermore, a somewhat more model dependent but nevertheless very promising scenario arises if the GUT breaking is restricted to certain singular points within the manifold spanned by the larger compactification radii

  16. GRIM-19 disrupts E6/E6AP complex to rescue p53 and induce apoptosis in cervical cancers.

    Directory of Open Access Journals (Sweden)

    Ying Zhou

    Full Text Available BACKGROUND: Our previous studies showed a down-regulation of GRIM-19 in primary human cervical cancers, and restoration of GRIM-19 induced tumor regression. The induction of tumor suppressor protein p53 ubiquitination and degradation by E6 oncoportein of high risk-HPV through forming a stable complex with E6AP is considered as a critical mechanism for cervical tumor development. The aims of this study were to determine the potential role of GRIM-19 in rescuing p53 protein and inducing cervical cancer cell apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The protein levels of GRIM-19 and p53 were detected in normal cervical tissues from 45 patients who underwent hysterectomy for reasons other than neoplasias of either the cervix or endometrium, and cervical cancer tissues from 60 patients with non-metastatic squamous epithelial carcinomas. Coimmunoprecipitation and GST pull-down assay were performed to examine the interaction of GRIM-19 with 18E6 and E6AP in vivo and in vitro respectively. The competition of 18E6 with E6AP in binding GRIM-19 by performing competition pull-down assays was designed to examine the disruption of E6/E6AP complex by GRIM-19. The augment of E6AP ubiquitination by GRIM-19 was detected in vivo and in vitro ubiquitination assay. The effects of GRIM-19-dependent p53 accumulation on cell proliferation, cell cycle, apoptosis were explored by MTT, flow cytometry and transmission electron microscopy respectively. The tumor suppression was detected by xenograft mouse model. CONCLUSION/SIGNIFICANCE: The levels of GRIM-19 and p53 were concurrently down regulated in cervical cancers. The restoration of GRIM-19 can induce ubiquitination and degradation of E6AP, and disrupt the E6/E6AP complex through the interaction of N-terminus of GRIM-19 with both E6 and E6AP, which protected p53 from degradation and promoted cell apoptosis. Tumor xenograft studies also revealed the suppression of p53 degradation in presence of GRIM-19. These data

  17. E6-lepton mixing and lepton magnetic moment

    International Nuclear Information System (INIS)

    Vendramin, I.

    1988-01-01

    The contributions to the lepton magnetic moment due to the E 6 -exotic fermions and an extra vector boson Z' have been considered. Using the experimental limits on the E 6 -lepton mixing angles, these contributions are at least one order of magnitude smaller than the standard-model ones

  18. Light higgsino for gauge coupling unification

    Directory of Open Access Journals (Sweden)

    Kwang Sik Jeong

    2017-06-01

    Full Text Available We explore gauge coupling unification and dark matter in high scale supersymmetry where the scale of supersymmetry breaking is much above the weak scale. The gauge couplings unify as precisely as in low energy supersymmetry if the higgsinos, whose mass does not break supersymmetry, are much lighter than those obtaining masses from supersymmetry breaking. The dark matter of the universe can then be explained by the neutral higgsino or the gravitino. High scale supersymmetry with light higgsinos requires a large Higgs mixing parameter for electroweak symmetry breaking to take place. It is thus naturally realized in models where superparticle masses are generated at loop level while the Higgs mixing parameter is induced at tree level, like in anomaly and gauge mediation of supersymmetry breaking.

  19. Local grand unification and string theory

    International Nuclear Information System (INIS)

    Nilles, Hans Peter; Vaudrevange, Patrick K.S.

    2009-09-01

    The low energy effective action of string theory depends strongly on the process of compactification and the localization of fields in extra dimensions. Explicit string constructions towards the minimal supersymmetric standard model (MSSM) reveal interesting results leading to the concept of local grand unification. Properties of the MSSM indicate that we might live at a special location close to an orbifold fixed point rather than a generic point in Calabi-Yau moduli space. We observe an enhancement of (discrete) symmetries that have various implications for the properties of the MSSM such as proton stability as well as solutions to the flavor problem, the m-problem and the strong CP-problem. (orig.)

  20. Light higgsino for gauge coupling unification

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Kwang Sik, E-mail: ksjeong@pusan.ac.kr

    2017-06-10

    We explore gauge coupling unification and dark matter in high scale supersymmetry where the scale of supersymmetry breaking is much above the weak scale. The gauge couplings unify as precisely as in low energy supersymmetry if the higgsinos, whose mass does not break supersymmetry, are much lighter than those obtaining masses from supersymmetry breaking. The dark matter of the universe can then be explained by the neutral higgsino or the gravitino. High scale supersymmetry with light higgsinos requires a large Higgs mixing parameter for electroweak symmetry breaking to take place. It is thus naturally realized in models where superparticle masses are generated at loop level while the Higgs mixing parameter is induced at tree level, like in anomaly and gauge mediation of supersymmetry breaking.

  1. Unification of SUSY breaking and GUT breaking

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Tatsuo [Department of Physics, Hokkaido University,Sapporo 060-0810 (Japan); Omura, Yuji [Department of Physics, Nagoya University,Nagoya 464-8602 (Japan)

    2015-02-18

    We build explicit supersymmetric unification models where grand unified gauge symmetry breaking and supersymmetry (SUSY) breaking are caused by the same sector. Besides, the SM-charged particles are also predicted by the symmetry breaking sector, and they give the soft SUSY breaking terms through the so-called gauge mediation. We investigate the mass spectrums in an explicit model with SU(5) and additional gauge groups, and discuss its phenomenological aspects. Especially, nonzero A-term and B-term are generated at one-loop level according to the mediation via the vector superfields, so that the electro-weak symmetry breaking and 125 GeV Higgs mass may be achieved by the large B-term and A-term even if the stop mass is around 1 TeV.

  2. Technicolor and Beyond: Unification in Theory Space

    DEFF Research Database (Denmark)

    Sannino, Francesco

    2010-01-01

    The salient features of models of dynamical electroweak symmetry breaking are reviewed. The ideal walking idea is introduced according to which one should carefully take into account the effects of the extended technicolor dynamics on the technicolor dynamics itself. The effects amount at the enh......The salient features of models of dynamical electroweak symmetry breaking are reviewed. The ideal walking idea is introduced according to which one should carefully take into account the effects of the extended technicolor dynamics on the technicolor dynamics itself. The effects amount...... supersymmetry and technicolor. The reason is to provide a unification of different extensions of the standard model. For example, this means that one can recover, according to the parameters and spectrum of the theory distinct extensions of the standard model, from supersymmetry to technicolor and unparticle...

  3. Natural supersymmetry and unification in five dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Abdalgabar, Ammar [National Institute for Theoretical Physics and School of Physics and Mandelstam Institute for Theoretical Physics, University of the Witwatersrand,Private Bag 3, Wits, 2050 (South Africa); Department of Physics, Sudan University of Science and Technology,Khartoum, 407 (Sudan); Cornell, Alan S. [National Institute for Theoretical Physics and School of Physics and Mandelstam Institute for Theoretical Physics, University of the Witwatersrand,Private Bag 3, Wits, 2050 (South Africa); Deandrea, Aldo [Université de Lyon,92, rue Pasteur, Lyon, F-69361 (France); IPNL, Université Lyon 1, CNRS/IN2P3,4 rue Fermi, Villeurbanne Cedex, F-69622 (France); Institut Universitaire de France,103 boulevard Saint-Michel, Paris, 75005 (France); McGarrie, Moritz [Faculty of Physics, University of Warsaw,Hoża 69, Warsaw, 00-681 (Poland)

    2016-01-14

    We explore unification and natural supersymmetry in a five dimensional extension of the standard model in which the extra dimension may be large, of the order of 1–10 TeV. Power law running generates a TeV scale A{sub t} term allowing for the observed 125 GeV Higgs and allowing for stop masses below 2 TeV, compatible with a natural SUSY spectrum. We supply the full one-loop RGEs for various models and use metastability to give a prediction that the gluino mass should be lighter than 3.5 TeV for A{sub t}≥−2.5 TeV, for such a compactification scale, with brane localised 3rd generation matter. We also discuss models in which only the 1st and 2nd generation of matter fields are located in the bulk. We also look at electroweak symmetry breaking in these models.

  4. Towards worldwide height unification using ocean information

    Directory of Open Access Journals (Sweden)

    P. L. Woodworth

    2015-03-01

    Full Text Available This paper describes how we are contributing to worldwide height system unification (WHSU by using ocean models together with sea level (tide gauge and altimeter information, geodetic (GPS and levelling data, and new geoid models based on information from the GRACE and GOCE gravity missions, to understand how mean sea level (MSL varies from place to place along the coast. For the last two centuries, MSL has been used to define datums for national levelling systems. However, there are many problems with this. One consequence of WHSU will be the substitution of conventional datums as a reference for heights with the use of geoid, as the only true "level" or datum. This work is within a number of GOCE-related activities funded by the European Space Agency. The study is focused on the coastlines of North America and Europe where the various datasets are most copious.

  5. SU(5) unification with TeV-scale leptoquarks

    Energy Technology Data Exchange (ETDEWEB)

    Cox, Peter [Kavli Institute for the Physics and Mathematics of the Universe (WPI), UTIAS,The University of Tokyo, Kashiwa, Chiba, 277-8583 (Japan); Kusenko, Alexander [Department of Physics and Astronomy, University of California,Los Angeles, CA, 90095-1547 (United States); Kavli Institute for the Physics and Mathematics of the Universe (WPI), UTIAS,The University of Tokyo, Kashiwa, Chiba, 277-8583 (Japan); Sumensari, Olcyr [Laboratoire de Physique Théorique, CNRS, Université Paris-Sud, Université Paris-Saclay,Orsay, 91405 (France); Instituto de Física, Universidade de São Paulo,C.P. 66.318, São Paulo, 05315-970 (Brazil); Yanagida, Tsutomu T. [Kavli Institute for the Physics and Mathematics of the Universe (WPI), UTIAS,The University of Tokyo, Kashiwa, Chiba, 277-8583 (Japan)

    2017-03-07

    It was previously noted that SU(5) unification can be achieved via the simple addition of light scalar leptoquarks from two split 10 multiplets. We explore the parameter space of this model in detail and find that unification requires at least one leptoquark to have mass below ≈16 TeV. We point out that introducing splitting of the 24 allows the unification scale to be raised beyond 10{sup 16} GeV, while a U(1){sub PQ} symmetry can be imposed to forbid dangerous proton decay mediated by the light leptoquarks. The latest bounds from LHC searches are combined and we find that a leptoquark as light as 400 GeV is still permitted. Finally, we discuss the interesting possibility that the leptoquarks required for unification could also be responsible for the 2.6σ deviation observed in the ratio R{sub K} at LHCb.

  6. Alternative Z"′ bosons in E_6

    International Nuclear Information System (INIS)

    Rojas, Eduardo; Erler, Jens

    2015-01-01

    We classify the quantum numbers of the extra U(1)"′ symmetries contained in E_6. In particular, we categorize the cases with rational charges and present the full list of models which arise from the chains of the maximal subgroups of E_6. As an application, the classification allows us to determine all embeddings of the Standard Model fermions in all possible decompositions of the fundamental representation of E_6 under its maximal subgroups. From this we find alternative chains of subgroups for Grand Unified Theories. We show how many of the known models including some new ones appear in alternative breaking patterns. We also use low energy constraints coming from parity-violating asymmetry measurements and atomic parity non-conservation to set limits on the E_6 motivated parameter space for a Z"′ boson mass of 1.2 TeV. We include projected limits for the present and upcoming QWEAK, MOLLER and SOLID experiments.

  7. From chaos to unification: U theory vs. M theory

    International Nuclear Information System (INIS)

    Ye, Fred Y.

    2009-01-01

    A unified physical theory called U theory, that is different from M theory, is defined and characterized. U theory, which includes spinor and twistor theory, loop quantum gravity, causal dynamical triangulations, E-infinity unification theory, and Clifford-Finslerian unifications, is based on physical tradition and experimental foundations. In contrast, M theory pays more attention to mathematical forms. While M theory is characterized by supersymmetry string theory, U theory is characterized by non-supersymmetry unified field theory.

  8. Carboranyl-Chlorin e6 as a Potent Antimicrobial Photosensitizer.

    Directory of Open Access Journals (Sweden)

    Elena O Omarova

    Full Text Available Antimicrobial photodynamic inactivation is currently being widely considered as alternative to antibiotic chemotherapy of infective diseases, attracting much attention to design of novel effective photosensitizers. Carboranyl-chlorin-e6 (the conjugate of chlorin e6 with carborane, applied here for the first time for antimicrobial photodynamic inactivation, appeared to be much stronger than chlorin e6 against Gram-positive bacteria, such as Bacillus subtilis, Staphyllococcus aureus and Mycobacterium sp. Confocal fluorescence spectroscopy and membrane leakage experiments indicated that bacteria cell death upon photodynamic treatment with carboranyl-chlorin-e6 is caused by loss of cell membrane integrity. The enhanced photobactericidal activity was attributed to the increased accumulation of the conjugate by bacterial cells, as evaluated both by centrifugation and fluorescence correlation spectroscopy. Gram-negative bacteria were rather resistant to antimicrobial photodynamic inactivation mediated by carboranyl-chlorin-e6. Unlike chlorin e6, the conjugate showed higher (compared to the wild-type strain dark toxicity with Escherichia coli ΔtolC mutant, deficient in TolC-requiring multidrug efflux transporters.

  9. Grand unification and subcritical hybrid inflation

    International Nuclear Information System (INIS)

    Buchmueller, Wilfried; Ishiwata, Koji

    2014-12-01

    We consider hybrid inflation for small couplings of the inflaton to matter such that the critical value of the inflaton field exceeds the Planck mass. It has recently been shown that inflation then continues at subcritical inflaton field values where quantum fluctuations generate an effective inflaton mass. The effective inflaton potential interpolates between a quadratic potential at small field values and a plateau at large field values. An analysis of the allowed parameter space leads to predictions for the scalar spectral index n s and the tensor-to-scalar ratio r similar to those of natural inflation. Using the range for n s and r favoured by the Planck data, we find that the energy scale of the plateau is constrained to the interval (1.6-2.4) x 10 16 GeV which includes the energy scale of gauge coupling unification in the supersymmetric standard model. The tensor-to-scalar ratio is predicted to have the lower bound r>0.049 for 60 e-folds before the end of inflation.

  10. Technicolor and Beyond: Unification in Theory Space

    International Nuclear Information System (INIS)

    Sannino, Francesco

    2010-01-01

    I will briefly review the salient features of models of dynamical electroweak symmetry breaking together with the traditional extensions needed to provide masses to the standard model fermions in absence of fundamental scalars. The idea walking idea is introduced according to which one should carefully take into account the effects of the extended technicolor dynamics on the technicolor dynamics itself. The interplay between the four fermion interactions stemming from the extended technicolor interactions and the technicolor model can strongly enhance the anomalous dimension of the mass of the techniquarks allowing to decouple the Flavor Changing Neutral Currents problem from the one of the generation of the large top mass. I will also review the Minimal Walking Technicolor (MWT) models. In the second part of this review I consider the interesting possibility to marry supersymmetry and technicolor. The reason is to provide a unification of different extensions of the standard model. For example, this means that one can recover, according to the parameters and spectrum of the theory distinct extensions of the standard model, from supersymmetry to technicolor and unparticle physiscs. A surprising result is that a minimal (in terms of the smallest number of fields) supersymmetrization of the MWT model leads to the maximal supersymmetry in four dimensions, i.e. N = 4 SYM.

  11. Local grand unification in the heterotic landscape

    International Nuclear Information System (INIS)

    Schmidt, Jonas

    2009-06-01

    We consider the possibility that the unification of the electroweak interactions and the strong force arises from string theory, at energies significantly lower than the string scale. As a tool, an effective grand unified field theory in six dimensions is derived from an anisotropic orbifold compactification of the heterotic string. It is explicitly shown that all anomalies cancel in the model, though anomalous Abelian gauge symmetries are present locally at the boundary singularities. In the supersymmetric vacuum additional interactions arise from higher-dimensional operators. We develop methods that relate the couplings of the effective theory to the location of the vacuum, and find that unbroken discrete symmetries play an important role for the phenomenology of orbifold models. An efficient algorithm for the calculation of the superpotential to arbitrary order is developed, based on symmetry arguments. We furthermore present a correspondence between bulk fields of the orbifold model in six dimensions, and the moduli fields that arise from compactifying four internal dimensions on a manifold with non-trivial gauge background. (orig.)

  12. Local grand unification in the heterotic landscape

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Jonas

    2009-07-15

    We consider the possibility that the unification of the electroweak interactions and the strong force arises from string theory, at energies significantly lower than the string scale. As a tool, an effective grand unified field theory in six dimensions is derived from an anisotropic orbifold compactification of the heterotic string. It is explicitly shown that all anomalies cancel in the model, though anomalous Abelian gauge symmetries are present locally at the boundary singularities. In the supersymmetric vacuum additional interactions arise from higher-dimensional operators. We develop methods that relate the couplings of the effective theory to the location of the vacuum, and find that unbroken discrete symmetries play an important role for the phenomenology of orbifold models. An efficient algorithm for the calculation of the superpotential to arbitrary order is developed, based on symmetry arguments. We furthermore present a correspondence between bulk fields of the orbifold model in six dimensions, and the moduli fields that arise from compactifying four internal dimensions on a manifold with non-trivial gauge background. (orig.)

  13. Finite Unification: Theory, Models and Predictions

    CERN Document Server

    Heinemeyer, S; Zoupanos, G

    2011-01-01

    All-loop Finite Unified Theories (FUTs) are very interesting N=1 supersymmetric Grand Unified Theories (GUTs) realising an old field theory dream, and moreover have a remarkable predictive power due to the required reduction of couplings. The reduction of the dimensionless couplings in N=1 GUTs is achieved by searching for renormalization group invariant (RGI) relations among them holding beyond the unification scale. Finiteness results from the fact that there exist RGI relations among dimensional couplings that guarantee the vanishing of all beta-functions in certain N=1 GUTs even to all orders. Furthermore developments in the soft supersymmetry breaking sector of N=1 GUTs and FUTs lead to exact RGI relations, i.e. reduction of couplings, in this dimensionful sector of the theory, too. Based on the above theoretical framework phenomenologically consistent FUTs have been constructed. Here we review FUT models based on the SU(5) and SU(3)^3 gauge groups and their predictions. Of particular interest is the Hig...

  14. Supersymmetry and the unification of fundamental interactions.

    Science.gov (United States)

    Fayet, P.

    Les physiciens élaborent progressivement une description unifée des lois de l'Univers, qui fait intervenir des principes de symétrie de plus en plus étendus. La supersymétrie, qui englobe la mécanique quantique et la relativité générale en opérant dans une extension de l'espace-temps ordinaire, appelée le superespace, est-elle l'un de ces principes fondamentaux? Dans cet article, l'auteur explique ce qu'est cette nouvelle symétrie, et comment, pour appliquer celle-ci au monde physique, il a été amené à envisager l'existence de toute une famille de nouvelles particules - comme les photinos, gluinos, squarks et sélectrons - que l'on recherche activement aujourd'hui. On espère parvenir à les détecter grâce aux nouvelles générations d'accélerateurs, et découvrir ainsi un nouveau principe auquel doivent satisfaire toutes les lois physiques, aussi fondamental que la relativité.

  15. Yukawa sector of minimal SO(10) unification

    Energy Technology Data Exchange (ETDEWEB)

    Babu, K.S. [Department of Physics, Oklahoma State University,Stillwater, OK, 74078 (United States); Bajc, Borut [Jožef Stefan Institute,Ljubljana, 1000 (Slovenia); Saad, Shaikh [Department of Physics, Oklahoma State University,Stillwater, OK, 74078 (United States)

    2017-02-28

    We show that in SO(10) models, a Yukawa sector consisting of a real 10{sub H}, a real 120{sub H} and a complex 126{sub H} of Higgs fields can provide a realistic fit to all fermion masses and mixings, including the neutrino sector. Although the group theory of SO(10) demands that the 10{sub H} and 120{sub H} be real, most constructions complexify these fields and impose symmetries exterior to SO(10) to achieve predictivity. The proposed new framework with real10{sub H} and real120{sub H} relies only on SO(10) gauge symmetry, and yet has a limited number of Yukawa parameters. Our analysis shows that while there are restrictions on the observables, a good fit to the entire fermion spectrum can be realized. Unification of gauge couplings is achieved with an intermediate scale Pati-Salam gauge symmetry. Proton decay branching ratios are calculable, with the leading decay modes being p→ν̄π{sup +} and p→e{sup +}π{sup 0}.

  16. Studying gaugino mass unification at the LHC

    International Nuclear Information System (INIS)

    Altunkaynak, Baris; Holmes, Michael; Nelson, Brent D.; Grajek, Phillip; Kane, Gordon

    2009-01-01

    We begin a systematic study of how gaugino mass unification can be probed at the CERN Large Hadron Collider (LHC) in a quasi-model independent manner. As a first step in that direction we focus our attention on the theoretically well-motivated mirage pattern of gaugino masses, a one-parameter family of models of which universal (high scale) gaugino masses are a limiting case. We improve on previous methods to define an analytic expression for the metric on signature space and use it to study one-parameter deviations from universality in the gaugino sector, randomizing over other soft supersymmetry-breaking parameters. We put forward three ensembles of observables targeted at the physics of the gaugino sector, allowing for a determination of this non-universality parameter without reconstructing individual mass eigenvalues or the soft supersymmetry-breaking gaugino masses themselves. In this controlled environment we find that approximately 80% of the supersymmetric parameter space would give rise to a model for which our method will detect non-universality in the gaugino mass sector at the 10% level with O(10 fb -1 ) of integrated luminosity. We discuss strategies for improving the method and for adding more realism in dealing with the actual experimental circumstances of the LHC.

  17. A supersymmetric standard model from a local E6 GUT

    International Nuclear Information System (INIS)

    Braam, Felix Klaus

    2012-02-01

    In this thesis we have investigated to what extent the exceptional Lie-group E 6 can serve as unified gauge group. In the presence of the full E 6 matter content, unifcation can be realized by increasing the degree of gauge symmetry above some intermediate scale. We found that a full E 6 gauge invariant theory is disfavoured by phenomenological observations like proton stability and the smallness of flavour changing neutral currents. An appropriate framework to embed E 6 into a model for particle physics are higher dimensional orbifold constructions, where E 6 is the gauge group in the bulk and the intermediate symmetry group is the common subset of E 6 subgroups residing at the fixed-points of the orbifold. In this way the degree of symmetry in four space-time dimensions is reduced, such that the operators leading to the aforementioned dsastrous phenomenological consequences can be forbidden independently. In order to derive the implications of the model for the current experiments at the Large Hadron Collider (LHC), we developed an automated spectrum generator. It uses Monte-Carlo Markov-Chain techniques to cope with the high dimensionality of the space of input parameters and the complex interdependencies in the evolution of the Lagrangian parameters from the orbifold compactification scale to the TeV scale. For the spectra obtained with this program, we performed Monte-Carlo simulations of the production and decay of the Z ' boson stemming from the additional U(1) ' , using our own implementation of the model into the event generator WHIZARD.

  18. SO(10) - Grand unification and fermion masses

    International Nuclear Information System (INIS)

    Oezer, A.D.

    2005-01-01

    In this work, we study SO(10) grand unification in its full extent by using different explicit matrix representations which exhibit the structure of SO(10) in a very transparent way. Our approach consists mainly of two stages: We derive the explicit expressions of the mass-eigenvalues and mass-eigenstates of the physical gauge bosons from a mass squared-matrix that contains all the information about the mixing parameters among the gauge fields and the phases which are sources for CP violation. In the light of this analysis, we derive the explicit expressions for the interaction Lagrangians of the charged currents, the neutral currents and the charged and colored currents in SO(10). We present explicit expressions of the vector and axial-vector couplings of the two neutral currents in SO(10). We show how the baryon, lepton and baryon minus lepton number violating processes and their explicit CP violating phases are accommodated in the SO(10) theory. The Higgs potential that we use to implement in the Higgs mechanism is constructed in a most general fashion through a careful study of the Higgs fields of SO(10), where we give special emphasis on illustrating the explicit matrix representation of these Higgs fields. The potential part of the Higgs Lagrangian will give us the properties of the minimum of the vacuum, and the kinetic part will give us the mass-squared matrix of the gauge bosons via spontaneous symmetry breakdown. The same Higgs multiplets will be coupled to fermions through a democratic Yukawa matrix. Thereby, we derive explicit expressions for the fermion masses of the third family including Majorana and Dirac masses for neutrinos. We introduce a flavor-eigenbasis for neutrinos and find the mass-eigenstates and mass-eigenvalues of the neutrinos. Explicit expressions for CP violation in the neutrino sector are obtained. In the second stage of our work, we evaluate all the above mentioned quantities. In addition, we present the values of the physical

  19. Unification of binary star ephemeris solutions

    International Nuclear Information System (INIS)

    Wilson, R. E.; Van Hamme, W.

    2014-01-01

    Time-related binary system characteristics such as orbital period, its rate of change, apsidal motion, and variable light-time delay due to a third body, are measured in two ways that can be mutually complementary. The older way is via eclipse timings, while ephemerides by simultaneous whole light and velocity curve analysis have appeared recently. Each has its advantages, for example, eclipse timings typically cover relatively long time spans while whole curves often have densely packed data within specific intervals and allow access to systemic properties that carry additional timing information. Synthesis of the two information sources can be realized in a one step process that combines several data types, with automated weighting based on their standard deviations. Simultaneous light-velocity-timing solutions treat parameters of apsidal motion and the light-time effect coherently with those of period and period change, allow the phenomena to interact iteratively, and produce parameter standard errors based on the quantity and precision of the curves and timings. The logic and mathematics of the unification algorithm are given, including computation of theoretical conjunction times as needed for generation of eclipse timing residuals. Automated determination of eclipse type, recovery from inaccurate starting ephemerides, and automated data weighting are also covered. Computational examples are given for three timing-related cases—steady period change (XY Bootis), apsidal motion (V526 Sagittarii), and the light-time effect due to a binary's reflex motion in a triple system (AR Aurigae). Solutions for all combinations of radial velocity, light curve, and eclipse timing input show consistent results, with a few minor exceptions.

  20. human papillomaviruses E6 and E7 oncoproteins

    Indian Academy of Sciences (India)

    Unknown

    Recent work has uncovered new cellular partners for these .... Hence it is evident that a fine balance exists between these that govern ... still suggest that E7 can have a more global effect on the general .... towards malignancy), increases life span of the cells. E6 ..... nism when expressed alone in HPV positive/negative cell.

  1. Unification of gauge couplings in radiative neutrino mass models

    DEFF Research Database (Denmark)

    Hagedorn, Claudia; Ohlsson, Tommy; Riad, Stella

    2016-01-01

    masses at one-loop level and (III) models with particles in the adjoint representation of SU(3). In class (I), gauge couplings unify in a few models and adding dark matter amplifies the chances for unification. In class (II), about a quarter of the models admits gauge coupling unification. In class (III......We investigate the possibility of gauge coupling unification in various radiative neutrino mass models, which generate neutrino masses at one- and/or two-loop level. Renormalization group running of gauge couplings is performed analytically and numerically at one- and two-loop order, respectively....... We study three representative classes of radiative neutrino mass models: (I) minimal ultraviolet completions of the dimension-7 ΔL = 2 operators which generate neutrino masses at one- and/or two-loop level without and with dark matter candidates, (II) models with dark matter which lead to neutrino...

  2. Einstein's dream : the space-time unification of fundamental forces

    Energy Technology Data Exchange (ETDEWEB)

    Salam, A [International Centre for Theoretical Physics, Trieste (Italy)

    1981-06-01

    The historical developments in physics which started with Galileo in the 11th century, Newton in the 17 century, culminated in the unification of space-time by Einstein in this century are traced. The theories put forward by Einstein himself and by subsequent workers in the field after him, regarding the unification of all basic forces of nature (i.e.) the electromagnetic and the gravitational ones and the weak and strong nuclear forces are discussed. The experiments being conducted in Kolar and other places to detect a heavier photon which would be a positive proof of the validity of the unification theory, are touched upon. The possible application of this concept even in industry has been pointed out.

  3. Human Papillomavirus 16 (HPV-16), HPV-18, and HPV-31 E6 Override the Normal Phosphoregulation of E6AP Enzymatic Activity.

    Science.gov (United States)

    Thatte, Jayashree; Banks, Lawrence

    2017-11-15

    The human papillomavirus (HPV) E6 oncoproteins recruit the cellular ubiquitin ligase E6AP/UBE3A to target cellular substrates for proteasome-mediated degradation, and one consequence of this activity is the E6 stimulation of E6AP autoubiquitination and degradation. Recent studies identified an autism-linked mutation within E6AP at T485, which was identified as a protein kinase A phosphoacceptor site and which could directly regulate E6AP ubiquitin ligase activity. In this study, we have analyzed how T485-mediated regulation of E6AP might affect E6 targeting of some of its known substrates. We show that modulation of T485 has no effect on the ability of E6 to direct either p53 or Dlg for degradation. Furthermore, T485 regulation has no effect on HPV-16 or HPV-31 E6-induced autodegradation of E6AP but does affect HPV-18 E6-induced autodegradation of E6AP. In cells derived from cervical cancers, we find low levels of both phosphorylated and nonphosphorylated E6AP in the nucleus. However, ablation of E6 results in a dramatic accumulation of phospho-E6AP in the cytoplasm, whereas nonphosphorylated E6AP accumulates primarily in the nucleus. Interestingly, E6AP phosphorylation at T485 confers association with 14-3-3 proteins, and this interaction seems to be important, in part, for the ability of E6 to recruit phospho-E6AP into the nucleus. These results demonstrate that HPV E6 overrides the normal phosphoregulation of E6AP, both in terms of its enzymatic activity and its subcellular distribution. IMPORTANCE Recent reports demonstrate the importance of phosphoregulation of E6AP for its normal enzymatic activity. Here, we show that HPV E6 is capable of overriding this regulation and can promote degradation of p53 and Dlg regardless of the phosphorylation status of E6AP. Furthermore, E6 interaction with E6AP also significantly alters how E6AP is subject to autodegradation and suggests that this is not a simple stimulation of an already-existing activity but rather a

  4. Dark Matter in SuperGUT Unification Models

    International Nuclear Information System (INIS)

    Olive, Keith A

    2011-01-01

    After a brief update on the prospects for dark matter in the constrained version of the MSSM (CMSSM) and its differences with models based on minimal supergravity (mSUGRA), I will consider the effects of unifying the supersymmetry-breaking parameters at a scale above M GUT . One of the consequences of superGUT unification, is the ability to take vanishing scalar masses at the unification scale with a neutralino LSP dark matter candidate. This allows one to resurrect no-scale supergravity as a viable phenomenological model.

  5. E6 and the bipartite entanglement of three qutrits

    International Nuclear Information System (INIS)

    Duff, M. J.; Ferrara, S.

    2007-01-01

    Recent investigations have established an analogy between the entropy of four-dimensional supersymmetric black holes in string theory and entanglement in quantum information theory. Examples include: (1) N=2 STU black holes and the tripartite entanglement of three qubits (2-state systems), where the common symmetry is [SL(2)] 3 and (2) N=8 black holes and the tripartite entanglement of seven qubits where the common symmetry is E 7 superset of [SL(2)] 7 . Here we present another example: N=8 black holes (or black strings) in five dimensions and the bipartite entanglement of three qutrits (3-state systems), where the common symmetry is E 6 superset of [SL(3)] 3 . Both the black hole (or black string) entropy and the entanglement measure are provided by the Cartan cubic E 6 invariant. Similar analogies exist for magic N=2 supergravity black holes in both four and five dimensions

  6. Dark matter in a constrained E6 inspired SUSY model

    International Nuclear Information System (INIS)

    Athron, P.; Harries, D.; Nevzorov, R.; Williams, A.G.

    2016-01-01

    We investigate dark matter in a constrained E 6 inspired supersymmetric model with an exact custodial symmetry and compare with the CMSSM. The breakdown of E 6 leads to an additional U(1) N symmetry and a discrete matter parity. The custodial and matter symmetries imply there are two stable dark matter candidates, though one may be extremely light and contribute negligibly to the relic density. We demonstrate that a predominantly Higgsino, or mixed bino-Higgsino, neutralino can account for all of the relic abundance of dark matter, while fitting a 125 GeV SM-like Higgs and evading LHC limits on new states. However we show that the recent LUX 2016 limit on direct detection places severe constraints on the mixed bino-Higgsino scenarios that explain all of the dark matter. Nonetheless we still reveal interesting scenarios where the gluino, neutralino and chargino are light and discoverable at the LHC, but the full relic abundance is not accounted for. At the same time we also show that there is a huge volume of parameter space, with a predominantly Higgsino dark matter candidate that explains all the relic abundance, that will be discoverable with XENON1T. Finally we demonstrate that for the E 6 inspired model the exotic leptoquarks could still be light and within range of future LHC searches.

  7. Photodynamic tissue adhesion with chlorin(e6) protein conjugates.

    Science.gov (United States)

    Khadem, J; Veloso, A A; Tolentino, F; Hasan, T; Hamblin, M R

    1999-12-01

    To test the hypothesis that a photodynamic laser-activated tissue solder would perform better in sealing scleral incisions when the photosensitizer was covalently linked to the protein than when it was noncovalently mixed. Conjugates and mixtures were prepared between the photosensitizer chlorin(e6) and various proteins (albumin, fibrinogen, and gelatin) in different ratios and used to weld penetrating scleral incisions made in human cadaveric eyes. A blue-green (488-514 nm) argon laser activated the adhesive, and the strength of the closure was measured by increasing the intraocular pressure until the wound showed leakage. Both covalent conjugates and noncovalent mixtures showed a light dose-dependent increase in leaking pressure. A preparation of albumin chlorin(e6) conjugate with additional albumin added (2.5 protein to chlorin(e6) molar ratio) showed significantly higher weld strength than other protein conjugates and mixtures. This is the first report of dye-protein conjugates as tissue solders. These conjugates may have applications in ophthalmology.

  8. String unification and leptophobic Z` in flipped SU(5)

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, J.L. [Rice Univ., Houston, TX (United States). Bonner Nuclear Labs.

    1997-01-01

    We summarize recent developments in the prediction for {alpha}{sub s}(M{sub Z}), self-consistent string unification and the dynamical determination of mass scales, and leptophobic Z` gauge bosons in the context of stringy flipped SU(5). (orig.).

  9. Natural fermion mass hierarchy and mixings in family unification

    International Nuclear Information System (INIS)

    Dent, James B.; Feger, Robert; Kephart, Thomas W.; Nandi, S.

    2011-01-01

    We present an SU(9) model of family unification with three light chiral families, and a natural hierarchy of charged fermion masses and mixings. The existence of singlet right handed neutrinos with masses about two orders of magnitude smaller than the GUT scale, as needed to understand the light neutrinos masses via the see-saw mechanism, is compelling in our model.

  10. Similarity-Based Unification: A Multi-Adjoint Approach

    Czech Academy of Sciences Publication Activity Database

    Medina, J.; Ojeda-Aciego, M.; Vojtáš, Peter

    2004-01-01

    Roč. 146, č. 1 (2004), s. 43-62 ISSN 0165-0114 Source of funding: V - iné verejné zdroje Keywords : similarity * fuzzy unification Subject RIV: BA - General Mathematics Impact factor: 0.734, year: 2004

  11. Einstein's Last Dream: The Space–Time Unification of Fundamental ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 1. Einstein's Last Dream: The Space – Time Unification of Fundamental Forces. Abdus Salam. Reflections Volume 3 Issue 1 January 1998 pp 81-88. Fulltext. Click here to view fulltext PDF. Permanent link:

  12. Neutrino masses and the unification of the SO(10) families

    International Nuclear Information System (INIS)

    Maalampi, J.; Enqvist, K.

    1980-01-01

    We show that the unification of the SO(10) families in SO(10+m) group can offer a solution to the neutrino mass problem. For simplicity we have restricted our analysis to SO(11), which contains - aside from generation mixing -the main novel feature of the theories of this kind: fermions that couple by V+A charged weak currents. (author)

  13. Unification of three linear models for the transient visual system

    NARCIS (Netherlands)

    Brinker, den A.C.

    1989-01-01

    Three different linear filters are considered as a model describing the experimentally determined triphasic impulse responses of discs. These impulse responses arc associated with the transient visual system. Each model reveals a different feature of the system. Unification of the models is

  14. A4 family symmetry and quark-lepton unification

    International Nuclear Information System (INIS)

    King, Stephen F.; Malinsky, Michal

    2007-01-01

    We present a model of quark and lepton masses and mixings based on A 4 family symmetry, a discrete subgroup of an SO(3) flavour symmetry, together with Pati-Salam unification. It accommodates tri-bimaximal neutrino mixing via constrained sequential dominance with a particularly simple vacuum alignment mechanism emerging through the effective D-term contributions to the scalar potential

  15. Introduction to unification of electromagnetic and weak interactions

    International Nuclear Information System (INIS)

    Martin, F.

    1980-01-01

    After reviewing the present status of weak interaction phenomenology we discuss the basic principles of gauge theories. Then we show how Higgs mechanism can give massive quanta of interaction. The so-called 'Weinberg-Salam' model, which unifies electromagnetic and weak interactions, is described. We conclude with a few words on unification with strong interactions and gravity [fr

  16. Unification of Radio Galaxies and their Accretion Jet Properties ...

    Indian Academy of Sciences (India)

    Abstract. We investigate the relation between black hole mass, Mbh, and jet power, Qjet, for a sample of BL Lacs and radio quasars. We find that BL Lacs are separated from radio quasars by the FR I/II dividing line in Mbh–Qjet plane, which strongly supports the unification scheme of FR. I/BL Lac and FR II/radio quasar.

  17. Educational Systems and Rising Inequality: Eastern Germany after Unification

    Science.gov (United States)

    von Below, Susanne; Powell, Justin J. W.; Roberts, Lance W.

    2013-01-01

    Educational systems considerably influence educational opportunities and the resulting social inequalities. Contrasting institutional regulations of both structures and contents, the authors present a typology of educational system types in Germany to analyze their effects on social inequality in eastern Germany after unification. After 1990, the…

  18. Law behind second law of thermodynamics - unification with cosmology

    International Nuclear Information System (INIS)

    Nielsen, Holger B.; Ninomiya, Masao

    2006-01-01

    In an abstract setting of a general classical mechanical system as a model for the universe we set up a general formalism for a law behind the second law of thermodynamics, i.e. really for 'initial conditions'. We propose a unification with the other laws by requiring similar symmetry and locality properties

  19. Interplay between grand unification and supersymmetry in SU(5 ...

    Indian Academy of Sciences (India)

    energy MSSM. break the rank, Aulakh and his collaborators [10–12] have showed that R-parity is exact all the way down to low energies. In this case, grand unification tells us something about supersymmetry and even dark matter. In this article ...

  20. E6 exotic quark production in ep collisions

    International Nuclear Information System (INIS)

    Hewett, J.L.

    1987-06-01

    We examine the possibility of producing exotic quarks from E 6 theories via flavor changing couplings in high energy ep collisions at HERA and the proposed LEP x LHC. We find that the rate is rather small and very mixing angle dependent. Assuming maximal mixing, the production rates are ≅10 to 30 events per year at HERA (for masses up to 100 GeV) and ≅200 events per year at LEP x LHC (for masses up to 300 GeV)

  1. Flux breaking of E6 in the generalised Hosotani model

    International Nuclear Information System (INIS)

    McLachlan, A.

    1989-01-01

    To break gauge symmetries in the Hosotani model, it is necessary to include periodic (Dirac) fermions and/or antiperiodic scalars which transform as single-valued faithful representations of the adjoint group. With this in mind, an E 6 Yang-Mills theory minimally coupled to periodic adjoint and antiperiodic fundamental fermions is examined. On breaking, even though the full rank six residual group depends on the numbers of spacetime dimensions and fermion families, the fundamental fermions surviving compactification only transform non-trivially under the omnipresent [SU(3)] 2 or SU(6) subgroup factors. (orig.)

  2. The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

    International Nuclear Information System (INIS)

    Manzo-Merino, Joaquin; Massimi, Paola; Lizano, Marcela; Banks, Lawrence

    2014-01-01

    The HPV-16 E6 and E6 ⁎ proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6 ⁎ . Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins to recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8

  3. The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

    Energy Technology Data Exchange (ETDEWEB)

    Manzo-Merino, Joaquin [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Massimi, Paola [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy); Lizano, Marcela, E-mail: lizanosoberon@gmail.com [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Banks, Lawrence, E-mail: banks@icgeb.org [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy)

    2014-02-15

    The HPV-16 E6 and E6{sup ⁎} proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6{sup ⁎}. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins to recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8.

  4. On generalized Melvin solution for the Lie algebra E6

    International Nuclear Information System (INIS)

    Bolokhov, S.V.; Ivashchuk, V.D.

    2017-01-01

    A multidimensional generalization of Melvin's solution for an arbitrary simple Lie algebra G is considered. The gravitational model in D dimensions, D ≥ 4, contains n 2-forms and l ≥ n scalar fields, where n is the rank of G. The solution is governed by a set of n functions H s (z) obeying n ordinary differential equations with certain boundary conditions imposed. It was conjectured earlier that these functions should be polynomials (the so-called fluxbrane polynomials). The polynomials H s (z), s = 1,.., 6, for the Lie algebra E 6 are obtained and a corresponding solution for l = n = 6 is presented. The polynomials depend upon integration constants Q s , s = 1,.., 6. They obey symmetry and duality identities. The latter ones are used in deriving asymptotic relations for solutions at large distances. The power-law asymptotic relations for E 6 -polynomials at large z are governed by the integer-valued matrix ν = A -1 (I + P), where A -1 is the inverse Cartan matrix, I is the identity matrix and P is a permutation matrix, corresponding to a generator of the Z 2 -group of symmetry of the Dynkin diagram. The 2-form fluxes Φ s , s = 1,.., 6, are calculated. (orig.)

  5. Analysis of the roles of E6 binding to E6TP1 and nuclear localization in the human papillomavirus type 31 life cycle

    International Nuclear Information System (INIS)

    Lee, Choongho; Wooldridge, Tonia R.; Laimins, Laimonis A.

    2007-01-01

    The E6 oncoproteins of high-risk human papillomaviruses provide important functions not only for malignant transformation but also in the productive viral life cycle. E6 proteins have been shown to bind to a number of cellular factors, but only a limited number of analyses have investigated the effects of these interactions on the viral life cycle. In this study, we investigated the consequences of HPV 31 E6 binding to E6TP1, a putative Rap1 GAP protein. HPV 16 E6 has been shown to bind as well as induce the rapid turnover of E6TP1, and similar effects were observed with HPV 31 E6. Mutation of amino acid 128 in HPV 31 E6 was found to abrogate the ability to bind and degrade E6TP1 but did not alter binding to another α-helical domain protein, E6AP. When HPV 31 genomes containing mutations at amino acid 128 were transfected into human keratinocytes, the viral DNAs were not stably maintained as episomes indicating the importance of this residue for pathogenesis. Many E6 binding partners including E6TP1 are cytoplasmic proteins, but E6 has been also reported to be localized to the nucleus. We therefore investigated the importance of E6 localization to the nucleus in the viral life cycle. Using a fusion of E6 to Green Fluorescent Protein, we mapped one component of the nuclear localization sequences to residues 121 to 124 of HPV 31 E6. Mutation of these residues in the context of the HPV 31 genome abrogated the ability for episomes to be stably maintained and impaired the ability to extend the life span of cells. These studies identify two activities of HPV 31 E6 that are important for its function in the viral life cycle and for extension of cell life span

  6. A doxology to Christ (Rev. 1:5e-6

    Directory of Open Access Journals (Sweden)

    J. C. de Smidt

    2006-07-01

    Full Text Available Revelation 1:5e-6 is a doxology, an eulogy on the characteristics (attributes of Christ. Christ’s churches celebrate the enduring love of Christ, who by a once-and-for-all historical act redeemed them from enslavement to sin. Through this redemptive achievement Christ obtained royal and priestly prerogatives for believers in the present. The meaning of this doxology is investigated from a “heilgeschichtlich” and covenantal context. The acts of Christ are framed by the acts of God; God thus is the “Principium Essendi”. The point of departure in this article is that an ontological relationship exists between the theologia naturalis and the theologia supra- naturalis in the final phase of God’s kingdom.

  7. The PDZ Ligand Domain of the Human Papillomavirus Type 16 E6 Protein Is Required for E6's Induction of Epithelial Hyperplasia In Vivo

    Science.gov (United States)

    Nguyen, Marie L.; Nguyen, Minh M.; Lee, Denis; Griep, Anne E.; Lambert, Paul F.

    2003-01-01

    Human papillomaviruses (HPVs) are the causative agent of warts. Infections with high-risk HPVs are associated with anogenital and head and neck cancers. One of the viral genes responsible for HPV's oncogenic activity is E6. Mice expressing the HPV-16 E6 protein in their epidermis (K14E6WT) develop epithelial hyperplasia and squamous carcinomas. Numerous cellular proteins interact with E6, some of which can be grouped based on common amino acid motifs in their E6-binding domains. One such group, the PDZ partners, including hDLG, hSCRIBBLE, MUPP1, and MAGI, bind to the carboxy-terminal four amino acids of E6 through their PDZ domains. E6's interaction with the PDZ partners leads to their degradation. Additionally, E6's binding to PDZ proteins has been correlated with its ability to transform baby rat kidney cells in tissue culture and to confer tumorigenicity onto cells in xenograft experiments. To address whether the ability of E6 to bind PDZ domain partners is necessary for E6 to confer epithelial hyperproliferation in vivo, we generated transgenic mice that express in stratified squamous epithelia a mutant of E6 lacking the last six amino acids at its carboxyl terminus, E6Δ146-151, from the human keratin 14 (K14) promoter. The K14E6Δ146-151 mice exhibit a radiation response similar to that of the K14E6WT mice, demonstrating that this protein, as predicted, retains an ability to inactivate p53. However, the K14E6Δ146-151 mice fail to display epithelial hyperplasia. These results indicate that an interaction of E6 with PDZ partners is necessary for its induction of epithelial hyperplasia. PMID:12768014

  8. Towards a new paradigm for quark-lepton unification

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Christopher [Laboratoire de Physique Subatomique et de Cosmologie, Université Grenoble-Alpes, CNRS/IN2P3,53 avenue des Martyrs, 38026 Grenoble Cedex (France)

    2017-05-03

    The quark and charged lepton mass patterns upset their naïve unification. In this paper, a new approach to solve this problem is proposed. Model-independently, we find that a successful unification can be achieved. A mechanism is identified by which the large top quark mass renders its third-generation leptonic partner very light. This state is thus identified with the electron. We then construct a toy model to implement dynamically this mechanism, using tree-level exchanges of vector leptons to relate the quark and charged lepton flavor structures. In a supersymmetric context, this same mechanism splits the squark masses, and third generation squarks end up much lighter than the others. Finally, the implementation of this mechanism in SU(5) GUT permits to avoid introducing any flavor structure beyond the two minimal Yukawa couplings, ensuring the absence of unknown mixing matrices and their potentially large impact on FCNC.

  9. Reconciling grand unification with strings by anisotropic compactifications

    International Nuclear Information System (INIS)

    Dundee, Ben; Raby, Stuart; Wingerter, Akin

    2008-01-01

    We analyze gauge coupling unification in the context of heterotic strings on anisotropic orbifolds. This construction is very much analogous to effective five-dimensional orbifold grand unified theory field theories. Our analysis assumes three fundamental scales: the string scale M S , a compactification scale M C , and a mass scale for some of the vectorlike exotics M EX ; the other exotics are assumed to get mass at M S . In the particular models analyzed, we show that gauge coupling unification is not possible with M EX =M C , and in fact we require M EX C ∼3x10 16 GeV. We find that about 10% of the parameter space has a proton lifetime (from dimension six gauge exchange) 10 33 yr 0 e + ) 36 yr. The other 80% of the parameter space gives proton lifetimes below Super-Kamiokande bounds. The next generation of proton decay experiments should be sensitive to the remaining parameter space.

  10. Reduced modular symmetries of threshold corrections and gauge coupling unification

    Energy Technology Data Exchange (ETDEWEB)

    Bailin, David; Love, Alex [Department of Physics & Astronomy, University of Sussex,Brighton, BN1 9QH (United Kingdom)

    2015-04-01

    We revisit the question of gauge coupling unification at the string scale in orbifold compactifications of the heterotic string for the supersymmetric Standard Model. In the presence of discrete Wilson lines threshold corrections with modular symmetry that is a subgroup of the full modular group arise. We find that reduced modular symmetries not previously reported are possible. We conjecture that the effects of such threshold corrections can be simulated using sums of terms built from Dedekind eta functions to obtain the appropriate modular symmetry. For the cases of the ℤ{sub 8}-I orbifold and the ℤ{sub 3}×ℤ{sub 6} orbifold it is easily possible to obtain gauge coupling unification at the “observed” scale with Kähler moduli T of approximately one.

  11. Grand unification in higher dimensions with split supersymmetry

    International Nuclear Information System (INIS)

    Schuster, Philip C.

    2006-01-01

    We investigate gauge coupling unification in higher dimensional GUT models with split supersymmetry. We focus on 5d and 6d orbifold GUTs, which permit a simple solution to several problems of 4D GUTs as well as control over GUT scale threshold corrections. In orbifold GUTs, calculable threshold corrections can raise or lower the prediction for α s (M Z ) in a way that depends on the location of Higgs fields. On the other hand, split supersymmetry lowers the prediction for α s (M Z ). Consequently, split supersymmetry changes the preferred location of the Higgs fields in orbifold GUTs. In the simplest models, we find that gauge coupling unification favors higgs doublets that live on the orbifold fixed points instead of in the bulk. In addition, relatively high scales of supersymmetry breaking of 10 10±2 GeV are generically favored

  12. Quantum gravity unification via transfinite arithmetic and geometrical averaging

    International Nuclear Information System (INIS)

    El Naschie, M.S.

    2008-01-01

    In E-Infinity theory, we have not only infinitely many dimensions but also infinitely many fundamental forces. However, due to the hierarchical structure of ε (∞) spacetime we have a finite expectation number for its dimensionality and likewise a finite expectation number for the corresponding interactions. Starting from the preceding fundamental principles and using the experimental findings as well as the theoretical value of the coupling constants of the electroweak and the strong forces we present an extremely simple averaging procedure for determining the quantum gravity unification coupling constant with and without super symmetry. The work draws heavily on previous results, in particular a paper, by the Slovian Prof. Marek-Crnjac [Marek-Crnjac L. On the unification of all fundamental forces in a fundamentally fuzzy Cantorian ε (∞) manifold and high energy physics. Chaos, Solitons and Fractals 2004;4:657-68

  13. Gauge-Higgs Unification Models in Six Dimensions with S2/Z2 Extra Space and GUT Gauge Symmetry

    Directory of Open Access Journals (Sweden)

    Cheng-Wei Chiang

    2012-01-01

    Full Text Available We review gauge-Higgs unification models based on gauge theories defined on six-dimensional spacetime with S2/Z2 topology in the extra spatial dimensions. Nontrivial boundary conditions are imposed on the extra S2/Z2 space. This review considers two scenarios for constructing a four-dimensional theory from the six-dimensional model. One scheme utilizes the SO(12 gauge symmetry with a special symmetry condition imposed on the gauge field, whereas the other employs the E6 gauge symmetry without requiring the additional symmetry condition. Both models lead to a standard model-like gauge theory with the SU(3×SU(2L×U(1Y(×U(12 symmetry and SM fermions in four dimensions. The Higgs sector of the model is also analyzed. The electroweak symmetry breaking can be realized, and the weak gauge boson and Higgs boson masses are obtained.

  14. Dark Matter after LHC Run I: Clues to Unification

    Directory of Open Access Journals (Sweden)

    Olive Keith A.

    2017-01-01

    Full Text Available After the results of Run I, can we still ‘guarantee’ the discovery of supersymmetry at the LHC? It is shown that viable dark matter models in CMSSM-like models tend to lie in strips (co-annihilation, funnel, focus point. The role of grand unification in constructing supersymmetric models is discussed and it is argued that non-supersymmetric GUTs such as SO(10 may provide solutions to many of the standard problems addressed by supersymmetry.

  15. Problems of CP-violation in early unification theories

    International Nuclear Information System (INIS)

    Liparteliani, A.G.; Monich, V.A.; Volkov, G.G.

    1985-01-01

    The present work studies possible mechanisms of P and CP-violation in the frames of an approach based on early unification of fundamental local symmetries, i.e., Pati-Salam four-colour symmetry, extended weak isotopic symmetry and that of quark-lepton generations. The work also studies the influence of generations mixing on the rates of rare processes in each of 3 classes of interactions

  16. Gauge coupling unification in realistic free-fermionic string models

    International Nuclear Information System (INIS)

    Dienes, K.R.; Faraggi, A.E.

    1995-01-01

    We discuss the unification of gauge couplings within the framework of a wide class of realistic free-fermionic string models which have appeared in the literature, including the flipped SU(5), SO(6)xSO(4), and various SU(3)xSU(2)xU(1) models. If the matter spectrum below the string scale is that of the Minimal Supersymmetric Standard Model (MSSM), then string unification is in disagreement with experiment. We therefore examine several effects that may modify the minimal string predictions. First, we develop a systematic procedure for evaluating the one-loop heavy string threshold corrections in free-fermionic string models, and we explicitly evaluate these corrections for each of the realistic models. We find that these string threshold corrections are small, and we provide general arguments explaining why such threshold corrections are suppressed in string theory. Thus heavy thresholds cannot resolve the disagreement with experiment. We also study the effect of non-standard hypercharge normalizations, light SUSY thresholds, and intermediate-scale gauge structure, and similarly conclude that these effects cannot resolve the disagreement with low-energy data. Finally, we examine the effects of additional color triplets and electroweak doublets beyond the MSSM. Although not required in ordinary grand unification scenarios, such states generically appear within the context of certain realistic free-fermionic string models. We show that if these states exist at the appropriate thresholds, then the gauge couplings will indeed unify at the string scale. Thus, within these string models, string unification can be in agreement with low-energy data. (orig.)

  17. Unification of Radio Galaxies and their Accretion Jet Properties

    Indian Academy of Sciences (India)

    2016-01-27

    Jan 27, 2016 ... We investigate the relation between black hole mass, bh, and jet power, jet, for a sample of BL Lacs and radio quasars. We find that BL Lacs are separated from radio quasars by the FR I/II dividing line in bh-jet plane, which strongly supports the unification scheme of FR I/BL Lac and FR II/radio ...

  18. Focus point gauge mediation in product group unification

    International Nuclear Information System (INIS)

    Bruemmer, Felix; Ibe, Masahiro; Tokyo Univ., Kashiwa; Yanagida, Tsutomu T.

    2013-03-01

    In certain models of gauge-mediated supersymmetry breaking with messenger fields in incomplete GUT multiplets, the radiative corrections to the Higgs potential cancel out during renormalization group running. This allows for relatively heavy superpartners and for a 125 GeV Higgs while the ne-tuning remains modest. In this paper, we show that such gauge mediation models with ''focus point'' behaviour can be naturally embedded into a model of SU(5) x U(3) product group unification.

  19. Exchange-Rate Unification with Black Market Leakages; Russia 1992

    OpenAIRE

    Linda S. Goldberg

    1993-01-01

    In 1992 Russia unified the multiple exchange rates that had applied to international transactions. This paper describes the multiple exchange rate system that existed in Russia prior to mid-1992 and undertakes a theoretical exploration of the effects of the exchange rate unification that took place in July 1992. The model developed here allows for leakages between official and black markets and permits flexibility of the exchange rates in both official and parallel currency markets. Within th...

  20. M theory: a possible unification of physics laws

    International Nuclear Information System (INIS)

    Fernandes, Alexandre da Silva; Silva, Diego Oliveira Nolasco da; Sousa, Claudio Manoel Gomes de

    2011-01-01

    Full text: Physics has two pillars which are mutually incompatible: quantum field theory and general relativity theory. Throughout its history, various unifications have been made, and in attempts to have a better understanding of the birth and formation of the Universe is also necessary to unify these pillars. This unification may require 11 dimensions, and 6 of them are compressed so that it cannot be seen with existing instruments. These dimensions are the spaces in which the strings vibrate, and each mode of vibration corresponds to a particle. The last dimension shows that the universe is a brane, it is in full motion in the multiverse and the collision of two branes can answer the biggest problem of cosmology: what was the Big Bang? Black holes can be explained using a theory that contains gravity and quantum mechanics. The theory is still being developed, some problems are being solved and the main one is the experimental problem, because it requires energy levels that are not yet achieved by current particle accelerators. This work presents M theory as a possibility of unification between the micro and macro, which maybe leading us to the theory of everything. (author)

  1. Probes of Yukawa unification in supersymmetric SO(10) models

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff, Susanne

    2009-10-23

    This work is composed as follows: In Chapter 1, the disposed reader is made familiar with the foundations of flavourphysics and Grand Unification, including group-theoretical aspects of SO(10). In Chapter 2, we introduce a specific supersymmetric GUT model based on SO(10) and designed to probe down-quark-lepton Yukawa unification. Within this framework we explore the effects of large atmospheric neutrino mixing in bottom-strange transitions on the mass difference and CP phase in B{sub s}- anti B{sub s} meson mixing. Chapter 3 is devoted to corrections to Yukawa unification. We derive constraints on Yukawa corrections for light fermions from K- anti K and B{sub d}- anti B {sub d} mixing. As an application we study implications of neutrino mixing effects in CP-violating K and B{sub d} observables on the unitrity triangle. Finally, in Chapter 4, we discuss effects of large tan {beta} in B{yields}(D){tau}{nu} decays with respect to their potential to discover charged Higgs bosons and to discriminate between different GUT models of flavour.

  2. M theory: a possible unification of physics laws

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Alexandre da Silva; Silva, Diego Oliveira Nolasco da; Sousa, Claudio Manoel Gomes de [Universidade Catolica de Brasilia (UCB), DF (Brazil)

    2011-07-01

    Full text: Physics has two pillars which are mutually incompatible: quantum field theory and general relativity theory. Throughout its history, various unifications have been made, and in attempts to have a better understanding of the birth and formation of the Universe is also necessary to unify these pillars. This unification may require 11 dimensions, and 6 of them are compressed so that it cannot be seen with existing instruments. These dimensions are the spaces in which the strings vibrate, and each mode of vibration corresponds to a particle. The last dimension shows that the universe is a brane, it is in full motion in the multiverse and the collision of two branes can answer the biggest problem of cosmology: what was the Big Bang? Black holes can be explained using a theory that contains gravity and quantum mechanics. The theory is still being developed, some problems are being solved and the main one is the experimental problem, because it requires energy levels that are not yet achieved by current particle accelerators. This work presents M theory as a possibility of unification between the micro and macro, which maybe leading us to the theory of everything. (author)

  3. Testing the AGN Unification Model in the Infrared

    International Nuclear Information System (INIS)

    Ramos Almeida, C; Levenson, N A; Radomski, J T; Alonso-Herrero, A; Asensio Ramos, A; Rodríguez Espinosa, J M; Pérez García, A M; Packham, C; Mason, R; Díaz-Santos, T

    2012-01-01

    We present near-to-mid-infrared spectral energy distributions (SEDs) for 21 Seyfert galaxies, using subarcsecond resolution imaging data. Our aim is to compare the properties Seyfert 1 (Sy1) and Seyfert 2 (Sy2) tori using clumpy torus models and a Bayesian approach to fit the infrared (IR) nuclear SEDs. These dusty tori have physical sizes smaller than 6 pc radius, as derived from our fits. Active galactic nuclei (AGN) unification schemes account for a variety of observational differences in terms of viewing geometry. However, we find evidence that strong unification may not hold, and that the immediate dusty surroundings of Sy1 and Sy2 nuclei are intrinsically different. The Type 2 tori studied here are broader, have more clumps, and these clumps have lower optical depths than those of Type 1 tori. The larger the covering factor of the torus, the smaller the probability of having direct view of the AGN, and vice-versa. In our sample, Sy2 tori have larger covering factors (C T = 0.95±0.02) and smaller escape probabilities than those of Sy1 (C T = 0.5±0.1). Thus, on the basis of the results presented here, the classification of a Seyfert galaxy may depend more on the intrinsic properties of the torus rather than on its mere inclination, in contradiction with the simplest unification model.

  4. Gauge coupling unification from unified theories in higher dimensions

    International Nuclear Information System (INIS)

    Hall, Lawrence J.; Nomura, Yasunori

    2002-01-01

    Higher dimensional grand unified theories, with gauge symmetry breaking by orbifold compactification, possess SU(5) breaking at fixed points, and do not automatically lead to tree-level gauge coupling unification. A new framework is introduced that guarantees precise unification--even the leading loop threshold corrections are predicted, although they are model dependent. Precise agreement with the experimental result, α s exp =0.117±0.002, occurs only for a unique theory, and gives α s KK =0.118±0.004±0.003. Remarkably, this unique theory is also the simplest, with SU(5) gauge interactions and two Higgs hypermultiplets propagating in a single extra dimension. This result is more successful and precise than that obtained from conventional supersymmetric grand unification, α s SGUT =0.130±0.004±Δ SGUT . There is a simultaneous solution to the three outstanding problems of 4D supersymmetric grand unified theories: a large mass splitting between Higgs doublets and their color triplet partners is forced, proton decay via dimension five operators is automatically forbidden, and the absence of fermion mass relations amongst light quarks and leptons is guaranteed, while preserving the successful m b /m τ relation. The theory necessarily has a strongly coupled top quark located on a fixed point and part of the lightest generation propagating in the bulk. The string and compactification scales are determined to be around 10 17 GeV and 10 15 GeV, respectively

  5. Precision LEP data, supersymmetric GUTs and string unification

    International Nuclear Information System (INIS)

    Ellis, J.; Kelley, S.; Nanopoulos, D.V.; Houston Area Research Center

    1990-01-01

    The precision of sin 2 θ w MS (m Z ) extracted from LEP data (0.233±0.001) confirms the prediction of minimal supersymmetric GUTs (0.235±0.004) within the errors of about 2%. Moreover, supersymmetric GUTs with three generations and a heavy top quark also predict m b =5.2±0.3 GeV in perfect agreement with potential model estimates (5.0±0.2 GeV). String unification would require that the effective grand unification scale m GUT be no larger than the effective string unification scale m SU , which is indeed consistent with the LEP data, which indicate m GUT ≅ 2x10 16 GeV in a minimal supersymmetric GUT, compared with the theoretical estimate m SU ≅ 10 17 GeV. Specific choices of the string model moduli could enforce m GUT =m SU even in minimal supersymmetric GUTs, whilst non-minimal supersymmetric GUTs can reconcile the successful predictions of sin 2 θ w with m GUT = m SU for generic values of the moduli, but tend to have m b too large. (orig.)

  6. Human papillomavirus type 16 E6-specific antitumor immunity is induced by oral administration of HPV16 E6-expressing Lactobacillus casei in C57BL/6 mice.

    Science.gov (United States)

    Lee, Tae-Young; Kim, Yang-Hyun; Lee, Kyung-Soon; Kim, Jeong-Ki; Lee, Il-Han; Yang, Jai-Myung; Sung, Moon-Hee; Park, Jong-Sup; Poo, Haryoung

    2010-11-01

    Given that local cell-mediated immunity (CMI) against the human papillomavirus type 16 E6 (HPV16 E6) protein is important for eradication of HPV16 E6-expressing cancer cells in the cervical mucosa, the HPV16 E6 protein may be a target for the mucosal immunotherapy of cervical cancer. Here, we expressed the HPV16 E6 antigen on Lactobacillus casei (L. casei) and investigated E6-specific CMI following oral administration of the L. casei-PgsA-E6 to mice. Surface expression of HPV16 E6 antigens was confirmed and mice were orally inoculated with the L. casei-PgsA or the L. casei-PgsA-E6. Compared to the L. casei-PgsA-treated mice, significantly higher levels of serum IgG and mucosal IgA were observed in L. casei-PgsA-E6-immunized mice; these differences were significantly enhanced after boost. Consistent with this, systemic and local CMI were significantly increased after the boost, as shown by increased counts of IFN-gamma-secreting cells in splenocytes, mesenteric lymph nodes (MLN), and vaginal samples. Furthermore, in the TC-1 tumor model, animals receiving the orally administered L. casei-PgsA-E6 showed reduced tumor size and increased survival rate versus mice receiving control (L. casei-PgsA) immunization. We also found that L. casei-PgsA-E6-induced antitumor effect was decreased by in vivo depletion of CD4(+) or CD8(+) T cells. Collectively, these results indicate that the oral administration of lactobacilli bearing the surface-displayed E6 protein induces T cell-mediated cellular immunity and antitumor effects in mice.

  7. The high-risk HPV E6 target scribble (hScrib is required for HPV E6 expression in cervical tumour-derived cell lines

    Directory of Open Access Journals (Sweden)

    Christian Kranjec

    2016-12-01

    Full Text Available The ability of high-risk HPV E6 oncoproteins to target cellular proteins which harbor PDZ domains is believed to play an important role in the virus life cycle and to influence the ability of these viruses to bring about malignant transformation. Whilst many of these PDZ proteins are potential tumour suppressors, involved in the control of cell polarity and cell-contact, recent studies suggest that mislocalisation or overexpression might result in the emergence of oncogenic functions. This has been shown most clearly for two E6 targets, hDlg and hScrib. In this study we show that hScrib plays such a role in HeLa cells, where its expression is required for maintaining high levels of HPV-18 E6 protein. Loss of hScrib has no effect on E6 stability but results in lower levels of E6 transcription and a reduced rate of E6 translation. We further show that, in the context of cervical tumour-derived cell lines, both hScrib and E6 cooperate in the activation of the S6 kinase signaling pathway, and thereby contribute towards maintaining high rates of protein translation. These results indicate that the residual hScrib that is present within HPV transformed cells is pro-oncogenic, and highlights the dual functions of E6 cell polarity targets. Keywords: HPV E6, hScrib, S6 kinase, Protein translation

  8. Direct Human Papillomavirus E6 Whole-Cell Enzyme-Linked Immunosorbent Assay for Objective Measurement of E6 Oncoproteins in Cytology Samples

    OpenAIRE

    Yang, Yi-Shan; Smith-McCune, Karen; Darragh, Teresa M.; Lai, Yvonne; Lin, Ju-Hwa; Chang, Ting-Chang; Guo, Hsiao-Yun; Kesler, Tiea; Carter, Alicia; Castle, Philip E.; Cheng, Shuling

    2012-01-01

    A novel, whole-cell enzyme-linked immunosorbent assay (ELISA) based on a non-type-specific anti-human papillomavirus (HPV) E6 antibody was tested on 182 residual cytological specimens. For samples with a designation of more severe than cervical intraepithelial neoplasia grade 3 (CIN3+), 83% tested positive for E6; in a subset with paired testing for E6 ELISA and HPV DNA, 72% tested E6 positive and 92% tested high-risk (HR)-HPV DNA positive (P = 0.2). Among the women with a less than CIN3 diag...

  9. SO(14) unification of 3+1 families

    International Nuclear Information System (INIS)

    Karadayi, H.R.

    1982-03-01

    It is shown that the unification of 3+1 families is possible within the framework of 64 dimensional spinor representation of SO(14). Special care is given for a description without the heavy excess fermions such as conjugate and mirror or completely exotic fermions of some family unification schemes. With the aid of an intrinsic ''L-R Asymmetry'' mechanism which we proposed recently, the conventional strong and electromagnetic interactions are obtained for all four families by concentrating only on the symmetry breaking SO(14) → SU(3)sub(c) x U(1)sub(e.m.). However, the conventional weak interactions of the first three families are obtained just as in the standard SU(2)sub(L) x U(1)sub(Y) model, while those of the prescribed fourth family show certain differences. This is what we mean by 3+1 family unification. All vector particles mediating strong, electromagnetic and weak interactions which are the subjects of present phenomenological tests are specified among the vector fields of SO(14) and their mass mechanisms leading to a consistent description of this low-energy phenomenology are studied with the aid of the Higgs multiplets 14, 364, 1716 and 2002 of SO(14). Moreover, the fermion mass mechanisms are considered with the aid of these scalar multiplets and the contributions from these scalars to the vector and fermion masses are explicitly calculated. All these calculations are carried out in the new mathematical technique for the Lie algebra representations which we introduced recently. (author)

  10. Reformulating XQuery queries using GLAV mapping and complex unification

    Directory of Open Access Journals (Sweden)

    Saber Benharzallah

    2016-01-01

    Full Text Available This paper describes an algorithm for reformulation of XQuery queries. The mediation is based on an essential component called mediator. Its main role is to reformulate a user query, written in terms of global schema, into queries written in terms of source schemas. Our algorithm is based on the principle of logical equivalence, simple and complex unification, to obtain a better reformulation. It takes XQuery query, global schema (written in XMLSchema, and mappings GLAV as input parameters and provides resultant query written in terms of source schemas. The results of implementation show the proper functioning of the algorithm.

  11. Focus point gauge mediation in product group unification

    Energy Technology Data Exchange (ETDEWEB)

    Bruemmer, Felix [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Ibe, Masahiro [Tokyo Univ., Kashiwa (Japan). Kavli IPMU, TODIAS; Tokyo Univ., Kashiwa (Japan). ICRR; Yanagida, Tsutomu T. [Tokyo Univ., Kashiwa (Japan). Kavli IPMU, TODIAS

    2013-03-15

    In certain models of gauge-mediated supersymmetry breaking with messenger fields in incomplete GUT multiplets, the radiative corrections to the Higgs potential cancel out during renormalization group running. This allows for relatively heavy superpartners and for a 125 GeV Higgs while the ne-tuning remains modest. In this paper, we show that such gauge mediation models with ''focus point'' behaviour can be naturally embedded into a model of SU(5) x U(3) product group unification.

  12. Nontrivial asymptotically nonfree gauge theories and dynamical unification of couplings

    International Nuclear Information System (INIS)

    Kubo, J.

    1995-01-01

    Evidence for the nontriviality of asymptotically nonfree (ANF) Yang-Mills theories is found on the basis of optimized perturbation theory. It is argued that these theories with matter couplings can be made nontrivial by means of the reduction of couplings, leading to the idea of the dynamical unification of couplings (DUC). The second-order reduction of couplings in the ANF SU(3)-gauged Higgs-Yukawa theory, which is assumed to be nontrivial here, is carried out to motivate independent investigations on its nontriviality and DUC

  13. INTRODUCTION A L'UNIFICATION DES INTERACTIONS ELECTROMAGNETIQUES ET FAIBLES

    OpenAIRE

    Martin , F.

    1980-01-01

    Après avoir décrit l'état actuel de la phénoménologie des interactions faibles on discute les principes de base des théories de jauge. On montre ensuite comment le mécanisme de Higgs permet d'obtenir des quanta d'interaction massifs. Le modèle dit de "Weinberg-Salam" permettant d'unifier les interactions électromagnétiques et faibles est présenté. On termine par quelques mots sur l'unification avec les interactions fortes et la gravitation.

  14. E6 as biogas highway from Gothenburg to Oslo. Final report; E6 som biogassvei fra Goeteborg til Oslo. Sluttrapport

    Energy Technology Data Exchange (ETDEWEB)

    Raadal, Hanne Lerche; Morken, John; Lileng, Knut

    2009-07-01

    The main goal of the project has been to contribute to reducing greenhouse gas emissions from road transport in the transition from fossil fuels to biogas. Biogas Fredrikstad AS has been the project owner, with FREVAR KF and Borgbuss AS as partners on the user side. Oestfold Research has been project manager with the University of Life Sciences (UMB) as part responsible for R&D efforts. Biogas Fredrikstad AS established in 2001 the first manufacturing plant and filling station for biogas as fuel. The project was supported by the Road Directorate through the support system for environmental friendly transport. The biogas produced from sewage sludge and biogas substrate (based on food waste). Based on the desire to establish a more accessible filling station in Fredrikstad, and to increase knowledge and competence in general about biogas as bio propellant, the project 'E6 as biogas highway from Gothenburg to Oslo' was granted as a RENERGI and SkatteFUNN project. The project started 1.1.2006 and ended 31.12.2008. The project has achieved useful synergies with relevant other projects that have taken place in parallel. Based on an overall assessment of costs, availability, opportunities for land area, etc, new filling station for biogas in Fredrikstad are planned and designed at the rotary intersection at the eastern bridgehead of Fredrikstad bridge. All permits in connection with the establishment of new filling station is available. In anticipation of the top financing, the start of the construction phase has been somewhat offset in time. It is applied for funds to support the establishment of the filling station from the newly created TransNova. The project has assessed and documented several conditions regarding use of biogas as a fuel, including: Environmental issues with the use of biogas as fuel; Potential and status of biogas production in Norway; Production of biogas in Fredrikstad and input to the optimization of the process of FREVAR KF; Driving

  15. HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Calmon, Marilia Freitas [Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto (Brazil); Sichero, Laura [Molecular Biology Laboratory, Centre for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo (Brazil); Boccardo, Enrique [Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo., São Paulo (Brazil); Villa, Luisa Lina [Department of Radiology and Oncology, Faculdade de Medicina, Universidade de São Paulo, São Paulo (Brazil); Rahal, Paula, E-mail: rahalp@yahoo.com.br [Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto (Brazil)

    2016-09-15

    Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.

  16. HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

    International Nuclear Information System (INIS)

    Calmon, Marilia Freitas; Sichero, Laura; Boccardo, Enrique; Villa, Luisa Lina; Rahal, Paula

    2016-01-01

    Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.

  17. The vacuum of the minimal nonsupersymmetric SO(10) unification

    International Nuclear Information System (INIS)

    Bertolini, Stefano; Di Luzio, Luca; Malinsky, Michal

    2010-01-01

    We study a class of nonsupersymmetric SO(10) grand-unified scenarios where the first stage of the symmetry breaking is driven by the vacuum expectation values of the 45-dimensional adjoint representation. Three-decade-old results claim that such a Higgs setting may lead exclusively to the flipped SU(5) x U(1) intermediate stage. We show that this conclusion is actually an artifact of the tree-level potential. The study of the accidental global symmetries emerging in various limits of the scalar potential offers a simple understanding of the tree-level result and a rationale for the drastic impact of quantum corrections. We scrutinize in detail the simplest and paradigmatic case of the 45 H +16 H Higgs sector triggering the breaking of SO(10) to the standard electroweak model. We show that the minimization of the one-loop effective potential allows for intermediate SU(4) C x SU(2) L x U(1) R and SU(3) c x SU(2) L x SU(2) R x U(1) B-L symmetric stages as well. These are the options favored by gauge unification. Our results, that apply whenever the SO(10) breaking is triggered by H >, open the path for hunting the simplest realistic scenario of nonsupersymmetric SO(10) grand unification.

  18. Grand Unification as a Bridge Between String Theory and Phenomenology

    Energy Technology Data Exchange (ETDEWEB)

    Pati, Jogesh C.

    2006-06-09

    In the first part of the talk, I explain what empirical evidence points to the need for having an effective grand unification-like symmetry possessing the symmetry SU(4)-color in 4D. If one assumes the premises of a future predictive theory including gravity--be it string/M theory or a reincarnation--this evidence then suggests that such a theory should lead to an effective grand unification-like symmetry as above in 4D, near the string-GUT-scale, rather than the standard model symmetry. Advantages of an effective supersymmetric G(224) = SU(2){sub L} x SU(2){sub R} x SU(4){sup c} or SO(10) symmetry in 4D in explaining (1) observed neutrino oscillations, (2) baryogenesis via leptogenesis, and (3) certain fermion mass-relations are noted. And certain distinguishing tests of a SUSY G(224) or SO(10)-framework involving CP and flavor violations (as in {mu} {yields} e{gamma}, {tau} {yields} {mu}{gamma}, edm's of the neutron and the electron) as well as proton decay are briefly mentioned. Recalling some of the successes we have had in our understanding of nature so far, and the current difficulties of string/M theory as regards the large multiplicity of string vacua, some comments are made on the traditional goal of understanding vis a vis the recently evolved view of landscape and anthropism.

  19. [Laboratory unification: advantages and disadvantages for clinical microbiology].

    Science.gov (United States)

    Andreu, Antonia; Matas, Lurdes

    2010-10-01

    This article aims to reflect on which areas or tasks of microbiology laboratories could be unified with those of clinical biochemistry, hematology, immunology or pathology laboratories to benefit patients and the health system, as well as the areas that should remain independent since their amalgamation would not only fail to provide a benefit but could even jeopardize the quality of microbiological diagnosis, and consequently patient care. To do this, the distinct analytic phases of diagnosis are analyzed, and the advantages and disadvantages of amalgamation are evaluated in each phase. The pros and cons of the unification of certain areas such as the computer system, occupational risk units, customer service, purchasing logistics, and materials storage, etc, are also discussed. Lastly, the effect of unification on urgent microbiology diagnosis is analyzed. Microbiological diagnosis should be unique. The microbiologist should perform an overall evaluation of the distinct techniques used for a particular patient, both those that involve direct diagnosis (staining, culture, antigen detection techniques or molecular techniques) and indirect diagnosis (antibody detection). Moreover, the microbiology laboratory should be independent, with highly trained technicians and specialists in microbiology that provide added value as experts in infection and as key figures in the process of establishing a correct etiological diagnosis. Copyright © 2010 Elsevier España S.L. All rights reserved.

  20. Grand Unification as a Bridge Between String Theory and Phenomenology

    Science.gov (United States)

    Pati, Jogesh C.

    In the first part of this paper, we explain what empirical evidence points to the need for having an effective grand unification-like symmetry possessing the symmetry SU(4)-color in 4D. If one assumes the premises of a future predictive theory including gravity — be it string/M-theory or a reincarnation — this evidence then suggests that such a theory should lead to an effective grand unification-like symmetry as above in 4D, near the string-GUT-scale, rather than the standard model symmetry. Advantages of an effective supersymmetric G(224) = SU(2)L × SU(2)R × SU(4)c or SO(10) symmetry in 4D in explaining (i) observed neutrino oscillations, (ii) baryogenesis via leptogenesis, and (iii) certain fermion mass-relations are noted. And certain distinguishing tests of a SUSY G(224) or SO(10)-framework involving CP and flavor violations (as in μ → eγ, τ → μγ, edm's of the neutron and the electron) as well as proton decay are briefly mentioned. Recalling some of the successes we have had in our understanding of nature so far, and the current difficulties of string/M-theory as regards the large multiplicity of string vacua, some comments are made on the traditional goal of understanding vis a vis the recently evolved view of landscape and anthropism.

  1. Grand Unification as a Bridge Between String Theory and Phenomenology

    International Nuclear Information System (INIS)

    Pati, J

    2006-01-01

    In the first part of the talk, I explain what empirical evidence points to the need for having an effective grand unification-like symmetry possessing the symmetry SU(4)-color in 4D. If one assumes the premises of a future predictive theory including gravity--be it string/M theory or a reincarnation--this evidence then suggests that such a theory should lead to an effective grand unification-like symmetry as above in 4D, near the string-GUT-scale, rather than the standard model symmetry. Advantages of an effective supersymmetric G(224) = SU(2) L x SU(2) R x SU(4) c or SO(10) symmetry in 4D in explaining (1) observed neutrino oscillations, (2) baryogenesis via leptogenesis, and (3) certain fermion mass-relations are noted. And certain distinguishing tests of a SUSY G(224) or SO(10)-framework involving CP and flavor violations (as in μ → eγ, τ → μγ, edm's of the neutron and the electron) as well as proton decay are briefly mentioned. Recalling some of the successes we have had in our understanding of nature so far, and the current difficulties of string/M theory as regards the large multiplicity of string vacua, some comments are made on the traditional goal of understanding vis a vis the recently evolved view of landscape and anthropism

  2. Unification of reactor elastomeric sealing based on material

    International Nuclear Information System (INIS)

    Sinha, N.K.; Raj, Baldev

    2012-01-01

    The unification of elastomeric sealing applications of Indian nuclear reactors based on a few qualified fluoroelastomer/perfluoroelastomer compounds and standardized approaches for finite element analysis (FEA) based design, manufacturing process and antifriction coatings is discussed. It is shown that the advance polymer architecture based Viton ® formulation developed for inflatable seals of 500 MWe Prototype Fast Breeder Reactor (PFBR) and its four basic variations can encompass other sealing applications of PFBR with minimum additional efforts on development and validation. Changing the blend ratio of Viton ® GBL 200S and 600S in inflatable seal formulation could extend its use to Pressurized Heavy Water Reactors (PHWRs). The higher operating temperature of Advanced Heavy Water Reactor (AHWR) seals expands the choice to perfluoroelastomers. FEA based on plane-strain/axisymmetric modeling (with Mooney–Rivlin as the basic constitutive model), seal manufacture by cold feed extrusion and injection molding as well as plasma Teflon-like coating belonging to two variations obtained from the development of inflatable seals provide the necessary standardization for unification. The gains in simplification of design, development and operation of seals along with the enhancements of safety and reliability are expected to be substantial.

  3. Radioimmunotherapy with an antibody to HPV16 E6 oncoprotein is effective in experimental cervical tumor expressing low levels of E6

    Science.gov (United States)

    Jiang, Zewei; Wang, Xing Guo; Einstein, Mark H; Goldberg, Gary L; Casadevall, Arturo

    2010-01-01

    Purpose HPV16 is associated with ∼50% of all cervical cancers worldwide. The E6 and E7 genes of oncogenic HPV types, such as HPV16, are necessary for the HPV transforming function and tumorogenesis making them ideal targets for novel treatments. Radioimmunotherapy employs systemically administered radiolabeled monoclonal antibodies (mAbs) that bind to tumor-associated antigens. Previously we demonstrated in mice that radioimmunotherapy targeting viral antigens with mAb to HPV16 E6 suppressed CasKi cervical tumors expressing high levels of E6 (∼600 copies of HPV per cell). However, that study opened the question whether radioimmunotherapy can suppress the growth of cervical tumors with low E6 and E7 expression, such as may be seen in patients. Experimental Design We evaluated the expression of E6 in patients' tumors and in the SiHa cell line expressing low levels of E6 and E7 (1–2 copies of HPV per cell) and found them comparable. We initiated SiHa tumors in nude mice, radiolabeled C1P5 mAb to E6 with a beta-emitter 188-Rhenium (188Re) and treated tumor-bearing mice with: (1) 200 µCi 188Re-C1P5 alone; (2) proteasome inhibitor MG132 alone; (3) MG132 followed by 200 µCi 188Re-C1P5; (4) unlabeled C1P5; (5) 200 µCi 188Re-18B7 (isotype-matching control mAb); (6) no treatment. 188Re-C1P5 alone and in combination with MG-132 significantly retarded tumor growth compared to all control groups. Conclusions Our data demonstrate the possibility to suppress tumor growth by targeting viral antigens even in cervical tumors with low E6 expression and provide additional evidence for the potential usefulness of radioimmunotherapy targeting HPV-related antigens in the clinic. PMID:20861673

  4. From Minimal to Realistic Supersymmetric SU(5) Grand Unification

    CERN Document Server

    Altarelli, Guido; Masina, I; Altarelli, Guido; Feruglio, Ferruccio; Masina, Isabella

    2000-01-01

    We construct and discuss a "realistic" example of SUSY SU(5) GUT model, with an additional U(1) flavour symmetry, that is not plagued by the need of large fine tunings, like those associated with doublet-triplet splitting in the minimal model, and that leads to an acceptable phenomenology. This includes coupling unification with a value of alpha_s(m_Z) in much better agreement with the data than in the minimal version, an acceptable hierarchical pattern for fermion masses and mixing angles, also including neutrino masses and mixings, and a proton decay rate compatible with present limits (but the discovery of proton decay should be within reach of the next generation of experiments). In the neutrino sector the preferred solution is one with nearly maximal mixing both for atmospheric and solar neutrinos.

  5. A proposal for unification of fatigue crack growth law

    Science.gov (United States)

    Kobelev, V.

    2017-05-01

    In the present paper, the new fractional-differential dependences of cycles to failure for a given initial crack length upon the stress amplitude in the linear fracture approach are proposed. The anticipated unified propagation function describes the infinitesimal crack length growths per increasing number of load cycles, supposing that the load ratio remains constant over the load history. Two unification fractional-differential functions with different number of fitting parameters are proposed. An alternative, threshold formulations for the fractional-differential propagation functions are suggested. The mean stress dependence is the immediate consequence from the considered laws. The corresponding formulas for crack length over the number of cycles are derived in closed form.

  6. Yukawa unification in moduli-dominant SUSY breaking

    International Nuclear Information System (INIS)

    Khalil, S.; Tatsuo Kobayashi

    1997-07-01

    We study Yukawa in string models with moduli-dominant SUSY breaking. This type of SUSY breaking in general leads to non-universal soft masses, i.e. soft scalar masses and gaugino masses. Such non-universality is important for phenomenological aspects of Yukawa unification, i.e., successful electroweak breaking, SUSY corrections to the bottom mass and the branching ratio of b → sγ. We show three regions in the whole parameter space which lead to successful electroweak breaking and allow small SUSY corrections to the bottom mass. For these three regions we investigated the b → sγ decay and mass spectra. (author). 26 refs, 6 figs

  7. Gauge-Higgs unification with brane kinetic terms

    International Nuclear Information System (INIS)

    Aranda, Alfredo; Diaz-Cruz, J. Lorenzo

    2006-01-01

    By identifying the Higgs field as an internal component of a higher-dimensional gauge field it is possible to solve the little hierarchy problem. The construction of a realistic model that incorporates such a gauge-Higgs unification is an important problem that demands attention. In fact, several attempts in this direction have already been put forward. In this Letter we single out one such attempt, a 6D SU(3) extended electroweak theory, where it is possible to obtain a Higgs mass prediction in accord with global fits. One shortcoming of the model is its prediction for the Weinberg angle, it is too large. We slightly modify the model by including brane kinetic terms in a way motivated by the orbifold action on the 6D fields. We show that in this way it is possible to obtain the correct Weinberg angle while keeping the desired results in the Higgs sector

  8. Grand unification and the fundamental problems of classical cosmology

    International Nuclear Information System (INIS)

    Turner, M.S.

    1981-01-01

    The accomplishments of classical cosmology are reviewed. In particular, the hot big bang model provides a reliable framework for understanding the evolution of the universe back to times at least as early as approx. 0.01 s after the big bang. At present there are (at least) six fundamental problems which have not yet been (completely) resolved. They are: (1) the origin of the baryon number-to-entropy ratio, (2) the origin of the isotropy, (3) the origin of the homogeneity and inhomogeneity, (4) the origin of the flatness, (5) the cosmological constant, and (6) the monopole problem. The role that grand unification has played, and may play in the resolution of these puzzles is discussed. Guth's inflationary universe, which addresses five of these six problems, is reviewed

  9. Vector-like quarks and leptons, SU(5) ⊗ SU(5) grand unification, and proton decay

    International Nuclear Information System (INIS)

    Lee, Chang-Hun; Mohapatra, Rabindra N.

    2017-01-01

    SU(5) ⊗ SU(5) provides a minimal grand unification scheme for fermions and gauge forces if there are vector-like quarks and leptons in nature. We explore the gauge coupling unification in a non-supersymmetric model of this type, and study its implications for proton decay. The properties of vector-like quarks and intermediate scales that emerge from coupling unification play a central role in suppressing proton decay. We find that in this model, the familiar decay mode p→e + π 0 may have a partial lifetime within the reach of currently planned experiments.

  10. Fundamental Elements and Interactions of Nature: A Classical Unification Theory

    Directory of Open Access Journals (Sweden)

    Tianxi Zhang

    2010-04-01

    Full Text Available A classical unification theory that completely unifies all the fundamental interactions of nature is developed. First, the nature is suggested to be composed of the following four fundamental elements: mass, radiation, electric charge, and color charge. All known types of matter or particles are a combination of one or more of the four fundamental elements. Photons are radiation; neutrons have only mass; protons have both mass and electric charge; and quarks contain mass, electric charge, and color charge. The nature fundamental interactions are interactions among these nature fundamental elements. Mass and radiation are two forms of real energy. Electric and color charges are considered as two forms of imaginary energy. All the fundamental interactions of nature are therefore unified as a single interaction between complex energies. The interaction between real energies is the gravitational force, which has three types: mass-mass, mass-radiation, and radiation-radiation interactions. Calculating the work done by the mass-radiation interaction on a photon derives the Einsteinian gravitational redshift. Calculating the work done on a photon by the radiation-radiation interaction derives a radiation redshift, which is much smaller than the gravitational redshift. The interaction between imaginary energies is the electromagnetic (between electric charges, weak (between electric and color charges, and strong (between color charges interactions. In addition, we have four imaginary forces between real and imaginary energies, which are mass-electric charge, radiation-electric charge, mass-color charge, and radiation-color charge interactions. Among the four fundamental elements, there are ten (six real and four imaginary fundamental interactions. This classical unification theory deepens our understanding of the nature fundamental elements and interactions, develops a new concept of imaginary energy for electric and color charges, and provides a

  11. Fundamental Elements and Interactions of Nature: A Classical Unification Theory

    Directory of Open Access Journals (Sweden)

    Zhang T. X.

    2010-04-01

    Full Text Available A classical unification theory that completely unifies all the fundamental interactions of nature is developed. First, the nature is suggested to be composed of the following four fundamental elements: mass, radiation, electric charge, and color charge. All known types of matter or particles are a combination of one or more of the four fundamental elements. Photons are radiation; neutrons have only mass; protons have both mass and electric charge; and quarks contain mass, electric charge, and color charge. The nature fundamental interactions are interactions among these nature fundamental elements. Mass and radiation are two forms of real energy. Electric and color charges are con- sidered as two forms of imaginary energy. All the fundamental interactions of nature are therefore unified as a single interaction between complex energies. The interac- tion between real energies is the gravitational force, which has three types: mass-mass, mass-radiation, and radiation-radiation interactions. Calculating the work done by the mass-radiation interaction on a photon derives the Einsteinian gravitational redshift. Calculating the work done on a photon by the radiation-radiation interaction derives a radiation redshift, which is much smaller than the gravitational redshift. The interaction between imaginary energies is the electromagnetic (between electric charges, weak (between electric and color charges, and strong (between color charges interactions. In addition, we have four imaginary forces between real and imaginary energies, which are mass-electric charge, radiation-electric charge, mass-color charge, and radiation- color charge interactions. Among the four fundamental elements, there are ten (six real and four imaginary fundamental interactions. This classical unification theory deep- ens our understanding of the nature fundamental elements and interactions, develops a new concept of imaginary energy for electric and color charges, and provides a

  12. Leptoquark mechanism of neutrino masses within the grand unification framework

    Science.gov (United States)

    Doršner, Ilja; Fajfer, Svjetlana; Košnik, Nejc

    2017-06-01

    We demonstrate the viability of the one-loop neutrino mass mechanism within the framework of grand unification when the loop particles comprise scalar leptoquarks (LQs) and quarks of the matching electric charge. This mechanism can be implemented in both supersymmetric and non-supersymmetric models and requires the presence of at least one LQ pair. The appropriate pairs for the neutrino mass generation via the up-type and down-type quark loops are S_3-R_2 and S_{1, 3}-\\tilde{R}_2, respectively. We consider two distinct regimes for the LQ masses in our analysis. The first regime calls for very heavy LQs in the loop. It can be naturally realized with the S_{1, 3}-\\tilde{R}_2 scenarios when the LQ masses are roughly between 10^{12} and 5 × 10^{13} GeV. These lower and upper bounds originate from experimental limits on partial proton decay lifetimes and perturbativity constraints, respectively. Second regime corresponds to the collider accessible LQs in the neutrino mass loop. That option is viable for the S_3-\\tilde{R}_2 scenario in the models of unification that we discuss. If one furthermore assumes the presence of the type II see-saw mechanism there is an additional contribution from the S_3-R_2 scenario that needs to be taken into account beside the type II see-saw contribution itself. We provide a complete list of renormalizable operators that yield necessary mixing of all aforementioned LQ pairs using the language of SU(5). We furthermore discuss several possible embeddings of this mechanism in SU(5) and SO(10) gauge groups.

  13. Prospects for mass unification at low energy scales

    International Nuclear Information System (INIS)

    Volkas, R.R.

    1995-01-01

    A simple Pati-Salam SU(4) model with a low symmetry breaking scale of about 1000 TeV is presented. The analysis concentrates on calculating radiative corrections to tree level mass relations for third generation fermions. The tree-level relation m b /m τ = 1 predicted by such models can receive large radiative corrections up to about 50% due to threshold effects at the mass unification scale. These corrections are thus of about the same importance as those that give rise to renormalisation group running. The high figure of 50% can be achieved because l-loop graphs involving the physical charged Higgs boson give corrections to m τ -m b that are proportional to the large top quark mass. These corrections can either increase or decrease m b /m τ depending on the value of an unknown parameter. They can also be made to vanish through a fine-tuning. A related model of tree-level t-b-τ unification which uses the identification of SU(2) R with custodial SU(2) is then discussed. A curious relation m b ∼ √2m τ is found to be satisfied at tree-level in this model. The overall conclusion of this work is that the tree-level relation m b =m τ at low scales such as 1000 TeV or somewhat higher can produce a successful value for m b /m τ after corrections, but one must be mindful that radiative corrections beyond those incorporated through the renormalisation group can be very important. 14 refs., 7 figs

  14. Prospects for mass unification at low energy scales

    Energy Technology Data Exchange (ETDEWEB)

    Volkas, R.R.

    1995-12-31

    A simple Pati-Salam SU(4) model with a low symmetry breaking scale of about 1000 TeV is presented. The analysis concentrates on calculating radiative corrections to tree level mass relations for third generation fermions. The tree-level relation m{sub b}/m{sub {tau}} = 1 predicted by such models can receive large radiative corrections up to about 50% due to threshold effects at the mass unification scale. These corrections are thus of about the same importance as those that give rise to renormalisation group running. The high figure of 50% can be achieved because l-loop graphs involving the physical charged Higgs boson give corrections to m{sub {tau}} -m{sub b} that are proportional to the large top quark mass. These corrections can either increase or decrease m{sub b}/m{sub {tau}} depending on the value of an unknown parameter. They can also be made to vanish through a fine-tuning. A related model of tree-level t-b-{tau} unification which uses the identification of SU(2){sub R} with custodial SU(2) is then discussed. A curious relation m{sub b}{approx} {radical}2m{sub {tau}} is found to be satisfied at tree-level in this model. The overall conclusion of this work is that the tree-level relation m{sub b}=m{sub {tau}} at low scales such as 1000 TeV or somewhat higher can produce a successful value for m{sub b}/m{sub {tau}} after corrections, but one must be mindful that radiative corrections beyond those incorporated through the renormalisation group can be very important. 14 refs., 7 figs.

  15. Leptoquark mechanism of neutrino masses within the grand unification framework

    Energy Technology Data Exchange (ETDEWEB)

    Dorsner, Ilja [University of Split, Faculty of Electrical Engineering, Mechanical Engineering and Naval Architecture in Split (FESB), Split (Croatia); Fajfer, Svjetlana; Kosnik, Nejc [University of Ljubljana, Department of Physics, Ljubljana (Slovenia); Jozef Stefan Institute, Jamova 39, P. O. Box 3000, Ljubljana (Slovenia)

    2017-06-15

    We demonstrate the viability of the one-loop neutrino mass mechanism within the framework of grand unification when the loop particles comprise scalar leptoquarks (LQs) and quarks of the matching electric charge. This mechanism can be implemented in both supersymmetric and non-supersymmetric models and requires the presence of at least one LQ pair. The appropriate pairs for the neutrino mass generation via the up-type and down-type quark loops are S{sub 3}-R{sub 2} and S{sub 1,3}-R{sub 2}, respectively. We consider two distinct regimes for the LQ masses in our analysis. The first regime calls for very heavy LQs in the loop. It can be naturally realized with the S{sub 1,3}-R{sub 2} scenarios when the LQ masses are roughly between 10{sup 12} and 5 x 10{sup 13} GeV. These lower and upper bounds originate from experimental limits on partial proton decay lifetimes and perturbativity constraints, respectively. Second regime corresponds to the collider accessible LQs in the neutrino mass loop. That option is viable for the S{sub 3}-R{sub 2} scenario in the models of unification that we discuss. If one furthermore assumes the presence of the type II see-saw mechanism there is an additional contribution from the S{sub 3}-R{sub 2} scenario that needs to be taken into account beside the type II see-saw contribution itself. We provide a complete list of renormalizable operators that yield necessary mixing of all aforementioned LQ pairs using the language of SU(5). We furthermore discuss several possible embeddings of this mechanism in SU(5) and SO(10) gauge groups. (orig.)

  16. Group theory approach to unification of gravity with internal symmetry gauge interactions. Part 1

    International Nuclear Information System (INIS)

    Samokhvalov, S.E.; Vanyashin, V.S.

    1990-12-01

    The infinite group of deformed diffeomorphisms of space-time continuum is put into the basis of the Gauge Theory of Gravity. This gives rise to some new ways for unification of gravity with other gauge interactions. (author). 7 refs

  17. Revisiting top-bottom-tau Yukawa unification in supersymmetric grand unified theories

    International Nuclear Information System (INIS)

    Tobe, Kazuhiro; Wells, James D.

    2003-01-01

    Third family Yukawa unification, as suggested by minimal SO(10) unification, is revisited in light of recent experimental measurements and theoretical progress. We characterize unification in a semi-model-independent fashion, and conclude that finite b quark mass corrections from superpartners must be non-zero, but much smaller than naively would be expected. We show that a solution that does not require cancellations of dangerously large tanβ effects in observables implies that scalar superpartner masses should be substantially heavier than the Z scale, and perhaps inaccessible to all currently approved colliders. On the other hand, gauginos must be significantly lighter than the scalars. We demonstrate that a spectrum of anomaly-mediated gaugino masses and heavy scalars works well as a theory compatible with third family Yukawa unification and dark matter observations

  18. Logarithmic unification from symmetries enhanced in the sub-millimeter infrared

    International Nuclear Information System (INIS)

    Arkani-Hamed, Nima; Dimopoulos, Savas; March-Russell, John

    1999-01-01

    In theories with TeV string scale and sub-millimeter extra dimensions the attractive picture of logarithmic gauge coupling unification at 10 16 GeV is seemingly destroyed. In this paper we argue to the contrary that logarithmic unification can occur in such theories. The rationale for unification is no longer that a gauge symmetry is restored at short distances, but rather that a geometric symmetry is restored at large distances in the bulk away from our 3-brane. The apparent ''running'' of the gauge couplings to energies far above the string scale actually arises from the logarithmic variation of classical fields in (sets of) two large transverse dimensions. We present a number of N = 2 and N = 1 supersymmetric D-brane constructions illustrating this picture for unification

  19. Radio Loud AGN Unification: Connecting Jets and Accretion

    Directory of Open Access Journals (Sweden)

    Meyer Eileen T.

    2013-12-01

    Full Text Available While only a fraction of Active Galactic Nuclei are observed to host a powerful relativistic jet, a cohesive picture is emerging that radio-loud AGN may represent an important phase in the evolution of galaxies and the growth of the central super-massive black hole. I will review my own recent observational work in radio-loud AGN unification in the context of understanding how and why jets form and their the connection to different kinds of accretion and growing the black hole, along with a brief discussion of possible connections to recent modeling work in jet formation. Starting from the significant observational advances in our understanding of jetted AGN as a population over the last decade thanks to new, more sensitive instruments such as Fermi and Swift as well as all-sky surveys at all frequencies, I will lay out the case for a dichotomy in the jetted AGN population connected to accretion mode onto the black hole. In recent work, we have identified two sub-populations of radio-loud AGN which appear to be distinguished by jet structure, where low-efficiency accreting systems produce ‘weak’ jets which decelerate more rapidly than the ’strong’ jets of black holes accreting near the Eddington limit. The two classes are comprised of: (1The weak jet sources, corresponding to the less collimated, edge-darkened FR Is, with a decelerating or spine-sheath jet with velocity gradients, and (2 The strong jet sources, having fast, collimated jets, and typically displaying strong emission lines. The dichotomy in the vp-Lp plane can be understood as a "broken power sequence" in which jets exist on one branch or the other based on the particular accretion mode (Georganopolous 2011.We suggest that the intrinsic kinetic power (as measured by low-frequency, isotropic radio emission, the orientation, and the accretion rate of the SMBH system are the the fundamental axes needed for unification of radio-loud AGN by studying a well-characterized sample

  20. Mutagenic Potential ofBos taurus Papillomavirus Type 1 E6 Recombinant Protein: First Description

    Directory of Open Access Journals (Sweden)

    Rodrigo Pinheiro Araldi

    2015-01-01

    Full Text Available Bovine papillomavirus (BPV is considered a useful model to study HPV oncogenic process. BPV interacts with the host chromatin, resulting in DNA damage, which is attributed to E5, E6, and E7 viral oncoproteins activity. However, the oncogenic mechanisms of BPV E6 oncoprotein per se remain unknown. This study aimed to evaluate the mutagenic potential of Bos taurus papillomavirus type 1 (BPV-1 E6 recombinant oncoprotein by the cytokinesis-block micronucleus assay (CBMNA and comet assay (CA. Peripheral blood samples of five calves were collected. Samples were subjected to molecular diagnosis, which did not reveal presence of BPV sequences. Samples were treated with 1 μg/mL of BPV-1 E6 oncoprotein and 50 μg/mL of cyclophosphamide (positive control. Negative controls were not submitted to any treatment. The samples were submitted to the CBMNA and CA. The results showed that BPV E6 oncoprotein induces clastogenesis per se, which is indicative of genomic instability. These results allowed better understanding the mechanism of cancer promotion associated with the BPV E6 oncoprotein and revealed that this oncoprotein can induce carcinogenesis per se. E6 recombinant oncoprotein has been suggested as a possible vaccine candidate. Results pointed out that BPV E6 recombinant oncoprotein modifications are required to use it as vaccine.

  1. Symmetry Breaking, Unification, and Theories Beyond the Standard Model

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Yasunori

    2009-07-31

    A model was constructed in which the supersymmetric fine-tuning problem is solved without extending the Higgs sector at the weak scale. We have demonstrated that the model can avoid all the phenomenological constraints, while avoiding excessive fine-tuning. We have also studied implications of the model on dark matter physics and collider physics. I have proposed in an extremely simple construction for models of gauge mediation. We found that the {mu} problem can be simply and elegantly solved in a class of models where the Higgs fields couple directly to the supersymmetry breaking sector. We proposed a new way of addressing the flavor problem of supersymmetric theories. We have proposed a new framework of constructing theories of grand unification. We constructed a simple and elegant model of dark matter which explains excess flux of electrons/positrons. We constructed a model of dark energy in which evolving quintessence-type dark energy is naturally obtained. We studied if we can find evidence of the multiverse.

  2. On the vacuum of the minimal nonsupersymmetric SO(10) unification

    CERN Document Server

    Bertolini, Stefano; Malinsky, Michal

    2010-01-01

    We study a class of nonsupersymmetric SO(10) grand unified scenarios where the first stage of the symmetry breaking is driven by the vacuum expectation values of the 45-dimensional adjoint representation. Three decade old results claim that such a Higgs setting may lead exclusively to the flipped SU(5) x U(1) intermediate stage. We show that this conclusion is actually an artifact of the tree level potential. The study of the accidental global symmetries emerging in various limits of the scalar potential offers a simple understanding of the tree level result and a rationale for the drastic impact of quantum corrections. We scrutinize in detail the simplest and paradigmatic case of the 45_{H} + 16_{H} Higgs sector triggering the breaking of SO(10) to the standard electroweak model. We show that the minimization of the one-loop effective potential allows for intermediate SU(4)_C x SU(2)_L x U(1)_R and SU(3)_c x SU(2)_L x SU(2)_R x U(1)_{B-L} symmetric stages as well. These are the options favoured by gauge unif...

  3. ARCHITECTURE E-MALL USING RUP (RATIONAL UNIFED PROCESS METHODS

    Directory of Open Access Journals (Sweden)

    Atin Triwahyuni

    2016-09-01

    Full Text Available Sistem Informasi dan teknologi saat ini telah berkembang dengan cepat dan memberikan dampak kedalam semua aspek kehidupan. Kebutuhan akan sistem informasi yang didukung dengan teknologi mulai dirasakan oleh berbagai kalangan masyarakat, salah satunya adalah kalangan masyarakat yang bergerak di dunia bisnis dan usaha, dengan memanfaatkan teknologi, setiap orang yang bergerak di dunia usaha dapat memperkenalkan produk mereka dengan menggunakan media internet, sehingga dapat meningkatkan penjualan dan memperluas pemasarannya, sedangkan pada media penjualan dagangan yang dijajakan masih secara konvensional, yaitu langsung bertatap muka dengan pelanggan untuk melihat maupun melakukan pembelian produk, dimana pelanggan terlebih dahulu menuju toko yang diinginkan, tapi dengan adanya sebuah website E-Mall ini, pelanggan bisa menemukan apa yang dicari tanpa harus mengunjungi toko tersebut. Metode yang digunakan dalam penelitian ini adalah metode RUP (Rational Unifed Process yang menggunakan konsep object oriented, dengan aktifitas yang berfokus pada pengembangan model dengan menggunakan Unified Model Language (UML. Penelitian yang telah dilakukan menghasilkan sebuah website yang dapat membantu dalam bisnis perdagangan pakaian online.

  4. Higgs mass in the gauge-Higgs unification

    International Nuclear Information System (INIS)

    Haba, Naoyuki; Takenaga, Kazunori; Yamashita, Toshifumi

    2005-01-01

    The gauge-Higgs unification theory identifies the zero mode of the extra-dimensional component of the gauge field as the usual Higgs doublet. Since this degree of freedom is the Wilson line phase, the Higgs does not have the mass term nor quartic coupling at the tree level. Through quantum corrections, the Higgs can take a vacuum expectation value, and its mass is induced. The radiatively induced mass tends to be small, although it can be lifted to O(100) GeV by introducing the O(10) numbers of bulk fields. Perturbation theory becomes unreliable when a large number of bulk fields are introduced. We reanalyze the Higgs mass based on useful expansion formulae for the effective potential and find that even a small number of bulk field can have the suitable heavy Higgs mass. We show that a small (large) number of bulk fields are enough (needed) when the SUSY breaking mass is large (small). We also study the case of introducing the soft SUSY breaking scalar masses in addition to the Scherk-Schwarz SUSY breaking and obtain the heavy Higgs mass due to the effect of the scalar mass

  5. Testing AGN unification via inference from large catalogs

    Science.gov (United States)

    Nikutta, Robert; Ivezic, Zeljko; Elitzur, Moshe; Nenkova, Maia

    2018-01-01

    Source orientation and clumpiness of the central dust are the main factors in AGN classification. Type-1 QSOs are easy to observe and large samples are available (e.g. in SDSS), but obscured type-2 AGN are dimmer and redder as our line of sight is more obscured, making it difficult to obtain a complete sample. WISE has found up to a million QSOs. With only 4 bands and a relatively small aperture the analysis of individual sources is challenging, but the large sample allows inference of bulk properties at a very significant level.CLUMPY (www.clumpy.org) is arguably the most popular database of AGN torus SEDs. We model the ensemble properties of the entire WISE AGN content using regularized linear regression, with orientation-dependent CLUMPY color-color-magnitude (CCM) tracks as basis functions. We can reproduce the observed number counts per CCM bin with percent-level accuracy, and simultaneously infer the probability distributions of all torus parameters, redshifts, additional SED components, and identify type-1/2 AGN populations through their IR properties alone. We increase the statistical power of our AGN unification tests even further, by adding other datasets as axes in the regression problem. To this end, we make use of the NOAO Data Lab (datalab.noao.edu), which hosts several high-level large datasets and provides very powerful tools for handling large data, e.g. cross-matched catalogs, fast remote queries, etc.

  6. Grand unification and the double beta-decay

    International Nuclear Information System (INIS)

    Faessler, A.

    1992-01-01

    Models of the unification of the electroweak and the strong interaction predict that the neutrino is a Majorana particle and therefore essentially identical with its own antiparticle. In such grand unified models the neutrino has also a finite mass and a slight right-handed weak interaction, since the model is left-right symmetric. These models have also left handed and right-handed vector bosons to mediate the weak interactions. If these models are correct the neutrinoless double beta-decay is feasable. Thus if one finds the neutrinoless double beta-decay one knows that the standard model can not be correct in which the neutrino is a Dirac particle and therefore different from its antiparticle. Although the neutrinoless double beta-decay has not been seen it is possible to extract from the lower limits of the lifetime against the double neutrinoless beta-decay upper limits for the effective electron-neutrino mass and for the effective mixing angle of the right-handed and the left-handed vector bosons mediating the weak interaction. One also can obtain an effective upper limit for the mass ratio of the light and the heavy vector bosons. The extraction of this physical quantities from the data is made difficult due to the fact that the weak interaction must not be diagonal in the representation of the mass matrix of the six neutrinos requested by such left-right symmetric models. (author)

  7. UNIFICATION OF PROCESSES OF SORTING OUT OF DESTROYED CONSTRUCTION OBJECTS

    Directory of Open Access Journals (Sweden)

    SHATOV S. V.

    2015-09-01

    Full Text Available Summary. Problem statement. Technogenic catastrophes, failures or natural calamities, result in destruction of build objects. Under the obstructions of destructions can be victims. The most widespread technogenic failure is explosions of gas. The structure of obstructions changes and depends on parameters and direction of explosion, firstly its size and location of wreckages. Sorting out of obstructions is carried out with machines and mechanisms which do not meet the requirements of these works, that predetermines of carrying out of rescue or restoration works on imperfect scheme , especially on the initial stages, and it increases terms and labour intensiveness of their conduct. Development technological solution is needed for the effective sorting out of destructions of construction objects. Purpose. Development of unification solution on the improvement of technological processes of sorting out of destructions of buildings and constructions. Conclusion. The analysis of experience of works shows on sorting out of the destroyed construction objects, show that they are carried out on imperfect scheme, which do not take into account character of destruction of objects and are based on the use of construction machines which do not meet the requirements of these processes, and lead to considerable resource losses. Developed unified scheme of sorting out of the destroyed construction objects depending on character of their destruction and possibility of line of works, and also with the use of build machines with a multipurpose equipment, provide the increase of efficiency of carrying out of rescue and construction works.

  8. The minimal GUT with inflaton and dark matter unification

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Heng-Yu; Gogoladze, Ilia [University of Delaware, Department of Physics and Astronomy, Bartol Research Institute, Newark, DE (United States); Hu, Shan [Hubei University, Department of Physics, Faculty of Physics and Electronic Sciences, Wuhan (China); Li, Tianjun [Chinese Academy of Sciences, Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Beijing (China); University of Chinese Academy of Sciences, School of Physical Sciences, Beijing (China); Wu, Lina [Chinese Academy of Sciences, Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Beijing (China); University of Electronic Science and Technology of China, School of Physical Electronics, Chengdu (China)

    2018-01-15

    Giving up the solutions to the fine-tuning problems, we propose the non-supersymmetric flipped SU(5) x U(1){sub X} model based on the minimal particle content principle, which can be constructed from the four-dimensional SO(10) models, five-dimensional orbifold SO(10) models, and local F-theory SO(10) models. To achieve gauge coupling unification, we introduce one pair of vector-like fermions, which form a complete SU(5) x U(1){sub X} representation. The proton lifetime is around 5 x 10{sup 35} years, neutrino masses and mixing can be explained via the seesaw mechanism, baryon asymmetry can be generated via leptogenesis, and the vacuum stability problem can be solved as well. In particular, we propose that inflaton and dark matter particles can be unified to a real scalar field with Z{sub 2} symmetry, which is not an axion and does not have the non-minimal coupling to gravity. Such a kind of scenarios can be applied to the generic scalar dark matter models. Also, we find that the vector-like particle corrections to the B{sub s}{sup 0} masses might be about 6.6%, while their corrections to the K{sup 0} and B{sub d}{sup 0} masses are negligible. (orig.)

  9. Electroweak symmetry breaking in supersymmetric gauge-Higgs unification models

    International Nuclear Information System (INIS)

    Choi, Kiwoon; Jeong, Kwang-Sik; Okumura, Ken-ichi; Haba, Naoyuki; Shimizu, Yasuhiro; Yamaguchi, Masahiro

    2004-01-01

    We examine the Higgs mass parameters and electroweak symmetry breaking in supersymmetric orbifold field theories in which the 4-dimensional Higgs fields originate from higher-dimensional gauge supermultiplets. It is noted that such gauge-Higgs unification leads to a specific boundary condition on the Higgs mass parameters at the compactification scale, which is independent of the details of supersymmetry breaking mechanism. With this boundary condition, phenomenologically viable parameter space of the model is severely constrained by the condition of electroweak symmetry breaking for supersymmetry breaking scenarios which can be realized naturally in orbifold field theories. For instance, if it is assumed that the 4-dimensional effective theory is the minimal supersymmetric standard model with supersymmetry breaking parameters induced by the Scherk-Schwarz mechanism, a correct electroweak symmetry breaking can not be achieved for reasonable range of parameters of the model, even when one includes additional contributions to the Higgs mass parameters from the auxiliary component of 4-dimensional conformal compensator. However if there exists a supersymmetry breaking mediated by brane superfields, sizable portion of the parameter space can give a correct electroweak symmetry breaking. (author)

  10. Dark matter as the signal of grand unification

    International Nuclear Information System (INIS)

    Kadastik, Mario; Kannike, Kristjan; Raidal, Martti

    2009-01-01

    We argue that the existence of dark matter (DM) is a possible consequence of grand unification (GUT) symmetry breaking. In GUTs like SO(10), discrete Z 2 matter parity (-1) 3(B-L) survives despite broken B-L, and group theory uniquely determines that the only possible Z 2 -odd matter multiplets belong to representation 16. We construct the minimal nonsupersymmetric SO(10) model containing one scalar 16 for DM and study its predictions below M G . We find that electroweak symmetry breaking occurs radiatively due to DM couplings to the standard model Higgs boson. For thermal relic DM the mass range M DM ∼O(0.1-1) TeV is predicted by model perturbativity up to M G . For M DM ∼O(1) TeV to explain the observed cosmic ray anomalies with DM decays, there exists a lower bound on the spin-independent direct detection cross section within the reach of planned experiments.

  11. Gauge unification, non-local breaking, open strings

    International Nuclear Information System (INIS)

    Trapletti, M.

    2005-01-01

    The issue of non-local GUT symmetry breaking is addressed in the context of open string model building. We study Z N xZ M ' orbifolds with all the GUT-breaking orbifold elements acting freely, as rotations accompanied by translations in the internal space. We consider open strings quantized on these backgrounds, distinguishing whether the translational action is parallel or perpendicular to the D-branes. GUT breaking is impossible in the purely perpendicular case, non-local GUT breaking is instead allowed in the purely parallel case. In the latter, the scale of breaking is set by the compactification moduli, and there are no fixed points with reduced gauge symmetry, where dangerous explicit GUT-breaking terms could be located. We investigate the mixed parallel+perpendicular case in a Z 2 xZ 2 ' example, having also a simplified field theory realization. It is a new S 1 /Z 2 xZ 2 ' orbifold-GUT model, with bulk gauge symmetry SU(5)xSU(5) broken locally to the Standard Model gauge group. In spite of the locality of the GUT symmetry breaking, there is no localized contribution to the running of the coupling constants, and the unification scale is completely set by the length of S 1

  12. The minimal GUT with inflaton and dark matter unification

    Science.gov (United States)

    Chen, Heng-Yu; Gogoladze, Ilia; Hu, Shan; Li, Tianjun; Wu, Lina

    2018-01-01

    Giving up the solutions to the fine-tuning problems, we propose the non-supersymmetric flipped SU(5)× U(1)_X model based on the minimal particle content principle, which can be constructed from the four-dimensional SO(10) models, five-dimensional orbifold SO(10) models, and local F-theory SO(10) models. To achieve gauge coupling unification, we introduce one pair of vector-like fermions, which form a complete SU(5)× U(1)_X representation. The proton lifetime is around 5× 10^{35} years, neutrino masses and mixing can be explained via the seesaw mechanism, baryon asymmetry can be generated via leptogenesis, and the vacuum stability problem can be solved as well. In particular, we propose that inflaton and dark matter particles can be unified to a real scalar field with Z_2 symmetry, which is not an axion and does not have the non-minimal coupling to gravity. Such a kind of scenarios can be applied to the generic scalar dark matter models. Also, we find that the vector-like particle corrections to the B_s^0 masses might be about 6.6%, while their corrections to the K^0 and B_d^0 masses are negligible.

  13. 3C 254: the alignment effect and unification schemes

    Science.gov (United States)

    Bremer, M. N.

    1997-01-01

    3C 254 is a radio-loud quasar at z=0.734. Optical line and continuum emission from the underlying galaxy is clearly extended and aligned with the radio axis; the object shows the so-called `alignment effect' which is often seen in powerful radio galaxies. This is the clearest case yet of the continuum alignment effect in a radio-loud quasar. The object is one of the most lobe-dominated 3C quasars; the significance of the aligned emission in this source is discussed in terms of orientation-based unification schemes for radio-loud quasars and radio galaxies. 3C 254 is a very asymmetric radio source and it is shown that the radio structure on the side with the shortest nucleus-hotspot distance is interacting with the emission-line gas surrounding the quasar. It is also shown that the quasar is surrounded by an overdensity of faint objects, consistent with a cluster or group of galaxies around the object.

  14. SU(8) family unification with boson-fermion balance

    CERN Multimedia

    CERN. Geneva

    2014-01-01

    Grand unification has been intensively investigated for over forty years, and many different approaches have been tried. In this talk I propose a model that involves three ingredients that do not appear in the usual constructions: (1) boson--fermion balance without full supersymmetry, (2) canceling the spin 1/2 fermion gauge anomalies against the anomaly from a gauged spin 3/2 gravitino, and (3) using a scalar field representation with non-zero U(1) generator to break the SU(8) gauge symmetry through a ground state which, before dynamical symmetry breaking, has a periodic U(1) generator structure. The model has a number of promising features: (1) natural incorporation of three families, (2) incorporation of the experimentally viable flipped SU(5) model, (3) a symmetry breaking pathway to the standard model using the scalar field required by boson-fermion balance, together with a stage of most attractive channel dynamical symmetry breaking, without postulating additional Higgs fields, (4) vanishing of bare Yuk...

  15. Evolution of Extragalactic Radio Sources and Quasar/Galaxy Unification

    Science.gov (United States)

    Onah, C. I.; Ubachukwu, A. A.; Odo, F. C.; Onuchukwu, C. C.

    2018-04-01

    We use a large sample of radio sources to investigate the effects of evolution, luminosity selection and radio source orientation in explaining the apparent deviation of observed angular size - redshift (θ - z) relation of extragalactic radio sources (EGRSs) from the standard model. We have fitted the observed θ - z data with standard cosmological models based on a flat universe (Ω0 = 1). The size evolution of EGRSs has been described as luminosity, temporal and orientation-dependent in the form DP,z,Φ ≍ P±q(1 + z)-m sinΦ, with q=0.3, Φ=59°, m=-0.26 for radio galaxies and q=-0.5, Φ=33°, m=3.1 for radio quasars respectively. Critical points of luminosity, logPcrit=26.33 WHz-1 and logDc=2.51 kpc (316.23 kpc) of the present sample of radio sources were also observed. All the results were found to be consistent with the popular quasar/galaxy unification scheme.

  16. Probing the design of grand unification through conservation laws

    International Nuclear Information System (INIS)

    Pati, J.C.

    1981-01-01

    The purpose of this talk is to note a few special consequences of gauging ''maximal'' quark-lepton symmetries such as SO(16), which is the maximal symmetry for a single family of fermions. Within these symmetries, violations for B, L and F are spontaneous rather than explicit. Furthermore these symmetries as a rule permit intermediate mass scales approx.(10 3 -10 6 GeV) and (10 8 -10 11 GeV) filling the so-called grand plateau between 10 2 and 10 15 GeV. It has been shown in earlier papers that within these symmetries proton may decay via four alternative models: i.e. proton→one or three leptons or antileptons plus mesons; some of which can coexist. It is now observed that even n-n-bar oscillations can coexist with (B-L) conserving proton-decays of the type p→e + π 0 etc. without posing any conflict with the cosmological generation of baryon-excess; both these processes can possess measurable strengths so as to be amenable to forthcoming searches. Search for alternative decay modes of proton and n-n-bar oscillations, even as processes in second and third generation experiments, would provide valuable information on the question of intermediate mass-scales and thereby on the design of grand unification

  17. The Human Papillomavirus E6 PDZ Binding Motif: From Life Cycle to Malignancy

    Directory of Open Access Journals (Sweden)

    Ketaki Ganti

    2015-07-01

    Full Text Available Cancer-causing HPV E6 oncoproteins are characterized by the presence of a PDZ binding motif (PBM at their extreme carboxy terminus. It was long thought that this region of E6 had a sole function to confer interaction with a defined set of cellular substrates. However, more recent studies have shown that the E6 PBM has a complex pattern of regulation, whereby phosphorylation within the PBM can regulate interaction with two classes of cellular proteins: those containing PDZ domains and the members of the 14-3-3 family of proteins. In this review, we explore the roles that the PBM and its ligands play in the virus life cycle, and subsequently how these can inadvertently contribute towards the development of malignancy. We also explore how subtle alterations in cellular signal transduction pathways might result in aberrant E6 phosphorylation, which in turn might contribute towards disease progression.

  18. Modernization and unification: Strategic goals for NASA STI program

    Science.gov (United States)

    Blados, W.; Cotter, Gladys A.

    1993-01-01

    Information is increasingly becoming a strategic resource in all societies and economies. The NASA Scientific and Technical Information (STI) Program has initiated a modernization program to address the strategic importance and changing characteristics of information. This modernization effort applies new technology to current processes to provide near-term benefits to the user. At the same time, we are developing a long-term modernization strategy designed to transition the program to a multimedia, global 'library without walls.' Notwithstanding this modernization program, it is recognized that no one information center can hope to collect all the relevant data. We see information and information systems changing and becoming more international in scope. We are finding that many nations are expending resources on national systems which duplicate each other. At the same time that this duplication exists, many useful sources of aerospace information are not being collected because of resource limitations. If nations cooperate to develop an international aerospace information system, resources can be used efficiently to cover expanded sources of information. We must consider forming a coalition to collect and provide access to disparate, multidisciplinary sources of information, and to develop standardized tools for documenting and manipulating this data and information. In view of recent technological developments in information science and technology, as well as the reality of scarce resources in all nations, it is time to explore the mutually beneficial possibilities offered by cooperation and international resource sharing. International resources need to be mobilized in a coordinated manner to move us towards this goal. This paper reviews the NASA modernization program and raises for consideration new possibilities for unification of the various aerospace database efforts toward a cooperative international aerospace database initiative that can optimize the cost

  19. CHAIRMEN'S PREFACE AND EDITORS' NOTE: Unification of Fundamental Interactions

    Science.gov (United States)

    Brink, Lars; Nilsson, Jan S.; Salomonson, Per; Skagerstam, Bo-Sture

    1987-01-01

    Chairmen's PrefaceIn 1984 we obtained a grant from the Nobel Foundation to organize a Nobel Symposium on "Unification of the Fundamental Interactions". In our proposal which we submitted in the fall of 1983 we stated that we wanted to cover the various attempts to unification such as GUT'S, supergravity, Kaluza-Klein theories and superstrings. What has happened in particle physics since then is already history. With the realization that certain superstring theories could be anomaly free, it became clear that these models could encompass earlier attempts to unification as well as solving the fundamental problem of quantum gravity. The excitement that some of us had felt for some time now spread through most of the particle physics community and this excitement certainly was evident during the Symposium. With the international advisory committee we originally chose a list of around 30 invitees which could best represent the various subjects listed above. When it came to the final planning of the programme essentially all talks dealt with superstrings! We were very fortunate that almost all of the invitees managed to come to the Symposium. From the western world only three were unable to participate, André Neveu, Steven Weinberg and Bruno Zumino. We certainly missed them during the meeting. We were particularly happy that Stephen Hawking managed to take part actively. Our real problem was to get participants from the Soviet Union. Out of eight invitations only one came through. We were very happy to have Renata Kallosh, who really did her utmost to enlighten us about not only her own work but also about recent progress in the USSR, However, we were very sorry that in spite of all our letters, telegrammes and endless attempts to get telephone calls through and despite the good relations between the Swedish and Soviet Academies of Sciences we had to miss Ludwig Faddeev, Valodja Gribov, Andrej Linde, Victor Ogievetsky, Sasha Polyakov, Misha Shifman and Arkadij

  20. Mathematical Modeling of E6-p53 interactions in Cervical Cancer

    Science.gov (United States)

    Khattak, Faryal; Haseeb, Muhammad; Fazal, Sahar; Bhatti, A I; Ullah, Mukhtar

    2017-04-01

    Background: Cervical cancer is the third most common cancer in women throughout the world. The human papillomavirus (HPV) E6 viral protein plays an essential role in proteasomal degradation of the cancer suppressant protein p53. As a result, p53 negative regulation and apoptosis relevant activities are abrogated, facilitating development of cervical cancer. Methods: A mathematical model of E6-p53 interactions was developed using mathematical laws. In-silico simulations were carried out on CellDesigner and as a test case the small molecule drug RITA was considered for its ability to rescue the functions of tumor suppressor p53 by inhibiting E6 mediated proteasomal degradation. Results: Using a computational model we scrutinized how p53 responds to RITA, and chemical reactions of this small molecule drug were incorporated to perceive the full effects. The evolved strategy allowed the p53 response and rescue of its tumor suppressor function to be delineated, RITA being found to block p53 interactions with E6 associated proteins. Conclusion: We could develop a model of E6-p53 interactions with incorporation of actions of the small molecule drug RITA. Suppression of E6 associated proteins by RITA induces accumulation of tumor suppressant p53. Using CellDesigner to encode the model ensured that it can be easily modified and extended as more data become available. This strategy should play an effective role in the development of therapies against cancer. Creative Commons Attribution License

  1. E6-associated transcription patterns in human papilloma virus 16-positive cervical tissues.

    Science.gov (United States)

    Lin, Kezhi; Lu, Xulian; Chen, Jun; Zou, Ruanmin; Zhang, Lifang; Xue, Xiangyang

    2015-01-01

    The change in transcription pattern induced by post-transcriptional RNA splicing is an important mechanism in the regulation of the early gene expression of human papilloma virus (HPV). The present study was conducted to establish a method to specifically amplify HPV-16 E6-associated transcripts. The E6-related transcripts from 63 HPV-16-positive cervical tumor tissue samples were amplified, consisting of eight cases of low-risk intraepithelial lesions, 38 cases of high-risk intraepithelial lesions and 17 cases of cervical cancer (CxCa). The appropriate amplified segments were recovered following agarose gel electrophoresis, and subjected to further sequencing and sequence alignment analysis. Six groups of E6 transcription patterns were identified from HPV-16-positive cervical tumor tissue, including five newly-discovered transcripts. Different HPV-16 E6-associated transcription patterns were detected during the development of CxCa. Over the course of the progression of the low-grade squamous intraepithelial lesions to CxCa, the specific HPV-16 E6-associated transcription patterns and the dominant transcripts were all different. As indicated by this study, the transcription pattern of the E6 early gene of HPV-16 was closely associated with the stages of cervical carcinogenesis, and may also be involved in the development of CxCa.

  2. Telomerase activation by the E6 gene product of human papillomavirus type 16.

    Science.gov (United States)

    Klingelhutz, A J; Foster, S A; McDougall, J K

    1996-03-07

    Activation of telomerase, a ribonucleoprotein complex that synthesizes telomere repeat sequences, is linked to cell immortalization and is characteristic of most cell lines and tumours. Here we show that expression of the human papillomavirus type 16 (HPV-16) E6 protein activates telomerase in early-passage human keratinocytes and mammary epithelial cells. This activation was observed in cells pre-crisis, that is, before they became immortal, and occurred within one passage of retroviral infection with vectors expressing HPV-16 E6. Studies using HPV-16 E6 mutants showed that there was no correlation between the ability of the mutants to activate telomerase and their ability to target p53 for degradation, suggesting that telomerase activation by HPV-16 E6 is p53 independent. Keratinocytes expressing wild-type HPV-16 E6 have an extended lifespan, but do not become immortal, indicating that telomerase activation and E6-mediate degradation of p53 are insufficient for their immortalization. These results show that telomerase activation is an intrinsic, but insufficient, component of transformation by HPV.

  3. Exploring the Use of Enterprise Content Management Systems in Unification Types of Organizations

    Directory of Open Access Journals (Sweden)

    Arshad Noreen Izza

    2014-03-01

    Full Text Available The aim of this paper is to better understand how highly standardized and integrated businesses known as unification types of organizations use Enterprise Content Management Systems (ECMS to support their business processes. Multiple case study approach was used to study the ways two unification organizations use their ECMS in their daily work practices. Arising from these case studies are insights into the differing ways in which ECMS is used to support businesses. Based on the comparisons of the two cases, this study proposed that unification organizations may use ECMS in four ways, for: (1 collaboration, (2 information sharing that supports a standardized process structure, (3 building custom workflows that support integrated and standardized processes, and (4 providing links and access to information systems. These findings may guide organizations that are highly standardized and integrated in fashion, to achieve their intended ECMS-use, to understand reasons for ECMS failures and underutilization and to exploit technologies investments.

  4. Model-based object classification using unification grammars and abstract representations

    Science.gov (United States)

    Liburdy, Kathleen A.; Schalkoff, Robert J.

    1993-04-01

    The design and implementation of a high level computer vision system which performs object classification is described. General object labelling and functional analysis require models of classes which display a wide range of geometric variations. A large representational gap exists between abstract criteria such as `graspable' and current geometric image descriptions. The vision system developed and described in this work addresses this problem and implements solutions based on a fusion of semantics, unification, and formal language theory. Object models are represented using unification grammars, which provide a framework for the integration of structure and semantics. A methodology for the derivation of symbolic image descriptions capable of interacting with the grammar-based models is described and implemented. A unification-based parser developed for this system achieves object classification by determining if the symbolic image description can be unified with the abstract criteria of an object model. Future research directions are indicated.

  5. Infrared fixed point solution for the top quark mass and unification of couplings in the MSSM

    International Nuclear Information System (INIS)

    Bardeen, W.A.; Carena, M.; Pokorski, S.; Wagner, C.E.M.

    1993-08-01

    We analyze the implications of the infrared quasi fixed point solution for the top quark mass in the Minimal Supersymmetric Standard Model. This solution could explain in a natural way the relatively large value of the top quark mass and, if confirmed experimentally, may be suggestive of the onset of nonperturbative physics at very high energy scales. In the framework of grand unification, the expected bottom quark -- tau lepton Yukawa coupling unification is very sensitive to the fixed point structure of the top quark mass. For the presently allowed values of the electroweak parameters and the bottom quark mass, the Yukawa coupling unification implies that the top quark mass must be within ten percent of its fixed point values

  6. Gauge unification of basic forces particularly of gravitation with strong interactions

    International Nuclear Information System (INIS)

    Salam, A.

    1977-01-01

    Corresponding to the two known types of gauge theories, Yang-Mills with spin-one mediating particles and Einstein Weyl with spin-two mediating particles, it is speculated that two distinct gauge unifications of the basic forces appear to be taking place. One is the familiar Yang-Mills unification of weak and electromagnetic forces with the strong. The second is the less familiar gauge unification of gravitation with spin-two tensor-dominated aspects of strong interactions. It is proposed that there are strongly interacting spin-two strong gravitons obeying Einstein's equations, and their existence gives a clue to an understanding of the (partial) confinement of quarks, as well as of the concept of hadronic temperature, through the use of Schwarzschild de-Sitter-like partially confining solitonic solutions of the strong gravity Einstein equation

  7. Study of theory and phenomenology of some classes of family symmetry and unification models

    International Nuclear Information System (INIS)

    Kane, Gordon L.; King, Steve F.; Peddie, Iain N.R.; Velasco-Sevilla, Liliana

    2005-01-01

    We review and compare theoretically and phenomenologically a number of possible family symmetries, which when combined with unification, could be important in explaining quark, lepton and neutrino masses and mixings, providing new results in several cases. Theoretical possibilities include abelian or non-abelian, symmetric or non symmetric Yukawa matrices, Grand Unification or not. Our main focus is on anomaly-free U(1) family symmetry combined with SU(5) unification, although we also discuss other possibilities. We provide a detailed phenomenological fit of the fermion masses and mixings for several examples, and discuss the supersymmetric flavour issues in such theories, including a detailed analysis of lepton flavour violation. We show that it is not possible to quantitatively and decisively discriminate between these different theoretical possibilities at the present time

  8. Ultrasensitive quantitation of human papillomavirus type 16 E6 oncogene sequences by nested real time PCR

    Directory of Open Access Journals (Sweden)

    López-Revilla Rubén

    2010-05-01

    Full Text Available Abstract Background We have developed an ultrasensitive method based on conventional PCR preamplification followed by nested amplification through real time PCR (qPCR in the presence of the DNA intercalating agent EvaGreen. Results Amplification mixtures calibrated with a known number of pHV101 copies carrying a 645 base pair (bp-long insert of the human papillomavirus type 16 (HPV16 E6 oncogene were used to generate the E6-1 amplicon of 645 bp by conventional PCR and then the E6-2 amplicon of 237 bp by nested qPCR. Direct and nested qPCR mixtures for E6-2 amplification corresponding to 2.5 × 102-2.5 × 106 initial pHV101 copies had threshold cycle (Ct values in the ranges of 18.7-29.0 and 10.0-25.0, respectively. The Ct of qPCR mixtures prepared with 1/50 volumes of preamplified mixtures containing 50 ng of DNA of the SiHa cell line (derived from an invasive cervical cancer with one HPV16 genome per cell was 19.9. Thermal fluorescence extinction profiles of E6-2 amplicons generated from pHV101 and SiHa DNA were identical, with a peak at 85.5°C. Conclusions Our method based on conventional preamplification for 15 cycles increased 10,750 times the sensitivity of nested qPCR for the quantitation of the E6 viral oncogene and confirmed that the SiHa cell line contains one E6-HPV16 copy per cell.

  9. Relict gravitational waves in the expanding Universe model and the grand unification scale

    International Nuclear Information System (INIS)

    Veryskin, A.V.; Rubakov, V.A.; Sazhin, M.V.

    1983-01-01

    The amplification of the vacuum fluctuations of the metric in the model of the expanding Universe was considered. The spectrum of the relict gravitational waves was chosen to be independent from the details of an evolution of the Universe after the phase transition. It is shown that the expanding Universe scenario is compatible with the experimental data on the anisotropy of the microwave background only if the vacuum energy density of the symmetric phase is much less than the Planck one. The theories of grand unification with not large values of the unification scale (one and a half order less than the Planck mass) are preferable from the point of view of cosmology

  10. Expressions of HPV 16-E6 in Esophageal Carcinoma and its Clinical Significance

    Directory of Open Access Journals (Sweden)

    Xing Zhao

    2015-07-01

    Full Text Available Background and Objective: The role of (Human Papilloma Virus HPV in cancer of certain anatomical location, such as cervix, has been widely recognized. The present study was conducted to explore the association between HPV 16-E6 protein and esophageal squamous cell carcinoma. Methods: SP immunohistochemical method was used to examine the expression of HPV 16-E6 in 50 cases of esophageal squamous cell carcinoma, 10 cases of normal esophageal squamous cell and 10 cases of adjacent tissue. Results: The expression of HPV 16-E6 was significantly higher in esophageal carcinoma than in normal esophageal mucosa and in adjacent tissue. The expressions of HPV 16-E6 had significant correlation with invasive depth (P<0.05, but not with patient age, lymph node metastasis, tumor size (P>0.05. Conclusion: HPV 16-E6 can promote the growth and metastasis of esophageal squamous cell carcinoma and can be a prognostic factor of esophageal squamous cell carcinoma.DOI: http://dx.doi.org/10.3126/jcmsn.v10i4.12970 JCMS Nepal 2014; 10(4:1-5 

  11. Particle physics models of inflation in supergravity and grand unification

    International Nuclear Information System (INIS)

    Kostka, Philipp Manuel

    2010-01-01

    magnetic monopoles at the end of the stage of inflation can be avoided. Finally, we sketch how in tribrid inflation models the concepts discussed in the two parts can be combined to realize inflation via Heisenberg symmetry in local supersymmetric SO(10) grand unification. (orig.)

  12. Polarimetry and Unification of Low-Redshift Radio Galaxies

    International Nuclear Information System (INIS)

    Cohen, Marshall H.; Ogle, Patrick M.; Tran, Hien D.; Goodrich, Robert W.; Miller, Joseph S.

    1999-01-01

    We have made high-quality measurements of the polarization spectra of 13 FR II radio galaxies and taken polarization images for 11 of these with the Keck telescopes. Seven of the eight narrow-line radio galaxies (NLRGs) are polarized, and six of the seven show prominent broad Balmer lines in polarized light. The broad lines are also weakly visible in total flux. Some of the NLRGs show bipolar regions with roughly circumferential polarization vectors, revealing a large reflection nebula illuminated by a central source. Our observations powerfully support the hidden quasar hypothesis for some NLRGs. According to this hypothesis, the continuum and broad lines are blocked by a dusty molecular torus, but can be seen by reflected, hence polarized, light. Classification as a NLRG, a broad-line radio galaxy (BLRG), or a quasar therefore depends on orientation. However, not all objects fit into this unification scheme. Our sample is biased toward objects known in advance to be polarized, but the combination of our results with the 1996 findings of Hill, Goodrich, and DePoy show that at least six out of a complete, volume and flux-limited sample of nine FR II NLRGs have broad lines, seen either in polarization or Pα.The BLRGs in our sample range from 3C 382, which has a quasar-like spectrum, to the highly reddened IRAS source FSC 2217+259. This reddening sequence suggests a continuous transition from unobscured quasar to reddened BLRG to NLRG. Apparently the obscuring torus does not have a distinct edge. The BLRGs have polarization images that are consistent with a point source broadened by seeing and diluted by starlight. We do not detect extended nebular or scattered emission, perhaps because it is swamped by the nuclear source. Our starlight-corrected BLRG spectra can be explained with a two-component model: a quasar viewed through dust and quasar light scattered by dust. The direct flux is more reddened than the scattered flux, causing the polarization to rise steeply

  13. Polarimetry and Unification of Low-Redshift Radio Galaxies

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Marshall H.; Ogle, Patrick M.; Tran, Hien D.; Goodrich, Robert W.; Miller, Joseph S.

    1999-11-01

    We have made high-quality measurements of the polarization spectra of 13 FR II radio galaxies and taken polarization images for 11 of these with the Keck telescopes. Seven of the eight narrow-line radio galaxies (NLRGs) are polarized, and six of the seven show prominent broad Balmer lines in polarized light. The broad lines are also weakly visible in total flux. Some of the NLRGs show bipolar regions with roughly circumferential polarization vectors, revealing a large reflection nebula illuminated by a central source. Our observations powerfully support the hidden quasar hypothesis for some NLRGs. According to this hypothesis, the continuum and broad lines are blocked by a dusty molecular torus, but can be seen by reflected, hence polarized, light. Classification as a NLRG, a broad-line radio galaxy (BLRG), or a quasar therefore depends on orientation. However, not all objects fit into this unification scheme. Our sample is biased toward objects known in advance to be polarized, but the combination of our results with the 1996 findings of Hill, Goodrich, and DePoy show that at least six out of a complete, volume and flux-limited sample of nine FR II NLRGs have broad lines, seen either in polarization or P{alpha}.The BLRGs in our sample range from 3C 382, which has a quasar-like spectrum, to the highly reddened IRAS source FSC 2217+259. This reddening sequence suggests a continuous transition from unobscured quasar to reddened BLRG to NLRG. Apparently the obscuring torus does not have a distinct edge. The BLRGs have polarization images that are consistent with a point source broadened by seeing and diluted by starlight. We do not detect extended nebular or scattered emission, perhaps because it is swamped by the nuclear source. Our starlight-corrected BLRG spectra can be explained with a two-component model: a quasar viewed through dust and quasar light scattered by dust. The direct flux is more reddened than the scattered flux, causing the polarization to rise

  14. An Adynamical, Graphical Approach to Quantum Gravity and Unification

    Science.gov (United States)

    Stuckey, W. M.; Silberstein, Michael; McDevitt, Timothy

    We use graphical field gradients in an adynamical, background independent fashion to propose a new approach to quantum gravity (QG) and unification. Our proposed reconciliation of general relativity (GR) and quantum field theory (QFT) is based on a modification of their graphical instantiations, i.e. Regge calculus and lattice gauge theory (LGT), respectively, which we assume are fundamental to their continuum counterparts. Accordingly, the fundamental structure is a graphical amalgam of space, time, and sources (in parlance of QFT) called a "space-time source element". These are fundamental elements of space, time, and sources, not source elements in space and time. The transition amplitude for a space-time source element is computed using a path integral with discrete graphical action. The action for a space-time source element is constructed from a difference matrix K and source vector J on the graph, as in lattice gauge theory. K is constructed from graphical field gradients so that it contains a non-trivial null space and J is then restricted to the row space of K, so that it is divergence-free and represents a conserved exchange of energy-momentum. This construct of K and J represents an adynamical global constraint (AGC) between sources, the space-time metric, and the energy-momentum content of the element, rather than a dynamical law for time-evolved entities. In this view, one manifestation of quantum gravity becomes evident when, for example, a single space-time source element spans adjoining simplices of the Regge calculus graph. Thus, energy conservation for the space-time source element includes contributions to the deficit angles between simplices. This idea is used to correct proper distance in the Einstein-de Sitter (EdS) cosmology model yielding a fit of the Union2 Compilation supernova data that matches ΛCDM without having to invoke accelerating expansion or dark energy. A similar modification to LGT results in an adynamical account of quantum

  15. Particle physics models of inflation in supergravity and grand unification

    Energy Technology Data Exchange (ETDEWEB)

    Kostka, Philipp Manuel

    2010-12-03

    production of stable magnetic monopoles at the end of the stage of inflation can be avoided. Finally, we sketch how in tribrid inflation models the concepts discussed in the two parts can be combined to realize inflation via Heisenberg symmetry in local supersymmetric SO(10) grand unification. (orig.)

  16. Hepatitis C virus induces E6AP-dependent degradation of the retinoblastoma protein.

    Directory of Open Access Journals (Sweden)

    Tsubasa Munakata

    2007-09-01

    Full Text Available Hepatitis C virus (HCV is a positive-strand RNA virus that frequently causes persistent infections and is uniquely associated with the development of hepatocellular carcinoma. While the mechanism(s by which the virus promotes cancer are poorly defined, previous studies indicate that the HCV RNA-dependent RNA polymerase, nonstructural protein 5B (NS5B, forms a complex with the retinoblastoma tumor suppressor protein (pRb, targeting it for degradation, activating E2F-responsive promoters, and stimulating cellular proliferation. Here, we describe the mechanism underlying pRb regulation by HCV and its relevance to HCV infection. We show that the abundance of pRb is strongly downregulated, and its normal nuclear localization altered to include a major cytoplasmic component, following infection of cultured hepatoma cells with either genotype 1a or 2a HCV. We further demonstrate that this is due to NS5B-dependent ubiquitination of pRb and its subsequent degradation via the proteasome. The NS5B-dependent ubiquitination of pRb requires the ubiquitin ligase activity of E6-associated protein (E6AP, as pRb abundance was restored by siRNA knockdown of E6AP or overexpression of a dominant-negative E6AP mutant in cells containing HCV RNA replicons. E6AP also forms a complex with pRb in an NS5B-dependent manner. These findings suggest a novel mechanism for the regulation of pRb in which the HCV NS5B protein traps pRb in the cytoplasm, and subsequently recruits E6AP to this complex in a process that leads to the ubiquitination of pRb. The disruption of pRb/E2F regulatory pathways in cells infected with HCV is likely to promote hepatocellular proliferation and chromosomal instability, factors important for the development of liver cancer.

  17. New World hantaviruses activate IFNlambda production in type I IFN-deficient vero E6 cells.

    Directory of Open Access Journals (Sweden)

    Joseph Prescott

    Full Text Available Hantaviruses indigenous to the New World are the etiologic agents of hantavirus cardiopulmonary syndrome (HCPS. These viruses induce a strong interferon-stimulated gene (ISG response in human endothelial cells. African green monkey-derived Vero E6 cells are used to propagate hantaviruses as well as many other viruses. The utility of the Vero E6 cell line for virus production is thought to owe to their lack of genes encoding type I interferons (IFN, rendering them unable to mount an efficient innate immune response to virus infection. Interferon lambda, a more recently characterized type III IFN, is transcriptionally controlled much like the type I IFNs, and activates the innate immune system in a similar manner.We show that Vero E6 cells respond to hantavirus infection by secreting abundant IFNlambda. Three New World hantaviruses were similarly able to induce IFNlambda expression in this cell line. The IFNlambda contained within virus preparations generated with Vero E6 cells independently activates ISGs when used to infect several non-endothelial cell lines, whereas innate immune responses by endothelial cells are specifically due to viral infection. We show further that Sin Nombre virus replicates to high titer in human hepatoma cells (Huh7 without inducing ISGs.Herein we report that Vero E6 cells respond to viral infection with a highly active antiviral response, including secretion of abundant IFNlambda. This cytokine is biologically active, and when contained within viral preparations and presented to human epithelioid cell lines, results in the robust activation of innate immune responses. We also show that both Huh7 and A549 cell lines do not respond to hantavirus infection, confirming that the cytoplasmic RNA helicase pathways possessed by these cells are not involved in hantavirus recognition. We demonstrate that Vero E6 actively respond to virus infection and inhibiting IFNlambda production in these cells might increase their utility

  18. Signatures of exotic fermions and other new ''low-energy'' phenomena in superstring E6

    International Nuclear Information System (INIS)

    Rosner, J.L.

    1986-03-01

    Superstring theories have drawn renewed attention to the exceptional group E 6 as a grand unified theory. We discuss the extra U(1) symmetries (beyond that in the standard SU(3) x SU(2) x U(1) model) that arise when E 6 is broken in such theories. These extra U(1)'s must lead to at least one extra neutral gauge boson, called Z', for which we give mass limits and branching ratios. Neutral current effects of this Z' and its direct production are discussed briefly. Finally, some signatures are noted of exotic fermions to which Z' can decay

  19. Building a Larger Tent for Public Health: Implications of the SOPHE-AAHE Unification

    Science.gov (United States)

    Goodman, Robert Mark

    2013-01-01

    The unification of the American Association for Health Education (AAHE) and the Society for Public Health Education (SOPHE) generates a long-desired synergy, a ramping up of our leadership influence in promoting health. It also serves as an ongoing opportunity to reflect on how we synergize the distinct philosophic, scientific, and practical…

  20. Do Unification Models Explain the X-ray Properties of Radio Sources?

    NARCIS (Netherlands)

    Wilkes, Belinda J.; Kuraszkiewicz, J.; Haas, M.; Barthel, P.; Willner, S. P.; Leipski, C.; Worrall, D.; Birkinshaw, M.; Antonucci, R. R.; Ashby, M.; Chini, R.; Fazio, G. G.; Lawrence, C. R.; Ogle, P. M.; Schulz, B.

    Chandra observations of a complete, flux-limited sample of 38 high-redshift (1 Unification models and lead to estimates of the covering

  1. Unification of Frequency direction Pilot-symbol Aided Channel Estimation (PACE) for OFDM

    DEFF Research Database (Denmark)

    Rom, Christian; Manchón, Carles Navarro; Deneire, Luc

    2007-01-01

    their specificities, namely the presence of virtual subcarriers and non-sample-spaced channels. To ease this choice, we propose a unified presentation of estimators encompassing most of the algorithms that can be found in literature, which only differ by the assumptions made on the channel. This unification leads...

  2. The unification of powerful radio-loud AGN: the multi-wavelength balance

    NARCIS (Netherlands)

    Podigachoski, Pece; Barthel, Peter; Haas, Martin; Leipski, Christian; Wilkes, Belinda; Rocca-Volmerange, Brigitte; Drouart, Guillaume

    2016-01-01

    Powerful radio-loud AGN, by virtue of their optically-thin low-frequency radio emission, represent unique targets in orientation-based unification studies, and in searches for orientation indicators and orientation invariants. Central in these efforts is the landmark Third Cambridge Catalog of Radio

  3. An approach to gauge hierarchy in the minimal SU(5) model of grand unification

    International Nuclear Information System (INIS)

    Ghose, P.

    1982-08-01

    It is shown that if all mass generation through spontaneous symmetry breaking is predominantly caused by scalar loops in the minimal SU(5) model of grand unification, it is possible to have an arbitrarily large gauge hierarchy msub(x) >> msub(w) with all Higgs bosons superheavy. No fine tuning is necessary in every order. (author)

  4. Europe '92: Consequences of the European Unification for Cultural Federalism in the Federal Republic of Germany.

    Science.gov (United States)

    Berggreen, Ingeborg

    1990-01-01

    Discusses consequences of European unification in the Federal Republic of Germany. Focuses on the relationships between the European Community, the federal government of Germany, and the German states. Suggests that the German states are aware of their responsibility to give education and culture a European dimension. (NL)

  5. 76 FR 15209 - 150th Anniversary of the Unification of Italy, 2011

    Science.gov (United States)

    2011-03-21

    ... fighting for the preservation of our own Union, Giuseppe Garibaldi's campaign for the unification of Italy... millions of American women and men of Italian descent who strengthen and enrich our Nation. Italy and the... thousand eleven, and of the Independence of the United States of America the two hundred and thirty-fifth...

  6. Occupational Analysis Products: Operations Management- AFSC 3E6X1 (CD-ROM)

    Science.gov (United States)

    computer laser optical disc (CD-ROM); 4 3/4 in.; 23.4 MB. SYSTEMS DETAIL NOTE: ABSTRACT: This is a report of an occupational survey of the Operations ... Management (AFSC 3E6X1, OSSN 2560, Feb 04) career ladder, conducted by the Occupational Analysis Flight, AFOMS. The OSR reports the findings of current

  7. Production of recombinant proteins GST L1, E6 and E7 tag HPV 16 ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-02-04

    Feb 4, 2009 ... targeting the viral oncoproteins E6 and E7 are markers for HPV-associated ... Luminex XYP plate handler, Luminex SD sheath fluid delivery system, a Pentium 4 .... expression mediated by a potato virus X derived vector of the E7 protein .... inflammation, and antioxidant nutrients – assessing their roles as.

  8. Superstring motivated gauge models based on a rank six subgroup of E6

    International Nuclear Information System (INIS)

    Lazarides, G.; Panagiotakopoulos, C.; Shafi, Q.

    1987-01-01

    We discuss gauge models based on a superstring motivated rank six subgroup of E 6 . Lepton number is an accidental unbroken symmetry of the models which leads to an essential stable proton. One of the neutral gauge bosons couples to B-L and may have mass below a TeV. (orig.)

  9. Detection of E6/E7 HPV oncogene transcripts as biomarker of cervical intaepithelial displasia

    Directory of Open Access Journals (Sweden)

    Mauro Carcheri

    2009-09-01

    Full Text Available It is widely accepted that only persistent infection with high risk types of Human Papillomavirus (HPV HR is a significant risk factor for the development of an invasive squamous cervical cancer. The overexpression of viral oncogenes E6/E7 of HPV is considered a necessary process for incurring in a malignant phenotype.A HPV infection can be identified by detection of HPV DNA in biological samples, but the DNAbased tests cannot delineate between transient or persistent and potentially transforming infection. Instead there is many evidence to suggest that detection of HPV gene expression may constitute a more specific approach to highlight a clinically significant infection. Especially seems that the detection of E6/E7 transcripts can be usefully used for identify the women with a persistent HPV infection that will can induce a future cervical cancer. The aim of our study is to investigate if the detection of oncogenic viral gene activity by detecting transcripts of the E6 and E7 genes can be most usefull of HPV-DNA test in the triage of ASCUS or low grade cervical lesions. Our results confirm that HPV E6/E7 mRNA test can be considered a promising method to stratify HPV positive women for risk of future high-grade cervical lesions or cervical intaepithelial neoplasia.

  10. Production of recombinant proteins GST L1, E6 and E7 tag HPV 16 ...

    African Journals Online (AJOL)

    In the present work recombinant proteins were produced for used in LUMINEX in order to undergo serological study of Tunisian female population. HPV types 16 L1, E6 and E7 sequences fused to their 3'-end to a sequence encoding the terminal undecapeptide of the SV40 large T-antigen (tag) were isolated from plasmids ...

  11. Gauge-Higgs unification with broken flavour symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Olschewsky, M.

    2007-05-15

    We study a five-dimensional Gauge-Higgs unification model on the orbifold S{sup 1}/Z{sub 2} based on the extended standard model (SM) gauge group SU(2){sub L} x U(1){sub Y} x SO(3){sub F}. The group SO(3){sub F} is treated as a chiral gauged flavour symmetry. Electroweak-, flavour- and Higgs interactions are unified in one single gauge group SU(7). The unified gauge group SU(7) is broken down to SU(2){sub L} x U(1){sub Y} x SO(3){sub F} by orbifolding and imposing Dirichlet and Neumann boundary conditions. The compactification scale of the theory is O(1) TeV. Furthermore, the orbifold S{sup 1}/Z{sub 2} is put on a lattice. This setting gives a well-defined staring point for renormalisation group (RG) transformations. As a result of the RG-flow, the bulk is integrated out and the extra dimension will consist of only two points: the orbifold fixed points. The model obtained this way is called an effective bilayered transverse lattice model. Parallel transporters (PT) in the extra dimension become nonunitary as a result of the blockspin transformations. In addition, a Higgs potential V({phi}) emerges naturally. The PTs can be written as a product e{sup A{sub y}}e{sup {eta}}e{sup A{sub y}} of unitary factors e{sup A{sub y}} and a selfadjoint factor e{sup {eta}}. The reduction 48 {yields} 35 + 6 + anti 6 + 1 of the adjoint representation of SU(7) with respect to SU(6) contains SU(2){sub L} x U(1){sub Y} x SO(3){sub F} leads to three SU(2){sub L} Higgs doublets: one for the first, one for the second and one for the third generation. Their zero modes serve as a substitute for the SM Higgs. When the extended SM gauge group SU(2){sub L} x U(1){sub Y} x SO(3){sub F} is spontaneously broken down to U(1){sub em}, an exponential gauge boson mass splitting occurs naturally. At a first step SU(2){sub L} x U(1){sub Y} x SO(3){sub F} is broken to SU(2){sub L} x U(1){sub Y} by VEVs for the selfadjoint factor e{sup {eta}}. This breaking leads to masses of flavour changing SO(3){sub F

  12. Gauge-Higgs unification with broken flavour symmetry

    International Nuclear Information System (INIS)

    Olschewsky, M.

    2007-05-01

    We study a five-dimensional Gauge-Higgs unification model on the orbifold S 1 /Z 2 based on the extended standard model (SM) gauge group SU(2) L x U(1) Y x SO(3) F . The group SO(3) F is treated as a chiral gauged flavour symmetry. Electroweak-, flavour- and Higgs interactions are unified in one single gauge group SU(7). The unified gauge group SU(7) is broken down to SU(2) L x U(1) Y x SO(3) F by orbifolding and imposing Dirichlet and Neumann boundary conditions. The compactification scale of the theory is O(1) TeV. Furthermore, the orbifold S 1 /Z 2 is put on a lattice. This setting gives a well-defined staring point for renormalisation group (RG) transformations. As a result of the RG-flow, the bulk is integrated out and the extra dimension will consist of only two points: the orbifold fixed points. The model obtained this way is called an effective bilayered transverse lattice model. Parallel transporters (PT) in the extra dimension become nonunitary as a result of the blockspin transformations. In addition, a Higgs potential V(Φ) emerges naturally. The PTs can be written as a product e A y e η e A y of unitary factors e A y and a selfadjoint factor e η . The reduction 48 → 35 + 6 + anti 6 + 1 of the adjoint representation of SU(7) with respect to SU(6) contains SU(2) L x U(1) Y x SO(3) F leads to three SU(2) L Higgs doublets: one for the first, one for the second and one for the third generation. Their zero modes serve as a substitute for the SM Higgs. When the extended SM gauge group SU(2) L x U(1) Y x SO(3) F is spontaneously broken down to U(1) em , an exponential gauge boson mass splitting occurs naturally. At a first step SU(2) L x U(1) Y x SO(3) F is broken to SU(2) L x U(1) Y by VEVs for the selfadjoint factor e η . This breaking leads to masses of flavour changing SO(3) F gauge bosons much above the compactification scale. Such a behaviour has no counterpart within the customary approximation scheme of an ordinary orbifold theory. This way tree

  13. Rare human papillomavirus 16 E6 variants reveal significant oncogenic potential

    Directory of Open Access Journals (Sweden)

    Tommasino Massimo

    2011-06-01

    Full Text Available Abstract The aim of this study was to determine whether low prevalence human papillomavirus (HPV 16 E6 variants differ from high prevalence types in their functional abilities. We evaluated functions relevant to carcinogenesis for the rarely-detected European variants R8Q, R10G and R48W as compared to the commonly detected L83V. Human immortalized keratinocytes (NIKS stably transduced with the E6 variants were used in most functional assays. Low and high prevalence E6 variants displayed similar abilities in abrogation of growth arrest and inhibition of p53 elevation induced by actinomycin D. Differences were detected in the abilities to dysregulate stratification and differentiation of NIKS in organotypic raft cultures, modulate detachment induced apoptosis (anoikis and hyperactivate Wnt signaling. No distinctive phenotype could be assigned to include all rare variants. Like L83V, raft cultures derived from variants R10G and R48W similarly induced hyperplasia and aberrantly expressed keratin 5 in the suprabasal compartment with significantly lower expression of keratin 10. Unlike L83V, both variants, and particularly R48W, induced increased levels of anoikis upon suspension in semisolid medium. R8Q induced a unique phenotype characterized by thin organotypic raft cultures, low expression of keratin 10, and high expression of keratins 5 and 14 throughout all raft layers. Interestingly, in a reporter based assay R8Q exhibited a higher ability to augment TCF/β-catenin transcription. The data suggests that differences in E6 variant prevalence in cervical carcinoma may not be related to the carcinogenic potential of the E6 protein.

  14. HPV E6 and E7 in hypoxia mediated tumorigenesis in cervical epithelial cells

    International Nuclear Information System (INIS)

    Kim, Charlotte Y.; Tsai, Mitchell; Graeber, Thomas G.; Peehl, Donna M.; Giaccia, Amato J.

    1996-01-01

    Objective: In our previous work, we found that hypoxia induces apoptosis in oncogenically transformed rodent cells and loss of the p53 tumor suppressor gene significantly reduces hypoxia induced cell death. In this report, we show that transformation of wild-type p53 expressing primary cervical epithelial cells with the E6 and E7 genes from high risk human papillomavirus (HPV) type 16 dramatically enhances their susceptibility to hypoxia induced apoptosis. Materials and Methods: Sub confluent primary normal human cervical epithelial cells and normal human fibroblasts were infected with retroviral vectors containing HPV16 E6 and E7 and the neomycin selectable marker using previously described techniques. Clones were selected and isolated in neomycin containing media. Exponentially growing cells were treated with hypoxia (0.02% O 2 ) using specially designed chambers, irradiated (800 cGy) using a cesium source, or grown under aerobic conditions (20% O 2 ) as a control. After treatment, cells were stained with Hoescht and propidium iodide and viewed with a fluorescent microscope for analysis of apoptotic cells. To determine increase in expression of p53, immuno blots were performed using whole cell extracts. Results: After a 48 hour exposure to hypoxic conditions, 40% of E6 and E7 transformed cervical cells exhibit morphologic features indicative of apoptosis, compared to 5% of untransformed cervical cells. Exposure of HPV E6 and E7 transformed cells to ionizing radiation, however, did not initiate apoptosis. Immunoblot assays show induction of p53 under hypoxic conditions but not by ionizing radiation, indicating that hypoxia is able to induce p53 in the presence of E6 and that hypoxia activates p53 by a pathway which is distinct from that of ionizing radiation. Furthermore, hypoxia did not induce apoptosis in normal human fibroblasts transformed with E6 and E7, suggesting that the cellular response to hypoxia is influenced by the cell type. Conclusion: These results

  15. New signals for vector-like down-type quark in U(1) of E_6

    Science.gov (United States)

    Das, Kasinath; Li, Tianjun; Nandi, S.; Rai, Santosh Kumar

    2018-01-01

    We consider the pair production of vector-like down-type quarks in an E_6 motivated model, where each of the produced down-type vector-like quark decays into an ordinary Standard Model light quark and a singlet scalar. Both the vector-like quark and the singlet scalar appear naturally in the E_6 model with masses at the TeV scale with a favorable choice of symmetry breaking pattern. We focus on the non-standard decay of the vector-like quark and the new scalar which decays to two photons or two gluons. We analyze the signal for the vector-like quark production in the 2γ +≥ 2j channel and show how the scalar and vector-like quark masses can be determined at the Large Hadron Collider.

  16. Dimensional reduction of exceptional E6,E8 gauge groups and flavour chirality

    International Nuclear Information System (INIS)

    Koca, M.

    1984-01-01

    Ten-dimensional Yang - Mills gauge theories based on the exceptional groups E 6 and E 8 are reduced to four-dimensional flavour-chiral Yang - Mills - Higgs theories where the extra six dimensions are identified with the compact G 2 /SU(3) and SO(7)/SO(6) coset spaces. A ten-dimensional E 8 theory leads to three families of SU(5), one of which lies in the 144-dimensional representation of SO(10)

  17. Single W production from heavy Z decay in E6 theories

    International Nuclear Information System (INIS)

    Rizzo, T.G.

    1987-02-01

    We examine the production of single W bosons in the decay of heavy Z bosons, which are present in the low energy limit of E 6 grand unified theories, via the process Z' → W + l - anti nu/sub l/. The branching ratio for this process is found to be sensitive to the Z'-fermion couplings as well as the amount of mixing between Z' and the usual standard model Z over a wide range of Z' masses

  18. Implications of results from the CERN e+e- collider LEP for SO(10) grand unification with two intermediate stages

    International Nuclear Information System (INIS)

    Deshpande, N.G.; Keith, E.; Pal, P.B.

    1993-01-01

    We consider the breaking of the grand unification group SO(10) to the standard model gauge group through several chains containing two intermediate stages. Using the values of the gauge coupling constants at a scale M Z derived from recent data from the CERN e + e- collider LEP, we determine the range of their intermediate and unification scales. In particular, we identify those chains that permit new gauge structure at relatively low energy (∼1 TeV)

  19. The Human Papillomavirus Type 16 E6 Gene Alone Is Sufficient To Induce Carcinomas in Transgenic Animals

    Science.gov (United States)

    Song, Shiyu; Pitot, Henry C.; Lambert, Paul F.

    1999-01-01

    High-risk human papillomaviruses (HPVs) are the causative agents of certain human cancers. HPV type 16 (HPV16) is the papillomavirus most frequently associated with cervical cancer in women. The E6 and E7 genes of HPV are expressed in cells derived from these cancers and can transform cells in tissue culture. Animal experiments have demonstrated that E6 and E7 together cause tumors. We showed previously that E6 and E7 together or E7 alone could induce skin tumors in mice when these genes were expressed in the basal epithelia of the skin. In this study, we investigated the role that the E6 gene plays in carcinogenesis. We generated K14E6 transgenic mice, in which the HPV16 E6 gene was directed in its expression by the human keratin 14 promoter (hK14) to the basal layer of the epidermis. We found that E6 induced cellular hyperproliferation and epidermal hyperplasia and caused skin tumors in adult mice. Interestingly, the tumors derived from E6 were mostly malignant, as opposed to the tumors from E7 mice, which were mostly benign. This result leads us to hypothesize that E6 may contribute differently than E7 to HPV-associated carcinogenesis; whereas E7 primarily contributes to the early stages of carcinogenesis that lead to the formation of benign tumors, E6 primarily contributes to the late stages of carcinogenesis that lead to malignancy. PMID:10364340

  20. THE UNIFICATION OF POWERFUL QUASARS AND RADIO GALAXIES AND THEIR RELATION TO OTHER MASSIVE GALAXIES

    Energy Technology Data Exchange (ETDEWEB)

    Podigachoski, Pece; Barthel, Peter [Kapteyn Astronomical Institute, University of Groningen, 9747 AD Groningen (Netherlands); Haas, Martin [Astronomisches Institut, Ruhr Universität, D-44801 Bochum (Germany); Leipski, Christian [Max-Planck Institut für Astronomie (MPIA), D-69117 Heidelberg (Germany); Wilkes, Belinda, E-mail: podigachoski@astro.rug.nl [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States)

    2015-06-10

    The unification model for powerful radio galaxies (RGs) and radio-loud quasars postulates that these objects are intrinsically the same but viewed along different angles. Herschel Space Observatory data permit the assessment of that model in the far-infrared spectral window. We analyze photometry from Spitzer and Herschel for the distant 3CR hosts, and find that RGs and quasars have different mid-infrared, but indistinguishable far-infrared colors. Both these properties, the former being orientation dependent and the latter orientation invariant, are in line with expectations from the unification model. Adding powerful radio-quiet active galaxies and typical massive star-forming (SF) galaxies to the analysis, we demonstrate that infrared colors not only provide an orientation indicator, but can also distinguish active from SF galaxies.

  1. Neutrino masses and b - τ unification in the supersymmetric standard model

    International Nuclear Information System (INIS)

    Vissani, F.; Smirnov, A.Yu.

    1994-05-01

    There are several indications that the Majorana masses of the right-handed neutrino components, M R , are at the intermediate scale: M R ∼ (10 10 - 10 12 ) GeV or even lighter. The renormalization effects due to large Yukawa couplings of neutrinos from region of momenta M R G are studied in the supersymmetric standard model. It is shown that neutrino renormalization effect can increase the m b /m τ ratio up to (10/15)%. This strongly disfavors m b - m τ unification for low values of tan β s . Lower bound on M R and tan β from the b - τ unification condition were found. The implications of the results to the see-saw mechanism of the neutrino mass generation are discussed. (author). 17 refs, 4 figs

  2. Gauge coupling unification in heterotic string models with gauge mediated supersymmetry breaking

    International Nuclear Information System (INIS)

    Anandakrishnan, Archana; Raby, Stuart

    2011-01-01

    We calculate the weak scale minimal supersymmetric standard model spectrum starting from a heterotic string theory compactified on an anisotropic orbifold. Supersymmetry breaking is mediated by vectorlike exotics that arise naturally in heterotic string theories. The messengers that mediate supersymmetry breaking come in incomplete grand unified theory (GUT) multiplets and give rise to nonuniversal gaugino masses at the GUT scale. Models with nonuniversal gaugino masses at the GUT scale have the attractive feature of allowing for precision gauge coupling unification at the GUT scale with negligible contributions from threshold corrections near the unification scale. The unique features of this minimally supersymmetric standard model spectrum are light gluinos and also large mass differences between the lightest and the next-to-lightest neutralinos and charginos which could lead to interesting signatures at the colliders.

  3. Gauge coupling running in minimal SU(3) x SU(2) x U(1) superstring unification

    CERN Document Server

    Ibáñez, L E; Ross, Graham G

    1991-01-01

    We study the evolution of the gauge coupling constants in string unification schemes in which the light spectrum below the compactification scale is exactly that of the minimal supersymmetric standard model. In the absence of string threshold corrections the predicted values $\\sin^2\\theta _W=0.218$ and $\\alpha _s=0.20$ are in gross conflict with experiment, but these corrections are generically important. One can express the string threshold corrections to $\\sin^2\\theta _W$ and $\\alpha_s$ in terms of certain $modular$ $weights$ of quark, lepton and Higgs superfields as well as the $moduli$ of the string model. We find that in order to get agreement with the experimental measurements within the context of this $minimal$ scheme, certain constraints on the $modular$ $weights$ of the quark, lepton and Higgs superfields should be obeyed. Our analysis indicates that this $minimal$ $string$ $unification$

  4. THE UNIFICATION OF POWERFUL QUASARS AND RADIO GALAXIES AND THEIR RELATION TO OTHER MASSIVE GALAXIES

    International Nuclear Information System (INIS)

    Podigachoski, Pece; Barthel, Peter; Haas, Martin; Leipski, Christian; Wilkes, Belinda

    2015-01-01

    The unification model for powerful radio galaxies (RGs) and radio-loud quasars postulates that these objects are intrinsically the same but viewed along different angles. Herschel Space Observatory data permit the assessment of that model in the far-infrared spectral window. We analyze photometry from Spitzer and Herschel for the distant 3CR hosts, and find that RGs and quasars have different mid-infrared, but indistinguishable far-infrared colors. Both these properties, the former being orientation dependent and the latter orientation invariant, are in line with expectations from the unification model. Adding powerful radio-quiet active galaxies and typical massive star-forming (SF) galaxies to the analysis, we demonstrate that infrared colors not only provide an orientation indicator, but can also distinguish active from SF galaxies

  5. Squark and slepton masses as probes of supersymmetric SO(10) unification

    Energy Technology Data Exchange (ETDEWEB)

    Balasubramanian Ananthanarayan; P. N. Pandita

    2003-09-01

    We carry out a detailed analysis of the non-universal supersymmetry breaking scalar masses arising in SO(10) supersymmetric unification. By considering patterns of squark and slepton masses, we show that a set of sum rules for the sfermion masses is independent of the manner in which SO(10) breaks. We discuss the reasons for this remarkable result. The phenomenology arising from such non-universality is shown to be practically unaffected by the symmetry breaking pattern.

  6. Bankruptcy and Voluntary Liquidation: Evidence for New Firms in East and West Germany after Unification

    OpenAIRE

    Prantl, Susanne

    2003-01-01

    Exploiting the unique economic situation after German unification, I investigate how exit decisions deviate between new firms in a transition and a comparatively stable market environment. Two competing exit mechanisms are considered: entrepreneurial self-selection via voluntary liquidation and external selection based on insolvency regulation. Distinguishing between the competing exit modes proves to be crucial in semi-parametric propor- tional hazard-rate estimations. Comparing East and Wes...

  7. How European unification has shaped the debate on measuring international financial integration

    OpenAIRE

    Pieterse-Bloem, Mary; Eijffinger, Sylvester

    2013-01-01

    textabstractIn this paper we analyse a chronicle of economic theory on international financial integration post-WWII to the present date. Our focus is on theories that have somehow quantify the state and speed of international financial integration. We are able to contrast and compare three distinct strands that have brought forward conditions for its measurement. It is shown that European unification provides much of the empirical testing ground for these measures of international financial ...

  8. Korean Unification and the Future of the U.S.-ROK Alliance

    Science.gov (United States)

    2016-02-01

    including the Korean People’s Army, which, by ROK estimates, numbers 1.2 million in the active force and some 7.7 million in the reserve , or...management. A broader alli- ance agenda would also place a premium on establishing an interagency or whole-of-government dialogue, fusing together...annualized gross domestic product (GDP). See Christine Kim, “Korean Unification May Cost South 7 Percent of GDP: Ministry,” Reuters, January 1, 2013

  9. Physics beyond the standard model in the non-perturbative unification scheme

    International Nuclear Information System (INIS)

    Kapetanakis, D.; Zoupanos, G.

    1990-01-01

    The non-perturbative unification scenario predicts reasonably well the low energy gauge couplings of the standard model. Agreement with the measured low energy couplings is obtained by assuming certain kind of physics beyond the standard model. A number of possibilities for physics beyond the standard model is examined. The best candidates so far are the standard model with eight fermionic families and a similar number of Higgs doublets, and the supersymmetric standard model with five families. (author)

  10. To the problem of control methods unification of natural and artificial radionuclide admission into environment

    International Nuclear Information System (INIS)

    Gedeonov, L.I.

    1981-01-01

    Radioactive substances (RAS) released into the environment during NPP operation form the fields of increased radiation level as compared with the natural background. Preservation of the environment from intolerable contamination requires deter-- mination of the effluent norm by concentration and quantity of RAS released to the environment for every source. The necessity of unification of the methods for radioactive nuclide control of the environment as well as means and conditions of this control are discussed [ru

  11. Towards unification of the Vorticity Confinement and Shock Capturing (TVD and ENO/WENO) methods

    Science.gov (United States)

    Sidilkover, David

    2018-04-01

    New multidimensional extensions of the TVD and finite difference ENO/WENO methods for the compressible flow equations are proposed. The novelty of the approach is in the discretization schemes that acquire by means of a single mechanism both shock-capturing and vorticity confinement capabilities. Thus, the new method can be interpreted as a unification of the two methodologies, intended initially for different purposes.

  12. Towards Unification of Methods for Speech, Audio, Picture and Multimedia Quality Assessment

    DEFF Research Database (Denmark)

    Zielinski, S.; Rumsey, F.; Bech, Søren

    2015-01-01

    attempting to “bridge the gap” between the quality assessment methods used in various disciplines are indicated. Prospective challenges faced by researchers in the unification process are outlined. They include development of unified scales, defining unified anchors, integration of objective models......The paper addresses the need to develop unified methods for subjective and objective quality assessment across speech, audio, picture, and multimedia applications. Commonalities and differences between the currently used standards are overviewed. Examples of the already undertaken research...

  13. Bounds on the number of possible Higgs particles using grand unification and exceptional Lie groups

    International Nuclear Information System (INIS)

    El Naschie, M.S.

    2008-01-01

    The total sum of dimensions of a magnum exceptional Lie symmetry groups hierarchy is 4α-bar o =(4)(137+k o )≅548. Dividing this value among the various quantum fields leads to the possibility of an eight degrees of freedom Higgs field. However analyzing the same situation using sub groups of the largest exceptional Lie group leads to the conclusion that we are likely to find three Higgs particles only at the energy scale of the standard model. Consequently five of the eight degrees of freedom are unlikely to materialize as particles at this particular energy scale. This conclusion is reinforced by an entirely different approach based on grand unification analysis which excludes any grand unification using 4HD, i.e. four Higgs doublets. This leaves us with one, two and three Higgs doublets. Noting that a super symmetric standard model with two Higgs doublets gives almost perfect grand unification and that the result agrees with our exceptional Lie symmetry groups analysis, we exclude everything else. The final result is that we expect to find at least three more Higgs particles leading to a total of 66 elementary particles while at a somewhat higher energy, the expected number of 69 particles found using E-infinity theory is obtained

  14. THE COMPLETION OF THE CHURCH UNIFICATION FROM 1700-1701 UNDER THE BISHOP ATANASIE

    Directory of Open Access Journals (Sweden)

    Florin-Alin OROS

    2013-11-01

    Full Text Available The religious unification around year 1700, betweeen a part of the Orthodox believers from Transylvania and the Church of Rome, of Catholic religion, had represented an event that left a profound spiritual mark on the Romanian and Transylvanian population. The efforts for a Unification had started under the Orthodox bishop from Transylvania, Teofil (1692-1697, a part of the Orthodox priests being willing to accept it for a series of rights and benefits. These efforts could not be accomplished because of the sudden death of the bishop in 1697. As a result of the endeavours of the next bishop of the Romanians, Atanasie, a part of the Orthodox believers had joined the new Greek-Catholic communion around 1700-1701. There is no doubt that this historical and religious endeavour was not an easy one, Atanasie being compelled to „sail” in the muddy waters of the religious structure in Transylvania. This oscillation between the Orthodox and Catholic religions, under the strict supervision of the Imperial authorities from Wien, had triggered the completion of the religious Unification at the beginning of the 18th century and the development of the Greek-Catholic church in Transylvania.

  15. Unification venoplasty to cope with recipient portal vein anomaly during living donor liver transplantation.

    Science.gov (United States)

    Kang, S-H; Hwang, S; Jung, D-H; Ahn, C-S; Moon, D-B; Ha, T-Y; Song, G-W; Kim, K-H; Park, G-C; Namgoong, J-M; Park, Y-H; Park, H-W; Jung, B-H; Lee, S-G

    2013-10-01

    To cope with recipient portal vein (PV) anomalies, such as early branching of the right posterior section (RPS), during living donor liver transplantation (LDLT) surgery, we performed a simulation study to standardize the surgical technique for unification portal venoplasty. This study included an observational analysis of conventional methods utilizing RPS PV, simulation-based design of a new surgical technique, and clinical application of this new technique. In a case encountering RPS PV, a mild anastomotic PV stenosis was persistent over 6 months postsurgery, indicating the need for technical refinement. After computational simulation analysis, we found that simple suturing of the PV branch patch automatically resulted in a funnel-shaped elongation. A prospective recipient study (n = 30) indicated that usual PV reconstruction via the PV bifurcation method is feasible in the absence of unusual donor or recipient PV anomaly. Retrospective living donor PV anatomy analysis (n = 20) revealed that 20-mm-long limbs of the first-order PV branches are necessary to make a 10- to l5-mm-long funneled PV stump. This technique of unification venoplasty for an anomalous recipient PV was applied to an adult patient undergoing LDLT with a right liver graft, for which it was shown to be technically feasible and effective. A simplified unification venoplasty technique was developed to cope with a recipient PV anomaly in adult LDLT. Copyright © 2013. Published by Elsevier Inc.

  16. Low-energy parity restoration and unification mass scale within maximal symmetries

    Directory of Open Access Journals (Sweden)

    Ajaya K. Mohanty

    1984-01-01

    Full Text Available We investigate the hierarchy of gauge boson masses in the maximal grand unified theory by studying the renormalization group equations for the running coupling constants associated with the symmetry breaking of SU(16viaSU(12 q×SU(4 l×U(1 |B|−|L| chain. Particular attention is given to the contribution of Higgs scalars to these equations. It is found that the intermediate mass scale ML, associated with right-handed gauge bosons could be as low as 10 3 GeV only for sin 2θ w(M L as high as 0.265 with α s(M L=0.13. In this chain of symmetry breaking, we have also examined the lowest unification mass that is allowed by the low-energy data for sin 2θ w(M L and the assumed gauge hierarchy. This has been done in two cases; first for the case where SU(3 c is vectorial, second, for the case where SU(3 c is axial. In both cases the lowest unification mass scales were found to be 10 13, 10 11, 10 8 and 10 7 GeV for sin 2θ w(M L = 0.22, 0.24, 0.26,and0.265 respectively with α s(M L = 0.13. The implication of these low unification masses on baryon non-conserving processes is also discussed.

  17. Photochemical Targeting Of Phagocytic Trabecular Meshwork Cells Using Chlorin E6 Coupled Microspheres

    Science.gov (United States)

    Latina, M. A.; Kobsa, P. H.; Rakestraw, S. L.; Crean, E. A.; Hasan, T.; Yarmush, M. L.

    1989-03-01

    We have investigated a novel and efficient delivery system utilizing photosensitizer-coupled-latex microspheres to photochemically target and kill phagocytic trabecular meshwork (TM) cells. TM cells are the most actively phagocytic cells within the anterior chamber of the eye and are located within an optically accessible discrete band. This delivery system, along with the property of cell photocytosis, will achieve double selectivity by combining preferential localization of the photosensitizer to the target cells with spatial localization of illumination on the target cells. All experiments were performed with preconfluent bovine TM cells, 3rd to 4th passage, plated in 15 mm wells. Chlorin e6 monoethylene diamine monoamide was conjugated to the surface of 1.0 Am MX Duke Scientific fluorescent latex microspheres. Spectroscopic analysis revealed an average of 1.3 x 10 -17 moles of chlorin e6 per microsphere. TM cells were incubated for 18 hours with 5 x 10 7 microspheres/ml in MEM with 10% FCS, washed with MEM, and irradiated through fresh media using an argon-pumped dye laser emitting .2 W at 660 nm. A dose-survival study indicated that energy doses of 10 J/cm2 or greater resulted in greater than 95% cell death as determined by ethidium bromide exclusion. Cell death could be demonstrated as early as 4 hours post-irradiation. TM cells incubated with a solution of chlorin e6 at a concentration equal to that conjugated to the microspheres showed no cell death. Unirradiated controls also showed no cell death.

  18. Photodynamic inactivation of bacteria using polyethylenimine-chlorin(e6) conjugates: Effect of polymer molecular weight, substitution ratio of chlorin(e6) and pH.

    Science.gov (United States)

    Huang, Liyi; Zhiyentayev, Timur; Xuan, Yi; Azhibek, Dulat; Kharkwal, Gitika B; Hamblin, Michael R

    2011-04-01

    Antimicrobial photodynamic therapy (APDT) is a novel technique to treat local infections. Previously we reported that the attachment of chlorin(e6) to polyethylenimine (PEI) polymers to form PEI-ce6 conjugates is an effective way to improve ce6 PDT activity against bacteria. The aim of this work was to explore how the polymer molecular weight, substitution ratio (SR) of ce6 and pH value affect the PDT efficacy. We have synthesized PEI-ce6(10) (MW = 60,000, SR = 1) and PEI-ce6(11) (MW = 60,000, SR = 5) and compared these with the previous PEI-ce6(9) (MW = 10,000, SR = 1). We tested the PDT efficacy of these three conjugates against Gram-negative E. coli and Gram-positive bacteria (S. aureus and E. fecalis) at three different pH values (5.0, 7.4, 10.0) that may affect the charge on both the bacterial cells and on the conjugate (that has both basic and acidic groups). PEI-ce6(9) and PEI-ce6(10) were the most effective against these tested bacteria. The PDT effect of all three conjugates depended on pH values. The effective order was pH = 10.0 > pH = 7.4 > pH = 5.0 on E. coli. For S. aureus and E. fecalis the order was pH = 5.0 > pH = 10.0 > pH = 7.4. PEI-ce6(11) PDT activity was worse than PEI-ce6(10) activity which is probably connected to the fact that ce6 molecules are self-quenched within the PEI-ce6(11) molecule. Ce6 quenching within the PEI-ce6 molecules was proved by analyzing fluorescence spectra of PEI-ce6 conjugates at different pH values. There were no differences in bacterial uptake between different pH values in three PEI-ce6 conjugates. We assume high pH (rather than low pH as was hypothesized) disaggregates the conjugates, so the higher pH was more effective than the lower pH against E. coli. But for Gram-positive bacteria, low pH was more effective possibly due to more overall positive charge on the conjugate. Copyright © 2011 Wiley-Liss, Inc.

  19. Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc

    Science.gov (United States)

    Kühnle, Simone; Mothes, Benedikt; Matentzoglu, Konstantin; Scheffner, Martin

    2013-01-01

    Inactivation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with development of the Angelman syndrome. Recently, it was reported that in mice, loss of E6AP expression results in increased levels of the synaptic protein Arc and a concomitant impaired synaptic function, providing an explanation for some phenotypic features of Angelman syndrome patients. Accordingly, E6AP has been shown to negatively regulate activity-regulated cytoskeleton-associated protein (Arc) and it has been suggested that E6AP targets Arc for ubiquitination and degradation. In our study, we provide evidence that Arc is not a direct substrate for E6AP and binds only weakly to E6AP, if at all. Furthermore, we show that down-regulation of E6AP expression stimulates estradiol-induced transcription of the Arc gene. Thus, we propose that Arc protein levels are controlled by E6AP at the transcriptional rather than at the posttranslational level. PMID:23671107

  20. Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest

    Energy Technology Data Exchange (ETDEWEB)

    Vliet-Gregg, Portia A.; Hamilton, Jennifer R. [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA (United States)

    2015-04-15

    High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21{sup Waf1/CIP1}, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV.

  1. Update of KASHIL-E6 library for shielding analysis and benchmark calculations

    International Nuclear Information System (INIS)

    Kim, D. H.; Kil, C. S.; Jang, J. H.

    2004-01-01

    For various shielding and reactor pressure vessel dosimetry applications, a pseudo-problem-independent neutron-photon coupled MATXS-format library based on the last release of ENDF/B-VI has been generated as a part of the update program for KASHIL-E6, which was based on ENDF/B-VI.5. It has VITAMIN-B6 neutron and photon energy group structures, i.e., 199 groups for neutron and 42 groups for photon. The neutron and photon weighting functions and the Legendre order of scattering are same as KASHIL-E6. The library has been validated through some benchmarks: the PCA-REPLICA and NESDIP-2 experiments for LWR pressure vessel facility benchmark, the Winfrith Iron88 experiment for validation of iron data, and the Winfrith Graphite experiment for validation of graphite data. These calculations were performed by the TRANSXlDANTSYS code system. In addition, the substitutions of the JENDL-3.3 and JEFF-3.0 data for Fe, Cr, Cu and Ni, which are very important nuclides for shielding analyses, were investigated to estimate the effects on the benchmark calculation results

  2. Modulation of DNA methylation by human papillomavirus E6 and E7 oncoproteins in cervical cancer

    Science.gov (United States)

    Sen, Prakriti; Ganguly, Pooja; Ganguly, Niladri

    2018-01-01

    Human papillomaviruses (HPVs) are double stranded circular DNA viruses that infect cutaneous and mucosal epithelial cells. Almost 99% of cervical cancer has a HPV infection. The early oncoproteins E6 and E7 are important in this cellular transformation process. Epigenetic mechanisms have long been known to result in decisive alterations in DNA, leading to alterations in DNA-protein interactions, alterations in chromatin structure and compaction and significant alterations in gene expression. The enzymes responsible for these epigenetic modifications are DNA methyl transferases (DNMTs), histone acetylases and deacetylases. Epigenetics has an important role in cancer development by modifying the cellular micro environment. In this review, the authors discuss the role of HPV oncoproteins E6 and E7 in modulating the epigenetic mechanisms inside the host cell. The oncoproteins induce the expression of DNMTs which lead to aberrant DNA methylations and disruption of the normal epigenetic processes. The E7 oncoprotein may additionally directly bind and induce methyl transferase activity of the enzyme. These modulations lead to altered gene expression levels, particularly the genes involved in apoptosis, cell cycle and cell adhesion. In addition, the present review discusses how epigenetic mechanisms may be targeted for possible therapeutic interventions for HPV mediated cervical cancer. PMID:29285184

  3. Confronting the conventional ideas of grand unification with fermion masses, neutrino oscillations and proton decay

    Energy Technology Data Exchange (ETDEWEB)

    Pati, J C [Department of Physics, University of Maryland, College Park (United States) and Stanford Linear Accelerator Center, Menlo Park (United States)

    2002-09-15

    It is noted that one is now in possession of a set of facts, which may be viewed as the matching pieces of a puzzle; in that all of them can be resolved by just one idea - that is grand unification. These include: (i) the observed family-structure, (ii) quantization of electric charge, (iii) meeting of the three gauge couplings, (iv) neutrino oscillations; in particular the mass squared-difference {delta}m{sup 2}({nu}{sub {mu}} - {nu}{sub {tau}}) (suggested by SuperK), (v) the intricate pattern of the masses and mixings of the fermions, including the smallness of V{sub cb} and the largeness of {theta}{sub {nu}{sub {mu}{nu}}{sub {tau}}}{sup osc}, and (vi) the need for B-L as a generator to implement baryogenesis (via leptogenesis). All these pieces fit beautifully together within a single puzzle board framed by supersymmetric unification, based on SO(10) or a string-unified G(224)-symmetry. The two notable pieces of the puzzle still missing, however, are proton decay and supersymmetry. A concrete proposal is presented, within a predictive SO(10)/G(224)- framework, that successfully describes the masses and mixings of all fermions, including the neutrinos - with eight predictions, all in agreement with observation. Within this framework, a systematic study of proton decay is carried out, which (a) pays special attention to its dependence on the fermion masses, including the superheavy Majorana masses of the right-handed neutrinos, and (b) limits the threshold corrections so as to preserve natural coupling unification. The study updates prior work by Babu, Pati and Wilczek, in the context of both MSSM and its (interesting) variant, the so-called ESSM, by allowing for improved values of the matrix elements and of the short and long-distance renormalization effects. It shows that a conservative upper limit on the proton lifetime is about (1/3 - 2) x 10{sup 34} years, with {nu}-barK{sup +} being the dominant decay mode, and quite possibly {mu}{sup p}+K{sup 0} and e

  4. Confronting the conventional ideas of grand unification with fermion masses, neutrino oscillations and proton decay

    International Nuclear Information System (INIS)

    Pati, J.C.

    2002-01-01

    It is noted that one is now in possession of a set of facts, which may be viewed as the matching pieces of a puzzle; in that all of them can be resolved by just one idea - that is grand unification. These include: (i) the observed family-structure, (ii) quantization of electric charge, (iii) meeting of the three gauge couplings, (iv) neutrino oscillations; in particular the mass squared-difference Δm 2 (ν μ - ν τ ) (suggested by SuperK), (v) the intricate pattern of the masses and mixings of the fermions, including the smallness of V cb and the largeness of θ ν μ ν τ osc , and (vi) the need for B-L as a generator to implement baryogenesis (via leptogenesis). All these pieces fit beautifully together within a single puzzle board framed by supersymmetric unification, based on SO(10) or a string-unified G(224)-symmetry. The two notable pieces of the puzzle still missing, however, are proton decay and supersymmetry. A concrete proposal is presented, within a predictive SO(10)/G(224)- framework, that successfully describes the masses and mixings of all fermions, including the neutrinos - with eight predictions, all in agreement with observation. Within this framework, a systematic study of proton decay is carried out, which (a) pays special attention to its dependence on the fermion masses, including the superheavy Majorana masses of the right-handed neutrinos, and (b) limits the threshold corrections so as to preserve natural coupling unification. The study updates prior work by Babu, Pati and Wilczek, in the context of both MSSM and its (interesting) variant, the so-called ESSM, by allowing for improved values of the matrix elements and of the short and long-distance renormalization effects. It shows that a conservative upper limit on the proton lifetime is about (1/3 - 2) x 10 34 years, with ν-barK + being the dominant decay mode, and quite possibly μ p +K 0 and e + π 0 being prominent. This in turn strongly suggests that an improvement in the current

  5. 78 FR 42530 - Prospective Grant of an Exclusive License: Human Papillomavirus 16 E2 and E6 Peptides for...

    Science.gov (United States)

    2013-07-16

    ... peptide from HPV 16. E6 peptide vaccines are potentially prophylactic or therapeutic for cervical cancer... Exclusive License: Human Papillomavirus 16 E2 and E6 Peptides for Cervical Cancer Vaccine Development AGENCY... principal place of business in Augusta, Georgia. The United States of America is an assignee to the patent...

  6. Intracellular scFvs against the viral E6 oncoprotein provoke apoptosis in human papillomavirus-positive cancer cells

    International Nuclear Information System (INIS)

    Lagrange, Magali; Boulade-Ladame, Charlotte; Mailly, Laurent; Weiss, Etienne; Orfanoudakis, Georges; Deryckere, Francois

    2007-01-01

    The E6 protein of human papillomavirus type 16 (16E6) is involved in the tumorigenesis of human cervical cells by targeting numerous cellular proteins. We have designed a strategy for neutralizing 16E6 based on the intracellular expression of single-chain Fv antibodies (scFvs) specific to 16E6. Recombinant adenovirus vectors were constructed to allow expression of two 16E6-binding scFvs and one 16E6-non-binding scFv in HPV16-positive and -negative cells. Expression of the scFvs provoked two types of effects: (i) inhibition of proliferation of all cell lines tested, this aspecific toxicity being likely due to the aggregation of unfolded scFvs; and (ii) apoptosis observed only in HPV16-positive cervical cancer cell lines after expression of 16E6-binding scFvs, this specific effect being proportional to the intracellular solubility of the scFvs. These data demonstrate the feasibility of intracellular immunization with anti-16E6 scFvs and highlight the importance of the solubility of the intracellular antibodies

  7. E2, E4, and E6 statistical decay spectra in 208Pb

    International Nuclear Information System (INIS)

    Teruya, N.; Wolynec, E.; Dias, H.

    1989-01-01

    Statistical decay spectra for the decay of giant resonances in 208 Pb by one neutron emission are calculated using the Hauser-Feshbach formalism and the experimental levels of the residual nucleus. The predicted decay spectra are compared with available experimental results. It is shown that the decay spectra are sensitive to multipole ad-mixtures of the excited state and can be used to study such admixtures. The available experimental data for the decay of the E2 resonances in 208 Pb contain spurious peaks that do not belong to the spectrum of 207 Pb. Theuuncertainty of the experimental data make it impossible to decide whether the decay is purely E2 or a mixture of 80% E2 plus 20% E6. (author) [pt

  8. Higgs boson production via Z, W bosons and toponium in the E6 superstring model

    International Nuclear Information System (INIS)

    Barger, V.; Whisnant, K.

    1988-01-01

    The authors examine the production of light Higgs bosons associated with electroweak symmetry-breaking in an E 6 superstring model in Z ω HZ * decays, in e + e - annihilation and in toponium decays. They find that the couplings of the lightest scalar Higgs boson H 1 0 in these models are very similar to those of the standard Higgs boson unless the pseudoscalar P 0 in the model has mass ≤ M z . Possible new modes for Higgs boson production not found in the standard model are presented. The authors give simple analytic expressions for the Higgs boson masses and mixing angles in the limit that the extra Z' gauge boson is heavy which clearly shows the production mechanisms that are favored for a given set of model parameters

  9. Disposition of PUREX facility tanks D5 and E6 uranium and plutonium solutions

    International Nuclear Information System (INIS)

    Harty, D.P.

    1993-12-01

    Approximately 9 kilograms of plutonium and 5 metric tons of uranium in a 1 molar nitric acid solution are being stored in two PUREX facility vessels, tanks D5 and E6. The plutonium was accumulated during cleanup activities of the plutonium product area of the PUREX facility. Personnel at PUREX recently completed a formal presentation to the Surplus Materials Peer Panel (SMPP) regarding disposition of the material currently in these tanks. The peer panel is a group of complex-wide experts who have been chartered by EM-64 (Office of Site and Facility Transfer) to provide a third party independent review of disposition decisions. The information presented to the peer panel is provided in the first section of this report. The panel was generally receptive to the information provided at that time and the recommendations which were identified

  10. Unification of gauge and gravity Chern-Simons theories in 3-D space-time

    Energy Technology Data Exchange (ETDEWEB)

    Saghir, Chireen A.; Shamseddine, Laurence W. [American University of Beirut, Physics Department, Beirut (Lebanon)

    2017-11-15

    Chamseddine and Mukhanov showed that gravity and gauge theories could be unified in one geometric construction provided that a metricity condition is imposed on the vielbein. In this paper we are going to show that by enlarging the gauge group we are able to unify Chern-Simons gauge theory and Chern-Simons gravity in 3-D space-time. Such a unification leads to the quantization of the coefficients for both Chern-Simons terms for compact groups but not for non-compact groups. Moreover, it leads to a topological invariant quantity of the 3-dimensional space-time manifold on which they are defined. (orig.)

  11. Gravity-assisted exact unification in minimal supersymmetric SU(5) and its gaugino mass spectrum

    International Nuclear Information System (INIS)

    Tobe, Kazuhiro; Wells, James D.

    2004-01-01

    Minimal supersymmetric SU(5) with exact unification is naively inconsistent with proton decay constraints. However, it can be made viable by a gravity-induced non-renormalizable operator connecting the adjoint Higgs boson and adjoint vector boson representations. We compute the allowed coupling space for this theory and find natural compatibility with proton decay constraints even for relatively light superpartner masses. The modifications away from the naive SU(5) theory have an impact on the gaugino mass spectrum, which we calculate. A combination of precision linear collider and large hadron collider measurements of superpartner masses would enable interesting tests of the high-scale form of minimal supersymmetric SU(5)

  12. The behaviour of effective coupling constants in 'finite' grand unification theories in curved spacetime

    International Nuclear Information System (INIS)

    Buchbinder, I.L.; Odintsov, S.D.; Lichtzier, I.M.

    1989-01-01

    The question of the behaviour of effective coupling constants in one-loop 'finite' grand unification theories in curved spacetime is investigated. It is shown that in strong gravitational fields the effective coupling constant, corresponding to the parameter of non-minimal interaction of scalar and gravitational fields, tends to the conformal value or increases in an exponential fashion. The one-loop effective potential is obtained with accuracy to linear curvature terms. It is shown that, in external supergravity, supersymmetric finite theories admit asymptotic conformal invariance. (Author)

  13. New fat Higgs: Increasing the MSSM Higgs mass with natural gauge unification

    International Nuclear Information System (INIS)

    Chang, Spencer; Kilic, Can; Mahbubani, Rakhi

    2005-01-01

    In this paper we increase the minimal supersymmetric standard model tree level Higgs mass bound to a value that is naturally larger than the LEP-II search constraint by adding to the superpotential a λSH u H d term, as in the next to minimal supersymmetric standard model, and UV completing with new strong dynamics before λ becomes nonperturbative. Unlike other models of this type, the Higgs fields remain elementary, alleviating the supersymmetric fine-tuning problem while maintaining unification in a natural way

  14. Biophysical characterization of the complex between human papillomavirus E6 protein and synapse-associated protein 97

    DEFF Research Database (Denmark)

    Chi, Celestine Ngang; Bach, Anders; Engström, Åke

    2011-01-01

    The E6 protein of human papillomavirus exhibits complex interaction patterns with several host proteins and their roles in HPV mediated oncogenesis have proved challenging to study. Here we use several biophysical techniques to explore the binding of E6 to the three PDZ domains of the tumor......, this quaternary complex has the same apparent hydrodynamic volume as the unliganded PDZ region, suggesting that a conformational change occurs in the PDZ region upon binding, a conclusion supported by kinetic experiments. Using NMR, we discovered a new mode of interaction between E6 and PDZ: a subset of residues...

  15. Optimizing the Activation of Chlorin e6 Utilizing Upconversion Energy Transfer

    Science.gov (United States)

    Avalos, Julio C.; Pedraza, Francisco J.; Sardar, Dhiraj K.

    2015-03-01

    Current cancer therapy techniques, such as chemotherapy and radiation therapy, possess several drawbacks including lack of selectivity resulting in harmful side effects. Photodynamic therapy (PDT) is one of the fastest emerging techniques due to its many advantages, including the use of nonionizing radiation, targeted delivery, and controlled doses. In PDT, photosensitizers (PSs) are activated inside targeted cells to produce irreversible damage inducing cell death. Since most PSs operate in the visible range, it is difficult to activate them due to the high attenuation of soft tissue. Upconverting nanoparticles (UCNP) are able to absorb in the NIR region, where light is less attenuated, and emit in the visible range, resulting in deeper tissue penetration. UCNPs are able to assist with the activation of the PS by energy transfer when the PS is conjugated onto the UCNP. Chlorin e6 (Ce6) is a commonly used PSs due to its ability to release reactive oxygen species (ROS), which is one of the main processes utilized in PDT. The UCNP studied contain a combination of rare earth doped ions including Erbium, Thulium, and Holmium precisely doped into the host nanocrystal to improve upconversion emission and energy transfer. The work presented will focus on exploring the factors that affect the activation of Ce6. The results will include the enhancement of Ce6 activation and ROS release when conjugated onto a rare earth-doped UCNP. This research was funded by NSF-PREM Grant No. DMR -0934218 and RISE Grant No. GM 060655.

  16. F4 , E6 and G2 exceptional gauge groups in the vacuum domain structure model

    Science.gov (United States)

    Shahlaei, Amir; Rafibakhsh, Shahnoosh

    2018-03-01

    Using a vacuum domain structure model, we calculate trivial static potentials in various representations of F4 , E6, and G2 exceptional groups by means of the unit center element. Due to the absence of the nontrivial center elements, the potential of every representation is screened at far distances. However, the linear part is observed at intermediate quark separations and is investigated by the decomposition of the exceptional group to its maximal subgroups. Comparing the group factor of the supergroup with the corresponding one obtained from the nontrivial center elements of S U (3 ) subgroup shows that S U (3 ) is not the direct cause of temporary confinement in any of the exceptional groups. However, the trivial potential obtained from the group decomposition into the S U (3 ) subgroup is the same as the potential of the supergroup itself. In addition, any regular or singular decomposition into the S U (2 ) subgroup that produces the Cartan generator with the same elements as h1, in any exceptional group, leads to the linear intermediate potential of the exceptional gauge groups. The other S U (2 ) decompositions with the Cartan generator different from h1 are still able to describe the linear potential if the number of S U (2 ) nontrivial center elements that emerge in the decompositions is the same. As a result, it is the center vortices quantized in terms of nontrivial center elements of the S U (2 ) subgroup that give rise to the intermediate confinement in the static potentials.

  17. Study of Higgs self couplings of a supersymmetric E6 model at the international linear collider

    International Nuclear Information System (INIS)

    Ham, S. W.; Han, K. D.; Lee, J. I.; Oh, S. K.

    2010-01-01

    We study the Higgs self couplings of a supersymmetric E 6 model that has two Higgs doublets and two Higgs singlets. The lightest scalar Higgs boson in the model may be heavier than 112 GeV, at the one-loop level, where the negative results for the Higgs search at the LEP2 experiments are taken into account. The contributions from the top and scalar top quark loops are included in the radiative corrections to the one-loop mass of the lightest scalar Higgs boson in the effective potential approximation. The effect of the Higgs self couplings may be observed in the production of the lightest scalar Higgs bosons in e + e - collisions at the International Linear Collider (ILC) via the double Higgs-strahlung process. For the center of mass energy of 500 GeV with an integrated luminosity of 500 fb -1 and an efficiency of 20%, we expect that at least 5 events of the lightest scalar Higgs boson may be produced at the ILC via the double Higgs-strahlung process.

  18. Chlorin e6 Conjugated Interleukin-6 Receptor Aptamers Selectively Kill Target Cells Upon Irradiation

    Directory of Open Access Journals (Sweden)

    Sven Kruspe

    2014-01-01

    Full Text Available Photodynamic therapy (PDT uses the therapeutic properties of light in combination with certain chemicals, called photosensitizers, to successfully treat brain, breast, prostate, and skin cancers. To improve PDT, current research focuses on the development of photosensitizers to specifically target cancer cells. In the past few years, aptamers have been developed to directly deliver cargo molecules into target cells. We conjugated the photosensitizer chlorin e6 (ce6 with a human interleukin-6 receptor (IL-6R binding RNA aptamer, AIR-3A yielding AIR-3A-ce6 for application in high efficient PDT. AIR-3A-ce6 was rapidly and specifically internalized by IL-6R presenting (IL-6R+ cells. Upon light irradiation, targeted cells were selectively killed, while free ce6 did not show any toxic effect. Cells lacking the IL-6R were also not affected by AIR-3A-ce6. With this approach, we improved the target specificity of ce6-mediated PDT. In the future, other tumor-specific aptamers might be used to selectively localize photosensitizers into cells of interest and improve the efficacy and specificity of PDT in cancer and other diseases.

  19. Reinventing Consumption Traditions through the Process of Unification of a Country: Understanding “Good Bye Lenin!”

    Directory of Open Access Journals (Sweden)

    Ece Ceren Engür

    2016-02-01

    Full Text Available This paper focuses on the change of consumption traditions in terms of re-unification of a country. The discussion bases on the movie, “Good Bye Lenin!”(2003 and chases the transformations on consumption trends in order to understand how the re-unification of East and West Germany influences the practices of everyday life after a four decade long segregation. The movie displays the 1990’s Germany during the times when the Berlin Wall falls and frames a family portrait which is dominated by an idealist and traditional mother character in the last days of her life.

  20. Signatures of lower-scale gauge coupling unification in the standard model due to extended Higgs sector

    International Nuclear Information System (INIS)

    Chizhov, M. V.; Bednyakov, V. A.

    2016-01-01

    The gauge coupling unification can be achieved at a unification scale around 5×10"1"3 GeV if the Standard Model scalar sector is extended with extra Higgs-like doublets. The relevant new scalar degrees of freedom in the form of chiral Z* and W* vector bosons might “be visible” already at about 700 GeV. Their eventual preferred coupling to the heavy quarks explains the non observation of these bosons in the first LHC run and provides promising expectation for the second LHC run.

  1. E6 and E7 Gene Polymorphisms in Human Papillomavirus Types-58 and 33 Identified in Southwest China.

    Directory of Open Access Journals (Sweden)

    Zuyi Chen

    Full Text Available Cancer of the cervix is associated with infection by certain types of human papillomavirus (HPV. The gene variants differ in immune responses and oncogenic potential. The E6 and E7 proteins encoded by high-risk HPV play a key role in cellular transformation. HPV-33 and HPV-58 types are highly prevalent among Chinese women. To study the gene intratypic variations, polymorphisms and positive selections of HPV-33 and HPV-58 E6/E7 in southwest China, HPV-33 (E6, E7: n = 216 and HPV-58 (E6, E7: n = 405 E6 and E7 genes were sequenced and compared to others submitted to GenBank. Phylogenetic trees were constructed by Maximum-likelihood and the Kimura 2-parameters methods by MEGA 6 (Molecular Evolutionary Genetics Analysis version 6.0. The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by PAML 4.8 (Phylogenetic Analyses by Maximun Likelihood version4.8 software. The positive sites of HPV-33 and HPV-58 E6/E7 were contrasted by ClustalX 2.1. Among 216 HPV-33 E6 sequences, 8 single nucleotide mutations were observed with 6/8 non-synonymous and 2/8 synonymous mutations. The 216 HPV-33 E7 sequences showed 3 single nucleotide mutations that were non-synonymous. The 405 HPV-58 E6 sequences revealed 8 single nucleotide mutations with 4/8 non-synonymous and 4/8 synonymous mutations. Among 405 HPV-58 E7 sequences, 13 single nucleotide mutations were observed with 10/13 non-synonymous mutations and 3/13 synonymous mutations. The selective pressure analysis showed that all HPV-33 and 4/6 HPV-58 E6/E7 major non-synonymous mutations were sites of positive selection. All variations were observed in sites belonging to major histocompatibility complex and/or B-cell predicted epitopes. K93N and R145 (I/N were observed in both HPV-33 and HPV-58 E6.

  2. Hierarchy of symmetry-breaking scales in SO(10) grand unification and particle masses

    International Nuclear Information System (INIS)

    Asatryan, G.M.; Ioannisyan, A.N.

    1987-01-01

    An SO(10) grand unification model is proposed in which the introduction of an additional discrete symmetry solves the problem of the quark mass spectrum arising in SO(10) breaking schemes with intermediate SU(4) x SU(2)/sub L/ x SU(2)/sub R/ or SU(3)/sub C/ x U(1)/sub B//sub -//sub L/ x SU(2)/sub L/ x SU(2)/sub R/ symmetry. When the breaking of this discrete symmetry is taken into account the condition that there exist only a single light Higgs boson leads to a relation between the b- and t-quark masses which makes it possible to fix the ratio of the grand unification scale M/sub X/ and the quark--lepton symmetry-breaking scale M/sub C/. The specific values of M/sub X/ and M/sub C/ and also the scale of the SU(2)/sub R/ symmetry breaking M/sub R/ depend on the experimental value of the Weinberg angle and are in agreement with the experimental data on proton decay

  3. Low-luminosity Blazars in Wise: A Mid-infrared View of Unification

    Science.gov (United States)

    Plotkin, Richard M.; Anderson, S. F.; Brandt, W. N.; Markoff, S.; Shemmer, O.; Wu, J.

    2012-01-01

    We use the preliminary data release from the Wide-Field Infrared Survey Explorer (WISE) to perform the first statistical study on the mid-infrared (IR) properties of a large number ( 102) of BL Lac objects -- low-luminosity Active Galactic Nuclei (AGN) with a jet beamed toward the Earth. As expected, many BL Lac objects are so highly beamed that their jet synchrotron emission dominates their IR spectral energy distributions (SEDs), and the shape of their SEDs in the IR correlates well with SED peak frequency. In other BL Lac objects, the jet is not strong enough to completely dilute the rest of the AGN, and we do not see observational signatures of the dusty torus from these weakly beamed BL Lac objects. While at odds with simple unification, the missing torus is consistent with recent suggestions that BL Lac objects are fed by radiatively inefficient accretion flows. We discuss implications on the ``nature vs. nurture" debate for FR I and FR II galaxies, and also on the standard orientation-based AGN unification model.

  4. In vitro studies of chlorin e6-assisted photodynamic inactivation of Helicobacter pylori

    Science.gov (United States)

    Simon, C.; Mohrbacher, C.; Hüttenberger, D.; Bauer-Marschall, Ina; Krickhahn, C.; Stachon, A.; Foth, H.-J.

    2014-03-01

    Helicobacter pylori (HP), a gram-negative microaerophilic bacterium located in gastric mucosa, plays an im- portant role in gastro carcinogenesis. Due to the increasing emergence of antibiotic resistance, photodynamic inactivation of bacteria presents a new approach to treat bacterial infections, like HP. In vitro experiments were performed to determine the irradiation conditions for a complete inactivation of HP with the photosensitizer Chlorin e6 (Ce6). The HP strain CCUG 38770 (Culture Collection, University of Gothenburg, Sweden) was routinely cultured under microaerophilic conditions, suspended in sodium chloride, incubated with Ce6 and irradiated briefly with red light of the appropriate wavelength of λ = 660 nm. Series of measurements of different Ce6-concentrations (0.1 μM - 100 μM) were carried out, whereby the incubation time was kept constant at 1 min. The absorbed energy dose has been selected in varying the irradiation time (1 s - 300 s) and the power density (4.5 mW/cm2 - 31 mW/cm2 ). Quantification of inactivation was performed by enumeration of the grown colonies. In addition, the accumulation of Ce6 in HP cells was studied more precisely by uorescence spectroscopy. With a Ce6 concentration of 100 μM and a power density of 9 mW cm2 , a 6-log10 reduction in the survival rate of HP was achieved within 30 seconds of irradiation. In conclusion the most relevant factor for the inactivation of HP is the exposure time of irradiation, followed by the concentration of Ce6 and the light intensity. Further studies with HP strains obtained from patient specimens are under current investigation.

  5. Strings: A possible alternative explanation for the Unification of Gravitation Field and Electromagnetic Field

    Science.gov (United States)

    Rivera, Susana

    Throughout the last century, since the last decades of the XIX century, until present day, there had been many attempts to achieve the unification of the Forces of Nature. First unification was done by James Clerk Maxwell, with his Electromagnetic Theory. Then Max Plank developed his Quantum Theory. In 1905, Albert Einstein gave birth to the Special Relativity Theory, and in 1916 he came out with his General Relativity Theory. He noticed that there was an evident parallelism between the Gravitational Force, and the Electromagnetic Force. So, he tried to unify these forces of Nature. But Quantum Theory interposed on his way. On the 1940’s it had been developed the Quantum Electrodynamics (QED), and with it, the unified field theory had an arise interest. On the 60’s and 70’s there was developed the Quantum Chromodynamics (QCD). Along with these theories came the discovery of the strong interaction force and weak interaction force. And though there had been many attempts to unify all these forces of the nature, it could only be achieved the Unification of strong interaction, weak interaction and Electromagnetic Force. On the late 80”s and throughout the last two decades, theories such as “super-string theory”, “or the “M-theory”, among others, groups of Scientists, had been doing grand efforts and finally they came out with the unification of the forces of nature, being the only limitation the use of more than 11 dimensions. Using an ingenious mathematical tool known as the super symmetries, based on the Kaluza - Klein work, they achieve this goal. The strings of these theories are in the rank of 10-33 m. Which make them undetectable. There are many other string theories. The GEUFT theory is based on the existence of concentrated energy lines, which vibrates, expands and contracts, submitting and absorbing energy, matter and antimatter, and which yields a determined geometry, that gives as a result the formation of stars, galaxies, nebulae, clusters

  6. Genus beta human papillomavirus E6 proteins vary in their effects on the transactivation of p53 target genes.

    Science.gov (United States)

    White, Elizabeth A; Walther, Johanna; Javanbakht, Hassan; Howley, Peter M

    2014-08-01

    The genus beta human papillomaviruses (beta HPVs) cause cutaneous lesions and are thought to be involved in the initiation of some nonmelanoma skin cancers (NMSCs), particularly in patients with the genetic disorder epidermodysplasia verruciformis (EV). We have previously reported that at least two of the genus beta HPV E6 proteins bind to and/or increase the steady-state levels of p53 in squamous epithelial cells. This is in contrast to a well-characterized ability of the E6 proteins of cancer-associated HPVs of genus alpha HPV, which inactivate p53 by targeting its ubiquitin-mediated proteolysis. In this study, we have investigated the ability of genus beta E6 proteins from eight different HPV types to block the transactivation of p53 target genes following DNA damage. We find that the E6 proteins from diverse beta HPV species and types vary in their capacity to block the induction of MDM2, p21, and proapoptotic genes after genotoxic stress. We conclude that some genus beta HPV E6 proteins inhibit at least some p53 target genes, although perhaps not by the same mechanism or to the same degree as the high-risk genus alpha HPV E6 proteins. This study addresses the ability of various human papillomavirus E6 proteins to block the activation of p53-responsive cellular genes following DNA damage in human keratinocytes, the normal host cell for HPVs. The E6 proteins encoded by the high-risk, cancer-associated HPV types of genus alpha HPV have a well-established activity to target p53 degradation and thereby inhibit the response to DNA damage. In this study, we have investigated the ability of genus beta HPV E6 proteins from eight different HPV types to block the ability of p53 to transactivate downstream genes following DNA damage. We find that some, but not all, genus beta HPV E6 proteins can block the transactivation of some p53 target genes. This differential response to DNA damage furthers the understanding of cutaneous HPV biology and may help to explain the

  7. The human papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis.

    Science.gov (United States)

    Spangle, Jennifer M; Münger, Karl

    2010-09-01

    The mammalian target of rapamycin (mTOR) kinase acts as a cellular rheostat that integrates signals from a variety of cellular signal transduction pathways that sense growth factor and nutrient availability as well as intracellular energy status. It was previously reported that the human papillomavirus type 16 (HPV16) E6 oncoprotein may activate the S6 protein kinase (S6K) through binding and E6AP-mediated degradation of the mTOR inhibitor tuberous sclerosis complex 2 (TSC2) (Z. Lu, X. Hu, Y. Li, L. Zheng, Y. Zhou, H. Jiang, T. Ning, Z. Basang, C. Zhang, and Y. Ke, J. Biol. Chem. 279:35664-35670, 2004; L. Zheng, H. Ding, Z. Lu, Y. Li, Y. Pan, T. Ning, and Y. Ke, Genes Cells 13:285-294, 2008). Our results confirmed that HPV16 E6 expression causes an increase in mTORC1 activity through enhanced phosphorylation of mTOR and activation of downstream signaling pathways S6K and eukaryotic initiation factor binding protein 1 (4E-BP1). However, we did not detect a decrease in TSC2 levels in HPV16 E6-expressing cells. We discovered, however, that HPV16 E6 expression causes AKT activation through the upstream kinases PDK1 and mTORC2 under conditions of nutrient deprivation. We show that HPV16 E6 expression causes an increase in protein synthesis by enhancing translation initiation complex assembly at the 5' mRNA cap and an increase in cap-dependent translation. The increase in cap-dependent translation likely results from HPV16 E6-induced AKT/mTORC1 activation, as the assembly of the translation initiation complex and cap-dependent translation are rapamycin sensitive. Lastly, coexpression of the HPV16 E6 and E7 oncoproteins does not affect HPV16 E6-induced activation of mTORC1 and cap-dependent translation. HPV16 E6-mediated activation of mTORC1 signaling and cap-dependent translation may be a mechanism to promote viral replication under conditions of limited nutrient supply in differentiated, HPV oncoprotein-expressing proliferating cells.

  8. The E7 protein of the cottontail rabbit papillomavirus immortalizes normal rabbit keratinocytes and reduces pRb levels, while E6 cooperates in immortalization but neither degrades p53 nor binds E6AP

    International Nuclear Information System (INIS)

    Ganzenmueller, Tina; Matthaei, Markus; Muench, Peter; Scheible, Michael; Iftner, Angelika; Hiller, Thomas; Leiprecht, Natalie; Probst, Sonja; Stubenrauch, Frank; Iftner, Thomas

    2008-01-01

    Human papillomaviruses (HPVs) cause cervical cancer and are associated with the development of non-melanoma skin cancer. A suitable animal model for papillomavirus-associated skin carcinogenesis is the infection of domestic rabbits with the cottontail rabbit papillomavirus (CRPV). As the immortalizing activity of CRPV genes in the natural target cells remains unknown, we investigated the properties of CRPV E6 and E7 in rabbit keratinocytes (RK) and their influence on the cell cycle. Interestingly, CRPV E7 immortalized RK after a cellular crisis but showed no such activity in human keratinocytes. Co-expressed CRPV E6 prevented cellular crisis. The HPV16 or CRPV E7 protein reduced rabbit pRb levels thereby causing rabbit p19 ARF induction and accumulation of p53 without affecting cellular proliferation. Both CRPV E6 proteins failed to degrade rabbit p53 in vitro or to bind E6AP; however, p53 was still inducible by mitomycin C. In summary, CRPV E7 immortalizes rabbit keratinocytes in a species-specific manner and E6 contributes to immortalization without directly affecting p53

  9. Supergravity Unification

    CERN Document Server

    Chamseddine, A H; Nath, Pran; Chamseddine, Ali H.; Nath, Pran

    2001-01-01

    A review is given of the historical developments of 1982 that lead to the supergravity unified model (SUGRA)with gravity mediated breaking of supersymmetry. Further developments and applications of the model in the period 1982-85 are also discussed. The supergravity unified model and its minimal version (mSUGRA) are currently among the leading candidates for physics beyond the Standard Model. A brief note on the developments from the present vantage point is included.

  10. Production of Human Papilloma Virus Type 16 E6 Oncoprotein as a Recombinant Protein in Eukaryotic Cells

    Science.gov (United States)

    Mirshahabi, H; Soleimanjahi, H; Pourpak, Z; Meshkat, Z; Hassan, ZM

    2012-01-01

    Background Cervical cancer is one of the most important and widespread cancer which affects women. There are several causes of cervical cancer; among them HPV types 16 and 18 are the most prominent ones which are recurrent and persistent infections. These genotypes are currently about 70% of cervical cancer causes in developing countries. Due to the importance of these viruses in cervical cancer, we pioneered the production of Human Papilloma Virus type16 E6 oncoprotein as a recombinant protein in order to develop a vaccine. Two HPV oncoproteins, E6 and E7, are consistently expressed in HPV-associated cancer cells and are responsible for malignant transformation. These oncogenic proteins represent ideal target antigens for developing vaccine and immunotherapeutic strategies against HPV-associated neoplasm. Methods In the present study, the cloned E6-oncoprotein of HPV16 in pTZ57R/T-E6 vector was used to produce professional expression vector. The target gene was subcloned in a eukaryotic expression vector. The pcDNA3-E6 vector was propagated in E.coli strain DH5α and transfected into CHO cells 72 hours post-transfection. Results The transfected cells were harvested; mRNA detection and the interest protein production were confirmed by western blot analysis using specific anti E6 monoclonal antibody. Conclusion HPV16-E6 target protein recognized by specific antibody could be an appropriate form of protein, which can be used for further studies. Due to potential effect of this protein, its DNA construction can be used for DNA vaccine in future studies. PMID:25780534

  11. Bioaugmentation with endophytic bacterium E6S homologous to Achromobacter piechaudii enhances metal rhizoaccumulation in host Sedum plumbizincicola

    Directory of Open Access Journals (Sweden)

    Ying eMa

    2016-02-01

    Full Text Available Application of hyperaccumulator–endophyte symbiotic systems is a potential approach to improve phytoremediation efficiency, since some beneficial endophytic bacteria are able to detoxify heavy metals, alter metal solubility in soil and facilitate plant growth. The objective of this study was to isolate multi-metal resistant and plant beneficial endophytic bacteria and to evaluate their role in enhancing plant growth and metal accumulation/translocation. The metal resistant endophytic bacterial strain E6S was isolated from stems of the Zn/Cd hyperaccumulator plant Sedum plumbizincicola growing in metalliferous mine soils using Dworkin and Foster salts minimal agar medium with 1-aminocyclopropane-1-carboxylate (ACC as the sole nitrogen source, and identified as homologous to Achromobacter piechaudii based on morphological and biochemical characteristics, partial 16S rDNA sequence and phylogenetic analysis. Strain E6S showed high level of resistance to various metals (Cd, Zn and Pb. Besides utilizing ACC, strain E6S exhibited plant beneficial traits, such as solubilization of phosphate and production of indole-3-acetic acid. Inoculation with E6S significantly increased the bioavailability of Cd, Zn and Pb in soil. In addition, bacterial cells bound considerable amounts of metal ions in the following order: Zn ˃ Cd ˃ Pb. Inoculation of E6S significantly stimulated plant biomass, uptake and bioaccumulation of Cd, Zn and Pb. However, E6S greatly reduced the root to shoot translocation of Cd and Zn, indicating that bacterial inoculation assisted the host plant to uptake and store heavy metals in its root system. Inoculation with the endophytic bacterium E6S homologous to A. piechaudii can improve phytostabilization of metalliferous soils due to its effective ability to enhance in situ metal rhizoaccumulation in plants.

  12. Ten years after the unification : East Germany and the relevance of modern theories of trade, location and growth

    NARCIS (Netherlands)

    Brakman, S.; Schramm, M.; Garretsen, Harry

    2000-01-01

    In the paper we analyse, ten years after the German unification, the relevance of modern theoretical developments on trade, location and growth for East Germany using sectoral and regional data. Given our discussion of stylized facts about industry growth, economies of scale and differences in

  13. Infrared fixed points and fixed lines in the top-bottom-tau sector in supersymmetric grand unification

    International Nuclear Information System (INIS)

    Schrempp, B.

    1994-10-01

    The two loop 'top-down' renormalization group flow for the top, bottom and tau Yukawa couplings, from μ=M GUT ≅O(10 16 GeV) to μ≅m t , is explored in the framework of supersymmetric grand unification; reproduction of the physical bottom and tau masses is required. Instead of following the recent trend of implementing exact Yukawa coupling unification i) a search for infrared (IR) fixed lines and fixed points in the m t pole -tan β plane is performed and ii) the extent to which these imply approximate Yukawa unification is determined. In the m t pole -tan β plane two IR fixed lines, intersecting in an IR fixed point, are located. The more attractive fixed line has a branch of almost constant top mass, m t pole ≅168≅180 GeV (close to the experimental value), for the large interval 2.5 GUT approximately. The less attractive fixed line as well as the fixed point at m t pole ≅170 GeV, tan β≅55 implement approximate top-bottom Yukawa unification at all scales μ. The renormalization group flow is attracted towards the IR fixed point by way of the more attractive IR fixed line. The fixed point and lines are distinct from the much quoted effective IR fixed point m t pole ≅O(200 GeV) sin β. (orig.)

  14. Network Dependency in Migration Flows – A Space-time Analysis for Germany since Re-unification

    DEFF Research Database (Denmark)

    Mitze, Timo

    The contribution of this paper is to analyse the role of network interdependencies in a dynamic panel data model for German internal migration fl ows since re-unification. So far, a capacious account of spatial patterns in German migration data is still missing in the empirical literature. In the...

  15. Degradation of p53 by human Alphapapillomavirus E6 proteins shows a stronger correlation with phylogeny than oncogenicity.

    Directory of Open Access Journals (Sweden)

    Leiping Fu

    2010-09-01

    Full Text Available Human Papillomavirus (HPV E6 induced p53 degradation is thought to be an essential activity by which high-risk human Alphapapillomaviruses (alpha-HPVs contribute to cervical cancer development. However, most of our understanding is derived from the comparison of HPV16 and HPV11. These two viruses are relatively distinct viruses, making the extrapolation of these results difficult. In the present study, we expand the tested strains (types to include members of all known HPV species groups within the Alphapapillomavirus genus.We report the biochemical activity of E6 proteins from 27 HPV types representing all alpha-HPV species groups to degrade p53 in human cells. Expression of E6 from all HPV types epidemiologically classified as group 1 carcinogens significantly reduced p53 levels. However, several types not associated with cancer (e.g., HPV53, HPV70 and HPV71 were equally active in degrading p53. HPV types within species groups alpha 5, 6, 7, 9 and 11 share a most recent common ancestor (MRCA and all contain E6 ORFs that degrade p53. A unique exception, HPV71 E6 ORF that degraded p53 was outside this clade and is one of the most prevalent HPV types infecting the cervix in a population-based study of 10,000 women. Alignment of E6 ORFs identified an amino acid site that was highly correlated with the biochemical ability to degrade p53. Alteration of this amino acid in HPV71 E6 abrogated its ability to degrade p53, while alteration of this site in HPV71-related HPV90 and HPV106 E6s enhanced their capacity to degrade p53.These data suggest that the alpha-HPV E6 proteins' ability to degrade p53 is an evolved phenotype inherited from a most recent common ancestor of the high-risk species that does not always segregate with carcinogenicity. In addition, we identified an amino-acid residue strongly correlated with viral p53 degrading potential.

  16. Suppression of HPV E6 and E7 expression by BAF53 depletion in cervical cancer cells

    International Nuclear Information System (INIS)

    Lee, Kiwon; Lee, Ah-Young; Kwon, Yunhee Kim; Kwon, Hyockman

    2011-01-01

    Highlights: → Integration of HPV into host genome critical for activation of E6 and E7 oncogenes. → BAF53 is essential for higher-order chromatin structure. → BAF53 knockdown suppresses E6 and E7 from HPV integrants, but not from episomal HPVs. → BAF53 knockdown decreases H3K9Ac and H4K12Ac on P105 promoter of integrated HPV 18. → BAF53 knockdown restores the p53-dependent signaling pathway in HeLa and SiHa cells. -- Abstract: Deregulation of the expression of human papillomavirus (HPV) oncogenes E6 and E7 plays a pivotal role in cervical carcinogenesis because the E6 and E7 proteins neutralize p53 and Rb tumor suppressor pathways, respectively. In approximately 90% of all cervical carcinomas, HPVs are found to be integrated into the host genome. Following integration, the core-enhancer element and P105 promoter that control expression of E6 and E7 adopt a chromatin structure that is different from that of episomal HPV, and this has been proposed to contribute to activation of E6 and E7 expression. However, the molecular basis underlying this chromatin structural change remains unknown. Previously, BAF53 has been shown to be essential for the integrity of higher-order chromatin structure and interchromosomal interactions. Here, we examined whether BAF53 is required for activated expression of E6 and E7 genes. We found that BAF53 knockdown led to suppression of expression of E6 and E7 genes from HPV integrants in cervical carcinoma cell lines HeLa and SiHa. Conversely, expression of transiently transfected HPV18-LCR-Luciferase was not suppressed by BAF53 knockdown. The level of the active histone marks H3K9Ac and H4K12Ac on the P105 promoter of integrated HPV 18 was decreased in BAF53 knockdown cells. BAF53 knockdown restored the p53-dependent signaling pathway in HeLa and SiHa cells. These results suggest that activated expression of the E6 and E7 genes of integrated HPV is dependent on BAF53-dependent higher-order chromatin structure or nuclear motor

  17. Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation.

    Science.gov (United States)

    Zhao, Carolyn Ying; Szekely, Laszlo; Bao, Wenjie; Selivanova, Galina

    2010-04-15

    Proteasomal degradation of p53 by human papilloma virus (HPV) E6 oncoprotein plays a pivotal role in the survival of cervical carcinoma cells. Abrogation of HPV-E6-dependent p53 destruction can therefore be a good strategy to combat cervical carcinomas. Here, we show that a small-molecule reactivation of p53 and induction of tumor cell apoptosis (RITA) is able to induce the accumulation of p53 and rescue its tumor suppressor function in cells containing high-risk HPV16 and HPV18 by inhibiting HPV-E6-mediated proteasomal degradation. RITA blocks p53 ubiquitination by preventing p53 interaction with E6-associated protein, required for HPV-E6-mediated degradation. RITA activates the transcription of proapoptotic p53 targets Noxa, PUMA, and BAX, and repressed the expression of pro-proliferative factors CyclinB1, CDC2, and CDC25C, resulting in p53-dependent apoptosis and cell cycle arrest. Importantly, RITA showed substantial suppression of cervical carcinoma xenografts in vivo. These results provide a proof of principle for the treatment of cervical cancer in a p53-dependent manner by using small molecules that target p53. (c)2010 AACR.

  18. NF-Y loss triggers p53 stabilization and apoptosis in HPV18-positive cells by affecting E6 transcription.

    Science.gov (United States)

    Benatti, Paolo; Basile, Valentina; Dolfini, Diletta; Belluti, Silvia; Tomei, Margherita; Imbriano, Carol

    2016-07-19

    The expression of the high risk HPV18 E6 and E7 oncogenic proteins induces the transformation of epithelial cells, through the disruption of p53 and Rb function. The binding of cellular transcription factors to cis-regulatory elements in the viral Upstream Regulatory Region (URR) stimulates E6/E7 transcription. Here, we demonstrate that the CCAAT-transcription factor NF-Y binds to a non-canonical motif within the URR and activates viral gene expression. In addition, NF-Y indirectly up-regulates HPV18 transcription through the transactivation of multiple cellular transcription factors. NF-YA depletion inhibits the expression of E6 and E7 genes and re-establishes functional p53. The activation of p53 target genes in turn leads to apoptotic cell death. Finally, we show that NF-YA loss sensitizes HPV18-positive cells toward the DNA damaging agent Doxorubicin, via p53-mediated transcriptional response.

  19. Unification and mechanistic detail as drivers of model construction: models of networks in economics and sociology.

    Science.gov (United States)

    Kuorikoski, Jaakko; Marchionni, Caterina

    2014-12-01

    We examine the diversity of strategies of modelling networks in (micro) economics and (analytical) sociology. Field-specific conceptions of what explaining (with) networks amounts to or systematic preference for certain kinds of explanatory factors are not sufficient to account for differences in modelling methodologies. We argue that network models in both sociology and economics are abstract models of network mechanisms and that differences in their modelling strategies derive to a large extent from field-specific conceptions of the way in which a good model should be a general one. Whereas the economics models aim at unification, the sociological models aim at a set of mechanism schemas that are extrapolatable to the extent that the underlying psychological mechanisms are general. These conceptions of generality induce specific biases in mechanistic explanation and are related to different views of when knowledge from different fields should be seen as relevant.

  20. Restrictions on two Higgs doublet models and CP violation at the unification scale

    International Nuclear Information System (INIS)

    Athanasiu, G.G.

    1987-04-01

    Bounds on charged Higgs masses and couplings in models with two Higgs doublets are examined that came from CP violation in the neutral K system. Bounds on charged Higgs masses and couplings in two Higgs doublet models are also obtained from their effects on neutral-B-meson mixing. The bounds are found to be comparable to those obtained with additional assumptions from the neutral K system. The three generation phase invariant measure of CP violation is shown to satisfy a simple and solvable renormalization group equation. Its value is seen to fall by four to eight orders of magnitude between the weak and grand unification scales in the standard model, as well as in its two Higgs and supersymmetric extensions

  1. GOCE++ Dynamical Coastal Topography and tide gauge unification using altimetry and GOCE

    DEFF Research Database (Denmark)

    Andersen, Ole Baltazar; Knudsen, Per; Nielsen, Karina

    Mean Dynamic Topography (MDT) of the ocean along a coastline which contributes/requires reconciling altimetry, tide gauge and vertical land motion. The fundamental use of the MDT computed using altimetry, ocean models or through the use of tide gauges has values of between -2 and +1 meters at different...... processes and physics responsible for sea level changes on various temporal/spatial scales. The study runs from October 2015 to march 2017 and involves elements like: Develop an approach to estimate a consistent DT at tide gauges, coastal areas, and open ocean; Validate the approach in well-surveyed areas......ESA has recently released a study on the potential of ocean levelling as a novel approach to the study of height system unification taking the recent development in geoid accuracy trough GOCE data into account. The suggested investigation involves the use of measurements and modelling to estimate...

  2. Some speculations on a causal unification of relativity, gravitation, and quantum mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Buonomano, V; Engel, A [Universidade Estadual de Campinas (Brazil). Instituto de Matematica

    1976-03-01

    Some speculations on a causal model that could provide a common conceptual foundation for relativity, gravitation, and quantum mechanics are presented. The present approach is a unification of three theories, the first being the repulsive theory of gravitational forces first proposed by Lesage who attempted to explain gravitational forces from the principle of conservation of momentum of the hypothetical particles gravitons. The second of these theories is the Brownian motion theory of quantum mechanics or stochastic mechanics, which treats the nondeterministic nature of quantum mechanics as being due to a Brownian motion of all objects. This Brownian motion being caused by the statistical variation in the graviton flux. The above two theories are unified in this article with the causal theory of special relativity. The Big Bang theory of the creation of the Universe is assumed. An experimental test is proposed.

  3. From b → sγ to the LSP detection rates in minimal string unification models

    International Nuclear Information System (INIS)

    Khalil, S.; Masiero, A.; Shafi, Q.

    1997-04-01

    We exploit the measured branching ratio for b → sγ to derive lower limits on the sparticle and Higgs masses in the minimal string unification models. For the LSP ('bino'), chargino and the lightest Higgs, these turn out to be 50, 90 and 75 GeV respectively. Taking account of the upper bounds on the mass spectrum from the LSP relic abundance, we estimate the direct detection rate for the latter to vary from 10 -1 to 10 -4 events/kg/day. The muon flux, produced by neutrinos from the annihilating LSP's, varies in the range 10 -2 - 10 -9 muons/m 2 /day. (author). 26 refs, 9 figs

  4. Hierarchy problem, gauge coupling unification at the Planck scale, and vacuum stability

    Directory of Open Access Journals (Sweden)

    Naoyuki Haba

    2015-11-01

    Full Text Available From the point of view of the gauge hierarchy problem, introducing an intermediate scale in addition to TeV scale and the Planck scale (MPl=2.4×1018 GeV is unfavorable. In that way, a gauge coupling unification (GCU is expected to be realized at MPl. We explore possibilities of GCU at MPl by adding a few extra particles with TeV scale mass into the standard model (SM. When extra particles are fermions and scalars (only fermions with the same mass, the GCU at MPl can (not be realized. On the other hand, when extra fermions have different masses, the GCU can be realized around 8πMPl without extra scalars. This simple SM extension has two advantages that a vacuum becomes stable up to MPl (8πMPl and a proton lifetime becomes much longer than an experimental bound.

  5. A test of unification towards the radio source PKS1413+135

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, M.C., E-mail: up200802537@fc.up.pt [Centro de Astrofísica, Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4150-007 Porto (Portugal); Julião, M.D., E-mail: meinf12013@fe.up.pt [Centro de Astrofísica, Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Faculdade de Engenharia, Universidade do Porto, Rua Dr Roberto Frias, 4200-465 Porto (Portugal); Martins, C.J.A.P., E-mail: Carlos.Martins@astro.up.pt [Centro de Astrofísica, Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Monteiro, A.M.R.V.L., E-mail: mmonteiro@fc.up.pt [Centro de Astrofísica, Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4150-007 Porto (Portugal); Department of Applied Physics, Delft University of Technology, P.O. Box 5046, 2600 GA Delft (Netherlands)

    2013-07-09

    We point out that existing astrophysical measurements of combinations of the fine-structure constant α, the proton-to-electron mass ratio μ and the proton gyromagnetic ratio g{sub p} towards the radio source PKS1413+135 can be used to individually constrain each of these fundamental couplings. While the accuracy of the available measurements is not yet sufficient to test the spatial dipole scenario, our analysis serves as a proof of concept as new observational facilities will soon allow significantly more robust tests. Moreover, these measurements can also be used to obtain constraints on certain classes of unification scenarios, and we compare the constraints obtained for PKS1413+135 with those previously obtained from local atomic clock measurements.

  6. Gauge unification of basic forces, particularly of gravitation with strong interactions

    International Nuclear Information System (INIS)

    Salam, A.

    1977-01-01

    An attempt is made to present a case for the use of both the Einstein--Weyl spin-two and the Yang--Mills spin-one gauge structures for describing strong interactions. By emphasizing both spin-one and -two aspects of this force, it is hoped that a unification of this force, on the one hand, with gravity theory and, on the other, with the electromagnetic and weak interactions can be achieved. A Puppi type of tetrahedral interralation of fundamental forces, with the strong force playing a pivotal role due to its mediation through both spin-one and -two quanta, is proposed. It is claimed that the gauge invariance of gravity theory permits the use of ambuguity-free nonpolynomial techniques and thereby the securing of relistic regularization in gravity-modified field theories with the Newtonian constant G/sub N/ providing a relistic cutoff. 37 references

  7. A test of unification towards the radio source PKS1413+135

    International Nuclear Information System (INIS)

    Ferreira, M.C.; Julião, M.D.; Martins, C.J.A.P.; Monteiro, A.M.R.V.L.

    2013-01-01

    We point out that existing astrophysical measurements of combinations of the fine-structure constant α, the proton-to-electron mass ratio μ and the proton gyromagnetic ratio g p towards the radio source PKS1413+135 can be used to individually constrain each of these fundamental couplings. While the accuracy of the available measurements is not yet sufficient to test the spatial dipole scenario, our analysis serves as a proof of concept as new observational facilities will soon allow significantly more robust tests. Moreover, these measurements can also be used to obtain constraints on certain classes of unification scenarios, and we compare the constraints obtained for PKS1413+135 with those previously obtained from local atomic clock measurements

  8. Vanishing corrections on intermediate scale and implications for unification of forces

    International Nuclear Information System (INIS)

    Parida, M.K.

    1996-02-01

    In two-step breakings of a class of grand unified theories including SO(10), we prove a theorem showing that the scale (M I ) where the Pati-Salam gauge symmetry with parity breaks down to the standard gauge group, has vanishing corrections due to all sources emerging from higher scales (μ > M I ) such as the one-loop and all higher-loop effects, the GUT-threshold, gravitational smearing, and string threshold effects. Implications of such a scale for the unification of gauge couplings with small Majorana neutrino masses are discussed. In string inspired SO(10), we show that M I ≅ 5 x 10 12 GeV, needed for neutrino masses, with the GUT scale M U ≅ M str can be realized provided certain particle states in the predicted spectrum are light. (author). 28 refs, 1 tab

  9. An Orientation-Based Unification of Young Jetted AGN: The Case of 3C 286

    Energy Technology Data Exchange (ETDEWEB)

    Berton, Marco [Dipartimento di Fisica e Astronomia “G. Galilei,” Università di Padova, Padova (Italy); Brera Astronomical Observatory (INAF), Merate (Italy); Foschini, Luigi; Caccianiga, Alessandro [Brera Astronomical Observatory (INAF), Merate (Italy); Ciroi, Stefano [Dipartimento di Fisica e Astronomia “G. Galilei,” Università di Padova, Padova (Italy); Congiu, Enrico [Dipartimento di Fisica e Astronomia “G. Galilei,” Università di Padova, Padova (Italy); Brera Astronomical Observatory (INAF), Merate (Italy); Cracco, Valentina; Frezzato, Michele; La Mura, Giovanni; Rafanelli, Piero, E-mail: marco.berton@unipd.it [Dipartimento di Fisica e Astronomia “G. Galilei,” Università di Padova, Padova (Italy)

    2017-07-25

    In recent years, the old paradigm according to which only high-mass black holes can launch powerful relativistic jets in active galactic nuclei (AGN) has begun to crumble. The discovery of γ-rays coming from narrow-line Seyfert 1 galaxies (NLS1s), usually considered young and growing AGN harboring a central black hole with mass typically lower than 10{sup 8} M{sub ⊙}, indicated that also these low-mass AGN can produce powerful relativistic jets. The search for parent population of γ-ray emitting NLS1s revealed their connection with compact steep-spectrum sources (CSS). In this proceeding we present a review of the current knowledge of these sources, we present the new important case of 3C 286, classified here for the fist time as NLS1, and we finally provide a tentative orientation based unification of NLS1s and CSS sources.

  10. An Orientation-Based Unification of Young Jetted AGN: The Case of 3C 286

    International Nuclear Information System (INIS)

    Berton, Marco; Foschini, Luigi; Caccianiga, Alessandro; Ciroi, Stefano; Congiu, Enrico; Cracco, Valentina; Frezzato, Michele; La Mura, Giovanni; Rafanelli, Piero

    2017-01-01

    In recent years, the old paradigm according to which only high-mass black holes can launch powerful relativistic jets in active galactic nuclei (AGN) has begun to crumble. The discovery of γ-rays coming from narrow-line Seyfert 1 galaxies (NLS1s), usually considered young and growing AGN harboring a central black hole with mass typically lower than 10 8 M ⊙ , indicated that also these low-mass AGN can produce powerful relativistic jets. The search for parent population of γ-ray emitting NLS1s revealed their connection with compact steep-spectrum sources (CSS). In this proceeding we present a review of the current knowledge of these sources, we present the new important case of 3C 286, classified here for the fist time as NLS1, and we finally provide a tentative orientation based unification of NLS1s and CSS sources.

  11. Electroweak symmetry breaking and mass spectra in six-dimensional gauge-Higgs grand unification

    Science.gov (United States)

    Hosotani, Yutaka; Yamatsu, Naoki

    2018-02-01

    The mass spectra of the standard model particles are reproduced in the SO(11) gauge-Higgs grand unification in six-dimensional warped space without introducing exotic light fermions. Light neutrino masses are explained by the gauge-Higgs seesaw mechanism. We evaluate the effective potential of the four-dimensional Higgs boson appearing as a fluctuation mode of the Aharonov-Bohm phase θ_H in the extra-dimensional space, and show that the dynamical electroweak symmetry breaking takes place with the Higgs boson mass m_H ˜ 125 GeV and θ_H ˜ 0.1. The Kaluza-Klein mass scale in the fifth dimension is approximately given by m_KK ˜ 1.230 TeV/sin θ_H.

  12. The Human Papillomavirus Type 16 E6 Oncoprotein Activates mTORC1 Signaling and Increases Protein Synthesis ▿ †

    OpenAIRE

    Spangle, Jennifer M.; Münger, Karl

    2010-01-01

    The mammalian target of rapamycin (mTOR) kinase acts as a cellular rheostat that integrates signals from a variety of cellular signal transduction pathways that sense growth factor and nutrient availability as well as intracellular energy status. It was previously reported that the human papillomavirus type 16 (HPV16) E6 oncoprotein may activate the S6 protein kinase (S6K) through binding and E6AP-mediated degradation of the mTOR inhibitor tuberous sclerosis complex 2 (TSC2) (Z. Lu, X. Hu, Y....

  13. NF-Y loss triggers p53 stabilization and apoptosis in HPV18-positive cells by affecting E6 transcription

    OpenAIRE

    Benatti, Paolo; Basile, Valentina; Dolfini, Diletta; Belluti, Silvia; Tomei, Margherita; Imbriano, Carol

    2016-01-01

    The expression of the high risk HPV18 E6 and E7 oncogenic proteins induces the transformation of epithelial cells, through the disruption of p53 and Rb function. The binding of cellular transcription factors to cis-regulatory elements in the viral Upstream Regulatory Region (URR) stimulates E6/E7 transcription. Here, we demonstrate that the CCAAT-transcription factor NF-Y binds to a non-canonical motif within the URR and activates viral gene expression. In addition, NF-Y indirectly up-regulat...

  14. Genetic variability in E6 and E7 oncogenes of human papillomavirus Type 16 from Congolese cervical cancer isolates

    OpenAIRE

    Boumba, Luc Magloire Anicet; Assoumou, Samira Zoa; Hilali, Lahoucine; Mambou, Jean Victor; Moukassa, Donatien; Ennaji, Mustapha Moulay

    2015-01-01

    Background The molecular epidemiological studies showed that some variants of HPV-16, distributed geographically, would present a higher risk of causing cervical cancer. This study aimed to analyze nucleotide changes of HPV-16 E6 and E7 genomic regions from infected Southwestern Congolese women. Methods DNA of twenty HPV-16 isolates was analyzed by amplifying the E6 and E7 genes using type-specific primers PCR and direct sequencing. The sequences obtained were aligned with the HPV-16 GenBank ...

  15. Restrictions on two Higgs doublet models and CP violation at the unification scale

    International Nuclear Information System (INIS)

    Athanasiu, G.G.

    1987-01-01

    In Part I we examine bounds from CP violation in the neutral K system on charged Higgs masses and couplings in models with two Higgs doublets. While CP violation is still due only to a non-zero phase in the Kobayashi-Maskawa matrix, there are additional short-distance contributions involving charged Higgs exchange rather than W boson exchange. By having CP violation in the mass matrix, but not in the kaon to two pions decay amplitude, largely due to Higgs exchange, it is possible to obtain a small value of ε'/ε. In Part II we obtain bounds on charged-Higgs-boson masses and couplings in two Higgs doublet models from their effects on neutral-B-meson mixing. The bounds are comparable to those obtained with additional assumptions from the neutral-K-system. Neutral-Higgs-boson effects on the spectrum and wave functions of tt bound states are examined in the same model. In the future they could lead to restrictions on, or discovery of, the corresponding neutral Higgs bosons if they have relatively low masses and enhanced couplings. Finally, in Part III, the three generation phase invariant measure of CP violation is shown to satisfy a simple and solvable renormalization group equation. Its value falls by four to eight orders of magnitude between the weak and grand unification scales in the standard model, as well as in its two Higgs and supersymmetric extensions. Such a small value of CP violation at the grand unification scale can pose a problem for baryogenesis; this avoided if there are heavy quarks with masses close to their fixed points

  16. Human Papillomavirus Type 16 E6 and E7 Oncoproteins Act Synergistically to Cause Head and Neck Cancer in Mice

    Science.gov (United States)

    Jabbar, Sean; Strati, Katerina; Shin, Myeong Kyun; Pitot, Henry C.; Lambert, Paul F.

    2010-01-01

    High-risk human papillomaviruses (HPVs) contribute to cervical and other anogenital cancers, and they are also linked etiologically to a subset of head and neck squamous cell carcinomas (HNSCC). We previously established a model for HPV-associated HNSCC in which we treated transgenic mice expressing the papillomaviral oncoproteins with the chemical carcinogen 4-nitroquinoline-1-oxide (4-NQO). We found that the HPV-16 E7 oncoprotein was highly potent in causing HNSCC, and its dominance masked any potential oncogenic contribution of E6, a second papillomaviral oncoprotein commonly expressed in human cancers. In the current study, we shortened the duration of treatment with 4-NQO to reduce the incidence of cancers and discovered a striking synergy between E6 and E7 in causing HNSCC. Comparing the oncogenic properties of wild-type versus mutant E6 genes in this model for HNSCC uncovered a role for some but not other cellular targets of E6 previously shown to contribute to cervical cancer. PMID:20797753

  17. Potentially large contributions to the muon anomalous magnetic moment from weak-isosinglet squarks in E6 superstring models

    International Nuclear Information System (INIS)

    Morris, D.A.

    1988-01-01

    We examine contributions to the anomalous magnetic moment of the muon from weak-isosinglet squarks found in E 6 superstring models. We find that such contributions are up to 2 orders of magnitude larger than those previously calculated and correspondingly require smaller Yukawa couplings in order to maintain agreement with the measured muon anomalous magnetic moment

  18. Human Papilloma Virus 16 E6 RNA Interference Enhances Cisplatin and Death Receptor-Mediated Apoptosis in Human Cervical Carcinoma Cells

    NARCIS (Netherlands)

    Tan, Shinta; Hougardy, Brigitte M. T.; Meersma, Gert J.; Schaap, Bessel; de Vries, Elisabeth G. E.; van der Zee, Ate G. J.; de Jong, Steven

    In cervical cancer, the p53 and retinoblastoma (pRb) tumor suppressor pathways are disrupted by the human papilloma virus (HPV) E6 and E7 oncoproteins, because E6 targets p53 and E7 targets pRb for rapid proteasome-mediated degradation. We have investigated whether E6 suppression with small

  19. High-Risk Human Papillomaviral Oncogenes E6 and E7 Target Key Cellular Pathways to Achieve Oncogenesis.

    Science.gov (United States)

    Yeo-Teh, Nicole S L; Ito, Yoshiaki; Jha, Sudhakar

    2018-06-08

    Infection with high-risk human papillomavirus (HPV) has been linked to several human cancers, the most prominent of which is cervical cancer. The integration of the viral genome into the host genome is one of the manners in which the viral oncogenes E6 and E7 achieve persistent expression. The most well-studied cellular targets of the viral oncogenes E6 and E7 are p53 and pRb, respectively. However, recent research has demonstrated the ability of these two viral factors to target many more cellular factors, including proteins which regulate epigenetic marks and splicing changes in the cell. These have the ability to exert a global change, which eventually culminates to uncontrolled proliferation and carcinogenesis.

  20. HPV8-E6 Interferes with Syntenin-2 Expression through Deregulation of Differentiation, Methylation and Phosphatidylinositide-Kinase Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Benjamin Marx

    2017-09-01

    Full Text Available The E6 oncoproteins of high-risk human papillomaviruses (HPV of genus alpha contain a short peptide sequence at the carboxy-terminus, the PDZ binding domain, with which they interact with the corresponding PDZ domain of cellular proteins. Interestingly, E6 proteins from papillomaviruses of genus beta (betaPV do not encode a comparable PDZ binding domain. Irrespective of this fact, we previously showed that the E6 protein of HPV8 (betaPV type could circumvent this deficit by targeting the PDZ protein Syntenin-2 through transcriptional repression (Lazic et al., 2012. Despite its high binding affinity to phosphatidylinositol-4,5-bisphosphate (PI(4,5P2, very little is known about Syntenin-2. This study aimed to extend the knowledge on Syntenin-2 and how its expression is controlled. We now identified that Syntenin-2 is expressed at high levels in differentiating and in lower amounts in keratinocytes cultured in serum-free media containing low calcium concentration. HPV8-E6 led to a further reduction of Syntenin-2 expression only in cells cultured in low calcium. In the skin of patients suffering from Epidermodysplasia verruciformis, who are predisposed to betaPV infection, Syntenin-2 was expressed in differentiating keratinocytes of non-lesional skin, but was absent in virus positive squamous tumors. Using 5-Aza-2′-deoxycytidine, which causes DNA demethylation, Syntenin-2 transcription was profoundly activated and fully restored in the absence and presence of HPV8-E6, implicating that E6 mediated repression of Syntenin-2 transcription is due to promoter hypermethylation. Since Syntenin-2 binds to PI(4,5P2, we further tested whether the PI(4,5P2 metabolic pathway might govern Syntenin-2 expression. PI(4,5P2 is generated by the activity of phosphatidylinositol-4-phosphate-5-kinase type I (PIP5KI or phosphatidylinositol-5-phosphate-4-kinase type II (PIP4KII isoforms α, β and γ. Phosphatidylinositide kinases have recently been identified as

  1. Raman chemical mapping reveals site of action of HIV protease inhibitors in HPV16 E6 expressing cervical carcinoma cells.

    Science.gov (United States)

    Kim, Dong-Hyun; Jarvis, Roger M; Allwood, J William; Batman, Gavin; Moore, Rowan E; Marsden-Edwards, Emma; Hampson, Lynne; Hampson, Ian N; Goodacre, Royston

    2010-12-01

    It has been shown that the HIV protease inhibitors indinavir and lopinavir may have activity against the human papilloma virus (HPV) type 16 inhibiting HPV E6-mediated proteasomal degradation of p53 in cultured cervical carcinoma cells. However, their mode and site of action is unknown. HPV-negative C33A cervical carcinoma cells and the same cells stably transfected with E6 (C33AE6) were exposed to indinavir and lopinavir at concentrations of 1 mM and 30 μM, respectively. The intracellular distribution of metabolites and metabolic changes induced by these treatments were investigated by Raman microspectroscopic imaging combined with the analysis of cell fractionation products by liquid chromatography-mass spectrometry (LC-MS). A uniform cellular distribution of proteins was found in drug-treated cells irrespective of cell type. Indinavir was observed to co-localise with nucleic acid in the nucleus, but only in E6 expressing cells. Principal components analysis (PCA) score maps generated on the full Raman hypercube and the corresponding PCA loadings plots revealed that the majority of metabolic variations influenced by the drug exposure within the cells were associated with changes in nucleic acids. Analysis of cell fractionation products by LC-MS confirmed that the level of indinavir in nuclear extracts was approximately eight-fold greater than in the cytoplasm. These data demonstrate that indinavir undergoes enhanced nuclear accumulation in E6-expressing cells, which suggests that this is the most likely site of action for this compound against HPV.

  2. Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

    Science.gov (United States)

    van de Wall, Stephanie; Walczak, Mateusz; van Rooij, Nienke; Hoogeboom, Baukje-Nynke; Meijerhof, Tjarko; Nijman, Hans W.; Daemen, Toos

    2015-01-01

    The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus. PMID:26343186

  3. Sonoporation delivery of monoclonal antibodies against human papillomavirus 16 E6 restores p53 expression in transformed cervical keratinocytes.

    Directory of Open Access Journals (Sweden)

    Melissa Togtema

    Full Text Available High-risk types of human papillomavirus (HPV, such as HPV16, have been found in nearly all cases of cervical cancer. Therapies targeted at blocking the HPV16 E6 protein and its deleterious effects on the tumour suppressor pathways of the cell can reverse the malignant phenotype of affected keratinocytes while sparing uninfected cells. Through a strong interdisciplinary collaboration between engineering and biology, a novel, non-invasive intracellular delivery method for the HPV16 E6 antibody, F127-6G6, was developed. The method employs high intensity focused ultrasound (HIFU in combination with microbubbles, in a process known as sonoporation. In this proof of principle study, it was first demonstrated that sonoporation antibody delivery into the HPV16 positive cervical carcinoma derived cell lines CaSki and SiHa was possible, using chemical transfection as a baseline for comparison. Delivery of the E6 antibody using sonoporation significantly restored p53 expression in these cells, indicating the antibody is able to enter the cells and remains active. This delivery method is targeted, non-cytotoxic, and non-invasive, making it more easily translatable for in vivo experiments than other transfection methods.

  4. Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

    Directory of Open Access Journals (Sweden)

    Stephanie van de Wall

    2015-03-01

    Full Text Available The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV targeting human papillomavirus (HPV. Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7 via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.

  5. The clinical value of HPV E6/E7 and STAT3 mRNA detection in cervical cancer screening.

    Science.gov (United States)

    Fan, Yibing; Shen, Zongji

    2018-02-11

    To explore the value of human papillomavirus (HPV) E6/E7 and signal transducer and activator of transcription 3 (STAT3) mRNA detection in the screening of cervical lesions. 192 patients with abnormal ThinPrep cytology test (TCT) results and/or high-risk HPV infection were screened to identify possible cervical lesions in cases. Diagnoses were confirmed by histopathology. Fluorescence in situ hybridization (FISH) was performed to detect and qualify the mRNAs of HPV E6/E7, STAT3, and Survivin in cervical exfoliated cells. In addition, the performance of separate and combined mRNA detection methods were compared with TCT, HR-HPV DNA schemes respectively. 1. Compared with HPVE6/E7 and STAT3 mRNA methods, Survivin mRNA assay had poor specificity (Sp), Youden index (YI) and concordance rate. 2. HPV E6/E7, STAT3, and STAT3 + HR-HPV methods had the best Sp, concordance rate and positive predictive value (PPV) for cervical lesions screening and atypical squamous cells of undetermined significance (ASCUS) triage. For screening of high grade squamous intraepithelial lesions or greater (HSILs+), no difference was observed in the Se of mRNA detection methods in comparison with that of TCT, HR-HPV and TCT + HR-HPV, whereas the false positive rate (FPR) decreased by 41.48%/55.99%/17.19% and the colposcopy referral rate reduced by about 20.00%/25.00%/11.17%. For triage of women with ASCUS, no difference was observed in the Se of mRNA detection methods as compared to that of HR-HPV (χ 2  = 1.05, P > 0.75), while the FPR decreased by 45.83%/37.50%/41.66% and the colposcopy referral rate reduced by 32.42%/22.60%/25.28%, respectively. The Se, YI, and PPV of the combined methods increased in comparison to each method alone. 3. Compared with the TCT + HR-HPV method, HPV E6/E7 + STAT3 method had perfect Sp (95.92%) and PPV (95.40%) for screening HSILs+, the FPR and colposcopy referral rate decreased by 31.06% and 22.48% respectively. 1. The expression of HPV E6/E

  6. E6D25E, HPV16 Asian variant shows specific proteomic pattern correlating in cells transformation and suppressive innate immune response

    International Nuclear Information System (INIS)

    Chopjitt, Peechanika; Pientong, Chamsai; Sunthamala, Nuchsupha; Kongyingyoes, Bunkerd; Haonon, Ornuma; Boonmars, Thidarut; Kikawa, Satomi; Nakahara, Tomomi; Kiyono, Tohru; Ekalaksananan, Tipaya

    2016-01-01

    HPV16 Asian variant (HPV16As) containing E6D25E oncogene, is commonly associated with cervical cancers of Asian populations. To explore a mechanism of E6D25E oncoprotein in carcinogenesis, we compared protein profiles in human keratinocytes expressing E6D25E with E6 of HPV16 prototype (E6Pro). A human cervical keratinocyte cell line, HCK1T, was transduced with retroviruses containing E6D25E or E6Pro genes. Biological properties of E6D25E or E6Pro transduced HCK1T cells were characterized. Protein profiles of the transduced HCK1T cells were analyzed using 2D-PAGE and characterized by mass spectrometry and western blotting. Reactomes of modulated proteins were analyzed by using the Reactome Knowledgebase. The E6D25E and E6Pro oncoproteins were comparable for their abilities to degrade p53 and suppress the induction of p21, and induce cell proliferation. Interestingly, the protein profiles of the HCK1T cells transduced with E6D25E showed specific proteomic patterns different from those with E6Pro. Among altered proteins, more than 1.5-fold up- or down- regulation was observed in E6D25E-expressing cells for gp96 and keratin7 which involved in activation of TLR signaling and transformation of squamocolumnar junction cells, respectively. This report describes new cellular proteins specifically targeted by E6D25E oncoprotein that may contribute to impair immune response against viral infection and cell transformation associated with oncogenic property of HPV16As variant. - Highlights: • E6D25E HPV16 specifically modulates protein profile of human keratinocytes. • E6D25E HPV16 modulates protein profile which involves in TLR signalling and transformation of squamocolumnar junction cells. • E6D25E oncoprotein may correlate to impair of immune response against viral infection and cells transformation.

  7. E6D25E, HPV16 Asian variant shows specific proteomic pattern correlating in cells transformation and suppressive innate immune response

    Energy Technology Data Exchange (ETDEWEB)

    Chopjitt, Peechanika; Pientong, Chamsai; Sunthamala, Nuchsupha [Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002 (Thailand); HPV & EBV and Carcinogenesis Research Group, Khon Kaen University (Thailand); Kongyingyoes, Bunkerd [Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002 (Thailand); Haonon, Ornuma; Boonmars, Thidarut [Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002 (Thailand); Kikawa, Satomi; Nakahara, Tomomi [Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 (Japan); Kiyono, Tohru, E-mail: tkiyono@ncc.go.jp [Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 (Japan); Ekalaksananan, Tipaya, E-mail: tipeka@kku.ac.th [Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002 (Thailand); HPV & EBV and Carcinogenesis Research Group, Khon Kaen University (Thailand)

    2016-09-09

    HPV16 Asian variant (HPV16As) containing E6D25E oncogene, is commonly associated with cervical cancers of Asian populations. To explore a mechanism of E6D25E oncoprotein in carcinogenesis, we compared protein profiles in human keratinocytes expressing E6D25E with E6 of HPV16 prototype (E6Pro). A human cervical keratinocyte cell line, HCK1T, was transduced with retroviruses containing E6D25E or E6Pro genes. Biological properties of E6D25E or E6Pro transduced HCK1T cells were characterized. Protein profiles of the transduced HCK1T cells were analyzed using 2D-PAGE and characterized by mass spectrometry and western blotting. Reactomes of modulated proteins were analyzed by using the Reactome Knowledgebase. The E6D25E and E6Pro oncoproteins were comparable for their abilities to degrade p53 and suppress the induction of p21, and induce cell proliferation. Interestingly, the protein profiles of the HCK1T cells transduced with E6D25E showed specific proteomic patterns different from those with E6Pro. Among altered proteins, more than 1.5-fold up- or down- regulation was observed in E6D25E-expressing cells for gp96 and keratin7 which involved in activation of TLR signaling and transformation of squamocolumnar junction cells, respectively. This report describes new cellular proteins specifically targeted by E6D25E oncoprotein that may contribute to impair immune response against viral infection and cell transformation associated with oncogenic property of HPV16As variant. - Highlights: • E6D25E HPV16 specifically modulates protein profile of human keratinocytes. • E6D25E HPV16 modulates protein profile which involves in TLR signalling and transformation of squamocolumnar junction cells. • E6D25E oncoprotein may correlate to impair of immune response against viral infection and cells transformation.

  8. Aspects of the flipped unification of strong, weak and electromagnetic interactions

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, J.; Hagelin, J.S.; Kelley, S.; Nanopoulos, D.V.

    1988-12-19

    We explore phenomenological aspects of a recently proposed flipped SU(5) x U(1) supersymmetric GUT which incorporates an economical and natural mechanism for splitting Higgs doublets and triplets, and can be derived from string theory. Using experimental values of sin/sup 2/theta/sub W/ and the strong QCD coupling, we estimate the grand unification scale M/sub G/, where the strong and weak coupling strengths are equal, and the superunification scale M/sub SU/, where all couplings are equal. We find typical values of M/sub G/ approx. = 10/sup 15/ to 10/sup 17/ GeV, with M/sub SU/ somewhat higher and close to the value suggested by string models. We discuss different mechanisms for baryon decay, finding that the dominant one is gauge-boson exchange giving rise to p -> e/sup +/ /sup 0/, anti /sup +/ and n -> e/sup +/ /sup -/, anti /sup 0/ with partial lifetimes approx. = 10/sup 35+-2/ y. We show that a large GUT symmetry-breaking scale M/sub G/ is naturally generated by radiative corrections to the effective potential if a small amount approx. = m/sub W/ of soft supersymmetry breaking is generated dynamically at a large scale. We analyze the low-energy effective theory obtained using the renormalization group equations, demonstrating that electroweak symmetry breaking is obtained if m/sub t/ approx. = 60 to 90 GeV. We analyze the spectrum of sparticles, with particular attention to neutralinos.

  9. The Unification of Space Qualified Integrated Circuits by Example of International Space Project GAMMA-400

    Science.gov (United States)

    Bobkov, S. G.; Serdin, O. V.; Arkhangelskiy, A. I.; Arkhangelskaja, I. V.; Suchkov, S. I.; Topchiev, N. P.

    The problem of electronic component unification at the different levels (circuits, interfaces, hardware and software) used in space industry is considered. The task of computer systems for space purposes developing is discussed by example of scientific data acquisition system for space project GAMMA-400. The basic characteristics of high reliable and fault tolerant chips developed by SRISA RAS for space applicable computational systems are given. To reduce power consumption and enhance data reliability, embedded system interconnect made hierarchical: upper level is Serial RapidIO 1x or 4x with rate transfer 1.25 Gbaud; next level - SpaceWire with rate transfer up to 400 Mbaud and lower level - MIL-STD-1553B and RS232/RS485. The Ethernet 10/100 is technology interface and provided connection with the previously released modules too. Systems interconnection allows creating different redundancy systems. Designers can develop heterogeneous systems that employ the peer-to-peer networking performance of Serial RapidIO using multiprocessor clusters interconnected by SpaceWire.

  10. b-τ unification with gaugino and s fermion mass non-universality

    International Nuclear Information System (INIS)

    Pallis, C.

    2004-01-01

    In the context of a SUSY GUT inspired MSSM version, the low energy consequences of the asymptotic b-τ Yukawa coupling unification are examined, under the assumption of universal or non-universal boundary conditions for the gaugino and s fermion masses. Gaugino non-universality is applied, so that the SUSY corrections to b-quark mass can be reconciled with the present experimental data on muon anomalous magnetic moment. Restrictions on the parameter space, originating from the cold dark matter abundance in the universe, the inclusive branching ratio of b→sγ and the accelerator data are, also, investigated and the scalar neutralino-proton cross section is calculated. In the case of a bino-like LSP and universal boundary conditions for the s fermion masses, the constraints, arising from the cold dark matter and BR(b→sγ) can be simultaneously satisfied, mainly thanks to the A-pole effect or the neutralino-stau coannihilations. In addition, s fermion mass non-universality provides the possibility of new coannihilation phenomena (neutralino-sbottom or neutralino-tau sneutrino-stau), which facilitate the simultaneous satisfaction of all the above requirements. In both cases above, the neutralino abundance can essentially decrease for a wino or higgsino like LSP creating regions of parameter space with additional neutralino-chargino and/or heavier neutralino coannihilations. The neutralino-sbottom mass proximity significantly ameliorates the detectability of LSP

  11. Toward a New Paradigm for the Unification of Radio Loud AGN and its Connection to Accretion

    Science.gov (United States)

    Georganpoulos, Markos; Meyer, Eileen T.; Fossati, Giovanni; Lister, Matthew L.

    2012-01-01

    We recently argued [21J that the collective properties. of radio loud active galactic nuclei point to the existence of two families of sources, one of powerful sources with single velocity jets and one of weaker jets with significant velocity gradients in the radiating plasma. These families also correspond to different accretion modes and therefore different thermal and emission line intrinsic properties: powerful sources have radiatively efficient accretion disks, while in weak sources accretion must be radiatively inefficient. Here, after we briefly review of our recent work, we present the following findings that support our unification scheme: (i) along the broken sequence of aligned objects, the jet kinetic power increases. (ii) in the powerful branch of the sequence of aligned objects the fraction of BLLs decreases with increasing jet power. (iii) for powerful sources, the fraction of BLLs increases for more un-aligned objects, as measured by the core to extended radio emission. Our results are also compatible with the possibility that a given accretion power produces jets of comparable kinetic power.

  12. Unification of space-time and internal symmetries through superstrings, with elementary or composite quarks

    International Nuclear Information System (INIS)

    Huebsch, T.

    1987-01-01

    Symmetry properties of a given physical system constrain greatly the theoretical models built in the attempt to describe the system. In complement, the symmetry properties of a system typically undergo dramatic changes during its evolution in time, underpinning the concept of phase transitions. Employing these two ideas we analyze models of Particle Physics at increasingly higher levels of unification, attempting to cover the wide span from the domain of experimentally accessible energies to scales where all the known interactions (including gravity) may be described as low-energy effects of the tremendous and intricate structure of Superstring theories. In particular, we study the scenario of compactification of the Heterotic Superstring theory involving Calabi-Yau manifolds and derive the basic properties of the effective point-field theory action, give a huge class of constructions and devise some techniques for future analysis. Further we study the possibility that the phase-transition from Superstrings to observed particles involves an intermediary phase where the observed particles exhibit compositeness, together with some consequences on the low-energy phenomenology. Finally we include our attempt to modify the SU(5) model, as one of the simplest Grand-unified models, to provide a solution to its difficulties. As we now show, the problems we were trying to address are so generic that some of them remain (in a disguised form) even at the present understanding of the Superstring theories, the most ample constructs of fundamental Physics so far

  13. Unigrace - A Project For The Unification of Gravity Systems In Central Europe

    Science.gov (United States)

    Richter, B.; Falk, R.; Erker, E.; Ruess, D.; Mäkinen, J.; Hinderer, J.; Marson, I.; Sledzinski, J.

    Because of the present trends of political and economical unification in Europe for- merly classified gravimetric data in Central Europe are becoming available. The dif- ferences, however, between gravity systems in this area are so large that they strongly affect the geoid, vertical datum definitions and height systems. It is therefore manda- tory to study system differences and to unify them. The project UNIGRACE aims at solving this problem by carrying out absolute grav- ity measurements with the most advanced technology at 17 selected sites in the coun- tries concerned. In a joint effort five European groups from Austria, Finland, France, Germany, Italy and Poland using their absolute gravimeters and partners from Bul- garia, Croatia, Czech Republic, Hungary, Romania, Slovakia and Slovenia cooperate in selecting and/or establishing the sites and performing the measurements as well as in connecting the absolute sites to the national gravimetric networks. As a result, a unique gravity system in Central Europe will be available. The project started on Jan. 1, 1998 and till the end of 2000 all selected gravity sites have been observed twice by absolute gravimeters. From these repeated measurements the final results for this project will be presented which was granted by the European Commission.

  14. L’Autriche face à la réunification allemande

    Directory of Open Access Journals (Sweden)

    Gérard Grelle

    2012-11-01

    Full Text Available La chute du Mur de Berlin, en 1989, fut certes pour l’Autriche un événement politique majeur, mais pas plus important que la fin du rideau de fer. En effet, quasiment « enclavée » entre plusieurs pays socialistes, l’Autriche considéra la disparition du rideau de fer comme une ouverture sans limite aux pays d’Europe Centrale et de l’Est. Au cours des vingt années qui suivirent ces événements, l’Autriche a largement contribué au développement politique, économique et social des pays de l’Est en pratiquant une politique d’échanges économiques et financiers avec ces pays afin d’aider à leur reconstruction. Dans un tel contexte, la chute du Mur de Berlin et la réunification allemande ont été appréhendées comme un simple élément du puzzle de la reconstruction européenne. Une telle stratégie a alors permis à l’Autriche de sortir définitivement de son inquiétude face à la persistance d’un danger « annexionniste » de la part de l’Allemagne.

  15. The Impact of Family Unification Housing Vouchers on Child Welfare Outcomes.

    Science.gov (United States)

    Pergamit, Michael; Cunningham, Mary; Hanson, Devlin

    2017-09-01

    This study addresses whether providing housing vouchers through the Family Unification Program (FUP) to families involved in the child welfare system reduces child maltreatment and the need for child welfare services. The study uses child welfare administrative data on 326 children in Portland, Oregon, and 502 children in San Diego, California from the point at which their families were referred to the program through 18 months post-referral. Using a quasi-experimental waitlist comparison design, probit regressions show little impact of FUP on preventing child removal from home, but some positive impact on reunification among children already placed out of home. Hazard estimations show receipt of FUP speeds up child welfare case closure. Impacts on new reports of abuse and neglect are mixed, but point toward reduced reports. Low rates of removal among intact comparison families and high rates of reunification for children in out-of-home care suggest poor targeting of housing resources. Housing vouchers are being given to families not bearing the risks the program is intended to address. The presence of some positive findings suggests that housing vouchers might help reduce child welfare involvement if better targeting were practiced by child welfare agencies. © Society for Community Research and Action 2017.

  16. 125 GeV Higgs boson mass from 5D gauge-Higgs unification

    Science.gov (United States)

    Carson, Jason; Okada, Nobuchika

    2018-03-01

    In the context of a simple gauge-Higgs unification (GHU) scenario based on the gauge group SU(3)×U(1)^' in a 5D flat space-time, we investigate the possibility of reproducing the observed Higgs boson mass of around 125 GeV. We introduce bulk fermion multiplets with a bulk mass and a (half-)periodic boundary condition. In our analysis, we adopt a low-energy effective theoretical approach of the GHU scenario, where the running Higgs quartic coupling is required to vanish at the compactification scale. Under this "gauge-Higgs condition," we investigate the renormalization group evolution of the Higgs quartic coupling and find a relation between the bulk mass and the compactification scale so as to reproduce the 125 GeV Higgs boson mass. Through quantum corrections at the one-loop level, the bulk fermions contribute to the Higgs boson production and decay processes and deviate the Higgs boson signal strengths at the Large Hadron Collider experiments from the Standard Model (SM) predictions. Employing the current experimental data that show that the Higgs boson signal strengths for a variety of Higgs decay modes are consistent with the SM predictions, we obtain lower mass bounds on the lightest mode of the bulk fermions to be around 1 TeV.

  17. Viable and testable SUSY GUTs with Yukawa unification the case of split trilinears

    CERN Document Server

    Guadagnoli, Diego; Straub, David M

    2009-01-01

    We explore general SUSY GUT models with exact third-generation Yukawa unification, but where the requirement of universal soft terms at the GUT scale is relaxed. We consider the scenario in which the breaking of universality inherits from the Yukawa couplings, i.e. is of minimal flavor violating (MFV) type. In particular, the MFV principle allows for a splitting between the up-type and the down-type soft trilinear couplings. We explore the viability of this trilinear splitting scenario by means of a fitting procedure to electroweak observables, quark masses as well as flavor-changing neutral current processes. Phenomenological viability singles out one main scenario. This scenario is characterized by a sizable splitting between the trilinear soft terms and a large mu term. Remarkably, this scenario does not invoke a partial decoupling of the sparticle spectrum, as in the case of universal soft terms, but instead it requires part of the spectrum, notably the lightest stop, the gluino and the lightest charginos...

  18. Attenuated Recombinant Influenza A Virus Expressing HPV16 E6 and E7 as a Novel Therapeutic Vaccine Approach.

    Directory of Open Access Journals (Sweden)

    Christoph Jindra

    Full Text Available Persistent infection with high-risk human papillomavirus (HPV types, most often HPV16 and HPV18, causes all cervical and most anal cancers, and a subset of vulvar, vaginal, penile and oropharyngeal carcinomas. Two prophylactic virus-like particle (VLPs-based vaccines, are available that protect against vaccine type-associated persistent infection and associated disease, yet have no therapeutic effect on existing lesions or infections. We have generated recombinant live-attenuated influenza A viruses expressing the HPV16 oncogenes E6 and E7 as experimental immunotherapeutic vaccine candidates. The influenza A virus life cycle lacks DNA intermediates as important safety feature. Different serotypes were generated to ensure efficient prime and boost immunizations. The immune response to vaccination in C57BL/6 mice was characterized by peptide ELISA and IFN-γ ELISpot, demonstrating induction of cell-mediated immunity to HPV16 E6 and E7 oncoproteins. Prophylactic and therapeutic vaccine efficacy was analyzed in the murine HPV16-positive TC-1 tumor challenge model. Subcutaneous (s.c. prime and boost vaccinations of mice with recombinant influenza A serotypes H1N1 and H3N2, followed by challenge with TC-1 cells resulted in complete protection or significantly reduced tumor growth as compared to control animals. In a therapeutic setting, s.c. vaccination of mice with established TC-1 tumors decelerated tumor growth and significantly prolonged survival. Importantly, intralesional vaccine administration induced complete tumor regression in 25% of animals, and significantly reduced tumor growth in 50% of mice. These results suggest recombinant E6E7 influenza viruses as a promising new approach for the development of a therapeutic vaccine against HPV-induced disease.

  19. E6 based mechanism for the generation of fermion electric dipole moments: An application to the solar neutrino puzzle

    International Nuclear Information System (INIS)

    Grifols, J.A.

    1987-01-01

    We discuss the electric dipole moments (EDM) of fermions generated by CP-violating phases associated to the new Yukawa couplings involving heavy matter E 6 fields predicted in the framework of superstring theories. While for neutron and electron it is not strictly necessary to resort to a superstring scenario to get a substantial EDM, in the neutrino case a sizeable EDM is a distinctive feature of the superstring. We thus focus on the neutrino EDM and discuss its relevance for the solution of the solar neutrino problem. (orig.)

  20. Immunogenicity of dendritic cell-based HPV16 E6/E7 peptide vaccines: CTL activation and protective effects

    Czech Academy of Sciences Publication Activity Database

    Indrová, Marie; Reiniš, Milan; Bubeník, Jan; Jandlová, Táňa; Bieblová, Jana; Vonka, V.; Velek, Jiří

    2004-01-01

    Roč. 50, č. 6 (2004), s. 184-193 ISSN 0015-5500 R&D Projects: GA MZd NC7148; GA MZd NR7807; GA ČR GA301/01/0985; GA ČR GA301/04/0492; GA AV ČR KSK5011112 Grant - others:Fogarty International Center(US) D43 TW000233 Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV16 E6/E7 peptides * dendritic cell s * cytotoxic lymphocytes Subject RIV: EC - Immunology Impact factor: 0.507, year: 2004

  1. Curcumin modulates cellular AP-1, NF-kB, and HPV16 E6 proteins in oral cancer.

    Science.gov (United States)

    Mishra, Alok; Kumar, Rakesh; Tyagi, Abhishek; Kohaar, Indu; Hedau, Suresh; Bharti, Alok C; Sarker, Subhodeep; Dey, Dipankar; Saluja, Daman; Das, Bhudev

    2015-01-01

    In this study, we investigated the effects of the natural antioxidant curcumin on the HPV16-positive oral carcinoma cell line 93VU147T and demonstrated that curcumin is not only a potent inhibitor for the activity of host nuclear transcription factors AP-1 and NF-kB but it also selectively suppresses transcription of the HPV16/E6 oncogene during the carcinogenic process in oral cancer cells. This study suggests a therapeutic potential of curcumin for high-risk human papilloma virus (HPV)-infected oral cancers.

  2. Practical Steps toward Computational Unification: Helpful Perspectives for New Systems, Adding Functionality to Existing Ones

    Science.gov (United States)

    Troy, R. M.

    2005-12-01

    With ever increasing amounts of Earth-Science funding being diverted to the war in Iraq, the Earth-Science community must now more than ever wring every bit of utility out of every dollar. We're not likely to get funded any projects perceived by others as "pie in the sky", so we have to look at already funded programs within our community and directing new programs in a unifying direction. We have not yet begun the transition to a computationally unifying, general-purpose Earth Science computing paradigm, though it was proposed at the Fall 2002 AGU meeting in San Francisco, and perhaps earlier. Encouragingly, we do see a recognition that more commonality is needed as various projects have as funded goals the addition of the processing and dissemination of new datatypes, or data-sets, if you prefer, to their existing repertoires. Unfortunately, the timelines projected for adding a datatype to an existing system are typically estimated at around two years each. Further, many organizations have the perception that they can only use their dollars to support exclusively their own needs as they don't have the money to support the goals of others, thus overlooking opportunities to satisfy their own needs while at the same time aiding the creation of a global GeoScience cyber-infrastructure. While Computational Unification appears to be an unfunded, impossible dream, at least for now, individual projects can take steps that are compatible with a unified community and can help build one over time. This session explores these opportunities. The author will discuss the issues surrounding this topic, outlining alternative perspectives on the points of difficulty, and proposing straight-forward solutions which every Earth Science data processing system should consider. Sub-topics include distributed meta-data, distributed processing, distributed data objects, interdisciplinary concerns, and scientific defensibility with an overall emphasis on how previously written processes

  3. Trains and the Italian Unification: the Time of the Railways Buildings

    Directory of Open Access Journals (Sweden)

    Stefano Maggi

    2011-04-01

    Full Text Available The physical construction of modern Italy began in 1861, with the foundation of the Kingdom of Italy. The historical period coincided with the early industrial development of north-western Italy, and so the new infrastructure system developed in response, on the one hand, to the need to join together all the fragmentary pieces that formed the country and, on the other, to the general tendency to strengthen those areas that were economically and industrially stronger even before unification. The system that was being created in the 1860s by the Italian State before unification suffered continuous interruptions and was substantially without transverse connections, those with more difficult construction caused by the need to cross the Apennines. Within five years, from 1861 to 1866, the size of the railway system doubled, going from little more than 2,000 km to more than 4,000. The management of railway was entrusted to limited companies. The government guaranteed the company a contribution for each kilometer of railway built. In 1863 the tracks extended down the Adriatic coast as far as Brindisi, in order to attract the transit of the India Mail London- Brindisi-Bombay, the most important trade of the world. In 1863 Rome was linked to Naples, in 1864 the line from Bologna to Florence via Pistoia was opened, in 1866 Rome was linked to Florence and Ancona and in 1867 with Pisa. In 1874 the Genoa-Pisa line were completed as far as the frontier with France; later, in 1879 the Naples-Foggia line went into operation. In the same period some of the longer tunnels were opened. Those of Fréjus was realised between 1857 and 1871. The Gottardo tunnel came into being in 1882 and the Sempione tunnel in 1906. The opening of the alpine passes effectively permitted the connection of Italy to central Europe, flinging open the doors to more and more easily reachable markets. In last twenty years of the 19th century, in Italy began the strong development of the

  4. Regulation of the Wnt/β-Catenin Signaling Pathway by Human Papillomavirus E6 and E7 Oncoproteins

    Directory of Open Access Journals (Sweden)

    Jesus Omar Muñoz Bello

    2015-08-01

    Full Text Available Cell signaling pathways are the mechanisms by which cells transduce external stimuli, which control the transcription of genes, to regulate diverse biological effects. In cancer, distinct signaling pathways, such as the Wnt/β-catenin pathway, have been implicated in the deregulation of critical molecular processes that affect cell proliferation and differentiation. For example, changes in β-catenin localization have been identified in Human Papillomavirus (HPV-related cancers as the lesion progresses. Specifically, β-catenin relocates from the membrane/cytoplasm to the nucleus, suggesting that this transcription regulator participates in cervical carcinogenesis. The E6 and E7 oncoproteins are responsible for the transforming activity of HPV, and some studies have implicated these viral oncoproteins in the regulation of the Wnt/β-catenin pathway. Nevertheless, new interactions of HPV oncoproteins with cellular proteins are emerging, and the study of the biological effects of such interactions will help to understand HPV-related carcinogenesis. Viruses 2015, 7 4735 This review addresses the accumulated evidence of the involvement of the HPV E6 and E7 oncoproteins in the activation of the Wnt/β-catenin pathway.

  5. UNIFICATION AND APPLICATIONS OF MODERN OCEANIC/ATMOSPHERIC DATA ASSIMILATION ALGORITHMS

    Institute of Scientific and Technical Information of China (English)

    QIAO Fang-li; ZHANG Shao-qing; YUAN Ye-li

    2004-01-01

    The key mathematics and applications of various modern atmospheric/oceanic data assimilation methods including Optimal Interpolation(OI),4-dimensional variational approach(4D-Var)and filters were systematically reviewed and classified.Based on the data assimilation philosophy,I.e.,using model dynamics to extract the observational information,the common character of the problem,such as the probabilistic nature of the evolution of the atmospheric/oceanic system,noisy and irregularly spaced observations,and the advantages and disadvantages of these data assimilation algorithms,were discussed.In the filtering framework,all modern data assimilation algorithms were unified: OI/3D-Var is a stationary filter,4D-Var is a linear(Kalman)filter and an ensemble of Kalman filters is able to construct a nonlinear filter.The nonlinear filter such as the Ensemble Kalman Filter(ENKF),Ensemble Adjustment Kalman Filter(EAKF)and Ensemble Transformation Kalman Filter(ETKF)can,to some extent,account for the non-Gaussian information of the prior distribution from the model.The flow-dependent covariance estimated by an ensemble filter may be introduced to OI and 4D-Var to improve these traditional algorithms.In practice,the performance of algorithms may depend on the specific numerical model and the choice of algorithm may depend on the specific problem.However,the unification of algorithms allows us to establish a unified test system to evaluate these algorithms,which provides more insights into data assimilation philosophies and helps improve data assimilation techniques.

  6. Fermionic minimal dark matter in 5D gauge-Higgs unification

    Science.gov (United States)

    Maru, Nobuhito; Okada, Nobuchika; Okada, Satomi

    2017-12-01

    We propose a minimal dark matter (MDM) scenario in the context of a simple gauge-Higgs unification (GHU) model based on the gauge group S U (3 )×U (1 )' in five-dimensional Minkowski space with a compactification of the fifth dimension on the 1S/Z2 orbifold. A pair of vectorlike S U (3 ) multiplet fermions in a higher-dimensional representation is introduced in the bulk, and the DM particle is identified with the lightest mass eigenstate among the components in the multiplets. In the original model description, the DM particle communicates with the Standard Model (SM) particles only through the bulk gauge interaction, and hence our model is the GHU version of the MDM scenario. There are two typical realizations of the DM particle in four-dimensional effective theory: (i) the DM particle is mostly composed of the SM S U (2 )L multiplets, or (ii) the DM is mostly composed of the SM S U (2 )L singlets. Since the case (i) is very similar to the original MDM scenario, we focus on the case (ii), which is a realization of the Higgs-portal DM scenario in the context of the GHU model. We identify an allowed parameter region to be consistent with the current experimental constraints, which will be fully covered by the direct dark matter detection experiments in the near future. In the presence of the bulk multiplet fermions in higher-dimensional S U (3 ) representations, we reproduce the 125 GeV Higgs boson mass through the renormalization group evolution of Higgs quartic coupling with the compactification scale of 10-100 TeV.

  7. CARINA data synthesis project: pH data scale unification and cruise adjustments

    Science.gov (United States)

    Velo, A.; Pérez, F. F.; Lin, X.; Key, R. M.; Tanhua, T.; de La Paz, M.; Olsen, A.; van Heuven, S.; Jutterström, S.; Ríos, A. F.

    2010-05-01

    Data on carbon and carbon-relevant hydrographic and hydrochemical parameters from 188 previously non-publicly available cruise data sets in the Artic Mediterranean Seas (AMS), Atlantic Ocean and Southern Ocean have been retrieved and merged to a new database: CARINA (CARbon IN the Atlantic Ocean). These data have gone through rigorous quality control (QC) procedures to assure the highest possible quality and consistency. The data for most of the measured parameters in the CARINA database were objectively examined in order to quantify systematic differences in the reported values. Systematic biases found in the data have been corrected in the data products, three merged data files with measured, calculated and interpolated data for each of the three CARINA regions; AMS, Atlantic Ocean and Southern Ocean. Out of a total of 188 cruise entries in the CARINA database, 59 reported pH measured values. All reported pH data have been unified to the Sea-Water Scale (SWS) at 25 °C. Here we present details of the secondary QC of pH in the CARINA database and the scale unification to SWS at 25 °C. The pH scale has been converted for 36 cruises. Procedures of quality control, including crossover analysis between cruises and inversion analysis are described. Adjustments were applied to the pH values for 21 of the cruises in the CARINA dataset. With these adjustments the CARINA database is consistent both internally as well as with the GLODAP data, an oceanographic data set based on the World Hydrographic Program in the 1990s. Based on our analysis we estimate the internal consistency of the CARINA pH data to be 0.005 pH units. The CARINA data are now suitable for accurate assessments of, for example, oceanic carbon inventories and uptake rates, for ocean acidification assessment and for model validation.

  8. CARINA data synthesis project: pH data scale unification and cruise adjustments

    Directory of Open Access Journals (Sweden)

    A. Velo

    2010-05-01

    Full Text Available Data on carbon and carbon-relevant hydrographic and hydrochemical parameters from 188 previously non-publicly available cruise data sets in the Artic Mediterranean Seas (AMS, Atlantic Ocean and Southern Ocean have been retrieved and merged to a new database: CARINA (CARbon IN the Atlantic Ocean.

    These data have gone through rigorous quality control (QC procedures to assure the highest possible quality and consistency. The data for most of the measured parameters in the CARINA database were objectively examined in order to quantify systematic differences in the reported values. Systematic biases found in the data have been corrected in the data products, three merged data files with measured, calculated and interpolated data for each of the three CARINA regions; AMS, Atlantic Ocean and Southern Ocean. Out of a total of 188 cruise entries in the CARINA database, 59 reported pH measured values. All reported pH data have been unified to the Sea-Water Scale (SWS at 25 °C.

    Here we present details of the secondary QC of pH in the CARINA database and the scale unification to SWS at 25 °C. The pH scale has been converted for 36 cruises. Procedures of quality control, including crossover analysis between cruises and inversion analysis are described. Adjustments were applied to the pH values for 21 of the cruises in the CARINA dataset. With these adjustments the CARINA database is consistent both internally as well as with the GLODAP data, an oceanographic data set based on the World Hydrographic Program in the 1990s. Based on our analysis we estimate the internal consistency of the CARINA pH data to be 0.005 pH units. The CARINA data are now suitable for accurate assessments of, for example, oceanic carbon inventories and uptake rates, for ocean acidification assessment and for model validation.

  9. On a testable unification of electromagnetics, general relativity, and quantum mechanics

    International Nuclear Information System (INIS)

    Bearden, T.E.; Rosenthal, W.

    1991-01-01

    Unrecognized for what it was, in 1903-1904 E.T. Whittaker (W) published a fundamental, engineerable theory of electogravitation (EG) in two profound papers. The first (W-1903) demonstrated a hidden bidirectional EM wave structure in the scalar potential of vacuum, and showed how to produce a standing scalar EM potential wave -- the same wave discovered experimentally four years earlier by Nikola Tesla. W-1903 is a hidden variable theory that shows how to determinsitically curve the local and/or distant spacetime using EM. W-1904 shows that all force field EM can be replaced by interferometry of two scalar potentials, anticipating the Aharonov-Bohm effect by 55 years and extending it to the engineerable macroscopic world. W-1903 shows how to turn EM into G-potential, curve local and/or distant spacetime, and directly engineer the virtual particle flux of vacuum. W-1904 shows how to turn G-potential and curvature of spacetime back into force-field EM, even at a distance. The papers implement Sahkarov's 1968 statement that gravitation is not a fundamental field of nature, gut a conglomerate of other fields. Separately applied to electromagnetic (EM), quantum mechanics (QM), and general relativity (GR), an extended superset of each results. The three supersets are Whittaker-unified, so that a testable, engineerable, unified field theory is generated. EM, QM, and GR each contained a fundamental error that blocked unification, and these three errors are explain. The Schroedinger potential can also be structured and altered, indicating the direct engineering of physical quantum change. Recently Ignatovich has pointed out this hidden bidirectional EM wave structure in the Schroedinger potential, without referencing Whittaker's 1903 discovery of the basic effect

  10. The Halo Occupation Distribution of obscured quasars: revisiting the unification model

    Science.gov (United States)

    Mitra, Kaustav; Chatterjee, Suchetana; DiPompeo, Michael A.; Myers, Adam D.; Zheng, Zheng

    2018-06-01

    We model the projected angular two-point correlation function (2PCF) of obscured and unobscured quasars selected using the Wide-field Infrared Survey Explorer (WISE), at a median redshift of z ˜ 1 using a five parameter Halo Occupation Distribution (HOD) parametrization, derived from a cosmological hydrodynamic simulation by Chatterjee et al. The HOD parametrization was previously used to model the 2PCF of optically selected quasars and X-ray bright active galactic nuclei (AGNs) at z ˜ 1. The current work shows that a single HOD parametrization can be used to model the population of different kinds of AGN in dark matter haloes suggesting the universality of the relationship between AGN and their host dark matter haloes. Our results show that the median halo mass of central quasar hosts increases from optically selected (4.1^{+0.3}_{-0.4} × 10^{12} h^{-1} M_{⊙}) and infra-red (IR) bright unobscured populations (6.3^{+6.2}_{-2.3} × 10^{12} h^{-1} M_{⊙}) to obscured quasars (10.0^{+2.6}_{-3.7} × 10^{12} h^{-1} M_{⊙}), signifying an increase in the degree of clustering. The projected satellite fractions also increase from optically bright to obscured quasars and tend to disfavour a simple `orientation only' theory of active galactic nuclei unification. Our results also show that future measurements of the small-scale clustering of obscured quasars can constrain current theories of galaxy evolution where quasars evolve from an IR-bright obscured phase to the optically bright unobscured phase.

  11. Waste management in a Europe in the process of unification; Abfallwirtschaft in einem zusammenwachsenden Europa

    Energy Technology Data Exchange (ETDEWEB)

    Hangen, H.O. [comp.

    1998-12-31

    In a Europe in the process of unification, waste management is an important and topical issue. Decisions in the environmental protection and waste management sectors are increasingly being taken in Brussels, at the European level, and no longer by national parliaments and governments. A unified economy calls for unified conditions of production. Environmental protection cannot stop at state frontiers.- The principle of waste disposal at short distance from the source of pollution, and the demand for Europe-wide tenders and contracts for services encompass a large field of tension, not only at first glance. The European sanitary landfills recommendation, valid also for the countries of the Mediterranean, and the ambitious aims of the technical code on municipal waste are an indication of the range of the economic and political issues due to arise at least transiently. The meeting should sharpen the problem awareness of persons involved with waste management and point out the dynamics of the process leading Europe into a unified waste management. (orig.) [Deutsch] Abfallwirtschaft in einem zusammenwachsenden Europa ist ein wichtiges und aktuelles Problem. Immer mehr Entscheidungen im Bereich des Umweltschutzes und der Abfallwirtschaft werden in Bruessel auf europaeischer Ebene und nicht mehr von den nationalen Parlamenten und Regierungen getroffen. Ein einheitlicher Wirtschaftsstandort verlangt auch einheitliche Produktionsbedingungen. Umweltschutz kann an Laendergrenzen nicht Halt machen. Das Prinzip der Naehe bei der Abfallbeseitigung und die Forderung der europaweiten Ausschreibung und Vergabe von Leistungen beinhaltet nicht nur auf den ersten Anschein ein grosses Spannungsfeld. Europaeische Deponierichtlinie, gueltig auch fuer die Laender des Mittelmeerraumes, und die hochgesteckten Ziele der TA-Siedlungsabfall zeigen die Spannweite und die wirtschaftliche und politische Problematik auf, die zumindest uebergangsweise auftritt. Die Tagung soll das

  12. X-RAY ABSORPTION, NUCLEAR INFRARED EMISSION, AND DUST COVERING FACTORS OF AGNs: TESTING UNIFICATION SCHEMES

    Energy Technology Data Exchange (ETDEWEB)

    Mateos, S.; Carrera, F. J.; Alonso-Herrero, A.; Hernán-Caballero, A.; Barcons, X. [Instituto de Física de Cantabria (CSIC-Universidad de Cantabria), E-39005, Santander (Spain); Ramos, A. Asensio; Almeida, C. Ramos [Instituto de Astrofísica de Canarias, E-38205, La Laguna, Tenerife (Spain); Watson, M. G.; Blain, A. [Physics and Astronomy, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); Caccianiga, A.; Ballo, L. [INAF-Osservatorio Astronomico di Brera, via Brera 28, I-20121 Milano (Italy); Braito, V., E-mail: mateos@ifca.unican.es [INAF-Osservatorio Astronomico di Brera, Via Bianchi 46, I-23807 Merate (Italy)

    2016-03-10

    We present the distributions of the geometrical covering factors of the dusty tori (f{sub 2}) of active galactic nuclei (AGNs) using an X-ray selected complete sample of 227 AGNs drawn from the Bright Ultra-hard XMM-Newton Survey. The AGNs have z from 0.05 to 1.7, 2–10 keV luminosities between 10{sup 42} and 10{sup 46} erg s{sup −1}, and Compton-thin X-ray absorption. Employing data from UKIDSS, 2MASS, and the Wide-field Infrared Survey Explorer in a previous work, we determined the rest-frame 1–20 μm continuum emission from the torus, which we model here with the clumpy torus models of Nenkova et al. Optically classified type 1 and type 2 AGNs are intrinsically different, with type 2 AGNs having, on average, tori with higher f{sub 2} than type 1 AGNs. Nevertheless, ∼20% of type 1 AGNs have tori with large covering factors, while ∼23%–28% of type 2 AGNs have tori with small covering factors. Low f{sub 2} are preferred at high AGN luminosities, as postulated by simple receding torus models, although for type 2 AGNs the effect is certainly small. f{sub 2} increases with the X-ray column density, which implies that dust extinction and X-ray absorption take place in material that share an overall geometry and most likely belong to the same structure, the putative torus. Based on our results, the viewing angle, AGN luminosity, and also f{sub 2} determine the optical appearance of an AGN and control the shape of the rest-frame ∼1–20 μm nuclear continuum emission. Thus, the torus geometrical covering factor is a key ingredient of unification schemes.

  13. Dynamical resonance shift and unification of resonances in short-pulse laser-cluster interaction

    Science.gov (United States)

    Mahalik, S. S.; Kundu, M.

    2018-06-01

    Pronounced maximum absorption of laser light irradiating a rare-gas or metal cluster is widely expected during the linear resonance (LR) when Mie-plasma wavelength λM of electrons equals the laser wavelength λ . On the contrary, by performing molecular dynamics (MD) simulations of an argon cluster irradiated by short 5-fs (FWHM) laser pulses it is revealed that, for a given laser pulse energy and a cluster, at each peak intensity there exists a λ —shifted from the expected λM—that corresponds to a unified dynamical LR at which evolution of the cluster happens through very efficient unification of possible resonances in various stages, including (i) the LR in the initial time of plasma creation, (ii) the LR in the Coulomb expanding phase in the later time, and (iii) anharmonic resonance in the marginally overdense regime for a relatively longer pulse duration, leading to maximum laser absorption accompanied by maximum removal of electrons from cluster and also maximum allowed average charge states for the argon cluster. Increasing the laser intensity, the absorption maxima is found to shift to a higher wavelength in the band of λ ≈(1 -1.5 ) λM than permanently staying at the expected λM. A naive rigid sphere model also corroborates the wavelength shift of the absorption peak as found in MD and unequivocally proves that maximum laser absorption in a cluster happens at a shifted λ in the marginally overdense regime of λ ≈(1 -1.5 ) λM instead of λM of LR. The present study is important for guiding an optimal condition laser-cluster interaction experiment in the short-pulse regime.

  14. Book Review of - The lightness of being: mass, ether, and unification of the forces

    International Nuclear Information System (INIS)

    Kronfeld, Andreas S.

    2009-01-01

    How can an electron be both a wave and a particle? At the same time? Because it is a quantum field. That key insight seems to be underappreciated, given the awe and mysticism that permeate most nontechnical discussions of modern physics. Perhaps the root of the problem is that most popularizations of quantum mechanics and of particle physics shy away from quantized fields, the natural language for microscopic phenomena. In 'The Lightness of Being: Mass, Ether, and the Unification of Forces', Frank Wilczek confronts quantum field theory head on, demystifying not only wave-particle duality but also the origin of mass for hadrons (that is, everyday matter). Wilczek is the Herman Feshbach Professor of Physics at MIT and a co-recipient of the 2004 Nobel Prize in Physics. His research has spanned almost all aspects of theoretical particle physics, with significant forays into condensed-matter physics and dense nuclear matter (condensed quark matter, one might say). Recurring themes are the richness of quantum chromodynamics (QCD) and the alluring ideas of unification. His breadth and depth make him a sought after speaker for colloquia and public lectures. Wilczek also contributes an occasional Reference Frame column to 'Physics Today'. The material in 'The Lightness of Being' reflects the scope of the author's research. The book consists of three parts: the quantum fields of QCD (the ether that makes mass), gravitation (the ether that feels mass), and unification. Part 1, which traces notions of mass from Isaac Newton's time through theoretical and computational results of the past 40 years, is the most substantial and original; it is rich, modern, and rooted in observed phenomena. Part 2 continues in the same vein as it connects gravity, also an observed phenomenon, to QCD. Part 3 is more conventional, for a popularization of particle physics, in its focus on speculative ideas that (still) await direct experimental tests. Readers of 'Physics Today' will know that

  15. Comparison between geodetic and oceanographic approaches to estimate mean dynamic topography for vertical datum unification: evaluation at Australian tide gauges

    Science.gov (United States)

    Filmer, M. S.; Hughes, C. W.; Woodworth, P. L.; Featherstone, W. E.; Bingham, R. J.

    2018-04-01

    The direct method of vertical datum unification requires estimates of the ocean's mean dynamic topography (MDT) at tide gauges, which can be sourced from either geodetic or oceanographic approaches. To assess the suitability of different types of MDT for this purpose, we evaluate 13 physics-based numerical ocean models and six MDTs computed from observed geodetic and/or ocean data at 32 tide gauges around the Australian coast. We focus on the viability of numerical ocean models for vertical datum unification, classifying the 13 ocean models used as either independent (do not contain assimilated geodetic data) or non-independent (do contain assimilated geodetic data). We find that the independent and non-independent ocean models deliver similar results. Maximum differences among ocean models and geodetic MDTs reach >150 mm at several Australian tide gauges and are considered anomalous at the 99% confidence level. These differences appear to be of geodetic origin, but without additional independent information, or formal error estimates for each model, some of these errors remain inseparable. Our results imply that some ocean models have standard deviations of differences with other MDTs (using geodetic and/or ocean observations) at Australian tide gauges, and with levelling between some Australian tide gauges, of ˜ ± 50 mm . This indicates that they should be considered as an alternative to geodetic MDTs for the direct unification of vertical datums. They can also be used as diagnostics for errors in geodetic MDT in coastal zones, but the inseparability problem remains, where the error cannot be discriminated between the geoid model or altimeter-derived mean sea surface.

  16. AGN UNIFICATION AT z ∼ 1: u - R COLORS AND GRADIENTS IN X-RAY AGN HOSTS

    International Nuclear Information System (INIS)

    Mark Ammons, S.; Rosario, David J. V.; Koo, David C.

    2011-01-01

    We present uncontaminated rest-frame u - R colors of 78 X-ray-selected active galactic nucleus (AGN) hosts at 0.5 1.1 kpc. These three observations imply that AGN obscuration is uncorrelated with the star formation rate beyond ∼1 kpc. These observations favor a unification scenario for intermediate-luminosity AGNs in which obscuration is determined geometrically. Scenarios in which the majority of intermediate-luminosity AGNs at z ∼ 1 are undergoing rapid, galaxy-wide quenching due to AGN-driven feedback processes are disfavored.

  17. On the Issue of the Unification of Norms on Jurisdiction in the Field of Civil Proceedings Within the European Union

    Directory of Open Access Journals (Sweden)

    Elena V. Maystrovich

    2016-12-01

    Full Text Available In this article author examines some issues of norms on jurisdiction unification in the field of civil proceedings within the European Union. Author emphasizes that as a result of the adoption of the new Regulation No. 1215/2012 "Brussels Ibis", which came into force in 2012, rules on jurisdiction in the field of civil proceedings have undergone a number of changes. Article deals with the draft of the proposed amendments and their practical implementation. Amendments, their significance, efficiency and correlation with the projected initially are analyzed.

  18. From physics to metaphysics. Physical unification and string approach; Von der Physik zur Metaphysik. Physikalische Vereinheitlichung und Stringansatz

    Energy Technology Data Exchange (ETDEWEB)

    Hedrich, R.

    2007-07-01

    In spite the string approach as attempt of a nomologically unified comprehension of all interactions inclusively the gravitation exists already over three decades the physical principles on which it is based are yet completely unclear; and not the most unimportant empirically provable quantitative prediction exists. Without empirical data, which would be incompatible with the stablished theories - quantum-field theoretical standard model anf general relativity - only the conceptual incompatibility of both together with the unification idea yields a motivation for the string approach. By this however physics threatens to exceed under consequent continuation of their hitherto successful strategies the methodological framework of empirical sciences.

  19. Human papillomavirus type 16 E2 and E6 are RNA-binding proteins and inhibit in vitro splicing of pre-mRNAs with suboptimal splice sites

    International Nuclear Information System (INIS)

    Bodaghi, Sohrab; Jia Rong; Zheng Zhiming

    2009-01-01

    Human papillomavirus type 16 (HPV16) genome expresses six regulatory proteins (E1, E2, E4, E5, E6, and E7) which regulate viral DNA replication, gene expression, and cell function. We expressed HPV16 E2, E4, E6, and E7 from bacteria as GST fusion proteins and examined their possible functions in RNA splicing. Both HPV16 E2, a viral transactivator protein, and E6, a viral oncoprotein, inhibited splicing of pre-mRNAs containing an intron with suboptimal splice sites, whereas HPV5 E2 did not. The N-terminal half and the hinge region of HPV16 E2 as well as the N-terminal and central portions of HPV16 E6 are responsible for the suppression. HPV16 E2 interacts with pre-mRNAs through its C-terminal DNA-binding domain. HPV16 E6 binds pre-mRNAs via nuclear localization signal (NLS3) in its C-terminal half. Low-risk HPV6 E6, a cytoplasmic protein, does not bind RNA. Notably, both HPV16 E2 and E6 selectively bind to the intron region of pre-mRNAs and interact with a subset of cellular SR proteins. Together, these findings suggest that HPV16 E2 and E6 are RNA binding proteins and might play roles in posttranscriptional regulation during virus infection

  20. Genetic immunization against cervical carcinoma : induction of cytotoxic T lymphocyte activity with a recombinant alphavirus vector expressing human papillomavirus type 16 E6 and E7

    NARCIS (Netherlands)

    Daemen, T; Pries, F; Bungener, L; Kraak, M; Regts, J; Wilschut, J

    infection of genital epithelial cells with human papillomavirus (HPV) types 16 and 18 is closely associated with the development of cervical carcinoma. The transforming potential of these high-risk HPVs depends on the expression of the E6 and E7 early viral gene products. Since the expression of E6

  1. Immortalization of normal human embryonic fibroblasts by introduction of either the human papillomavirus type 16 E6 or E7 gene alone.

    Science.gov (United States)

    Yamamoto, Akito; Kumakura, Shin-ichi; Uchida, Minoru; Barrett, J Carl; Tsutsui, Takeki

    2003-09-01

    The ability of the human papillomavirus type 16 (HPV-16) E6 or E7 gene to induce immortalization of normal human embryonic fibroblast WHE-7 cells was examined. WHE-7 cells at 9 population doublings (PD) were infected with retrovirus vectors encoding either HPV-16 E6 or E7 alone or both E6 and E7 (E6/E7). One of 4 isolated clones carrying E6 alone became immortal and is currently at >445 PD. Four of 4 isolated clones carrying E7 alone escaped from crisis and are currently at >330 PD. Three of 5 isolated clones carrying E6/E7 were also immortalized and are currently at >268 PD. The immortal clone carrying E6 only and 2 of the 3 immortal clones carrying E6/E7 expressed a high level of E6 protein, and all the immortal clones carrying E7 alone and the other immortal clone carrying E6/E7 expressed a high level of E7 protein when compared to their mortal or precrisis clones. The immortal clones expressing a high level of E6 or E7 protein were positive for telomerase activity or an alternative mechanism of telomere maintenance, respectively, known as ALT (alternative lengthening of telomeres). All the mortal or precrisis clones were negative for both phenotypes. All the immortal clones exhibited abrogation of G1 arrest after DNA damage by X-ray irradiation. The expression of INK4a protein (p16(INK4a)) was undetectable in the E6-infected mortal and immortal clones, whereas Rb protein (pRb) was hyperphosphorylated only in the immortal clone. The p16(INK4a) protein was overexpressed in all the E7-infected immortal clones and their clones in the pre-crisis period as well as all the E6/E7-infected mortal and immortal clones, but the pRb expression was downregulated in all of these clones. These results demonstrate for the first time to our knowledge that HPV-16 E6 or E7 alone can induce immortalization of normal human embryonic fibroblasts. Inactivation of p16(INK4a)/pRb pathways in combination with activation of a telomere maintenance mechanism is suggested to be necessary for

  2. Identification and characterization of a cluster of transcription start sites located in the E6 ORF of human papillomavirus type 16

    DEFF Research Database (Denmark)

    Rosenstierne, Maiken W; Vinther, Jeppe; Hansen, Christina N

    2003-01-01

    Human papillomavirus type 16 (HPV-16) is the prototype strain among the malignant types of HPV in the western world. The main promoter, P97, located in front of the E6 ORF, has been shown to control expression of the oncogenes E6 and E7. These oncogenes are expressed continuously in HPV-16......-transformed cells. In contrast to malignant HPV types, non-malignant HPV types have separate promoters driving the expression of E6 and E7. Experiments have shown that the translation of E7 is more efficient from monocistronic than bicistronic transcripts encoding both E6 and E7. Here, identification...... of a cluster of transcription start sites located in the E6 ORF of HPV-16 is presented. Transcripts from this region contain the E7 ORF as the first reading frame. The cluster consists of multiple transcription start sites located around nt 441. Additional transcription start sites were identified in a cluster...

  3. [Influence of physiologic 17 beta-estradiol concentrations on gene E6 expression in HVP type 18 in vitro].

    Science.gov (United States)

    Dziubińska-Parol, Izabella; Gasowska, Urszula; Rzymowska, Jolanta; Kwaśniewska, Anna

    2003-09-01

    Many recent studies indicate that long term use of contraceptives is a strong risk factor in the development of cervical cancer. Steroid hormones, in persistent papilloma virus infection act on various levels, one of them is enhancing transforming activity of the virus. The aim of the study was to estimate if physiological concentrations of 17 beta-estradiol could influence expression of viral transforming genes. HeLa cell lines were incubated with three different physiological concentrations and and on the third day of incubation the level of E6 gene expression was determined. Results show no differences in expression between the control culter, and cultures incubated with physiological concentrations. It indicates that normal levels of 17 beta-estradiol don't play role in transforming process but it also shows need to analyse higher levels of hormones by quantitative analyses in prospective studies.

  4. Design of a Circularly Polarized Galileo E6-Band Textile Antenna by Dedicated Multiobjective Constrained Pareto Optimization

    Directory of Open Access Journals (Sweden)

    Arnaut Dierck

    2015-01-01

    Full Text Available Designing textile antennas for real-life applications requires a design strategy that is able to produce antennas that are optimized over a wide bandwidth for often conflicting characteristics, such as impedance matching, axial ratio, efficiency, and gain, and, moreover, that is able to account for the variations that apply for the characteristics of the unconventional materials used in smart textile systems. In this paper, such a strategy, incorporating a multiobjective constrained Pareto optimization, is presented and applied to the design of a Galileo E6-band antenna with optimal return loss and wide-band axial ratio characteristics. Subsequently, different prototypes of the optimized antenna are fabricated and measured to validate the proposed design strategy.

  5. Pharmacokinetics of Chlorin e6-Cobalt Bis(Dicarbollide Conjugate in Balb/c Mice with Engrafted Carcinoma

    Directory of Open Access Journals (Sweden)

    Arthur B. Volovetsky

    2017-11-01

    Full Text Available The necessary precondition for efficient boron neutron capture therapy (BNCT is control over the content of isotope 10B in the tumor and normal tissues. In the case of boron-containing porphyrins, the fluorescent part of molecule can be used for quantitative assessment of the boron content. Study Objective: We performed a study of the biodistribution of the chlorin e6-Cobalt bis(dicarbollide conjugate in carcinoma-bearing Balb/c mice using ex vivo fluorescence imaging, and developed a mathematical model describing boron accumulation and release based on the obtained experimental data. Materials and Methods: The study was performed on Balb/c tumor-bearing mice (CT-26 tumor model. A solution of the chlorin e6-Cobalt bis(dicarbollide conjugate (CCDC was injected into the blood at a dose of 10 mg/kg of the animal’s weight. Analysis of the fluorescence signal intensity was performed at several time points by spectrofluorimetry in blood and by laser scanning microscopy in muscle, liver, and tumor tissues. The boron content in the same samples was determined by mass spectroscopy with inductively coupled plasma. Results: Analysis of a linear approximation between the fluorescence intensity and boron content in the tissues demonstrated a satisfactory value of approximation reliability with a Spearman’s rank correlation coefficient of r = 0.938, p < 0.01. The dynamics of the boron concentration change in various organs, calculated on the basis of the fluorescence intensity, enabled the development of a model describing the accumulation of the studied compound and its distribution in tissues. The obtained results reveal a high level of correspondence between the model and experimental data.

  6. Genome analysis of two type 6 echovirus (E6) strains recovered from sewage specimens in Greece in 2006.

    Science.gov (United States)

    Kyriakopoulou, Zaharoula; Pliaka, Vaia; Tsakogiannis, Dimitris; Ruether, Irina G A; Komiotis, Dimitris; Gartzonika, Constantina; Levidiotou-Stefanou, Stamatina; Markoulatos, Panayotis

    2012-04-01

    Echovirus 6 (E6) is one of the main enteroviral serotypes that was isolated from cases of aseptic meningitis and encephalitis during the last years in Greece. Two E6 (LR51A5 and LR61G3) were isolated from the sewage treatment plant unit in Larissa, Greece, in May 2006, 1 year before their characterization from aseptic meningitis cases. The two isolates were initially found to be intra-serotypic recombinants in the genomic region VP1, a finding that initiated a full genome sequence analysis. In the present study, nucleotide, amino acid, and phylogenetic analyses for all genomic regions were conducted. For the detection of recombination events, Simplot and bootscan analyses were carried out. The continuous phylogenetic relationship in 2C-3D genomic region of strains LR51A5 and LR61G3 with E30 isolated in France in 2002-2005 indicated that the two strains were recombinants. SimPlot and Bootscan analyses confirmed that LR51A5 and LR61G3 carry an inter-serotypic recombination in the 2C genomic region. The present study provide evidence that recombination events occurred in the regions VP1 (intraserotypic) and non-capsid (interserotypic) during the evolution of LR51A5 and LR61G3, supporting the statement that the genomes of circulating enteroviruses are a mosaic of genomic regions of viral strains of the same or different serotypes. In conclusion, full genome sequence analysis of circulating enteroviral strains is a prerequisite to understand the complexity of enterovirus evolution.

  7. Some comments on flipped SU(5)xU(1) and flipped unification in general

    International Nuclear Information System (INIS)

    Barr, S.M.

    1989-01-01

    A general group-theoretical discussion of flipped embeddings is given. In addition to the well-known flipped SU(5) and flipped SO(10), the existence of flipped E 6 and E 7 is shown, as well as several families and special cases of flipped embeddings. A possible physical reason, essentially based on the group theory of flipped embeddings, why nature prefers the low-energy group SU(3)xSU(2)xU(1) to alternatives such as SU(4)xU(1) and SU(5) is pointed out

  8. The Civil Identity Registry Unification and Personal Data Protection in Brazil

    Directory of Open Access Journals (Sweden)

    José Renato Gaziero Cella

    2016-06-01

    Full Text Available There has long been treated the idea of discipline society and control society, dealing, for example, the works of Michel Foucault and Gilles Deleuze. The contemporary brought numerous developments in relation to the concepts assigned by Foucault and Deleuze, and many of these results were predicted by the analysis of events by these thinkers, however we are still in search for understanding the evolution of societies in relation to power and its maintenance, Law, Ethics, and possible future social outcomes. It is necessary to understand the dialectics of this topic to understand the current situation and thinking about the future. The scope of this paper is to understand the social control and the ramifications of power called the Information Society, both in public and in the private sphere. The state of the art, with the advent of internet, it is significant in the history of communications in terms of speed and agility. In light of the theoretical framework chosen for the development of this paper, the control is established by the idea of discipline and the society of control is the successor to the disciplinary paradigm (the discipline is already incorporated. For Deleuze, surveillance and monitoring activities are forms of control, ie, the reinvention of Jeremy Bentham’s panopticon. The ramifications of this form of society make use of the internet and its easy access to propagate the largest number of people possible, whether through social networking programs, reality shows, including surveillance cameras, just like George Orwell referred in his book 1984. We intend to analyze the information quickly overcomes the lack of security, given that it is today, for example, cases such as the Steering Committee of the National Civil Identification Record System - Brazilian Sirc, just implement a project- emission pilot of the new ID card - RIC, where you may have a unification of personal data and the bureaucracy of citizen service services

  9. Unification in the low radio luminosity regime: evidence from optical line emission

    Science.gov (United States)

    Marchã, M. J. M.; Browne, I. W. A.; Jethava, N.; Antón, S.

    2005-08-01

    We address the question of whether or not the properties of all low-luminosity flat spectrum radio sources, not just the obvious BL Lac objects, are consistent with them being the relativistically beamed counterparts of the low radio luminosity radio galaxies (the Fanaroff-Riley type 1, FR I). We have accumulated data on a well-defined sample of low redshift, core-dominated, radio sources all of which have one-sided core-jet structures seen with very long baseline interferometry, just like most BL Lac objects. We first compare the emission-line luminosities of the sample of core-dominated radio sources with a matched sample of FR I radio galaxies. The emission lines in the core-dominated objects are on average significantly more luminous than those in the comparison sample, inconsistent with the simplest unified models in which there is no orientation dependence of the line emission. We then compare the properties of our core-dominated sample with those of a sample of radio-emitting UGC galaxies selected without bias to core strength. The core-dominated objects fit well on the UGC correlation between line emission and radio core strength found by Verdoes Kleijn et al. The results are not consistent with all the objects participating in a simple unified model in which the observed line emission is orientation independent, though they could fit a single, unified model provided that some FR I radio galaxies have emission line regions that become more visible when viewed along the jet axis. However, they are equally consistent with a scenario in which, for the majority of objects, beaming has minimal effect on the observed core luminosities of a large fraction of the FR I population and that intrinsically stronger cores simply give rise to stronger emission lines. We conclude that FR I unification is much more complex than usually portrayed, and models combining beaming with an intrinsic relationship between core and emission line strengths need to be explored.

  10. Classification of three-family grand unification in string theory. II. The SU(5) and SU(6) models

    International Nuclear Information System (INIS)

    Kakushadze, Z.; Tye, S.H.

    1997-01-01

    Requiring that supersymmetric SU(5) and SU(6) grand unifications in the heterotic string theory must have three chiral families, adjoint (or higher representation) Higgs fields in the grand unified gauge group, and a non-Abelian hidden sector, we construct such string models within the framework of free conformal field theory and asymmetric orbifolds. Within this framework, we construct all such string models via Z 6 asymmetric orbifolds that include a Z 3 outerautomorphism, the latter yielding a level-three current algebra for the grand unification gauge group SU(5) or SU(6). We then classify all such Z 6 asymmetric orbifolds that result in models with a non-Abelian hidden sector. All models classified in this paper have only one adjoint (but no other higher representation) Higgs field in the grand unified gauge group. This Higgs field is neutral under all other gauge symmetries. The list of hidden sectors for three-family SU(6) string models are SU(2), SU(3), and SU(2)circle-times SU(2). In addition to these, three-family SU(5) string models can also have an SU(4) hidden sector. Some of the models have an apparent anomalous U(1) gauge symmetry. copyright 1997 The American Physical Society

  11. Predictions of the Higgs mass and the weak mixing angle in the 6D gauge-Higgs unification

    International Nuclear Information System (INIS)

    Hasegawa, Kouhei; Lim, Chong-Sa; Maru, Nobuhito

    2016-01-01

    In the gauge-Higgs unification with multiple extra spaces, the Higgs self-coupling is on the order of g 2 and the Higgs boson is predicted to be light, being consistent with the LHC results. When the gauge group is simple, the weak mixing angle is also predictable. We address a question on whether there exists a model of gauge-Higgs unification in six-dimensional space-time, which successfully predicts the mass ratios of the Higgs boson and weak gauge bosons. First, using a useful formula, we give a general argument on the condition for obtaining a realistic prediction of the weak mixing angle sin 2 θ W = 1/4, and find that triplet and sextet representations of the minimal SU(3) gauge group lead to the realistic prediction. Concerning the Higgs mass, we notice that, in the models with one Higgs doublet, the predicted Higgs mass is always the same: M H = 2M W . However, by extending our discussion to the models with two Higgs doublets, the situation changes: we obtain an interesting prediction M H ≤ 2M W at the leading order of the perturbation. Thus, it is possible to recover the observed Higgs mass, 125 GeV, for a suitable choice of the parameter. The situation is in clear contrast to the case of the minimal supersymmetric standard model, where M H ≤ M Z at the classical level and the predicted Higgs mass cannot recover the observed value. (author)

  12. Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

    International Nuclear Information System (INIS)

    Zacapala-Gómez, Ana Elvira; Del Moral-Hernández, Oscar; Villegas-Sepúlveda, Nicolás; Hidalgo-Miranda, Alfredo; Romero-Córdoba, Sandra Lorena

    2016-01-01

    We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such as adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.

  13. Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

    Energy Technology Data Exchange (ETDEWEB)

    Zacapala-Gómez, Ana Elvira, E-mail: zak_ana@yahoo.com.mx [Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Gro., México (Mexico); Del Moral-Hernández, Oscar, E-mail: odelmoralh@gmail.com [Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Gro., México (Mexico); Villegas-Sepúlveda, Nicolás, E-mail: nvillega@cinvestav.mx [Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D.F., México (Mexico); Hidalgo-Miranda, Alfredo, E-mail: ahidalgo@inmegen.gob.mx [Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), México, D.F., México (Mexico); Romero-Córdoba, Sandra Lorena, E-mail: sromero_cordoba@hotmail.com [Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), México, D.F., México (Mexico); and others

    2016-01-15

    We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such as adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.

  14. High E6 Gene Expression Predicts for Distant Metastasis and Poor Survival in Patients With HPV-Positive Oropharyngeal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Khwaja, Shariq S.; Baker, Callie; Haynes, Wesley; Spencer, Christopher R.; Gay, Hiram; Thorstad, Wade [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Adkins, Douglas R. [Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri (United States); Nussenbaum, Brian [Department of Otolaryngology – Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Chernock, Rebecca D. [Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri (United States); Lewis, James S. [Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee (United States); Wang, Xiaowei, E-mail: xwang@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2016-07-15

    Purpose: Patients with human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma (OPSCC) have a favorable prognosis. As a result, de-escalation clinical trials are under way. However, approximately 10% of patients will experience distant recurrence even with standard-of-care treatment. Here, we sought to identify novel biomarkers to better risk-stratify HPV-positive patients with OPSCC. Methods and Materials: Gene expression profiling by RNA sequencing (RNA-seq) and quantitative polymerase chain reaction was performed on HPV-positive OPSCC primary tumor specimens from patients with and without distant metastasis (DM). Results: RNA-seq analysis of 39 HPV-positive OPSCC specimens revealed that patients with DM had 2-fold higher E6 gene expression levels than did patients without DM (P=.029). This observation was confirmed in a validation cohort comprising 93 patients with HPV-positive OPSCC. The mean normalized E6 expression level in the 17 recurring primary specimens was 13 ± 2 compared with 8 ± 1 in the remaining 76 nonrecurring primaries (P=.001). Receiver operating characteristic analysis established an E6 expression level of 7.3 as a cutoff for worse recurrence-free survival (RFS). Patients from this cohort with high E6 gene expression (E6-high) (n=51, 55%) had more cancer-related deaths (23% vs 2%, P<.001) and DM (26% vs 5%, P<.001) than did patients with low E6 gene expression (E6-low) (n=42, 45%). Kaplan-Meier survival analysis revealed that E6-high had worse RFS (95% vs 69%, P=.004) and cancer-specific survival (97% vs 79%, P=.007). E6-high maintained statistical significance in multivariate regression models balancing surgery, chemotherapy, nodal stage, and smoking status. Gene set enrichment analysis demonstrated that tumors with high E6 expression were associated with P53, epidermal growth factor receptor, activating transcription factor-2, and transforming growth factor-β signaling pathways. Conclusion: High E6 gene expression

  15. Leptogenesis as an origin of hot dark matter and baryon asymmetry in the E6 inspired SUSY models

    Science.gov (United States)

    Nevzorov, R.

    2018-04-01

    We explore leptogenesis within the E6 inspired U (1) extension of the MSSM in which exact custodial symmetry forbids tree-level flavour-changing transitions and the most dangerous baryon and lepton number violating operators. This supersymmetric (SUSY) model involves extra exotic matter beyond the MSSM. In the simplest phenomenologically viable scenarios the lightest exotic fermions are neutral and stable. These states should be substantially lighter than 1eV forming hot dark matter in the Universe. The low-energy effective Lagrangian of the SUSY model under consideration possesses an approximate global U(1)E symmetry associated with the exotic states. The U(1)E symmetry is explicitly broken because of the interactions between the right-handed neutrino superfields and exotic matter supermultiplets. As a consequence the decays of the lightest right-handed neutrino/sneutrino give rise to both U(1)E and U(1) B - L asymmetries. When all right-handed neutrino/sneutrino are relatively light ∼106-107GeV the appropriate amount of the baryon asymmetry can be induced via these decays if the Yukawa couplings of the lightest right-handed neutrino superfields to the exotic matter supermultiplets vary between ∼10-4-10-3.

  16. WAF1 induction and infection by HPV E6 as a determinants of radiosensitivity in human cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Harima, Yoko; Oka, Atsutoshi; Harima, Keizo; Tanaka, Yoshimasa [Kansai Medical Univ., Moriguchi, Osaka (Japan)

    1998-02-01

    To establish a new predictor of outcome for human cervical carcinoma treatment, the relationship between WAF1 mRNA levels during treatment, human papilloma virus (HPV) infection and tumor radiosensitivity were investigated. Forty patients with uterine cervical carcinoma were treated with definitive radiotherapy. Only those patients who beard wild-type p53 were included into present clinical trial. p53 status was investigated using SSCP analysis. HPV E6 was determined by PCR, WAF1 mRNA was estimated by RT-PCR. Twenty-one patients achieved complete response (CR), 11 patients achieved partial response (PR), and 8 patients had no change (NC). The increase in WAF1 mRNA after irradiation at 10.8 Gy positively correlated both with better treatment response and improved survival. Although the infection by HPV did not directly influence on the survival rate, it decreased the inducibility of WAF1. p53-dependent activation of WAF1 gene expression during treatment may be a strong determinant of the efficacy of cervical cancer radiotherapy. (author)

  17. WAF1 induction and infection by HPV E6 as a determinants of radiosensitivity in human cervical cancer

    International Nuclear Information System (INIS)

    Harima, Yoko; Oka, Atsutoshi; Harima, Keizo; Tanaka, Yoshimasa

    1998-01-01

    To establish a new predictor of outcome for human cervical carcinoma treatment, the relationship between WAF1 mRNA levels during treatment, human papilloma virus (HPV) infection and tumor radiosensitivity were investigated. Forty patients with uterine cervical carcinoma were treated with definitive radiotherapy. Only those patients who beard wild-type p53 were included into present clinical trial. p53 status was investigated using SSCP analysis. HPV E6 was determined by PCR, WAF1 mRNA was estimated by RT-PCR. Twenty-one patients achieved complete response (CR), 11 patients achieved partial response (PR), and 8 patients had no change (NC). The increase in WAF1 mRNA after irradiation at 10.8 Gy positively correlated both with better treatment response and improved survival. Although the infection by HPV did not directly influence on the survival rate, it decreased the inducibility of WAF1. p53-dependent activation of WAF1 gene expression during treatment may be a strong determinant of the efficacy of cervical cancer radiotherapy. (author)

  18. Recommendations of technical specifications for ethanol and its blends (E6) and the infrastructure for their management in Mexico; Recomendaciones de especificaciones tecnicas para el etanol y sus mezclas (E6) y la infraestructura para su manejo en Mexico

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-15

    This paper describes the importance and benefits of using ethanol-gasoline blend as a substitute for pure gasoline. It presents data of global ethanol market, as well as major producers, processes involved for different raw materials and productivity indicators. It discusses the main properties to be monitored in ethanol and the importance of each one. It also examines the impact of the addition of ethanol in automotive gasoline and the influence of each property in the operation of the cars and the environment. It presents an assessment of the international specifications anhydrous ethanol used in the United States, Brazil and the European Union as well as suggestions for limits harmonization of the main parameters and methodologies, from recently published studies (White Paper-Bioetahnol Guidelines Task Force and to Ethanol from Worldwide Fuel Charter Committee). It includes the specification of Brazilian gasoline, added with 25% of ethanol (E25). It suggests an anhydrous ethanol specification and a specification for gasoline mixtures / ethanol E6 for implementation in Mexico. It presents a prioritization of laboratory testing methods for ethanol and ethanol-blended gasoline in three categories, indicating the most appropriate test to be used at different points in the distribution chain of products. It discusses the impact of ethanol on the distribution facilities for fuels, actions to control potential problems, selection of materials and equipment, safety procedures and presents the mixing gasoline / ethanol. It also describes the Brazilian system of production / distribution of fuels and the experience of this country to control fuel quality from the legislation. It includes a table with the top teams, their costs, Brazilian suppliers and a list of Brazilian standards for fuel storage and transport. Finally, we present some suggestions that may be important to ensure the evolution of specifications of ethanol and ethanol-blended gasoline in the course of the

  19. The human papillomavirus type 11 and 16 E6 proteins modulate the cell-cycle regulator and transcription cofactor TRIP-Br1

    International Nuclear Information System (INIS)

    Gupta, Sanjay; Takhar, Param Parkash S; Degenkolbe, Roland; Heng Koh, Choon; Zimmermann, Holger; Maolin Yang, Christopher; Guan Sim, Khe; I-Hong Hsu, Stephen; Bernard, Hans-Ulrich

    2003-01-01

    The genital human papillomaviruses (HPVs) are a taxonomic group including HPV types that preferentially cause genital and laryngeal warts ('low-risk types'), such as HPV-6 and HPV-11, or cancer of the cervix and its precursor lesions ('high-risk types'), such as HPV-16. The transforming processes induced by these viruses depend on the proteins E5, E6, and E7. Among these oncoproteins, the E6 protein stands out because it supports a particularly large number of functions and interactions with cellular proteins, some of which are specific for the carcinogenic HPVs, while others are shared among low- and high-risk HPVs. Here we report yeast two-hybrid screens with HPV-6 and -11 E6 proteins that identified TRIP-Br1 as a novel cellular target. TRIP-Br1 was recently detected by two research groups, which described two separate functions, namely that of a transcriptional integrator of the E2F1/DP1/RB cell-cycle regulatory pathway (and then named TRIP-Br1), and that of an antagonist of the cyclin-dependent kinase suppression of p16INK4a (and then named p34SEI-1). We observed that TRIP-Br1 interacts with low- and high-risk HPV E6 proteins in yeast, in vitro and in mammalian cell cultures. Transcription activation of a complex consisting of E2F1, DP1, and TRIP-Br1 was efficiently stimulated by both E6 proteins. TRIP-Br1 has an LLG E6 interaction motif, which contributed to the binding of E6 proteins. Apparently, E6 does not promote degradation of TRIP-Br1. Our observations imply that the cell-cycle promoting transcription factor E2F1/DP1 is dually targeted by HPV oncoproteins, namely (i) by interference of the E7 protein with repression by RB, and (ii) by the transcriptional cofactor function of the E6 protein. Our data reveal the natural context of the transcription activator function of E6, which has been predicted without knowledge of the E2F1/DP1/TRIP-Br/E6 complex by studying chimeric constructs, and add a function to the limited number of transforming properties shared

  20. Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes ▿

    OpenAIRE

    Hyland, Paula L.; McDade, Simon S.; McCloskey, Rachel; Dickson, Glenda J.; Arthur, Ken; McCance, Dennis J.; Patel, Daksha

    2011-01-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2...

  1. The GEM Theory of the Unification of Gravitation and Electro-Magnetism

    Science.gov (United States)

    Brandenburg, J. E.

    2012-01-01

    The GEM (Gravity Electro-Magnetism), theory is presented as an alloy of Sakharov and Kaluza-Klein approaches to field unification. GEM uses the concept of gravity fields as Poynting fields to postulate that the non-metric portion of the EM stress tensor becomes the metric tensor in strong fields leading to "self-censorship". Covariant formulation of the GEM theory is accomplished through definition of the spacetime metric tensor as a portion of the EM stress tensor normalized by its own trace: gab = 4(FcaFcb )/(FabFab), it is found that this results in a massless ground state vacuum and a Newtonian gravitation potential f=1/2 E2/B2 =GM/r , where E, B and F are part of the vacuum Zero Point Fluctuation (ZPF) and M and r are the mass and distance from the center of a gravitating body and G is the Newton gravitation constant. It is found that a Lorentz flat-space metric is recovered in the limit of a vacuum full spectrum ZPF. The vacuum ZPF energy and vacuum quantities G, h, c, gives birth to particles quantities mp, me, e,-e in a process triggered by the appearance of the Kaluza-Klein fifth dimension, where also the EM and gravity forces split from each other in a process correlated to the splitting apart of protons and electrons. The separate appearance of the proton and electron occurs as the splitting of a light-like spacetime interval of zero-length into a finite space-like portion containing three subdimensions identified with the quarks and a time-like portion identified with the electron. The separation of mass with charge for the electron and proton pair comes about from a U(1) symmetry with a rotation in imaginary angle. A logarithmic variation of charge with mass for the proton-electron pair results and leads to the formula ln(ro/rp) = s, where s = (mp/me)1/2 , where mp and me are the electron and proton masses respectively and where ro =e2/moc2 , and where mo = (mpme)1/2 and where rp is the Planck length . This leads to the formula G=e2/mo2aexp(-2s)=6

  2. A high-throughput cellular assay to quantify the p53-degradation activity of E6 from different human papillomavirus types.

    Science.gov (United States)

    Gagnon, David; Archambault, Jacques

    2015-01-01

    A subset of human papillomaviruses (HPVs), known as the high-risk types, are the causative agents of cervical cancer and other malignancies of the anogenital region and oral mucosa. The capacity of these viruses to induce cancer and to immortalize cells in culture relies in part on a critical function of their E6 oncoprotein, that of promoting the poly-ubiquitination of the cellular tumor suppressor protein p53 and its subsequent degradation by the proteasome. Here, we describe a cellular assay to measure the p53-degradation activity of E6 from different HPV types. This assay is based on a translational fusion of p53 to Renilla luciferase (Rluc-p53) that remains sensitive to degradation by high-risk E6 and whose steady-state levels can be accurately measured in standard luciferase assays. The p53-degradation activity of any E6 protein can be tested and quantified in transiently transfected cells by determining the amount of E6-expression vector required to reduce by half the levels of RLuc-p53 luciferase activity (50 % effective concentration [EC50]). The high-throughput and quantitative nature of this assay makes it particularly useful to compare the p53-degradation activities of E6 from several HPV types in parallel.

  3. Distribution of human papilloma virus type 16 E6/E7 gene mutation in cervical precancer or cancer: A case control study in Guizhou Province, China.

    Science.gov (United States)

    Yang, Yingjie; Ren, Jie; Zhang, Qizhu

    2016-02-01

    HPV-16 varies geographically and is correlated with cervical cancer genesis and progression. This study aimed to determine the distribution of HPV-16 E6/E7 genetic variation in patients with invasive cervical cancer or precancer in Guizhou Province, China. A case-control study was designed, and the distribution of HPV-16 E6/E7 genetic variation was compared among women with cervical cancer, precancer, and sexually active without cervical lesion. HPV infection was detected through flow-through hybridization and gene chip techniques to determine the prevalence of HPV 16 E6/E7 genetic variation. Among 90 specimens (30 cervical cancer, 30 precancer, 30 controls), 81 were subjected to HPV-16 E6/E7 gene sequencing. The rates of DNA sequence mutation and amino acid mutation were 76.5% (62/81) and 66.7% (54/81), respectively. Both E6 and E7 genes showed higher mutation rate than their prototypes. The prevalence of E6/E7 mutation significantly differed between the cervical cancer and the controls (P prevalent in cervical cancer or precancer than those in the controls. The possible correlation between genetic variation and cancerigenesis may be used to design an HPV vaccine for cervical carcinoma. © 2015 Wiley Periodicals, Inc.

  4. Economic strategy of Arab to cope with EC unification; Establishment of blocks for economic unification. EC togo o niranda Arab keizai senryaku; Keizai togo e no block ka gensho

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Hideki (The Inst. of energy Economics, Tokyo (Japan))

    1990-01-01

    The agreement of the Arab Coopration Council (ACC) mentions the final aim of achieving the common market type economic unification by promoting economic cooperation within the area. All the ACC member nations are facing economical difficulties, and are in need of outside financial help. ACC was followed by the Arab Maghreb Union (AMU). The AMU is giving priority to the economic cooperation and cooperative projects within the area seeking tangible advantages, and its distinguishing characters and aims are analyzed. The accumulated debt problem of the AMU member nations is as serious as that of the ACC. The births of the ACC and AMU mean that the Arab world became a tripolar structure together with the Gulf Cooperation Council (GCC) established in 1981. The desire for the estblishment of Arab common market is common for the ACC, AMU and GCC. Problems confronting the GCC, ACC and AMU are described. 11 refs., 2 figs., 11 tabs.

  5. Unification of Active Galactic Nuclei at X-rays and soft gamma-rays

    International Nuclear Information System (INIS)

    Beckmann, Volker

    2010-01-01

    Through the work on X-ray and gamma-ray data of AGN I contributed significantly to the progress in the unification of AGN since I finished my PhD in 2000. The study of the evolutionary behaviour of X-ray selected N blazars (Beckmann and Wolter 2001; Beckmann et al. 2002, 2003b; Beckmann 2003) shows that their evolution is not as strongly negative as indicated by previous studies. The overall luminosity function is consistent with no evolution in the 0.1-2.4 keV band as seen by ROSAT/PSPC. There is still a difference compared to the luminosity function of FSRQ and LBL, which seem to show a positive evolution, indicating that they have been more luminous and/or numerous at cosmological distances. We indicated a scenario in order to explain this discrepancy, in which the high luminous FSRQ develop into the fainter LBL and finally into the BL Lac objects with high frequency peaks in their spectral energy distribution but overall low bolometric luminosity. Studying the variability pattern of hard X-ray selected Seyfert galaxies, we actually found differences between type 1 and type 2 objects, in the sense that type 2 seemed to be more variable (Beckmann et al. 2007a). This breaking of the unified model is caused by the different average luminosity of the absorbed and unabsorbed sources, as discussed in Sect. 4.7.3. This can be explained by a larger inner disk radius when the AGN core is most active (the so-called receding disc model). The work on the sample characteristics of hard X-ray detected AGN also led to the proof that the average intrinsic spectra of type 1 and type 2 objects are the same when reflection processes are taken into account (Beckmann et al. 2009d). This also explains why in the past Seyfert 2 objects were seen to have harder X-ray spectra than Seyfert 1, as the stronger reflection hump in the type 2 objects makes the spectra appear to be flatter, although the underlying continuum is the same. Further strong evidence for the unification scheme comes

  6. In-vivo optical detection of cancer using chlorin e6 – polyvinylpyrrolidone induced fluorescence imaging and spectroscopy

    International Nuclear Information System (INIS)

    Chin, William WL; Thong, Patricia SP; Bhuvaneswari, Ramaswamy; Soo, Khee Chee; Heng, Paul WS; Olivo, Malini

    2009-01-01

    Photosensitizer based fluorescence imaging and spectroscopy is fast becoming a promising approach for cancer detection. The purpose of this study was to examine the use of the photosensitizer chlorin e6 (Ce6) formulated in polyvinylpyrrolidone (PVP) as a potential exogenous fluorophore for fluorescence imaging and spectroscopic detection of human cancer tissue xenografted in preclinical models as well as in a patient. Fluorescence imaging was performed on MGH human bladder tumor xenografted on both the chick chorioallantoic membrane (CAM) and the murine model using a fluorescence endoscopy imaging system. In addition, fiber optic based fluorescence spectroscopy was performed on tumors and various normal organs in the same mice to validate the macroscopic images. In one patient, fluorescence imaging was performed on angiosarcoma lesions and normal skin in conjunction with fluorescence spectroscopy to validate Ce6-PVP induced fluorescence visual assessment of the lesions. Margins of tumor xenografts in the CAM model were clearly outlined under fluorescence imaging. Ce6-PVP-induced fluorescence imaging yielded a specificity of 83% on the CAM model. In mice, fluorescence intensity of Ce6-PVP was higher in bladder tumor compared to adjacent muscle and normal bladder. Clinical results confirmed that fluorescence imaging clearly captured the fluorescence of Ce6-PVP in angiosarcoma lesions and good correlation was found between fluorescence imaging and spectral measurement in the patient. Combination of Ce6-PVP induced fluorescence imaging and spectroscopy could allow for optical detection and discrimination between cancer and the surrounding normal tissues. Ce6-PVP seems to be a promising fluorophore for fluorescence diagnosis of cancer

  7. Recommendations of technical specifications for ethanol and its blends (E6) and the infrastructure for their management in Mexico; Recomendaciones de especificaciones tecnicas para el etanol y sus mezclas (E6) y la infraestructura para su manejo en Mexico

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-15

    This paper describes the importance and benefits of using ethanol-gasoline blend as a substitute for pure gasoline. It presents data of global ethanol market, as well as major producers, processes involved for different raw materials and productivity indicators. It discusses the main properties to be monitored in ethanol and the importance of each one. It also examines the impact of the addition of ethanol in automotive gasoline and the influence of each property in the operation of the cars and the environment. It presents an assessment of the international specifications anhydrous ethanol used in the United States, Brazil and the European Union as well as suggestions for limits harmonization of the main parameters and methodologies, from recently published studies (White Paper-Bioetahnol Guidelines Task Force and to Ethanol from Worldwide Fuel Charter Committee). It includes the specification of Brazilian gasoline, added with 25% of ethanol (E25). It suggests an anhydrous ethanol specification and a specification for gasoline mixtures / ethanol E6 for implementation in Mexico. It presents a prioritization of laboratory testing methods for ethanol and ethanol-blended gasoline in three categories, indicating the most appropriate test to be used at different points in the distribution chain of products. It discusses the impact of ethanol on the distribution facilities for fuels, actions to control potential problems, selection of materials and equipment, safety procedures and presents the mixing gasoline / ethanol. It also describes the Brazilian system of production / distribution of fuels and the experience of this country to control fuel quality from the legislation. It includes a table with the top teams, their costs, Brazilian suppliers and a list of Brazilian standards for fuel storage and transport. Finally, we present some suggestions that may be important to ensure the evolution of specifications of ethanol and ethanol-blended gasoline in the course of the

  8. Double unification of particles with fields and electricity with gravity in non-empty space of continuous complex energies

    Directory of Open Access Journals (Sweden)

    Bulyzhenkov Igor E.

    2016-01-01

    Full Text Available Non-empty space reading of Maxwell equations as local energy identities explains why a Coulomb field is carried rigidly by electrons in experiments. The analytical solution of the Poisson equation defines the sharp radial shape of charged elementary densities which are proportional to continuous densities of electric self-energy. Both Coulomb field and radial charge densities are free from energy divergences. Non-empty space of electrically charged mass-energy can be described by complex analytical densities resulting in real values for volume mass integrals and in imaginary values for volume charge integrals. Imaginary electric charges in the Newton gravitational law comply with real Coulomb forces. Unification of forces through complex charges rids them of radiation self-acceleration. Strong gravitational fields repeal probe bodies that might explainthe accelerated expansion of the dense Metagalaxy. Outward and inward spherical waves form the standing wave process within the radial carrier of complex energy.

  9. Sparticle mass hierarchies, simplified models from SUGRA unification, and benchmarks for LHC Run-II SUSY searches

    International Nuclear Information System (INIS)

    Francescone, David; Akula, Sujeet; Altunkaynak, Baris; Nath, Pran

    2015-01-01

    Sparticle mass hierarchies contain significant information regarding the origin and nature of supersymmetry breaking. The hierarchical patterns are severely constrained by electroweak symmetry breaking as well as by the astrophysical and particle physics data. They are further constrained by the Higgs boson mass measurement. The sparticle mass hierarchies can be used to generate simplified models consistent with the high scale models. In this work we consider supergravity models with universal boundary conditions for soft parameters at the unification scale as well as supergravity models with nonuniversalities and delineate the list of sparticle mass hierarchies for the five lightest sparticles. Simplified models can be obtained by a truncation of these, retaining a smaller set of lightest particles. The mass hierarchies and their truncated versions enlarge significantly the list of simplified models currently being used in the literature. Benchmarks for a variety of supergravity unified models appropriate for SUSY searches at future colliders are also presented. The signature analysis of two benchmark models has been carried out and a discussion of the searches needed for their discovery at LHC Run-II is given. An analysis of the spin-independent neutralino-proton cross section exhibiting the Higgs boson mass dependence and the hierarchical patterns is also carried out. It is seen that a knowledge of the spin-independent neutralino-proton cross section and the neutralino mass will narrow down the list of the allowed sparticle mass hierarchies. Thus dark matter experiments along with analyses for the LHC Run-II will provide strong clues to the nature of symmetry breaking at the unification scale.

  10. Transforming properties of Felis catus papillomavirus type 2 E6 and E7 putative oncogenes in vitro and their transcriptional activity in feline squamous cell carcinoma in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Altamura, Gennaro, E-mail: gennaro.altamura@unina.it [Department of Veterinary Medicine and Animal Productions, General Pathology and Pathological Anatomy Unit, University of Naples Federico II, Via Delpino 1, 80137 Naples (Italy); Corteggio, Annunziata, E-mail: ancorteg@unina.it [Department of Veterinary Medicine and Animal Productions, General Pathology and Pathological Anatomy Unit, University of Naples Federico II, Via Delpino 1, 80137 Naples (Italy); Pacini, Laura, E-mail: PaciniL@students.iarc.fr [Infections and Cancer Biology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon (France); Conte, Andrea, E-mail: andreaconte88@hotmail.it [Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via Pansini 5, 80131 Naples (Italy); Pierantoni, Giovanna Maria, E-mail: gmpieran@unina.it [Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via Pansini 5, 80131 Naples (Italy); Tommasino, Massimo, E-mail: tommasinom@iarc.fr [Infections and Cancer Biology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon (France); Accardi, Rosita, E-mail: accardir@iarc.fr [Infections and Cancer Biology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon (France); Borzacchiello, Giuseppe, E-mail: borzacch@unina.it [Department of Veterinary Medicine and Animal Productions, General Pathology and Pathological Anatomy Unit, University of Naples Federico II, Via Delpino 1, 80137 Naples (Italy)

    2016-09-15

    Felis catus papillomavirus type 2 (FcaPV2) DNA is found in feline cutaneous squamous cell carcinomas (SCCs); however, its biological properties are still uncharacterized. In this study, we successfully expressed FcaPV2 E6 and E7 putative oncogenes in feline epithelial cells and demonstrated that FcaPV2 E6 binds to p53, impairing its protein level. In addition, E6 and E7 inhibited ultraviolet B (UVB)-triggered accumulation of p53, p21 and pro-apoptotic markers such as Cleaved Caspase3, Bax and Bak, suggesting a synergistic action of the virus with UV exposure in tumour pathogenesis. Furthermore, FcaPV2 E7 bound to feline pRb and impaired pRb levels, resulting in upregulation of the downstream pro-proliferative genes Cyclin A and Cdc2. Importantly, we demonstrated mRNA expression of FcaPV2 E2, E6 and E7 in feline SCC samples, strengthening the hypothesis of a causative role in the development of feline SCC. - Highlights: • FcaPV2 E6 binds to and deregulates feline p53 protein. • FcaPV2 E7 binds to and deregulates feline pRb protein. • FcaPV2 oncogenes inhibit UVB-induced apoptosis. • FcaPV2 E6E7 and E7 increase the lifespan of primary cells. • FcaPV2 E2, E6 and E7 are expressed at the mRNA level in feline SCC in vivo.

  11. Dual expression of Epstein-Barr virus, latent membrane protein-1 and human papillomavirus-16 E6 transform primary mouse embryonic fibroblasts through NF-κB signaling.

    Science.gov (United States)

    Shimabuku, Tetsuya; Tamanaha, Ayumi; Kitamura, Bunta; Tanabe, Yasuka; Tawata, Natsumi; Ikehara, Fukino; Arakaki, Kazunari; Kinjo, Takao

    2014-01-01

    The prevalence of Epstein-Barr virus (EBV) and high-risk human papilloma virus (HPV) infections in patients with oral cancer in Okinawa, southwest islands of Japan, has led to the hypothesis that carcinogenesis is related to EBV and HPV co-infection. To explore the mechanisms of transformation induced by EBV and HPV co-infection, we analyzed the transformation of primary mouse embryonic fibroblasts (MEFs) expressing EBV and HPV-16 genes, alone or in combination. Expression of EBV latent membrane protein-1 (LMP-1) alone or in combination with HPV-16 E6 increased cell proliferation and decreased apoptosis, whereas single expression of EBV nuclear antigen-1 (EBNA-1), or HPV-16 E6 did not. Co-expression of LMP-1 and E6 induced anchorage-independent growth and tumor formation in nude mice, whereas expression of LMP-1 alone did not. Although the singular expression of these viral genes showed increased DNA damage and DNA damage response (DDR), co-expression of LMP-1 and E6 did not induce DDR, which is frequently seen in cancer cells. Furthermore, co-expression of LMP-1 with E6 increased NF-κB signaling, and the knockdown of LMP-1 or E6 in co-expressing cells decreased cell proliferation, anchorage independent growth, and NF-κB activation. These data suggested that expression of individual viral genes is insufficient for inducing transformation and that co-expression of LMP-1 and E6, which is associated with suppression of DDR and increased NF-κB activity, lead to transformation. Our findings demonstrate the synergistic effect by the interaction of oncogenes from different viruses on the transformation of primary MEFs.

  12. E6 variants of human papillomavirus 18 differentially modulate the protein kinase B/phosphatidylinositol 3-kinase (akt/PI3K) signaling pathway

    International Nuclear Information System (INIS)

    Contreras-Paredes, Adriana; Cruz-Hernandez, Erick de la; Martinez-Ramirez, Imelda; Duenas-Gonzalez, Alfonso; Lizano, Marcela

    2009-01-01

    Intra-type genome variations of high risk Human papillomavirus (HPV) have been associated with a differential threat for cervical cancer development. In this work, the effect of HPV18 E6 isolates in Akt/PKB and Mitogen-associated protein kinase (MAPKs) signaling pathways and its implication in cell proliferation were analyzed. E6 from HPV types 16 and 18 are able to bind and promote degradation of Human disc large (hDlg). Our results show that E6 variants differentially modulate hDlg degradation, rebounding in levels of activated PTEN and PKB. HPV18 E6 variants are also able to upregulate phospho-PI3K protein, strongly correlating with activated MAPKs and cell proliferation. Data was supported by the effect of E6 silencing in HPV18-containing HeLa cells, as well as hDlg silencing in the tested cells. Results suggest that HPV18 intra-type variations may derive in differential abilities to activate cell-signaling pathways such as Akt/PKB and MAPKs, directly involved in cell survival and proliferation

  13. In Vitro and In Vivo Synergistic Therapeutic Effect of Cisplatin with Human Papillomavirus16 E6/E7 CRISPR/Cas9 on Cervical Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Shuai Zhen

    2016-12-01

    Full Text Available PURPOSE: Human papillomavirus (HPV type 16 is one of the major etiologic factors of cervical cancer. Our study aims to investigate the potentiality of the antiviral clustered regularly interspaced short palindromic repeat (CRISPR/CRISPR-associated Cas9 system (CRISPR/Cas9 targeting the E6 and E7 oncogenes of HPV16 as a potential chemosensitizer of cisplatin (cis-diaminedichloroplatinum II; CDDP for cervical cancer. METHODS: Specifically, the therapeutic efficacy of combination of CDDP and HPV16 E6 + E7-CRISPR/Cas9 was assessed in cervical cancer cells and cervical cancer xenograft models. RESULTS: In vitro experiments showed that long-term exposure of SiHa cells to the HPV16 E6 + E7-CRISPR/Cas9 induced apoptosis, and its pro-apoptosis effect became more obvious when combined with CDDP. In vivo study found the efficacy of the combination of HPV16 E6 + E7-CRISPR/Cas9 and CDDP were superior to either of the treatments in term of apoptosis induction and metastasis inhibition. CONCLUSION: Collectively, our results suggested that HPV16 E6 + E7-CRISPR/Cas9 could be an effective sensitizer of CDDP chemotherapy in cervical cancer.

  14. Identification of a horizontal gauge boson in hadronic collisions

    International Nuclear Information System (INIS)

    Bagneid, A.A.

    2002-01-01

    We compare distributions of leptons produced in hadronic collisions, by a horizontal neutral gauge boson, Z ' , suggested by the Sp(6) L x U(1) Y model, to those produced by other theoretically motivated neutral gauge bosons occurring in left-right symmetric models and in superstring-inspired E 6 models. Forward-backward asymmetries in the gauge boson leptonic decay are found to be sensitive to specific forms of the couplings. The asymmetries are expected to be maximal for Z ' , distinguishing it from the other Z's. (orig.)

  15. Phenomenological analysis of supersymmetric σ-models on coset spaces SO(10)/U(5) and E6/[SO(10)xU(1)

    International Nuclear Information System (INIS)

    Nyawelo, T.S.

    2004-12-01

    We discuss some phenomenological aspects of gauged supersymmetric σ-models on homogeneous coset-spaces E 6 /[SO(10)xU(1)] and SO(10)/U(5) which are some of the most interesting for phenomenology. We investigate in detail the vacuum configurations of these models, and study the resulting consequences for supersymmetry breaking and breaking of the internal symmetry. Some supersymmetric minima for both models with gauged full isometry groups E 6 and SO(10) are physically problematic as the Kaehler metric becomes singular ad hence the kinetic terms of the Goldstone boson multiplets vanish. This leads us to introduce recently proposed soft supersymmetry-breaking mass terms which displace the minimum away from the singulax point. A non-singular Kaehler metric breaks the linear subgroup SO(10)xU(1) of the E 6 model spontaneously. The particle spectrum of all these different models is computed. (author)

  16. Mitotic control of human papillomavirus genome-containing cells is regulated by the function of the PDZ-binding motif of the E6 oncoprotein

    Science.gov (United States)

    Marsh, Elizabeth K.; Delury, Craig P.; Davies, Nicholas J.; Weston, Christopher J.; Miah, Mohammed A.L.; Banks, Lawrence; Parish, Joanna L.

    2017-01-01

    The function of a conserved PDS95/DLG1/ZO1 (PDZ) binding motif (E6 PBM) at the C-termini of E6 oncoproteins of high-risk human papillomavirus (HPV) types contributes to the development of HPV-associated malignancies. Here, using a primary human keratinocyte-based model of the high-risk HPV18 life cycle, we identify a novel link between the E6 PBM and mitotic stability. In cultures containing a mutant genome in which the E6 PBM was deleted there was an increase in the frequency of abnormal mitoses, including multinucleation, compared to cells harboring the wild type HPV18 genome. The loss of the E6 PBM was associated with a significant increase in the frequency of mitotic spindle defects associated with anaphase and telophase. Furthermore, cells carrying this mutant genome had increased chromosome segregation defects and they also exhibited greater levels of genomic instability, as shown by an elevated level of centromere-positive micronuclei. In wild type HPV18 genome-containing organotypic cultures, the majority of mitotic cells reside in the suprabasal layers, in keeping with the hyperplastic morphology of the structures. However, in mutant genome-containing structures a greater proportion of mitotic cells were retained in the basal layer, which were often of undefined polarity, thus correlating with their reduced thickness. We conclude that the ability of E6 to target cellular PDZ proteins plays a critical role in maintaining mitotic stability of HPV infected cells, ensuring stable episome persistence and vegetative amplification. PMID:28061478

  17. Novel anti-metastatic action of cidofovir mediated by inhibition of E6/E7, CXCR4 and Rho/ROCK signaling in HPV tumor cells.

    Directory of Open Access Journals (Sweden)

    Abdessamad Amine

    Full Text Available Cervical cancer is frequently associated with HPV infection. The expression of E6 and E7 HPV oncoproteins is a key factor in its carcinogenicity and might also influence its virulence, including metastatic conversion. The cellular mechanisms involved in metastatic spread remain elusive, but pro-adhesive receptors and their ligands, such as SDF-1alpha and CXCR4 are implicated. In the present study, we assessed the possible relationship between SDF-1alpha/CXCR4 signaling, E6/E7 status and the metastatic process. We found that SDF-1alpha stimulated the invasion of E6/E7-positive cancer cell lines (HeLa and TC-1 in Matrigel though CXCR4 and subsequent Rho/ROCK activation. In pulmonary metastatic foci generated by TC-1 cells IV injection a high proportion of cells expressed membrane-associated CXCR4. In both cases models (in vitro and in vivo cell adhesion and invasion was abrogated by CXCR4 immunological blockade supporting a contribution of SDF-1alpha/CXCR4 to the metastatic process. E6 and E7 silencing using stable knock-down and the approved anti-viral agent, Cidofovir decreased CXCR4 gene expression as well as both, constitutive and SDF-1alpha-induced cell invasion. In addition, Cidofovir inhibited lung metastasis (both adhesion and invasion supporting contribution of E6 and E7 oncoproteins to the metastatic process. Finally, potential signals activated downstream SDF-1alpha/CXCR4 and involved in lung homing of E6/E7-expressing tumor cells were investigated. The contribution of the Rho/ROCK pathway was suggested by the inhibitory effect triggered by Cidofovir and further confirmed using Y-27632 (a small molecule ROCK inhibitor. These data suggest a novel and highly translatable therapeutic approach to cervix cancer, by inhibition of adhesion and invasion of circulating HPV-positive tumor cells, using Cidofovir and/or ROCK inhibition.

  18. The combinational effect of E6/E7 siRNA and anti-miR-182 on apoptosis induction in HPV16-positive cervical cells.

    Science.gov (United States)

    Javadi, Hamidreza; Lotfi, Abbas Sahebghadam; Hosseinkhani, Saman; Mehrani, Hossein; Amani, Jafar; Soheili, Zahra Soheila; Hojati, Zahra; Kamali, Mehdi

    2018-06-06

    In the present research, we assumed that reducing the amounts of E6 and E7 oncoproteins by a specific siRNA sequence and recovering p53 and RB proteins, along with the recovery of the FOXO1 protein by applying anti-miR-182, would increase apoptosis and reduce proliferation rate in cancer cells. The HPV16-positive CaSki cervical cancer cell line was used. 48 hours after transfection of siRNA for targeting E6 and E7 oncoproteins and anti-miR-182, expression of its cellular targets p53, p21 and FOXO1 was assessed by real-time PCR, western blot analysis and immunocytofluorescence staining. In all treatments, apoptosis rate and viability were evaluated using Annexin-V-FITC apoptosis detection kits and MTT assays, respectively. Among the designed siRNAs, E6-1 and E7-2 proved the most effective in reducing E6 and E7 expressions by increasing the apoptotic rates to 12.4% and 16%, respectively, after 48 hours. Also, using anti-miR-182 increased apoptotic rate to 12.7% 48 hours after transfection of cervical cancer cells. The combinational use of either E6-1 or E7-2 siRNAs with anti-miR-182 resulted in a rise in apoptosis to 19.3% and 26%, respectively, higher than those obtained from the individual application of either without anti-miR-182. The simultaneous use of siRNA E6-1 and siRNA E7-2 with cisplatin increased sensitivity to cisplatin and reduced the viability of the cancer cells as compared to the use of cisplatin alone. The simultaneous use of cisplatin and anti-miR-182 had no considerable effect on viability or apoptosis rate compared to cisplatin alone.

  19. Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes

    Directory of Open Access Journals (Sweden)

    Arnouk Hilal

    2009-08-01

    Full Text Available Abstract Background Infection with high-risk type human papilloma viruses (HPVs is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein features. Results Six replicate measurements were performed for each group using two-dimensional difference gel electrophoresis (2D-DIGE. The median within-group coefficient of variation was 19–21%. Significance of between-group differences was tested based on Significance Analysis of Microarray and fold change. Expression of 170 (23% of the protein features changed significantly in immortalized cells compared to primary keratinocytes. Most of these changes were qualitatively similar in cells immortalized by E6, E7, or E6/7 expression, indicating convergence on a common phenotype, but fifteen proteins (~2% were outliers in this regulatory pattern. Ten demonstrated opposite regulation in E6- and E7-expressing cells, including the cell cycle regulator p16INK4a; the carbohydrate binding protein Galectin-7; two differentially migrating forms of the intermediate filament protein Cytokeratin-7; HSPA1A (Hsp70-1; and five unidentified proteins. Five others had a pattern of expression that suggested cooperativity between the co-expressed oncoproteins. Two of these were identified as forms of the small heat shock protein HSPB1 (Hsp27. Conclusion This large-scale analysis provides a framework for understanding the cooperation between E6 and E7 oncoproteins in HPV-driven carcinogenesis.

  20. Mitotic control of human papillomavirus genome-containing cells is regulated by the function of the PDZ-binding motif of the E6 oncoprotein.

    Science.gov (United States)

    Marsh, Elizabeth K; Delury, Craig P; Davies, Nicholas J; Weston, Christopher J; Miah, Mohammed A L; Banks, Lawrence; Parish, Joanna L; Higgs, Martin R; Roberts, Sally

    2017-03-21

    The function of a conserved PDS95/DLG1/ZO1 (PDZ) binding motif (E6 PBM) at the C-termini of E6 oncoproteins of high-risk human papillomavirus (HPV) types contributes to the development of HPV-associated malignancies. Here, using a primary human keratinocyte-based model of the high-risk HPV18 life cycle, we identify a novel link between the E6 PBM and mitotic stability. In cultures containing a mutant genome in which the E6 PBM was deleted there was an increase in the frequency of abnormal mitoses, including multinucleation, compared to cells harboring the wild type HPV18 genome. The loss of the E6 PBM was associated with a significant increase in the frequency of mitotic spindle defects associated with anaphase and telophase. Furthermore, cells carrying this mutant genome had increased chromosome segregation defects and they also exhibited greater levels of genomic instability, as shown by an elevated level of centromere-positive micronuclei. In wild type HPV18 genome-containing organotypic cultures, the majority of mitotic cells reside in the suprabasal layers, in keeping with the hyperplastic morphology of the structures. However, in mutant genome-containing structures a greater proportion of mitotic cells were retained in the basal layer, which were often of undefined polarity, thus correlating with their reduced thickness. We conclude that the ability of E6 to target cellular PDZ proteins plays a critical role in maintaining mitotic stability of HPV infected cells, ensuring stable episome persistence and vegetative amplification.

  1. Rat primary embryo fibroblast cells suppress transformation by the E6 and E7 genes of human papillomavirus type 16 in somatic hybrid cells.

    OpenAIRE

    Miyasaka, M; Takami, Y; Inoue, H; Hakura, A

    1991-01-01

    The E6 and E7 genes of human papillomavirus type 16 (HPV-16) transform established lines of rat cells but not rat cells in primary culture irrespective of the expression of the two genes. The reason for this difference between the susceptibilities of cell lines and primary cells was examined by using hybrid cells obtained by somatic cell fusion of rat cell lines transformed by the E6 and E7 genes of HPV-16 and freshly isolated rat embryo fibroblast cells. In these hybrid cells, transformed ph...

  2. Gene silencing of HPV16 E6/E7 induced by promoter-targeting siRNA in SiHa cells

    OpenAIRE

    Hong, D; Lu, W; Ye, F; Hu, Y; Xie, X

    2009-01-01

    Background: Recently, transcriptional gene silencing induced by small interfering RNA (siRNA) was found in mammalian and human cells. However, previous studies focused on endogenous genes. Methods: In this study, we designed siRNA targeting the promoter of human papillomavirus 16 E6/E7 and transfected it into the cervical cancer cell line, SiHa. E6 and E7 mRNA and protein expression were detected in cells treated by promoter-targeting siRNA. Futhermore, cellular growth, proliferation, apoptos...

  3. Forty years of the first attempt at the electroweak unification and of the prediction of the weak neutral boson Z0

    International Nuclear Information System (INIS)

    Leite Lopes, J.

    1998-03-01

    The author describes his first in 1958 at the unification of electromagnetic and weak interactions and his prediction in the same paper of the neutral Z 0 boson which would be the intermediate quantum exchanged in an eventual electron-neutron weak interaction (as muonic neutrinos were not known at that time). In annex he transcribes copies of letters from Steven Weinberg, Abdus Salam and Bruno Pontecorvo and comments by C.N. Yang and J. Tiomno. (author)

  4. Detection of human papillomavirus type 18 E6 and E7-specific CD4+ T-helper 1 immunity in relation to health versus disease

    NARCIS (Netherlands)

    Welters, Marij J. P.; van der Logt, Pauline; van den Eeden, Susan J. F.; Kwappenberg, Kitty M. C.; Drijfhout, Jan Wouter; Fleuren, Gert Jan; Kenter, Gemma G.; Melief, Cornelis J. M.; van der Burg, Sjoerd H.; Offringa, Rienk

    2006-01-01

    The most common high-risk human papillomavirus types, HPV16 and 18, differ markedly with respect to their interaction with the host. Clearance of HPV18 infections generally takes longer and HPV18-positive cancers have a poorer prognosis. We therefore evaluated Th1-type immunity against the E6 and E7

  5. IFN-β antiproliferative effect and miRNA regulation in Human Papilloma Virus E6- and E7-transformed keratinocytes.

    Science.gov (United States)

    Chiantore, Maria Vincenza; Mangino, Giorgio; Iuliano, Marco; Zangrillo, Maria Simona; De Lillis, Ilaria; Vaccari, Gabriele; Accardi, Rosita; Tommasino, Massimo; Fiorucci, Gianna; Romeo, Giovanna

    2017-01-01

    Human Papilloma Viruses (HPVs) are the causative agents of cervical cancer although other types of cancers are associated with HPV infection. Type I Interferons can interfere with HPV E6- and/or E7-dependent transformation and can affect microRNA (miRNA) expression. Cancer cells show a specific pattern of miRNA expression and HPVs are able to modulate miRNAs expressed in infected cells. Keratinocytes transduced with E6 and E7 from mucosal HPV-16 or cutaneous HPV-38 (K16 and K38) were studied to analyze the involvement of HPV oncoproteins in the anti-proliferative activity of IFN-β. In view of our previous data showing senescence induction by the cytokine in K38 cells, we observe that IFN-β treatment leads to p53-indipendent apoptosis in K16 cells whereas induces senescence in K16 cells if E6 is silenced and p53 expression is restored. The levels of selected miRNAs, deregulated in K16 and K38 cells, can be modulated by IFN-β when E6 and E7 proteins of HPV-16, but not HPV-38, are expressed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, M. F.; Duk, J. M.; Burger, M. P.; de Bruijn, H. W.; Stolz, E.; Herbrink, P.

    1999-01-01

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  7. Maintenance of vascular endothelial cell-specific properties after immortalization with an amphotrophic replication-deficient retrovirus containing human papilloma virus 16 E6/E7 DNA

    NARCIS (Netherlands)

    Fontijn, R.; Hop, C.; Brinkman, H. J.; Slater, R.; Westerveld, A.; van Mourik, J. A.; Pannekoek, H.

    1995-01-01

    Primary human vascular endothelial cells were immortalized by the integration of a single DNA copy of an amphotrophic, replication-deficient retrovirus containing the E6/E7 genes of human papilloma virus. To date, the resulting cell lines, designated EC-RF7 and EC-RF24, have been cultured for more

  8. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, MFD; Duk, JM; Burger, MPM; de Bruijn, HWA; Stolz, E; Herbrink, P

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  9. Cervical Cancers Require the Continuous Expression of the Human Papillomavirus Type 16 E7 Oncoprotein Even in the Presence of the Viral E6 Oncoprotein

    Science.gov (United States)

    Jabbar, Sean F.; Park, Soyeong; Schweizer, Johannes; Berard-Bergery, Marthe; Pitot, Henry C.; Lee, Denis; Lambert, Paul F.

    2012-01-01

    High-risk human papillomaviruses (HPV), such as HPV-16, are etiologic agents of a variety of anogenital and oral malignancies, including nearly all cases of cervical cancer. Cervical cancers arising in transgenic mice that express HPV-16 E7 in an inducible manner require the continuous expression of E7 for their maintenance. However, in HPV-associated cancers in vivo, E6 and E7 invariably are co-expressed. In this study, we investigated whether cervical cancers rely on the continuous expression of E7 in the context of constitutively expressed E6. We placed the inducible HPV-16 E7 transgene onto a background in which HPV-16 E6 was constitutively expressed. In transgenic mice with high-grade cervical dysplastic lesions and cervical cancer, repressing the expression of E7 led to the regression of all cancers and the vast majority of high-grade dysplastic lesions. In addition, cervical cancers were occasionally observed in transgenic mice in which E7 was repressed and then re-expressed. Our findings therefore indicate that even in the presence of constitutively expressed E6, the continuous expression of E7 is required for the maintenance of cervical cancers and most precancerous lesions. These data have important implications for the potential clinical use of drugs designed to inhibit the expression and/or function of E7 to treat HPV-associated cancers. PMID:22700879

  10. Human papillomavirus E6/E7 oncogenes promote mouse ear regeneration by increasing the rate of wound re-epithelization and epidermal growth.

    Science.gov (United States)

    Valencia, Concepción; Bonilla-Delgado, José; Oktaba, Katarzyna; Ocádiz-Delgado, Rodolfo; Gariglio, Patricio; Covarrubias, Luis

    2008-12-01

    Mammals have limited regeneration capacity. We report here that, in transgenic mice (Tg(bK6-E6/E7)), the expression of the E6/E7 oncogenes of human papilloma virus type 16 (HPV16) under the control of the bovine keratin 6 promoter markedly improves the mouse's capacity to repair portions of the ear after being wounded. Increased repair capacity correlates with an increased number of epidermal proliferating cells. In concordance with the expected effects of the E6 and E7 oncogenes, levels of p53 decreased and those of p16 in epidermal cells increased. In addition, we observed that wound re-epithelization proceeded faster in transgenic than in wild-type animals. After the initial re-epithelization, epidermal cell migration from the intact surrounding tissue appears to be a major contributor to the growing epidermis, especially in the repairing tissue of transgenic mice. We also found that there is a significantly higher number of putative epidermal stem cells in Tg(bK6-E6/E7) than in wild-type mice. Remarkably, hair follicles and cartilage regenerated within the repaired ear tissue, without evidence of tumor formation. We propose that the ability to regenerate ear portions is limited by the capacity of the epidermis to repair itself and grow.

  11. The BPS spectrum of the 4d {N}=2 SCFT's H 1, H 2, D 4, E 6, E 7, E 8

    Science.gov (United States)

    Cecotti, Sergio; Del Zotto, Michele

    2013-06-01

    Extending results of 1112.3984, we show that all rank 1 {N}=2 SCFT's in the sequence H 1, H 2, D 4 E 6, E 7, E 8 have canonical finite BPS chambers containing precisely 2 h(F) = 12(∆ - 1) hypermultiplets. The BPS spectrum of the canonical BPS chambers saturates the conformal central charge c, and satisfies some intriguing numerology.

  12. Computational identification, characterization and validation of potential antigenic peptide vaccines from hrHPVs E6 proteins using immunoinformatics and computational systems biology approaches.

    Directory of Open Access Journals (Sweden)

    Abbas Khan

    Full Text Available High-risk human papillomaviruses (hrHPVs are the most prevalent viruses in human diseases including cervical cancers. Expression of E6 protein has already been reported in cervical cancer cases, excluding normal tissues. Continuous expression of E6 protein is making it ideal to develop therapeutic vaccines against hrHPVs infection and cervical cancer. Therefore, we carried out a meta-analysis of multiple hrHPVs to predict the most potential prophylactic peptide vaccines. In this study, immunoinformatics approach was employed to predict antigenic epitopes of hrHPVs E6 proteins restricted to 12 Human HLAs to aid the development of peptide vaccines against hrHPVs. Conformational B-cell and CTL epitopes were predicted for hrHPVs E6 proteins using ElliPro and NetCTL. The potential of the predicted peptides were tested and validated by using systems biology approach considering experimental concentration. We also investigated the binding interactions of the antigenic CTL epitopes by using docking. The stability of the resulting peptide-MHC I complexes was further studied by molecular dynamics simulations. The simulation results highlighted the regions from 46-62 and 65-76 that could be the first choice for the development of prophylactic peptide vaccines against hrHPVs. To overcome the worldwide distribution, the predicted epitopes restricted to different HLAs could cover most of the vaccination and would help to explore the possibility of these epitopes for adaptive immunotherapy against HPVs infections.

  13. Les représentations de la réunification allemande dans l’ex-Yougoslavie

    Directory of Open Access Journals (Sweden)

    Laurent Hassid

    2012-06-01

    Full Text Available La réunification allemande a été perçue de manière différente dans les États de l’ex-Yougoslavie. En Serbie, république la plus peuplée de la Fédération et où se trouve le pouvoir central, elle est crainte comme le symbole d’une possible désintégration. En Croatie et en Slovénie s’est ainsi répandue l’idée que « si l’Allemagne peut se réunifier, la Yougoslavie peut bien se désintégrer » (Entretien avec Vladimir Radomirovic, ancien rédacteur en chef du quotidien serbe Politika et fondateur en 2009 de Pistaljka, site Internet qui dénonce la corruption dans les Balkans - www.pistaljka.rs. Au risque de provoquer une crise au sein de la CEE, l’Allemagne a poussé les autres grandes puissances du continent, dont la France, à reconnaître rapidement les indépendances des deux républiques. Pour comprendre les différentes représentations de la réunification allemande dans les Balkans, il est nécessaire d’étudier également les perceptions de la chute du Mur de Berlin, un an plus tôt. Symbole d’un communisme qui n’est pas tombé partout dans l’ex-Yougoslavie à partir de 1991, il a néanmoins grandement participé à la désintégration de la Fédération. Vingt ans après, l’Allemagne reste un acteur majeur dans la région, mais a abandonné une partie de son influence économique et politique au profit de l’Union européenne, notamment à partir de l’introduction de l’euro qui prend la place du mark, ancienne devise de référence.

  14. Standard coupling unification in SO(10), hybrid seesaw neutrino mass and leptogenesis, dark matter, and proton lifetime predictions

    Energy Technology Data Exchange (ETDEWEB)

    Parida, M.K.; Nayak, Bidyut Prava; Satpathy, Rajesh [Centre of Excellence in Theoretical and Mathematical Sciences,Siksha ‘O’ Anusandhan University,Khandagiri Square, Bhubaneswar 751030 (India); Awasthi, Ram Lal [Indian Institute of Science Education and Research,Knowledge City, Sector 81, SAS Nagar, Manauli 140306 (India)

    2017-04-12

    We discuss gauge coupling unification of SU(3){sub C}×SU(2){sub L}×U(1){sub Y} descending directly from non-supersymmetric SO(10) while providing solutions to the three outstanding problems of the standard model: neutrino masses, dark matter, and the baryon asymmetry of the universe. Conservation of matter parity as gauged discrete symmetry for the stability and identification of dark matter in the model calls for high-scale spontaneous symmetry breaking through 126{sub H} Higgs representation. This naturally leads to the hybrid seesaw formula for neutrino masses mediated by heavy scalar triplet and right-handed neutrinos. Being quadratic in the Majorana coupling, the seesaw formula predicts two distinct patterns of right-handed neutrino masses, one hierarchical and another not so hierarchical (or compact), when fitted with the neutrino oscillation data. Predictions of the baryon asymmetry via leptogenesis are investigated through the decays of both the patterns of RHν masses. A complete flavor analysis has been carried out to compute CP-asymmetries including washouts and solutions to Boltzmann equations have been utilised to predict the baryon asymmetry. The additional contribution to vertex correction mediated by the heavy left-handed triplet scalar is noted to contribute as dominantly as other Feynman diagrams. We have found successful predictions of the baryon asymmetry for both the patterns of right-handed neutrino masses. The SU(2){sub L} triplet fermionic dark matter at the TeV scale carrying even matter parity is naturally embedded into the non-standard fermionic representation 45{sub F} of SO(10). In addition to the triplet scalar and the triplet fermion, the model needs a nonstandard color octet fermion of mass ∼5×10{sup 7} GeV to achieve precision gauge coupling unification at the GUT mass scale M{sub U}{sup 0}=10{sup 15.56} GeV. Threshold corrections due to superheavy components of 126{sub H} and other representations are estimated and found to be

  15. A prime/boost strategy using DNA/fowlpox recombinants expressing the genetically attenuated E6 protein as a putative vaccine against HPV-16-associated cancers.

    Science.gov (United States)

    Bissa, Massimiliano; Illiano, Elena; Pacchioni, Sole; Paolini, Francesca; Zanotto, Carlo; De Giuli Morghen, Carlo; Massa, Silvia; Franconi, Rosella; Radaelli, Antonia; Venuti, Aldo

    2015-03-05

    Considering the high number of new cases of cervical cancer each year that are caused by human papilloma viruses (HPVs), the development of an effective vaccine for prevention and therapy of HPV-associated cancers, and in particular against the high-risk HPV-16 genotype, remains a priority. Vaccines expressing the E6 and E7 proteins that are detectable in all HPV-positive pre-cancerous and cancer cells might support the treatment of HPV-related lesions and clear already established tumors. In this study, DNA and fowlpox virus recombinants expressing the E6F47R mutant of the HPV-16 E6 oncoprotein were generated, and their correct expression verified by RT-PCR, Western blotting and immunofluorescence. Immunization protocols were tested in a preventive or therapeutic pre-clinical mouse model of HPV-16 tumorigenicity using heterologous (DNA/FP) or homologous (DNA/DNA and FP/FP) prime/boost regimens. The immune responses and therapeutic efficacy were evaluated by ELISA, ELISPOT assays, and challenge with TC-1* cells. In the preventive protocol, while an anti-E6-specific humoral response was just detectable, a specific CD8(+) cytotoxic T-cell response was elicited in immunized mice. After the challenge, there was a delay in cancer appearance and a significant reduction of tumor volume in the two groups of E6-immunized mice, thus confirming the pivotal role of the CD8(+) T-cell response in the control of tumor growth in the absence of E6-specific antibodies. In the therapeutic protocol, in-vivo experiments resulted in a higher number of tumor-free mice after the homologous DNA/DNA or heterologous DNA/FP immunization. These data establish a preliminary indication for the prevention and treatment of HPV-related tumors by the use of DNA and avipox constructs as safe and effective immunogens following a prime/boost strategy. The combined use of recombinants expressing both E6 and E7 proteins might improve the antitumor efficacy, and should represent an important approach to

  16. Topics in gauge theories and unification of elementary particle interactions: Progress report for period April 1, 1986-June 30, 1987

    International Nuclear Information System (INIS)

    Srivastava, Y.N.; Vaughn, M.T.

    1987-06-01

    Work is reported on: minjets and the rise of the total cross-section in QCD; quantum electrodynamic effects in macroscopic circuits; experimental search for electroweak effects in circuits; baryonium states with heavy quarks; E 6 superpotentials and heterotic string phenomenology; and computer graphic representations of solutions to classical field equations

  17. Post-sphaleron baryogenesis and n- anti n oscillation in non-SUSY SO(10) GUT with gauge coupling unification

    International Nuclear Information System (INIS)

    Patra, Sudhanwa; Pritimita, Prativa

    2014-01-01

    ''Post-sphaleron baryogenesis'', a fresh and profound mechanism of baryogenesis accounts for the matter-antimatter asymmetry of our present universe in a framework of Pati-Salam symmetry. We attempt here to embed this mechanism in a non-SUSY SO(10) grand unified theory by reviving a novel symmetry breaking chain with Pati-Salam symmetry as an intermediate symmetry breaking step and as well to address post-sphaleron baryogenesis and neutron-antineutron oscillation in a rational manner. The Pati-Salam symmetry based on the gauge group SU(2) L x SU(2) R x SU(4) C is realized in our model at 10 5 -10 6 GeV and the mixing time for the neutron-antineutron oscillation process having ΔB = 2 is found to be τ n- anti n ≅ 10 8 -10 10 s with the model parameters, which is within the reach of forthcoming experiments. Other novel features of the model include low scale right-handed W R ± , Z R gauge bosons, explanation for neutrino oscillation data via the gauged inverse (or extended) seesaw mechanism and most importantly TeV scale color sextet scalar particles responsible for an observable n- anti n oscillation which may be accessible to LHC. We also look after gauge coupling unification and an estimation of the proton lifetime with and without the addition of color sextet scalars. (orig.)

  18. Towards a unification of the hierarchical reference theory and the self-consistent Ornstein-Zernike approximation.

    Science.gov (United States)

    Reiner, A; Høye, J S

    2005-12-01

    The hierarchical reference theory and the self-consistent Ornstein-Zernike approximation are two liquid state theories that both furnish a largely satisfactory description of the critical region as well as phase coexistence and the equation of state in general. Furthermore, there are a number of similarities that suggest the possibility of a unification of both theories. As a first step towards this goal, we consider the problem of combining the lowest order gamma expansion result for the incorporation of a Fourier component of the interaction with the requirement of consistency between internal and free energies, leaving aside the compressibility relation. For simplicity, we restrict ourselves to a simplified lattice gas that is expected to display the same qualitative behavior as more elaborate models. It turns out that the analytically tractable mean spherical approximation is a solution to this problem, as are several of its generalizations. Analysis of the characteristic equations shows the potential for a practical scheme and yields necessary conditions that any closure to the Ornstein-Zernike relation must fulfill for the consistency problem to be well posed and to have a unique differentiable solution. These criteria are expected to remain valid for more general discrete and continuous systems, even if consistency with the compressibility route is also enforced where possible explicit solutions will require numerical evaluations.

  19. Upregulation of HPV E6 and E7 genes in human cervix carcinoma cell lines leads to both an increase in radiation resistance and alterations in apoptosis

    International Nuclear Information System (INIS)

    Kamradt, M.; Krueger, E.; McCall, A.; Manker, C.; Rudnick, S.; Erlich, E.; Khodarev, N; Vaughan, A.T.M.

    1996-01-01

    Purpose: Stage I-III cervical cancer is commonly treated with external beam radiotherapy with curative intent. We have shown that the presence of the artificial steroid dexamethasone can increase the radiation resistance of HPV+ve cervical tumors. Dexamethasone treatment enhances cell proliferation by upregulation of HPV 18 E6 and E7 genes through a glucocorticoid responsive element within the HPV promoter region. The goal of this study is to understand the mechanism whereby steroid treatment produces enhanced radioresistance in cervical tumors. Methods: Four cervical tumor cell lines and one squamous carcinoma cell line (SQ-20B) were used. Each cell line was exposed to 0 - 8 Gy of gamma irradiation in the presence or absence of 1 μM dexamethasone (Dx) and assayed for cell survival using a clonogenic assay. Parallel samples were examined by fluorescence microscopy after Triton X-100 permeabilization and propidium iodide staining 1, 2 and 4 days post irradiation. Nuclei containing the characteristic multi-lobular structure and condensed appearance of apoptosis were recorded. To confirm the presence of apoptosis in these cells a terminal deoxynucleotide transferase staining reaction was carried out to label the free DNA ends characteristic of apoptosis. Results: Administration of Dx increased radiation resistance in all HPV+ve E6 and E7 expressing cell lines studied, a similar effect was seen in two additional HPV 18+ve cervical carcinoma cell lines ME180 and MS751 (data not shown). No effect was seen in the HPV-ve cell lines, or C41 K6 containing anti-sense E6 and E7 genes. Introduction of the anti-sense E6 and E7 sequences into C41 did not affect their ability to undergo radiation-induced apoptosis though Dx administration reduced the amount of apoptosis seen. Conversely, Dx treatment of the HeLa cell line increased radioresistance but did not affect the ability of these cells to engage apoptosis. Conclusion: All (5) cervical cell lines studied containing HPV 18

  20. Oncogenes E6-E7 de los Papilomavirus Humanos de alto riesgo detectados por PCR en Biopsias de pene incluidas en parafina

    Directory of Open Access Journals (Sweden)

    I Guerrero

    1999-01-01

    Full Text Available La alta prevalencia del papilomavirus humano (PVH, referida a nivel mundial, en lesiones genitales de ambos sexos, el rol del varón como reservorio pasivo del virus, y el incremento de la mortalidad por cáncer genital en la mujer en nuestro país, motiva la detección y correlación de los oncogenes de los PVH de alto riesgo con la neoplasia de pene. Informamos de diez casos de biopsias de carcinoma escamoso de pene, incluidos en parafina, los cuales fueron investigados para la presencia de los oncogenes E6-E7 de PVH de alto riesgo, utilizando cebadores tipo específico para los PVH -16 y 18, mediante la reacción en cadena de la polimerasa (PCR. El 40% de los casos mostró un producto de amplificación ADN E6-E7 de los PVH estudiados, correspondiendo el 75% de ellos a detección simple por PVH-18 y el 25% presentó detección mixta ADN E6 - E7 del PVH-16 y 18 simultáneamente. El producto de amplificación fue sometido a comprobación por análisis de restricción específico. La prevalencia obtenida de los oncogenes E6-E7 de los PVH de alto riesgo, usando un método tan sensible como la PCR, apoya el rol de estos virus en el proceso de carcinogénesis de la neoplasia de pene.

  1. The cellular uptake of antisense oligonucleotid of E6 mRNA into cervical cancer cells by DOPE-modified hydroxyapatite nanoparticles

    OpenAIRE

    Negin Saffarzadeh; Seyed Mehdi Kalantar; Ali Jebali; Seyed Hossein Hekmatimoghaddam; Mohammad Hassan Sheikhha; Ehsan Farashahi

    2014-01-01

    Objective(s): Although several chemical and physical methods for gene delivery have been introduced, their cytotoxicity, non-specific immune responses and the lack of biodegradability remain the main issues. In this study, hydroxyapatite nanoparticles (NPs) and 1,2-dioleoyl-sn-glycero-3-phosphoethanol​amine (DOPE)-modified hydroxyapatite NPs was coated with antisense oligonucleotide of E6 mRNA, and their uptakes into the cervical cancer cell line were evaluated. Materials and Methods: Calcium...

  2. Intracellular human papillomavirus E6, E7 mRNA quantification predicts CIN 2+ in cervical biopsies better than Papanicolaou screening for women regardless of age.

    Science.gov (United States)

    Pierry, Deirdre; Weiss, Gerald; Lack, Benjamin; Chen, Victor; Fusco, Judy

    2012-08-01

    Cervical cancer screening in women younger than 30 years relies on cervical cytology because of the poor performance of human papillomavirus (HPV) DNA testing in this age group. To determine the performance of in-cell HPV E6, E7 mRNA quantification (HPV OncoTect) for the detection of high-grade cervical intraepithelial neoplasia in women younger than 30 years. We analyzed 3133 cytology specimens from a screening population of women aged 19-75 years investigate HPV OncoTect as a triage/secondary screening test for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology in women younger than 30 years. Test results were compared to histology in 246 cases. The sensitivity of E6, E7 mRNA was 89% for CIN 2+ and 100% for CIN 3+ lesions in women 30 years and older. In women younger than 30 years, the sensitivity of E6, E7 mRNA for CIN 2+ lesions was 88% for CIN 2+ and 92% for CIN 3+ lesions. Abnormal cytology (≥ASCUS) exhibited a sensitivity of 89% for CIN 2+ and 100% for CIN 3+ in women 30 years and older and 96% sensitivity for CIN 2+ and 93% sensitivity for CIN 3+ in women younger than 30. The specificity of E6, E7 mRNA was >80% for CIN 2+ and CIN 3+ in both groups of women compared to a specificity of abnormal cytology of ASCUS/LSIL triage in women including those younger than 30 years.

  3. Molecular screening of compounds to the predicted Protein-Protein Interaction site of Rb1-E7 with p53- E6 in HPV

    Science.gov (United States)

    Shaikh, Faraz; Sanehi, Parvish; Rawal, Rakesh

    2012-01-01

    Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. Human Papillomaviruses (HPVs) which are heterogeneous groups of small double stranded DNA viruses are considered as the primary cause of cervical cancer, involved in 90% of all Cervical Cancers. Two early HPV genes, E6 and E7, are known to play crucial role in tumor formation. E6 binds with p53 and prevents its translocation and thereby inhibit the ability of p53 to activate or repress target genes. E7 binds to hypophosphorylated Rb and thereby induces cells to enter into premature S-phase by disrupting Rb-E2F complexes. The strategy of the research work was to target the site of interaction of Rb1 -E7 & p53-E6. A total of 88 compounds were selected for molecular screening, based on comprehensive literature survey for natural compounds with anti-cancer activity. Molecular docking analysis was carried out with Molegro Virtual Docker, to screen the 88 chosen compounds and rank them according to their binding affinity towards the site of interaction of the viral oncoproteins and human tumor suppressor proteins. The docking result revealed that Nicandrenone a member of Withanolides family of chemical compounds as the most likely molecule that can be used as a candidate drug against HPV induced cervical cancer. Abbreviations HPV - Human Papiloma Virus, HTSP - Human Tumor Suppressor Proteins, VOP - Viral oncoproteins. PMID:22829740

  4. Risk of progression of early cervical lesions is associated with integration and persistence of HPV-16 and expression of E6, Ki-67, and telomerase

    Directory of Open Access Journals (Sweden)

    Arianna Vega-Peña

    2013-01-01

    Full Text Available Background: Low-grade squamous intraepithelial lesions (LSIL are the earliest lesions of the uterine cervix, the persistence and integration of high-risk human papillomavirus (HR-HPV as type 16, which promotes the development of more aggressive lesions. Aim: To select more aggressive lesions with tendency to progress to invasive cervical cancer. Materials and Methods: A total of 75 cytological specimens in liquid base (Liqui-PREP were analyzed: 25 specimens were with no signs of SIL (NSIL and without HPV; 25 NSIL with HPV-16, and 25 with both LSIL and HPV-16. The expression of Ki-67, telomerase, and viral E6 was evaluated by immunocytochemistry; and the detection of viral DNA was done by polymerase chain reaction (PCR and restriction fragment length polymorphism (RFLPs for genotyping or sequencing of HPV-16. The physical state of HPV-16 was evaluated by in situ hybridization with amplification with tyramide. Results: Of the total group, 58.6% had LSIL associated with persistence and of these 59.3% was associated with integrated state of HPV as intense expression of E6, Ki-67 (P = 0.013, P = 0.055 has except for the expression of telomerase present a non-significant association (P<0.341. Conclusions: Overexpression of E6 and Ki-67 is associated with the integration of HPV-16, favoring viral persistence, and increasing the risk of progression in women with NSIL and LSIL.

  5. Successful treatment with allogeneic stem cell transplantation followed by DLI and TKIs for e6a2 BCR-ABL-positive acute myeloid leukaemia

    Science.gov (United States)

    Harada, Yasuhiko; Nishiwaki, Satoshi; Sugimoto, Takumi; Onodera, Koichi; Goto, Tatsunori; Sato, Takahiko; Kamoshita, Sonoko; Kawashima, Naomi; Seto, Aika; Okuno, Shingo; Yamamoto, Satomi; Iwasaki, Toshihiro; Ozawa, Yukiyasu; Miyamura, Koichi; Akatsuka, Yoshiki; Sugiura, Isamu

    2017-01-01

    Abstract Rationale: Patients with the e6a2 BCR-ABL transcript, 1 of the atypical transcripts, have been reported to have a poor prognosis, and allogeneic stem cell transplantation (ASCT) can be considered as additional therapy. However, long-term survival after ASCT for this disease is rare. Patient concerns: This report concerns a 55-year-old female patient with e6a2 BCR-ABL-positive acute myeloid leukemia including the outcome of ASCT followed by donor lymphocyte infusion (DLI). Diagnoses: The breakpoint was confirmed by direct sequencing. Her minimal residual disease could be detected by nested reverse-transcription polymerase chain reaction using primers for the minor BCR-ABL (e1a2) transcript. Interventions: Treatment with tyrosine kinase inhibitors (TKIs) and ASCT followed by DLI. Outcomes: Despite multiple cytogenetic and molecular relapses after ASCT, she remains in molecular remission at 46 months after ASCT. Lessons: This case indicates the efficacy of the combination of the graft-versus-leukemia effect and TKIs for e6a2 BCR-ABL-positive acute leukemia. When the Philadelphia chromosome with an unusual chromosomal breakpoint is suggested, we should clarify the breakpoint because that information can aid molecular assessments and decisions to provide an additional or alternative therapy. PMID:29390324

  6. Morphoproteomics, E6/E7 in-situ hybridization, and biomedical analytics define the etiopathogenesis of HPV-associated oropharyngeal carcinoma and provide targeted therapeutic options.

    Science.gov (United States)

    Brown, Robert E; Naqvi, Syed; McGuire, Mary F; Buryanek, Jamie; Karni, Ron J

    2017-08-17

    Human papillomavirus (HPV) has been identified as an etiopathogenetic factor in oropharyngeal squamous cell carcinoma. The HPV E6 and E7 oncogenes are instrumental in promoting proliferation and blocking differentiation leading to tumorigenesis. Although surgical intervention can remove such tumors, the potential for an etiologic field effect with recurrent disease is real. A downstream effector of E7 oncoprotein, enhancer of zeste homolog 2 (EZH2), is known to promote proliferation and to pose a block in differentiation and in turn, could lead to HPV-induced malignant transformation. However, the EZH2 pathway is amenable to low toxicity therapies designed to promote differentiation to a more benign state and prevent recurrent disease by inhibiting the incorporation of HPV into the genome. This is the first study using clinical specimens to demonstrate EZH2 protein expression in oropharyngeal carcinoma (OPC). The study included eight patients with oropharyngeal carcinoma, confirmed p16INK4a- positive by immunohistochemistry (IHC). The tissue expression of E6/E7 messenger RNA (mRNA) was measured by RNAscope® in-situ hybridization technology. Expression of EZH2, Ki-67, and mitotic indices were assessed by morphoproteomic analysis. Biomedical analytics expanded the results with data from Ingenuity Pathway Analysis (IPA) and KEGG databases to construct a molecular network pathway for further insights. Expression of E6 and E7 oncogenes in p16INK4a- positive oropharyngeal carcinoma was confirmed. EZH2 and its correlates, including elevated proliferation index (Ki-67) and mitotic progression were also present. Biomedical analytics validated the relationship between HPV- E6 and E7 and the expression of the EZH2 pathway. There is morphoproteomic and mRNA evidence of the association of p16INK4a-HPV infection with the E6 and E7 oncogenes and the expression of EZH2, Ki-67 and mitotic progression in oropharyngeal carcinoma. The molecular network biology was confirmed by

  7. Single-tube multiplex PCR using type-specific E6/E7 primers and capillary electrophoresis genotypes 21 human papillomaviruses in neoplasia

    Directory of Open Access Journals (Sweden)

    Warenholt Janina

    2011-01-01

    Full Text Available Abstract Background Human papillomavirus (HPV E6/E7 type-specific oncogenes are required for cervical carcinogenesis. Current PCR protocols for genotyping high-risk HPV in cervical screening are not standardized and usually use consensus primers targeting HPV capsid genes, which are often deleted in neoplasia. PCR fragments are detected using specialized equipment and extra steps, including probe hybridization or primer extension. In published papers, analytical sensitivity is typically compared with a different protocol on the same sample set. A single-tube multiplex PCR containing type-specific primers was developed to target the E6/E7 genes of two low-risk and 19 high-risk genotypes (HPV6, 11 and 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82 and the resulting short fragments were directly genotyped by high-resolution fluorescence capillary electrophoresis. Results The method was validated using long oligonucleotide templates, plasmid clones and 207 clinical samples of DNA from liquid-based cytology, fresh and formalin-fixed specimens and FTA Microcards® imprinted with cut tumor surfaces, swabbed cervical cancers or ejected aspirates from nodal metastases of head and neck carcinomas. Between one and five long oligonucleotide targets per sample were detected without false calls. Each of the 21 genotypes was detected in the clinical sample set with up to five types simultaneously detected in individual specimens. All 101 significant cervical neoplasias (CIN 2 and above, except one adenocarcinoma, contained E6/E7 genes. The resulting genotype distribution accorded with the national pattern with HPV16 and 18 accounting for 69% of tumors. Rare HPV types 70 and 73 were present as the sole genotype in one carcinoma each. One cervical SCC contained DNA from HPV6 and 11 only. Six of twelve oropharyngeal cancer metastases and three neck metastases of unknown origin bore E6/E7 DNA; all but one were HPV16. One neck

  8. Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes ▿

    Science.gov (United States)

    Hyland, Paula L.; McDade, Simon S.; McCloskey, Rachel; Dickson, Glenda J.; Arthur, Ken; McCance, Dennis J.; Patel, Daksha

    2011-01-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future. PMID:21865393

  9. Evidence for alteration of EZH2, BMI1, and KDM6A and epigenetic reprogramming in human papillomavirus type 16 E6/E7-expressing keratinocytes.

    Science.gov (United States)

    Hyland, Paula L; McDade, Simon S; McCloskey, Rachel; Dickson, Glenda J; Arthur, Ken; McCance, Dennis J; Patel, Daksha

    2011-11-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future.

  10. The Non-Coding RNA Ontology (NCRO): a comprehensive resource for the unification of non-coding RNA biology.

    Science.gov (United States)

    Huang, Jingshan; Eilbeck, Karen; Smith, Barry; Blake, Judith A; Dou, Dejing; Huang, Weili; Natale, Darren A; Ruttenberg, Alan; Huan, Jun; Zimmermann, Michael T; Jiang, Guoqian; Lin, Yu; Wu, Bin; Strachan, Harrison J; He, Yongqun; Zhang, Shaojie; Wang, Xiaowei; Liu, Zixing; Borchert, Glen M; Tan, Ming

    2016-01-01

    In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for the domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. The NCRO ontology is free and open to all users, accessible at: http://purl.obolibrary.org/obo/ncro.owl.

  11. Unification of cosmology and the second law of thermodynamics. Proposal for solving the cosmological constant and inflation problems

    International Nuclear Information System (INIS)

    Nielsen, Holger B.; Ninomiya, Masao

    2006-01-01

    We seek to unify the second law of thermodynamics with other physical laws, or, at least to find a law underlying the second law of thermodynamics. Assuming no fine tuning, using a random Hamiltonian, we argue just from the equations of motion - without the second law - that entropy cannot first increase and then decrease except with the rather strict restriction S large ≤ S small1 + S small2 . Here S large is the large' entropy in the intermediate era, while S small1 and S small2 are the entropies at certain times before and after the S large era. From this theorem asserting that there can exist no strong maximum for the entropy, we argue that an S 1 cyclic time model world could have entropy that varies by at most a factor of two and would not be phenomenologically realistic. With an open ended time axis (-∞, ∞)=R, some law underlying the second law of thermodynamics is needed if the entropy is not maximal (i.e. that heat death having y occurred at the start). We derive such a law behind the second law - or a unification of the second law with other laws - by assigning a probability weight P for finding the world/system in various places in phase space. In such a model, P is almost unified with the rest as P=exp(-2S Im ), with S Im being the imaginary part of the action. We quite naturally derive the second law for practical purposes, a Big Bang with two-sided time directions, and find that there is a need for a Hamiltonian density with a well-defined bottom. Assuming that the cosmological constant is a dynamical variable in the sense that it is counted as on 'initial condition', we even solve in our model the cosmological constant problem without using the anthropic principle. (author)

  12. Synthesis of 6-Substituted 2-Pyrones Starting from Renewable Resources: Total Synthesis of Sibirinone, (E)-6-(Pent-1-en-1-yl)-2H-pyran-2-one, and (E)-6-(Hept-1-en-1-yl)-2H-pyran-2-one.

    Science.gov (United States)

    Dobler, Daniel; Reiser, Oliver

    2016-11-04

    An atom-economic reaction sequence to 6-substituted 2-pyrones was developed starting from furfuryl alcohol, a renewable resource made from bran or bagasse, and aldehydes, utilizing a thermal rearrangement of cyclopentadienone epoxides as key step. Derivatives bearing a hydroxyalkyl side chain could be enzymatically resolved, providing access to enantiomerically pure 2-pyrones, or converted to alkenyl-substituted 2-pyrones such as naturally occurring sibirinone, (E)-6-(pent-1-en-1-yl)-2H-pyran-2-one, and (E)-6-(hept-1-en-1-yl)-2H-pyran-2-one.

  13. Forty years of the first attempt at the electroweak unification and of the prediction of the weak neutral boson Z{sub 0}

    Energy Technology Data Exchange (ETDEWEB)

    Leite Lopes, J [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil)

    1998-03-01

    The author describes his first in 1958 at the unification of electromagnetic and weak interactions and his prediction in the same paper of the neutral Z{sub 0} boson which would be the intermediate quantum exchanged in an eventual electron-neutron weak interaction (as muonic neutrinos were not known at that time). In annex he transcribes copies of letters from Steven Weinberg, Abdus Salam and Bruno Pontecorvo and comments by C.N. Yang and J. Tiomno. (author) 24 refs., 5 figs.

  14. In situ hybridization detection methods for HPV16 E6/E7 mRNA in identifying transcriptionally active HPV infection of oropharyngeal carcinoma: an updating.

    Science.gov (United States)

    Volpi, Chiara C; Ciniselli, Chiara M; Gualeni, Ambra V; Plebani, Maddalena; Alfieri, Salvatore; Verderio, Paolo; Locati, Laura; Perrone, Federica; Quattrone, Pasquale; Carbone, Antonino; Pilotti, Silvana; Gloghini, Annunziata

    2018-04-01

    The aim of this study is to compare 2 in situ hybridization (ISH) detection methods for human papilloma virus (HPV) 16 E6/E7 mRNA, that is, the RNAscope 2.0 High Definition (HD) and the upgraded RNAscope 2.5 HD version. The RNAscope 2.5 HD has recently replaced the RNAscope 2.0 HD detection kit. Therefore, this investigation starts from the need to analytically validate the new mRNA ISH assay and, possibly, to refine the current algorithm for HPV detection in oropharyngeal squamous cell carcinoma with the final goal of applying it to daily laboratory practice. The study was based on HPV status and on generated data, interpreted by a scoring algorithm. The results highlighted that the compared RNAscope HPV tests had a good level of interchangeability and enabled to identify oropharyngeal squamous cell carcinoma that are truly driven by high-risk HPV infection. This was also supported by the comparison of the RNAscope HPV test with HPV E6/E7 mRNA real-time reverse-transcription polymerase chain reaction in a fraction of cases where material for HPV E6/E7 mRNA real-time reverse-transcription polymerase chain reaction was available. Furthermore, the algorithm that associates p16 immunohistochemistry with the identification of HPV mRNA by RNAscope was more effective than the one that associated p16 immunohistochemistry with the identification of HPV DNA by ISH. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. ABCG2-mediated suppression of chlorin e6 accumulation and photodynamic therapy efficiency in glioblastoma cell lines can be reversed by KO143.

    Science.gov (United States)

    Abdel Gaber, Sara A; Müller, Patricia; Zimmermann, Wolfgang; Hüttenberger, Dirk; Wittig, Rainer; Abdel Kader, Mahmoud H; Stepp, Herbert

    2018-01-01

    Photodynamic therapy (PDT) of malignant brain tumors is a promising adjunct to standard treatment, especially if tumor stem cells thought to be responsible for tumor progression and therapy resistance were also susceptible to this kind of treatment. However, some photosensitizers have been reported to be substrates of ABCG2, one of the membrane transporters mediating resistance to chemotherapy. Here we investigate, whether inhibition of ABCG2 can restore sensitivity to photosensitizer chlorin e6-mediated PDT. Accumulation of chlorin e6 in wild type U87 and doxycycline-inducible U251 glioblastoma cells with or without induction of ABCG2 expression or ABCG2 inhibition by KO143 was analyzed using flow cytometry. In U251 cells, ABCG2 was inducible by doxycycline after stable transfection with a tet-on expression plasmid. Tumor sphere cultivation under low attachment conditions was used to enrich for cells with stem cell-like properties. PDT was done on monolayer cell cultures by irradiation with laser light at 665nm. Elevated levels of ABCG2 in U87 cells grown as tumor spheres or in U251 cells after ABCG2 induction led to a 6-fold lower accumulation of chlorin e6 and the light dose needed to reduce cell viability by 50% (LD50) was 2.5 to 4-fold higher. Both accumulation and PDT response can be restored by KO143, an efficient non-toxic inhibitor of ABCG2. Glioblastoma stem cells might escape phototoxic destruction by ABCG2-mediated reduction of photosensitizer accumulation. Inhibition of ABCG2 during photosensitizer accumulation and irradiation promises to restore full susceptibility of this crucial tumor cell population to photodynamic treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. E6 and E7 oncogene expression by human papilloma virus (HPV) and the aggressive behavior of recurrent laryngeal papillomatosis (RLP).

    Science.gov (United States)

    Shehata, Bahig M; Otto, Kristen J; Sobol, Steven E; Stockwell, Christina A; Foulks, Cora; Lancaster, Wayne; Gregoire, Lucie; Hill, Charles E

    2008-01-01

    Recurrent laryngeal papillomatosis (RLP), a chronic disease associated with human papilloma virus (HPV), requires serial surgical procedures for debulking, resulting in debilitating long-term dysphonia, laryngeal scarring, and rarely malignant degeneration. Human papilloma virus 11 tumors have been widely accepted as more aggressive than HPV 6 tumors; however, the clinical course has been difficult to predict at disease onset, and the biologic mediators of proliferation have not been well characterized. A retrospective case review of 43 patients (4 months to 10 years at diagnosis) was performed on children treated for recurrent laryngeal papillomatosis. Patient charts were reviewed for demographic information, age at RLP diagnosis, approximate frequency of surgical intervention, and absolute number of surgical procedures performed. Human papilloma virus subtyping was performed. Expression analysis of the HPV-encoded E6 and E7 oncogenes was performed by reverse-transcriptase polymerase chain reaction. Fourteen patients had subtype 11 (33%) and 29 patients had subtype 6 (67%). As expected, HPV 11 patients showed a more aggressive clinical course than HPV 6 patients. However, 38% of patients with subtype 6 (11 patients) followed a clinical course that mirrored the more severe subtype 11 patients. These patients expressed the disease at a younger age (P < 0.0002) and showed higher levels of E6 and E7 oncogenes compared to the patients with the more indolent course. Although HPV subtype and early onset of RLP are well characterized prognostic factors, our study documents the significance of E6 and E7 oncogene expression as potential biologic mediators of proliferation and thereby clinical behavior.

  17. Modulation of basal cell fate during productive and transforming HPV-16 infection is mediated by progressive E6-driven depletion of Notch.

    Science.gov (United States)

    Kranjec, Christian; Holleywood, Christina; Libert, Diane; Griffin, Heather; Mahmood, Radma; Isaacson, Erin; Doorbar, John

    2017-08-01

    In stratified epithelia such as the epidermis, homeostasis is maintained by the proliferation of cells in the lower epithelial layers and the concomitant loss of differentiated cells from the epithelial surface. These differentiating keratinocytes progressively stratify and form a self-regenerating multi-layered barrier that protects the underlying dermis. In such tissue, the continual loss and replacement of differentiated cells also limits the accumulation of oncogenic mutations within the tissue. Inactivating mutations in key driver genes, such as TP53 and NOTCH1, reduce the proportion of differentiating cells allowing for the long-term persistence of expanding mutant clones in the tissue. Here we show that through the expression of E6, HPV-16 prevents the early fate commitment of human keratinocytes towards differentiation and confers a strong growth advantage to human keratinocytes. When E6 is expressed either alone or with E7, it promotes keratinocyte proliferation at high cell densities, through the combined inactivation of p53 and Notch1. In organotypic raft culture, the activity of E6 is restricted to the basal layer of the epithelium and is enhanced during the progression from productive to abortive or transforming HPV-16 infection. Consistent with this, the expression of p53 and cleaved Notch1 becomes progressively more disrupted, and is associated with increased basal cell density and reduced commitment to differentiation. The expression of cleaved Notch1 is similarly disrupted also in HPV-16-positive cervical lesions, depending on neoplastic grade. When taken together, these data depict an important role of high-risk E6 in promoting the persistence of infected keratinocytes in the basal and parabasal layers through the inactivation of gene products that are commonly mutated in non-HPV-associated neoplastic squamous epithelia. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great

  18. Calculation of Sodium Fire Test-I (Run-E6) using sodium combustion analysis code ASSCOPS version 2.0

    Energy Technology Data Exchange (ETDEWEB)

    Nakagiri, Toshio; Ohno, Shuji; Miyake, Osamu [Power Reactor and Nuclear Fuel Development Corp., Oarai, Ibaraki (Japan). Oarai Engineering Center

    1997-11-01

    The calculation of Sodium Fire Test-I (Run-E6) was performed using the ASSCOPS (Analysis of Simultaneous Sodium Combustions in Pool and Spray) code version 2.0 in order to determine the parameters used in the code for the calculations of sodium combustion behavior of small or medium scale sodium leak, and to validate the applicability of the code. The parameters used in the code were determined and the validation of the code was confirmed because calculated temperatures, calculated oxygen concentration and other calculated values almost agreed with the test results. (author)

  19. UV Radiation Activates Toll-Like Receptor 9 Expression in Primary Human Keratinocytes, an Event Inhibited by Human Papillomavirus 38 E6 and E7 Oncoproteins.

    Science.gov (United States)

    Pacini, Laura; Ceraolo, Maria Grazia; Venuti, Assunta; Melita, Giusi; Hasan, Uzma A; Accardi, Rosita; Tommasino, Massimo

    2017-10-01

    Several lines of evidence indicate that cutaneous human papillomavirus (HPV) types belonging to the beta genus of the HPV phylogenetic tree synergize with UV radiation in the development of skin cancer. Accordingly, the E6 and E7 oncoproteins from some beta HPV types are able to deregulate pathways related to immune response and cellular transformation. Toll-like receptor 9 (TLR9), in addition to playing a role in innate immunity, has been shown to be involved in the cellular stress response. Using primary human keratinocytes as experimental models, we have shown that UV irradiation (and other cellular stresses) activates TLR9 expression. This event is closely linked to p53 activation. Silencing the expression of p53 or deleting its encoding gene affected the activation of TLR9 expression after UV irradiation. Using various strategies, we have also shown that the transcription factors p53 and c-Jun are recruited onto a specific region of the TLR9 promoter after UV irradiation. Importantly, the E6 and E7 oncoproteins from beta HPV38, by inducing the accumulation of the p53 antagonist ΔNp73α, prevent the UV-mediated recruitment of these transcription factors onto the TLR9 promoter, with subsequent impairment of TLR9 gene expression. This study provides new insight into the mechanism that mediates TLR9 upregulation in response to cellular stresses. In addition, we show that HPV38 E6 and E7 are able to interfere with this mechanism, providing another explanation for the possible cooperation of beta HPV types with UV radiation in skin carcinogenesis. IMPORTANCE Beta HPV types have been suggested to act as cofactors in UV-induced skin carcinogenesis by altering several cellular mechanisms activated by UV radiation. We show that the expression of TLR9, a sensor of damage-associated molecular patterns produced during cellular stress, is activated by UV radiation in primary human keratinocytes (PHKs). Two transcription factors known to be activated by UV radiation, p53

  20. Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers

    OpenAIRE

    Chang, J T-C; Kuo, T-F; Chen, Y-J; Chiu, C-C; Lu, Y-C; Li, H-F; Shen, C-R; Cheng, A-J

    2010-01-01

    Infection with high-risk types (type 16 or type 18) of human papillomaviruses (HPVs) increases a patient's risk of cervical cancer. Given the importance of the cervix and the severe side effects resulting from traditional cancer therapies, this study aimed to achieve targeted inhibition of viral oncogenes in tumor cells using small interfering RNAs (siRNA). To accomplish this, we developed nine siRNAs against either the E6 or E7 genes of HPV-16 or HPV-18 in several combinations, yielding siRN...

  1. Fowlpox virus recombinants expressing HPV-16 E6 and E7 oncogenes for the therapy of cervical carcinoma elicit humoral and cell-mediated responses in rabbits.

    Science.gov (United States)

    Radaelli, Antonia; Pozzi, Eleana; Pacchioni, Sole; Zanotto, Carlo; Morghen, Carlo De Giuli

    2010-04-21

    Around half million new cases of cervical cancer arise each year, making the development of an effective therapeutic vaccine against HPV a high priority. As the E6 and E7 oncoproteins are expressed in all HPV-16 tumour cells, vaccines expressing these proteins might clear an already established tumour and support the treatment of HPV-related precancerous lesions. Three different immunisation regimens were tested in a pre-clinical trial in rabbits to evaluate the humoral and cell-mediated responses of a putative HPV-16 vaccine. Fowlpoxvirus (FP) recombinants separately expressing the HPV-16 E6 (FPE6) and E7 (FPE7) transgenes were used for priming, followed by E7 protein boosting. All of the protocols were effective in eliciting a high antibody response. This was also confirmed by interleukin-4 production, which increased after simultaneous priming with both FPE6 and FPE7 and after E7 protein boost. A cell-mediated immune response was also detected in most of the animals. These results establish a preliminary profile for the therapy with the combined use of avipox recombinants, which may represent safer immunogens than vaccinia-based vectors in immuno-compromised individuals, as they express the transgenes in most mammalian cells in the absence of a productive replication.

  2. Fowlpox virus recombinants expressing HPV-16 E6 and E7 oncogenes for the therapy of cervical carcinoma elicit humoral and cell-mediated responses in rabbits

    Directory of Open Access Journals (Sweden)

    Pacchioni Sole

    2010-04-01

    Full Text Available Abstract Background Around half million new cases of cervical cancer arise each year, making the development of an effective therapeutic vaccine against HPV a high priority. As the E6 and E7 oncoproteins are expressed in all HPV-16 tumour cells, vaccines expressing these proteins might clear an already established tumour and support the treatment of HPV-related precancerous lesions. Methods Three different immunisation regimens were tested in a pre-clinical trial in rabbits to evaluate the humoral and cell-mediated responses of a putative HPV-16 vaccine. Fowlpoxvirus (FP recombinants separately expressing the HPV-16 E6 (FPE6 and E7 (FPE7 transgenes were used for priming, followed by E7 protein boosting. Results All of the protocols were effective in eliciting a high antibody response. This was also confirmed by interleukin-4 production, which increased after simultaneous priming with both FPE6 and FPE7 and after E7 protein boost. A cell-mediated immune response was also detected in most of the animals. Conclusion These results establish a preliminary profile for the therapy with the combined use of avipox recombinants, which may represent safer immunogens than vaccinia-based vectors in immuno-compromised individuals, as they express the transgenes in most mammalian cells in the absence of a productive replication.

  3. Establishment and characterization of murine small cell lung carcinoma cell lines derived from HPV-16 E6/E7 transgenic mice.

    Science.gov (United States)

    Carraresi, Laura; Martinelli, Rosanna; Vannoni, Alessandro; Riccio, Massimo; Dembic, Maja; Tripodi, Sergio; Cintorino, Marcella; Santi, Spartaco; Bigliardi, Elisa; Carmellini, Mario; Rossini, Mara

    2006-01-08

    We have established two murine cell lines derived from Small Cell Lung Carcinomas (SCLCs) developed by HPV-E6/E7 transgenic mice. These cells named PPAP-9 and PPAP-10 were isolated from mice bearing tumors, 9 and 10 months old, respectively. The cells, 5 microm in diameter, express HPV oncoproteins and sustain tumor formation after subcutaneous injection in syngenic mice. A detailed analysis indicated the epithelial origin and the neuroendocrine differentiation of these cells. We showed by confocal immunofluorescence the expression of the epithelial marker cytokeratin 5, whose gene promoter was used to direct the expression of HPV E6/E. Cells express several neuroendocrine markers such as CGRP, MAP-2, Ash1, CgrA, Scg2. The neuroendocrine differentiation of these cells was further confirmed by electron microscopy demonstrating neuropeptides secreting granules in their cytoplasm. Furthermore, in agreement with the altered expression observed in the majority of human SCLC we showed in these cells the absence of both p53 and pRB and a dramatic reduction in the expression of Caveolin-1.

  4. Transcriptional profiling of Vero E6 cells over-expressing SARS-CoV S2 subunit: Insights on viral regulation of apoptosis and proliferation

    International Nuclear Information System (INIS)

    Yeung, Y.-S.; Yip, C.-W.; Hon, C.-C.; Chow, Ken Y.C.; Ma, Iris C.M.; Zeng Fanya; Leung, Frederick C.C.

    2008-01-01

    We have previously demonstrated that over-expression of spike protein (S) of severe acute respiratory syndrome coronavirus (SARS-CoV) or its C-terminal subunit (S2) is sufficient to induce apoptosis in vitro. To further investigate the possible roles of S2 in SARS-CoV-induced apoptosis and pathogenesis of SARS, we characterized the host expression profiles induced upon S2 over-expression in Vero E6 cells by oligonucleotide microarray analysis. Possible activation of mitochondrial apoptotic pathway in S2 expressing cells was suggested, as evidenced by the up-regulation of cytochrome c and down-regulation of the Bcl-2 family anti-apoptotic members. Inhibition of Bcl-2-related anti-apoptotic pathway was further supported by the diminution of S2-induced apoptosis in Vero E6 cells over-expressing Bcl-xL. In addition, modulation of CCN E2 and CDKN 1A implied the possible control of cell cycle arrest at G1/S phase. This study is expected to extend our understanding on the pathogenesis of SARS at a molecular level

  5. The cellular uptake of antisense oligonucleotid of E6 mRNA into cervical cancer cells by DOPE-modified hydroxyapatite nanoparticles

    Directory of Open Access Journals (Sweden)

    Negin Saffarzadeh

    2014-10-01

    Full Text Available Objective(s: Although several chemical and physical methods for gene delivery have been introduced, their cytotoxicity, non-specific immune responses and the lack of biodegradability remain the main issues. In this study, hydroxyapatite nanoparticles (NPs and 1,2-dioleoyl-sn-glycero-3-phosphoethanol​amine (DOPE-modified hydroxyapatite NPs was coated with antisense oligonucleotide of E6 mRNA, and their uptakes into the cervical cancer cell line were evaluated. Materials and Methods: Calcium nitrate and diammonium phosphate were used for the synthesis of the hydroxyapatite nanoparticle. Thus, they were coated with polyethylene glycol (PEG, DOPE and antisense oligonucleotide of E6 mRNA using a cross-linker. Then, hydroxyapatite NPs and DOPE-modified hydroxyapatite NPs were incubated 48 hours with cervical cancer cells and their uptakes were evaluated by fluorescent microscopy. Results: The hydroxyapatite NPs had different shapes and some agglomeration with average size of 100 nm. The results showed DOPE-modified hydroxyapatite NPs had higher uptake than hydroxyapatite NPs (P

  6. Human papillomavirus E6 and E7 oncoproteins alter cell cycle progression but not radiosensitivity of carcinoma cells treated with low-dose-rate radiation

    International Nuclear Information System (INIS)

    DeWeese, Theodore L.; Walsh, Jonathan C.; Dillehay, Larry E.; Kessis, Theodore D.; Hedrick, Lora; Cho, Kathleen R.; Nelson, William G.

    1997-01-01

    Purpose: Low-dose-rate radiation therapy has been widely used in the treatment of urogenital malignancies. When continuously exposed to low-dose-rate ionizing radiation, target cancer cells typically exhibit abnormalities in replicative cell-cycle progression. Cancer cells that arrest in the G2 phase of the cell cycle when irradiated may become exquisitely sensitive to killing by further low-dose-rate radiation treatment. Oncogenic human papillomaviruses (HPVs), which play a major role in the pathogenesis of uterine cervix cancers and other urogenital cancers, encode E6 and E7 transforming proteins known to abrogate a p53-dependent G1 cell-cycle checkpoint activated by conventional acute-dose radiation exposure. This study examined whether expression of HPV E6 and E7 oncoproteins by cancer cells alters the cell-cycle redistribution patterns accompanying low-dose-rate radiation treatment, and whether such alterations in cell-cycle redistribution affect cancer cell killing. Methods and Materials: RKO carcinoma cells, which contain wild-type P53 alleles, and RKO cell sublines genetically engineered to express HPV E6 and E7 oncoproteins, were treated with low-dose-rate (0.25-Gy/h) radiation and then assessed for p53 and p21WAF1/CIP1 polypeptide induction by immunoblot analysis, for cell-cycle redistribution by flow cytometry, and for cytotoxicity by clonogenic survival assay. Results: Low-dose-rate radiation of RKO carcinoma cells triggered p53 polypeptide elevations, p21WAF1/CIP1 induction, and arrest in the G1 and G2 phases of the cell cycle. In contrast, RKO cells expressing E6 and E7 transforming proteins from high-risk oncogenic HPVs (HPV 16) arrested in G2, but failed to arrest in G1, when treated with low-dose-rate ionizing radiation. Abrogation of the G1 cell-cycle checkpoint activated by low-dose-rate radiation exposure appeared to be a characteristic feature of transforming proteins from high-risk oncogenic HPVs: RKO cells expressing E6 from a low

  7. Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems

    Directory of Open Access Journals (Sweden)

    Wolf Yuri I

    2011-07-01

    comparison continue to reveal unexpected homologous relationship among Cas proteins. Unification of Cas protein families previously considered unrelated provides for improvement in the classification of CRISPR-Cas systems and a reconstruction of their evolution. Open peer review This article was reviewed by Malcolm White (nominated by Purficacion Lopez-Garcia, Frank Eisenhaber and Igor Zhulin. For the full reviews, see the Reviewers' Comments section.

  8. HPV E6/E7 RNA in situ hybridization signal patterns as biomarkers of three-tier cervical intraepithelial neoplasia grade.

    Directory of Open Access Journals (Sweden)

    Mark F Evans

    Full Text Available Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3 based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL. In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH. Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4, and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3% CIN 1, 22/22 (100% CIN 2 and in 32/32 (100% CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7% showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5% by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: P<0.0001. These data are consistent with productive phase HPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay's high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e

  9. HPV E6/E7 RNA In Situ Hybridization Signal Patterns as Biomarkers of Three-Tier Cervical Intraepithelial Neoplasia Grade

    Science.gov (United States)

    Evans, Mark F.; Peng, Zhihua; Clark, Kelli M.; Adamson, Christine S.-C.; Ma, Xiao-Jun; Wu, Xingyong; Wang, Hongwei; Luo, Yuling; Cooper, Kumarasen

    2014-01-01

    Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3) based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH). Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4), and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3%) CIN 1, 22/22 (100%) CIN 2 and in 32/32 (100%) CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens) by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7%) showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5%) by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: PHPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay’s high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e.g. among young women) or when ‘LSIL vs. HSIL’ assignment is

  10. Evaluation of immunological cross-reactivity between clade A9 high-risk human papillomavirus types on the basis of E6-Specific CD4+ memory T cell responses

    NARCIS (Netherlands)

    van den Hende, Muriel; Redeker, Anke; Kwappenberg, Kitty M. C.; Franken, Kees L. M. C.; Drijfhout, Jan W.; Oostendorp, Jaap; Valentijn, A. Rob P. M.; Fathers, Loraine M.; Welters, Marij J. P.; Melief, Cornelis J. M.; Kenter, Gemma G.; van der Burg, Sjoerd H.; Offringa, Rienk

    2010-01-01

    CD4(+) T cell responses against the E6 oncoprotein of human papillomavirus (HPV) type 16 and 5 closely related members of clade A9 (HPV31, 33, 35, 52, and 58) were charted in peripheral blood mononuclear cell cultures from healthy subjects and patients who underwent HPV16 E6/E7-specific vaccination.

  11. A promoter within the E6 ORF of human papillomavirus type 16 contributes to the expression of the E7 oncoprotein from a monocistronic mRNA

    DEFF Research Database (Denmark)

    Glahder, Jacob-Andreas Harald; Hansen, Christina N; Vinther, Jeppe

    2003-01-01

    RNA that encodes E7 as the first open reading frame (ORF) has been identified. We recently identified a transcription initiation site within the E6 ORF of HPV-16 at nt 542. In the present study we have characterized the P542 promoter, which putatively controls monocistronic expression of E7. The monocistronic m...... from nt 226 to 409. Furthermore, the translation initiation of E7 is most abundant from the monocistronic mRNA. We have also shown that the P542 promoter is downregulated by the transcription factor activator protein 4 (AP-4) and the differentiation-dependent factor hSkn-1a, both binding downstream...... of the transcription initiation site. In conclusion, we have found that P542 is a relatively weak promoter compared with P97 and may be downregulated in differentiated epithelial cells....

  12. Ultrasound-assisted interaction between chlorin-e6 and human serum albumin: pH dependence, singlet oxygen production, and formulation effect

    Science.gov (United States)

    Mocanu, Mihaela N.; Yan, Fei

    2018-02-01

    The interaction between chlorin e6 (Ce6) and human serum albumin (HSA) in the presence and absence of ultrasound have been investigated by ultraviolet-visible absorption spectroscopy and fluorescence spectroscopy. Ce6 is found to bind strongly to HSA at or near physiological pH conditions, but the strength of the binding is significantly weakened at lower pHs. The intrinsic fluorescence of HSA is incrementally quenched with increasing concentration of Ce6, and the quenching is enhanced after exposure to high-frequency ultrasound. Our experimental results suggest that Ce6-induced sonodynamic oxidation of HSA is mainly mediated by singlet oxygen. The formulation of Ce6 by high molecular weight polyvinylpyrrolidone (PVP) increased its stability in aqueous solutions and its quantum yield of singlet oxygen under ultrasound irradiation.

  13. Asymptotically Safe Grand Unification

    DEFF Research Database (Denmark)

    Bajc, Borut; Sannino, Francesco

    2016-01-01

    the inclusion of gravity, by generating an interacting ultraviolet fixed point, similar to the one recently discovered in non-supersymmetric gauge-Yukawa theories. Employing a-maximization, a-theorem, unitarity bounds, as well as positivity of other central charges we nonperturbatively rule out this possibility...

  14. Grand unification and supergravity

    International Nuclear Information System (INIS)

    Nanopoulos, D.V.

    Grand Unified Theories (GUTs) are very successful, but they suffer from fine-tuning or hierarchy problems. It seems that more symmetry beyond the gauge symmetry is needed and indeed supersymmetric GUTs may provide the correct framework in solving the hierarchy problems. These are reviewed. From the results discussed, it is seen that for the first time in particle physics, gravity seems to play a dominant role. It may be responsible for GUT breaking, SU(2) x U(1) breaking, fermion masses, proton decay and a consistent cosmological picture. Supergravity seems to offer a consistent, effective theory for energies below the Planck scale to N=1 local SUSY but also, in the context of N=8 extended supergravity with a dynamically realized SU(8), there may be a consistent fundamental unified theory of all interactions. (U.K.)

  15. Supersymmetric family unification

    International Nuclear Information System (INIS)

    Frampton, P.H.; Kephart, T.W.

    1983-01-01

    The superheavy symmetry breaking of the gauge group in supersymmetrized unified theories is studied. The requirement that supersymmetry be unbroken strongly constrains the possible gauge group breaking, and we systematize such constraints group theoretically. In model building, one issue is whether to permit an adjoint matter superfield with concomitant color exotic fermions. A second issue is that of naturalness which is complicated by the well-known supersymmetry non-renormalization theorems. Both with and without an adjoint matter superfield, the most promising group appears to be SU(9) where three families can be naturally accommodated, at least for low-energy gauge group SU(3) x SU(2) x U(1). With an extra U(1) factor, as advocated by Fayet, the non-renormalization theorem must be exploited. (orig.)

  16. Unification of string dualities

    International Nuclear Information System (INIS)

    Sen, A.

    1997-01-01

    We argue that all conjectured dualities involving various string, M- and F-theory compactifications can be 'derived' from the conjectured duality between type I and SO(32) heterotic string theory, T-dualities and the definition of M-and F-theories. (orig.)

  17. Asymptotically safe grand unification

    Energy Technology Data Exchange (ETDEWEB)

    Bajc, Borut [J. Stefan Institute,1000 Ljubljana (Slovenia); Sannino, Francesco [CP-Origins & the Danish IAS, University of Southern Denmark,Campusvej 55, DK-5230 Odense M (Denmark); Université de Lyon, France, Université Lyon 1, CNRS/IN2P3, UMR5822 IPNL,F-69622 Villeurbanne Cedex (France)

    2016-12-28

    Phenomenologically appealing supersymmetric grand unified theories have large gauge representations and thus are not asymptotically free. Their ultraviolet validity is limited by the appearance of a Landau pole well before the Planck scale. One could hope that these theories save themselves, before the inclusion of gravity, by generating an interacting ultraviolet fixed point, similar to the one recently discovered in non-supersymmetric gauge-Yukawa theories. Employing a-maximization, a-theorem, unitarity bounds, as well as positivity of other central charges we nonperturbatively rule out this possibility for a broad class of prime candidates of phenomenologically relevant supersymmetric grand unified theories. We also uncover candidates passing these tests, which have either exotic matter or contain one field decoupled from the superpotential. The latter class of theories contains a model with the minimal matter content required by phenomenology.

  18. Prognostic value of HPV E6/E7 mRNA assay in women with negative colposcopy or CIN1 histology result: a follow-up study.

    Directory of Open Access Journals (Sweden)

    Paolo Giorgi Rossi

    Full Text Available Pap test, and especially HPV DNA test, identify a large group of women who do not have any clinically relevant lesions, i.e., CIN2+ (Cervical Intraepithelial Neoplasia grade 2 or worse, but who are at greater risk of getting lesions in the future. The follow up of these women needs new biomarkers with prognostic value. The objective of this study is to evaluate the prognostic value of E6/E7 mRNA over-expression assay (PreTect HPV-Proofer, Norchip for 5 HR-HPV types (16, 18, 31, 33, and 45 for progression to CIN2+ after a negative colposcopy. This prospective study, conducted at four Italian centres, enrolled 673 women with either a negative colposcopy or a negative or CIN1 histology. The clinical end-point was histological confirmation of CIN2+. Women were classified at baseline according to mRNA results and managed according to local colposcopy protocols. At least one conclusive follow-up test was obtained for 347 women (25 months average lapse since recruitment, range 5-74. Only seven CIN2+ were detected during follow up, three among the 82 women positive for mRNA at baseline, two among the 250 negative (Fisher exact test, p = 0.02, and two among the 12 with an invalid test. Absolute CIN2+ risk was 6.7/1,000 person/years in the whole cohort. The absolute CIN2+ risk was 18.4/1,000 person/years and 3.6/1,000 person/years in mRNA-positive and mRNA-negative women, respectively. In conclusion, E6/E7 mRNA over-expression appears to be a good candidate as a prognostic biomarker to manage HR-HPV DNA-positive women with negative colposcopy or histology, particularly in order to decrease follow-up intensity in those who are negative.

  19. Glucocorticoid regulation of a novel HPV-E6-p53-miR-145 pathway modulates invasion and therapy resistance of cervical cancer cells.

    Science.gov (United States)

    Shi, Ming; Du, Libin; Liu, Dan; Qian, Lu; Hu, Meiru; Yu, Ming; Yang, Zhengyan; Zhao, Mingzhen; Chen, Changguo; Guo, Liang; Wang, Lina; Song, Lun; Ma, Yuanfang; Guo, Ning

    2012-10-01

    Glucocorticoids are stress-responsive neuroendocrine mediators and play an important role in malignant progression, especially in solid tumours. We demonstrate a novel mechanism by which glucocorticoids modulate p53-dependent miR-145 expression in HPV-positive cervical cancer cells through induction of E6 proteins. We found that expression of miR-145 was reduced in cervical cancer tissues. Cortisol induced HPV-E6 expression and suppressed p53 and miR-145 in cervical cancer cells. MiR-145 expression in cervical cancer cells was wild-type p53-dependent, and cortisol-induced down-regulation of miR-145 expression prevented chemotherapy-induced apoptosis, whereas over-expression of miR-145 enhanced sensitivity to mitomycin and reversed the chemoresistance induced by glucocorticoids. We also show that miR-145 augments the effects of p53 by suppressing the inhibitors of p53 in cervical cancer cells, suggesting that miR-145 plays a role in p53 tumour suppression. Finally, we demonstrate that miR-145 inhibits both the motility and invasion of cervical cancer cells. Our findings identify a novel pathway through which the neuroendocrine macroenvironment affects cervical tumour growth, invasion and therapy resistance and show that miR-145 may serve as a target for cervical cancer therapy. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. The synergistic transactivation of the hepatitis B viral (HBV) pregenomic promoter by the E6 protein of human papillomavirus type 16 (HPV-16 E6) with HBV X protein was mediated through the AP1 site of E element in the enhancer I (EnI) in human liver cell.

    Science.gov (United States)

    Lee, D H; Choi, B H; Rho, H M

    1999-11-01

    Infection by HBV of a cell already infected with other viral species or vice versa has been suggested as being involved in hepatocellular carcinoma. Using the CAT assay method, we investigated the interactive roles of HBx and potentially oncogenic and transactivating viral early proteins such as Ad5 E1A, HPV-16 E6, and SV40 T ag. In the presence of HBx, only HPV-16 E6 showed significant synergistic transactivation of EnI. We further investigated the function of the HPV-16 E6 using deletion, heterologous promoter, and mutation analyses on the EnI promoter. The results showed that the synergistic effect was mediated through the AP1 site of the E element in EnI by the direct activation of AP1 and support the idea that the infection by HBV of the cell with other viral species such as HPV-16 could increase the transcription activity of the HBV and other oncogenes containing an AP1 site in the promoter. Copyright 1999 Academic Press.

  1. Aespoe Task Force on modelling of groundwater flow and transport of solutes. Review of Tasks 6D, 6E, 6F and 6F2

    International Nuclear Information System (INIS)

    Hodgkinson, David

    2007-09-01

    This report forms part of an independent review of the specifications, execution and results of Task 6 of the Aespoe Task Force on Modelling of Groundwater Flow and Transport of Solutes, which is seeking to provide a bridge between site characterization and performance assessment approaches to modelling solute transport in fractured rock. The objectives of Task 6 are: To assess simplifications used in Performance Assessment (PA) models. To determine how, and to what extent, experimental tracer and flow experiments can constrain the range of parameters used in PA models. To support the design of Site Characterisation (SC) programmes to ensure that the results have optimal value for performance assessment calculations. To improve the understanding of site-specific flow and transport behaviour at different scales using site characterisation models. The present report is concerned with Tasks 6D, 6E, 6F and 6F2. It follows on from two previous reviews of Tasks 6A, 6B and 6B2, and Task 6C. In Task 6D the transport of tracers through a fracture network is modelled using the conditions of the C2 TRUE-Block Scale tracer test, based on the synthetic structural model developed in Task 6C. Task 6E extends the Task 6D transport calculations to a reference set of PA time scales and boundary conditions. Task 6F consists of a series of 'benchmark' studies on single features from the Task 6C hydrostructural model in order to improve the understanding of differences between the participating models. Task 6F2 utilises models set up for Tasks 6E and 6F to perform additional sensitivity studies with the aim of increasing the understanding of how models behave, the reason for differences in modelling results, and the sensitivity of models to various assumptions and parameter values. Eight modelling teams representing five organisations participated in this exercise using Discrete Fracture Network (DFN), continuum and channel network concepts implemented in a range of different codes and

  2. Aespoe Task Force on modelling of groundwater flow and transport of solutes. Review of Tasks 6D, 6E, 6F and 6F2

    Energy Technology Data Exchange (ETDEWEB)

    Hodgkinson, David (Quintessa, Henley-on-Thames (GB))

    2007-09-15

    This report forms part of an independent review of the specifications, execution and results of Task 6 of the Aespoe Task Force on Modelling of Groundwater Flow and Transport of Solutes, which is seeking to provide a bridge between site characterization and performance assessment approaches to modelling solute transport in fractured rock. The objectives of Task 6 are: To assess simplifications used in Performance Assessment (PA) models. To determine how, and to what extent, experimental tracer and flow experiments can constrain the range of parameters used in PA models. To support the design of Site Characterisation (SC) programmes to ensure that the results have optimal value for performance assessment calculations. To improve the understanding of site-specific flow and transport behaviour at different scales using site characterisation models. The present report is concerned with Tasks 6D, 6E, 6F and 6F2. It follows on from two previous reviews of Tasks 6A, 6B and 6B2, and Task 6C. In Task 6D the transport of tracers through a fracture network is modelled using the conditions of the C2 TRUE-Block Scale tracer test, based on the synthetic structural model developed in Task 6C. Task 6E extends the Task 6D transport calculations to a reference set of PA time scales and boundary conditions. Task 6F consists of a series of 'benchmark' studies on single features from the Task 6C hydrostructural model in order to improve the understanding of differences between the participating models. Task 6F2 utilises models set up for Tasks 6E and 6F to perform additional sensitivity studies with the aim of increasing the understanding of how models behave, the reason for differences in modelling results, and the sensitivity of models to various assumptions and parameter values. Eight modelling teams representing five organisations participated in this exercise using Discrete Fracture Network (DFN), continuum and channel network concepts implemented in a range of different

  3. Epigonal Conditioned Media from Bonnethead Shark, Sphyrna tiburo, Induces Apoptosis in a T-Cell Leukemia Cell Line, Jurkat E6-1

    Directory of Open Access Journals (Sweden)

    Courtney Bennett

    2013-08-01

    Full Text Available Representatives of Subclass Elasmobranchii are cartilaginous fish whose members include sharks, skates, and rays. Because of their unique phylogenetic position of being the most primitive group of vertebrates to possess all the components necessary for an adaptive immune system, the immune regulatory compounds they possess may represent the earliest evolutionary forms of novel compounds with the potential for innovative therapeutic applications. Conditioned medium, generated from short term culture of cells from the epigonal organ of bonnethead sharks (Sphyrna tiburo, has been shown to have potent reproducible cytotoxic activity against a variety of human tumor cell lines in vitro. Existing data suggest that epigonal conditioned medium (ECM exerts this cytotoxic activity through induction of apoptosis in target cells. This manuscript describes apoptosis induction in a representative tumor cell line, Jurkat E6-1, in response to treatment with ECM at concentrations of 1 and 2 mg/mL. Data indicate that ECM exposure initiates the mitochondrial pathway of apoptosis through activation of caspase enzymes. Future purification of ECM components may result in the isolation of an immune-regulatory compound with potential therapeutic benefit for treatment of human cancer.

  4. The CD8⁺ T Cell-Mediated Immunity Induced by HPV-E6 Uploaded in Engineered Exosomes Is Improved by ISCOMATRIXTM Adjuvant.

    Science.gov (United States)

    Manfredi, Francesco; di Bonito, Paola; Ridolfi, Barbara; Anticoli, Simona; Arenaccio, Claudia; Chiozzini, Chiara; Baz Morelli, Adriana; Federico, Maurizio

    2016-11-09

    We recently described the induction of an efficient CD8⁺ T cell-mediated immune response against a tumor-associated antigen (TAA) uploaded in engineered exosomes used as an immunogen delivery tool. This immune response cleared tumor cells inoculated after immunization, and controlled the growth of tumors implanted before immunization. We looked for new protocols aimed at increasing the CD8⁺ T cell specific response to the antigen uploaded in engineered exosomes, assuming that an optimized CD8⁺ T cell immune response would correlate with a more effective depletion of tumor cells in the therapeutic setting. By considering HPV-E6 as a model of TAA, we found that the in vitro co-administration of engineered exosomes and ISCOMATRIX TM adjuvant, i.e., an adjuvant composed of purified ISCOPREP TM saponin, cholesterol, and phospholipids, led to a stronger antigen cross-presentation in both B- lymphoblastoid cell lines ( and monocyte-derived immature dendritic cells compared with that induced by the exosomes alone. Consistently, the co-inoculation in mice of ISCOMATRIX TM adjuvant and engineered exosomes induced a significant increase of TAA-specific CD8⁺ T cells compared to mice immunized with the exosomes alone. This result holds promise for effective usage of exosomes as well as alternative nanovesicles in anti-tumor therapeutic approaches.

  5. The CD8+ T Cell-Mediated Immunity Induced by HPV-E6 Uploaded in Engineered Exosomes Is Improved by ISCOMATRIXTM Adjuvant

    Science.gov (United States)

    Manfredi, Francesco; di Bonito, Paola; Ridolfi, Barbara; Anticoli, Simona; Arenaccio, Claudia; Chiozzini, Chiara; Baz Morelli, Adriana; Federico, Maurizio

    2016-01-01

    We recently described the induction of an efficient CD8+ T cell-mediated immune response against a tumor-associated antigen (TAA) uploaded in engineered exosomes used as an immunogen delivery tool. This immune response cleared tumor cells inoculated after immunization, and controlled the growth of tumors implanted before immunization. We looked for new protocols aimed at increasing the CD8+ T cell specific response to the antigen uploaded in engineered exosomes, assuming that an optimized CD8+ T cell immune response would correlate with a more effective depletion of tumor cells in the therapeutic setting. By considering HPV-E6 as a model of TAA, we found that the in vitro co-administration of engineered exosomes and ISCOMATRIXTM adjuvant, i.e., an adjuvant composed of purified ISCOPREPTM saponin, cholesterol, and phospholipids, led to a stronger antigen cross-presentation in both B- lymphoblastoid cell lines ( and monocyte-derived immature dendritic cells compared with that induced by the exosomes alone. Consistently, the co-inoculation in mice of ISCOMATRIXTM adjuvant and engineered exosomes induced a significant increase of TAA-specific CD8+ T cells compared to mice immunized with the exosomes alone. This result holds promise for effective usage of exosomes as well as alternative nanovesicles in anti-tumor therapeutic approaches. PMID:27834857

  6. A comparative study of the processes of generation of singlet oxygen upon irradiation of aqueous preparations on the basis of chlorin e6 and coproporphyrin III

    Science.gov (United States)

    Bagrov, I. V.; Belousova, I. M.; Gorelov, S. I.; Dobrun, M. V.; Kiselev, V. M.; Kislyakov, I. M.; Kris'ko, A. V.; Kris'ko, T. K.

    2017-02-01

    The photosensitizing ability of an agent based on chlorin e6 (Photoditazin), which is used for photodynamic diagnosis and therapy, is compared with that of a new preparation on the basis of coproporphyrin III in the environment of a phosphate buffer and a simulated biological environment (albumin solution). The efficiency of singlet-oxygen production was estimated by EPR spectroscopy and spectroscopy in the UV and visible ranges with the use of "chemical traps" of singlet oxygen. By irradiating drugs with LED emission centered at λmax = 520 nm, we determined the quantum yield of singlet-oxygen production in a buffer solution; the obtained values are 0.60 and 0.37 for chlorine and coproporphyrin, respectively. The steady-state concentration of singlet oxygen upon irradiation of solutions of the studied photosensitizers with concentrations of 12-43 μM and the density of radiation power within the 6-96 W/cm2 region was found to be in the region of 1010-1011 molecules/cm3. It is shown that the introduction into the solution of egg albumin (0.1%) reduces the sensitizing properties of the two drugs by two to three times, while the efficiencies of the preparations with respect to singlet-oxygen production become almost identical (0.19 and 0.17).

  7. Quantification of a Novel Photosensitizer of Chlorin e6-C15-Monomethyl Ester in Beagle Dog Plasma Using HPLC: Application to Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    Xiuxiu Li

    2017-04-01

    Full Text Available Chlorin e6-C15-monomethyl ester (CMME is a novel photosensitizer, which is synthetized from the degradation products of silkworm excrement. Preclinical studies on the promising photosensitizer CMME are necessary to determine its therapeutic efficacy and druglikeness. A high-performance liquid chromatography with UV detection (HPLC–UV method was established for the determination of CMME in beagle dog plasma. The sample preparation involved a protein-precipitation method with acetonitrile after the addition of tanshinone IIA as an internal standard (IS. CMME and the IS were separated on a Diamonsil C18 (2 column (100 mm × 4.6 mm, 5 μm with a isocratic system of methanol–water containing 20 mM ammonium acetate with 0.3% glacial acetic acid (85:15, v/v. The flow rate was 1.0 mL/min with UV detection using a wavelength of 400 nm. The method was sensitive enough with a lower limit of quantitation (LLOQ of 0.05 μg/mL and had a good linearity (r2 > 0.999 over the linear range of 0.05–5.00 μg/mL. The intra-day and inter-day accuracies ranged from 98.5% to 102.8% and precisions (RSD were within 6.8%. The validated method was successfully applied to the pharmacokinetic study of CMME after intravenous administration of single and multiple doses in beagle dogs.

  8. Antioxidant Properties and PC12 Cell Protective Effects of a Novel Curcumin Analogue (2E,6E-2,6-Bis(3,5- dimethoxybenzylidenecyclohexanone (MCH

    Directory of Open Access Journals (Sweden)

    Gui-Zhen Ao

    2014-03-01

    Full Text Available The antioxidative properties of a novel curcumin analogue (2E,6E-2,6-bis(3,5-dimethoxybenzylidenecyclohexanone (MCH were assessed by several in vitro models, including superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging and PC12 cell protection from H2O2 damage. MCH displayed superior O2•− quenching abilities compared to curcumin and vitamin C. In vitro stability of MCH was also improved compared with curcumin. Exposure of PC12 cells to 150 µM H2O2 caused a decrease of antioxidant enzyme activities, glutathione (GSH loss, an increase in malondialdehyde (MDA level, and leakage of lactate dehydrogenase (LDH, cell apoptosis and reduction in cell viability. Pretreatment of the cells with MCH at 0.63–5.00 µM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. MCH enhanced cellular expression of transcription factor NF-E2-related factor 2 (Nrf2 at the transcriptional level. Moreover, MCH could mitigate intracellular accumulation of reactive oxygen species (ROS, the loss of mitochondrial membrane potential (MMP, and the increase of cleaved caspase-3 activity induced by H2O2. These results show that MCH protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS, activating the Nrf2 cytoprotective pathway and prevention of apoptosis.

  9. Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears.

    Science.gov (United States)

    Ren, Chenchen; Zhu, Yuanhang; Yang, Li; Zhang, Xiaoan; Liu, Ling; Ren, Chunying

    2018-02-01

    The aim of this study was to investigate the clinical performance of high risk (HR) HPV E6/E7 mRNA assay in detecting cervical high-grade intraepithelial neoplasia and cancer among women with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou (Pap) smears. A total of 160 patients with ASCUS who underwent HR-HPV DNA assay, HR-HPV E6/E7 mRNA assay and colposcopy biopsy at Third Affiliated Hospital of Zhengzhou University, China, from December 2015 to March 2017, were enrolled. Logistic regression analysis was used to evaluate the relationship between pathological results with clinical biologic factors. Univariate analysis showed that the qualitative results of HR-HPV DNA, qualitative results of HR-HPV E6/E7 mRNA and expression levels of HR-HPV E6/E7 mRNA were risk factors of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (all P HPV E6/E7 mRNA was associated with high-grade CIN and cervical cancer (OR = 8.971, 95% CI = 2.572-31.289, P = 0.001). An optimal cut-off value of ≥ 558.26 copies/ml was determined using receiver operating characteristic curve, and specificity of cut-off value were higher than E6/E7 mRNA qualitative assay and DNA qualitative assay. HPV E6/E7 mRNA quantitative assay may be a valuable tool in triage of ASCUS pap smears. A high specificity of E6/E7 mRNA quantitative assay as a triage test in women with ASCUS can be translated into a low referral for colposcopy.

  10. D-term contributions and CEDM constraints in E6 × SU(2)F × U(1)A SUSY GUT model

    Science.gov (United States)

    Shigekami, Yoshihiro

    2017-11-01

    We focus on E6 × SU(2)F × U(1)A supersymmetric (SUSY) grand unified theory (GUT) model. In this model, realistic Yukawa hierarchies and mixings are realized by introducing all allowed interactions with 𝓞(1) coefficients. Moreover, we can take stop mass is smaller than the other sfermion masses. This type of spectrum called by natural SUSY type sfermion mass spectrum can suppress the SUSY contributions to flavor changing neutral current (FCNC) and stabilize weak scale at the same time. However, light stop predicts large up quark CEDM and stop contributions are not decoupled. Since there is Kobayashi-Maskawa phase, stop contributions to the up quark CEDM is severely constrained even if all SUSY breaking parameters and Higgsino mass parameter μ are real. In this model, real up Yukawa couplings are realized at the GUT scale because of spontaneous CP violation. Therefore CEDM bounds are satisfied, although up Yukawa couplings are complex at the SUSY scale through the renormalization equation group effects. We calculated the CEDMs and found that EDM constraints can be satisfied even if stop mass is 𝓞(1) TeV. In addition, we investigate the size of D-terms in this model. Since these D-term contributions is flavor dependent, the degeneracy of sfermion mass spectrum is destroyed and the size of D-term is strongly constrained by FCNCs when SUSY breaking scale is the weak scale. However, SUSY breaking scale is larger than 1 TeV in order to obtain 125 GeV Higgs mass, and therefore sizable D-term contribution is allowed. Furthermore, we obtained the non-trivial prediction for the difference of squared sfermion mass.

  11. A prospective study of women with ASCUS or LSIL pap smears at baseline and HPV E6/E7 mRNA positive: a 3-year follow-up.

    Science.gov (United States)

    Bruno, M T; Ferrara, M; Fava, V; Barrasso, G; Panella, M M

    2018-04-01

    Human papillomavirus (HPV) testing is used in the triage of women with a borderline smear result. The efficiency of testing women with a low-grade squamous intraepithelial lesion (LSIL) and atypical squamous cells of undetermined significance (ASCUS) is less clear. For this reason we used a new HPV test that detects E6/E7 messenger RNA (mRNA), which might have a higher specificity. The objective of this prospective study was to assess whether HPV E6/E7 mRNA positivity in women with ASCUS and LSIL at baseline, is able to predict those women who have a high risk of developing a histological cervical intraepithelial neoplasia (CIN2) or worse lesion. We took into consideration the women's age and HPV DNA genotype and followed them up for 3 years. Cervical samples from women with high-risk HPV (HR-HPV) DNA-positive ASCUS (n = 90) or LSIL (n = 222) were tested for the presence of HR-HPV E6/E7 mRNA and the women were monitored for the development of histopathologically verified CIN2+. Thirteen patients with ASCUS and 17 with LSIL did not complete follow-up. All patients with LSIL and ASCUS, enrolled in this study, had confirmed lesions at the colposcopic examination. Follow-up was available for 312 women, 193 were positive in the HR-HPV DNA test and 93 had a HPV E6/E7 mRNA positive test. Finally, 22 women positive in the HPV DNA test for high-risk genotypes and with positive E6/E7 mRNA had a histologically confirmed CIN2+. Only two cases with negative HPV E6/E7 mRNA had CIN2+. The study shows that women positive in the HPV E6/E7 mRNA test have a greater risk of malignant progression of cervical lesions and therefore deserve greater attention and earlier check-ups.

  12. HPV16型E6/E7遺伝子発現誘導が正常ヒト線維芽細胞に及ぼす影響の検討

    OpenAIRE

    黄田, 光博; 清水, 久美子; 白澤, 浩; 清水, 文七; 磯野, 可一

    1997-01-01

    HPV16型E6/E7遺伝子発現を亜鉛により誘導可能な正常ヒト線維芽細胞を樹立し, HPV-16型E6/E7がヒト線維芽細胞に及ぼす影響を細胞学的及び分子生物学的に検討した。HPV-16型E6/E7の発現誘導による正常ヒト線維芽細胞の形態変化は観察されなかったが, E6/E7の発現誘導により, 細胞飽和密度の上昇が観察された。またマウス10T1/2細胞で観察されるE6のHMG-I(Y)発現への影響は, ヒト線維芽細胞では見いだされなかったが, E6/E7によりc-mycの発現が誘導されうることが明らかになった。この結果はE6/E7の細胞不死化に及ぼす過程を究明する上で有用であると考えられる。...

  13. HPV E6/E7 mRNA Testing Is More Specific than Cytology in Post-Colposcopy Follow-Up of Women with Negative Cervical Biopsy

    Science.gov (United States)

    Sørbye, Sveinung Wergeland; Arbyn, Marc; Fismen, Silje; Gutteberg, Tore Jarl; Mortensen, Elin Synnøve

    2011-01-01

    Background In Norway, women with negative or low-grade cervical biopsies (normal/CIN1) are followed up after six months in order to decide on further follow-up or recall for screening at three-year intervals. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures whereas a low risk of high-grade disease among triage negative women assures safety. Materials and Methods At the University Hospital of North Norway, cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in post-colposcopy follow-up of women with negative or low-grade biopsy. In this study, women with negative biopsy after high grade cytology (ASC-H/HSIL) and/or positive HPV mRNA test in the period 2005–2009 were included (n = 520). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as study endpoint. Results Of 520 women with negative or low-grade biopsy, 124 women (23.8%) had CIN2+ in follow-up biopsy. The sensitivity and specificity of the HPV mRNA test were 89.1% (95% CI, 80.1–98.1) and 92.5% (95% CI, 88.2–96.7), respectively. The ratios of sensitivity, specificity and PPV of HPV mRNA testing compared to repeat cytology for finding CIN2+ was 1.05 (95% CI: 0.92–1.21), 1.21 (95% CI: 1.12–1.32), and 1.49 (95% CI: 1.20–1.86), respectively. The PPV of mRNA was 77.3% (95% CI, 59.8–94.8) in women aged 40 or older. Conclusion Women with negative cervical biopsy require follow-up before resumption of routine screening. Post-colposcopy HPV mRNA testing was as sensitive but more specific than post-colposcopy cytology. In addition, the HPV mRNA test showed higher PPV. A positive mRNA test post-colposcopy could justify treatment in women above 40 years. PMID:21998748

  14. Photoinactivation Using Visible Light Plus Water-Filtered Infrared-A (vis+wIRA and Chlorine e6 (Ce6 eradicates Planktonic Periodontal Pathogens and Subgingival Biofilms

    Directory of Open Access Journals (Sweden)

    Ali Al-Ahmad

    2016-11-01

    Full Text Available Alternative treatment methods for pathogens and microbial biofilms are required due to the widespread rise in antibiotic resistance. Antimicrobial photodynamic therapy (aPDT has recently gained attention as a novel method to eradicate pathogens. The aim of this study was to evaluate the antimicrobial effects of a novel aPDT method using visible light (vis and water infiltrated infrared A (wIRA in combination with chlorine e6 (Ce6 against different periodontal pathogens in planktonic form and within in situ subgingival oral biofilms. Eight different periodontal pathogens were exposed to aPDT using vis+wIRA and 100 µg/ml Ce6 in planktonic culture. Additionally, pooled subgingival dental biofilm was also treated by aPDT and the number of viable cells determined as colony forming units (CFU. Live/dead staining was used in combination with confocal laser scanning microscopy (CLSM to visualize and quantify antimicrobial effects within the biofilm samples. Untreated negative controls as well as 0.2 % chlorhexidine (CHX-treated positive controls were used. All eight tested periodontal pathogens including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Eikenella corrodens, Actinomyces odontolyticus, Fusobacterium nucleatum, Parvimonas micra, Slackia exigua and Atopopium rimae and the aPDT-treated subgingival biofilm were eliminated over the ranges of 3.43 - 8.34 and 3.91 - 4.28 log10 CFU in the log10 scale, respectively. Thus, aPDT showed bactericidal effects on the representative pathogens as well as on the in situ subgingival biofilm. The live/dead staining also revealed a significant reduction (33.45 % of active cells within the aPDT-treated subgingival biofilm. Taking the favorable tissue healing effects of vis+wIRA into consideration, the significant antimicrobial effects revealed in this study highlight the potential of aPDT using this light source in combination with Ce6 as an adjunctive method to treat periodontitis as well as

  15. Multi-component fermionic dark matter and IceCube PeV scale neutrinos in left-right model with gauge unification

    Science.gov (United States)

    Borah, Debasish; Dasgupta, Arnab; Dey, Ujjal Kumar; Patra, Sudhanwa; Tomar, Gaurav

    2017-09-01

    We consider a simple extension of the minimal left-right symmetric model (LRSM) in order to explain the PeV neutrino events seen at the IceCube experiment from a heavy decaying dark matter. The dark matter sector is composed of two fermions: one at PeV scale and the other at TeV scale such that the heavier one can decay into the lighter one and two neutrinos. The gauge annihilation cross sections of PeV dark matter are not large enough to generate its relic abundance within the observed limit. We include a pair of real scalar triplets Ω L,R which can bring the thermally overproduced PeV dark matter abundance into the observed range through late time decay and consequent entropy release thereby providing a consistent way to obtain the correct relic abundance without violating the unitarity bound on dark matter mass. Another scalar field, a bitriplet under left-right gauge group is added to assist the heavier dark matter decay. The presence of an approximate global U(1) X symmetry can naturally explain the origin of tiny couplings required for long-lived nature of these decaying particles. We also show, how such an extended LRSM can be incorporated within a non-supersymmetric SO(10) model where the gauge coupling unification at a very high scale naturally accommodate a PeV scale intermediate symmetry, required to explain the PeV events at IceCube.

  16. Faut-il avoir peur de l’Allemagne? Représentations belges de la réunification allemande à travers 'Le Soir' et 'De Standaard'

    Directory of Open Access Journals (Sweden)

    Geneviève Duchenne

    2012-11-01

    Full Text Available Cet article revisite deux grands titres de la presse quotidienne belge, à savoir De Standaard et Le Soir, pour découvrir les perceptions qui entourèrent les événements qui se sont succédés entre l’été 1989 et l’automne 1990. Comment les différentes composantes de la société belge ont-elles réagi aux perspectives ouvertes par la chute du mur de Berlin ? Existait-il un décalage entre des élites convaincues depuis longtemps de la nécessité vitale de faire l’Europe et une population mue par un sentiment européen fort peu passionné ? Existait-il des différences de perception entre le Nord et le Sud du pays ? La réunification allemande fut-elle l’enjeu d’un débat passionné ? Le cas échéant, comment ce débat fut-il instrumentalisé ? C’est à ces quelques questions que l’article entend répondre tout en oubliant pas qu’il faudra approfondir la recherche et l’élargir notamment à d’autres sources.

  17. [Unification of methods for determining the trace quantities of lead, zinc, sodium and potassium ions in the assessment of drinking water adn transfusion fluid quality].

    Science.gov (United States)

    Popkov, V A; Golovina, N V; Evgrafov, A A

    2001-01-01

    The results of long-term studies made by the Department of General Chemistry, I. M. Sechenov Moscow Medical Academy, that deals with unification of methods for determining some ions of metals (lead, zinc, sodium, and potassium) in the assessment of the quality of drinking water and transfusion fluids are summarized. A procedure was developed to determine the trace impurities of zinc, lead, and silver by atomic absorption spectrometry (AAS) by using sorption concentration. C-80-2-aminothiazole, a new sorbent synthesized at the Research Institute of Polymers, was used to detect these ions in the drinking water. With regards to the chosen optimal conditions, drinking water samples were analyzed via their direct spraying in the air-acetylene flame. The prior sorption concentration determined drinking water zinc and lead ions in the concentrations equal to or less than their permissible dose concentrations. The studies indicated that the used methods to determine the trace quantities of metals in the drinking water and aqueous solutions show a high sensitivity, rapidity, simplicity of sample preparation.

  18. Prime-boost therapeutic vaccination in mice with DNA/DNA or DNA/Fowlpox virus recombinants expressing the Human Papilloma Virus type 16 E6 and E7 mutated proteins fused to the coat protein of Potato virus X.

    Science.gov (United States)

    Illiano, Elena; Bissa, Massimiliano; Paolini, Francesca; Zanotto, Carlo; De Giuli Morghen, Carlo; Franconi, Rosella; Radaelli, Antonia; Venuti, Aldo

    2016-10-02

    The therapeutic antitumor potency of a prime-boost vaccination strategy was explored, based on the mutated, nontransforming forms of the E6 (E6 F47R ) and E7 (E7 GGG ) oncogenes of Human Papilloma Virus type 16 (HPV16), fused to the Potato virus X (PVX) coat protein (CP) sequence. Previous data showed that CP fusion improves the immunogenicity of tumor-associated antigens and may thus increase their efficacy. After verifying the correct expression of E6 F47R CP and E7 GGG CP inserted into DNA and Fowlpox virus recombinants by Western blotting and immunofluorescence, their combined use was evaluated for therapy in a pre-clinical mouse model of HPV16-related tumorigenicity. Immunization protocols were applied using homologous (DNA/DNA) or heterologous (DNA/Fowlpox) prime-boost vaccine regimens. The humoral immune responses were determined by ELISA, and the therapeutic efficacy evaluated by the delay in tumor appearance and reduced tumor volume after inoculation of syngeneic TC-1* tumor cells. Homologous DNA/DNA genetic vaccines were able to better delay tumor appearance and inhibit tumor growth when DNAE6 F47R CP and DNAE7 GGG CP were administered in combination. However, the heterologous DNA/Fowlpox vaccination strategy was able to delay tumor appearance in a higher number of animals when E6 F47R CP and in particular E7 GGG CP were administered alone. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. The influence of proteasome inhibitor MG132, external radiation and unlabeled antibody on the tumor uptake and biodistribution of 188Re-labeled anti-E6 C1P5 antibody in cervical cancer in mice

    Science.gov (United States)

    Phaeton, Rébécca; Wang, Xing Guo; Einstein, Mark H.; Goldberg, Gary L.; Casadevall, Arturo; Dadachova, Ekaterina

    2009-01-01

    Background Human Papillomavirus (HPV) infection is considered a necessary step for the development of cervical cancer and >95% of all cervical cancers have detectable HPV sequences. We have recently demonstrated the efficacy of radioimmunotherapy (RIT) which targeted viral oncoprotein E6 in treatment of experimental cervical cancer We hypothesized that pre-treatment of tumor cells with various agents which cause cell death and/or elevation of E6 levels would increase the accumulation of radiolabeled antibodies to E6 in cervical tumors. Methods HPV-16 positive CasKi cells were treated in vitro with up to 6 Gy of external radiation, or proteasome inhibitor MG-132 or unlabeled anti-E6 antibody C1P5 and cell death was assessed. Biodistribution of 188Rhenium (188Re)-labeled C1P5 antibody was performed in both control and radiation MG-132 treated CasKi tumor-bearing nude mice. Results . 188Re-C1P5 antibody demonstrated tumor specificity and very low uptake and fast clearance from the major organs. The amount of tumor uptake was enhanced by MG-132 but was unaffected by pre-treatment with radiation. In addition, in vitro studies demonstrated an unanticipated effect of unlabeled antibody on the amount of cell death, a finding that was suggested by our previous in vivo studies in CasKi tumor model. Conclusion We demonstrated that pre-treatment of cervical tumors with proteasome inhibitor MG-132 and with unlabeled antibody to E6 can serve as a means to generate non-viable cancer cells and to elevate the levels of target oncoproteins in the cells for increasing the accumulation of targeted radiolabeled antibodies in tumors. These results favor further development of RIT of cervical cancers targeting viral antigens. PMID:20127955

  20. Acute dose and low dose-rate irradiation of carcinoma cells expressing human papillomavirus E6 and E7 oncoproteins - the significance of p53, Rb and G1 arrest status

    International Nuclear Information System (INIS)

    DeWeese, Theodore L.; Walsh, Jonathan C.; Dillehay, Larry E.; Shao, Y.; Kessis, Theodore D.; Cho, Kathleen R.; Nelson, William G.

    1995-01-01

    Purpose: The development of carcinomas in a number of sites including the cervix, vulva and anus have been associated with cellular infection by human papillomaviruses (HPV), including HPV 16 and HPV 18. The mechanism by which these viruses contribute to tumor development or progression seems in part to be related to the integration of the viral genome into the host cells DNA, and the binding of p53 protein by the HPV E6 oncoprotein as well as the binding of the retinoblastoma (Rb) protein and Rb-like proteins by the HPV E7 oncoprotein. These interactions lead to loss of p53 and Rb function including loss of the G 1 cell cycle checkpoint. Although it is believed that both p53 and Rb play a role in the radiosensitivity of the cell, whether alteration in either protein enhances or diminishes cellular radiation response is not clear from the literature. Because HPV-associated tumors such as cervical cancer are often treated with acute dose and/or low dose-rate radiation, we set out to evaluate the radiation response of several carcinoma cell sublines expressing either oncogenic E6 or E7 to both types of radiation, and to determine if p53/Rb dependent G 1 arrest is an important determinant of cell fate after irradiation. Materials and Methods: We have previously developed a series of RKO colorectal carcinoma cell sublines expressing both low-risk (HPV 11) and high-risk (HPV 16) E6 and E7 genes. p53-dependent G 1 arrest is intact in RKO parental cells and cells expressing low-risk E6 proteins, while the G 1 arrest is abrogated in cells expressing high-risk E6 or E7. Clonogenic survival was assessed after exposure to acute dose (1 Gy/min) and low dose-rate (0.25 Gy/hour) radiation. The radiobiologic parameters α, β and the surviving fraction at 2 Gy (SF2) were determined. SDS-PAGE/immunoblotting was carried out to assess both p53 and p21 WAF1/CIP1 levels after exposure to radiation. Flow cytometry was performed before and after exposure to low dose-rate radiation to