Conformal superalgebras via tractor calculus

NASA Astrophysics Data System (ADS)

Lischewski, Andree

2015-01-01

We use the manifestly conformally invariant description of a Lorentzian conformal structure in terms of a parabolic Cartan geometry in order to introduce a superalgebra structure on the space of twistor spinors and normal conformal vector fields formulated in purely algebraic terms on parallel sections in tractor bundles. Via a fixed metric in the conformal class, one reproduces a conformal superalgebra structure that has been considered in the literature before. The tractor approach, however, makes clear that the failure of this object to be a Lie superalgebra in certain cases is due to purely algebraic identities on the spinor module and to special properties of the conformal holonomy representation. Moreover, it naturally generalizes to higher signatures. This yields new formulas for constructing new twistor spinors and higher order normal conformal Killing forms out of existing ones, generalizing the well-known spinorial Lie derivative. Moreover, we derive restrictions on the possible dimension of the space of twistor spinors in any metric signature.

Integrability conditions for Killing-Yano tensors and conformal Killing-Yano tensors

NASA Astrophysics Data System (ADS)

Batista, Carlos

2015-01-01

The integrability conditions for the existence of a conformal Killing-Yano tensor of arbitrary order are worked out in all dimensions and expressed in terms of the Weyl tensor. As a consequence, the integrability conditions for the existence of a Killing-Yano tensor are also obtained. By means of such conditions, it is shown that in certain Einstein spaces one can use a conformal Killing-Yano tensor of order p to generate a Killing-Yano tensor of order (p -1 ) . Finally, it is proved that in maximally symmetric spaces the covariant derivative of a Killing-Yano tensor is a closed conformal Killing-Yano tensor and that every conformal Killing-Yano tensor is uniquely decomposed as the sum of a Killing-Yano tensor and a closed conformal Killing-Yano tensor.

Marginally outer trapped surfaces and symmetries

NASA Astrophysics Data System (ADS)

Carrasco, Alberto; Mars, Marc

2009-05-01

We study properties of outermost marginally outer trapped surfaces in slices of space-times possessing certain symmetries, like isometries, homotheties or conformal Killings. In particular, we find restrictions on these surfaces for the vector field generating the symmetry. As an application we give a result of non-existence of outermost marginally outer trapped surfaces in accelerated Friedmann-Lemaître-Roberson-Walker spacetimes.

Eisenhart lifts and symmetries of time-dependent systems

NASA Astrophysics Data System (ADS)

Cariglia, M.; Duval, C.; Gibbons, G. W.; Horváthy, P. A.

2016-10-01

Certain dissipative systems, such as Caldirola and Kannai's damped simple harmonic oscillator, may be modelled by time-dependent Lagrangian and hence time dependent Hamiltonian systems with n degrees of freedom. In this paper we treat these systems, their projective and conformal symmetries as well as their quantisation from the point of view of the Eisenhart lift to a Bargmann spacetime in n + 2 dimensions, equipped with its covariantly constant null Killing vector field. Reparametrisation of the time variable corresponds to conformal rescalings of the Bargmann metric. We show how the Arnold map lifts to Bargmann spacetime. We contrast the greater generality of the Caldirola-Kannai approach with that of Arnold and Bateman. At the level of quantum mechanics, we are able to show how the relevant Schrödinger equation emerges naturally using the techniques of quantum field theory in curved spacetimes, since a covariantly constant null Killing vector field gives rise to well defined one particle Hilbert space. Time-dependent Lagrangians arise naturally also in cosmology and give rise to the phenomenon of Hubble friction. We provide an account of this for Friedmann-Lemaître and Bianchi cosmologies and how it fits in with our previous discussion in the non-relativistic limit.

Generalized wave operators, weighted Killing fields, and perturbations of higher dimensional spacetimes

NASA Astrophysics Data System (ADS)

Araneda, Bernardo

2018-04-01

We present weighted covariant derivatives and wave operators for perturbations of certain algebraically special Einstein spacetimes in arbitrary dimensions, under which the Teukolsky and related equations become weighted wave equations. We show that the higher dimensional generalization of the principal null directions are weighted conformal Killing vectors with respect to the modified covariant derivative. We also introduce a modified Laplace–de Rham-like operator acting on tensor-valued differential forms, and show that the wave-like equations are, at the linear level, appropriate projections off shell of this operator acting on the curvature tensor; the projection tensors being made out of weighted conformal Killing–Yano tensors. We give off shell operator identities that map the Einstein and Maxwell equations into weighted scalar equations, and using adjoint operators we construct solutions of the original field equations in a compact form from solutions of the wave-like equations. We study the extreme and zero boost weight cases; extreme boost corresponding to perturbations of Kundt spacetimes (which includes near horizon geometries of extreme black holes), and zero boost to static black holes in arbitrary dimensions. In 4D our results apply to Einstein spacetimes of Petrov type D and make use of weighted Killing spinors.

Euclidean supersymmetric solutions with the self-dual Weyl tensor

NASA Astrophysics Data System (ADS)

Nozawa, Masato

2017-07-01

We explore the Euclidean supersymmetric solutions admitting the self-dual gauge field in the framework of N = 2 minimal gauged supergravity in four dimensions. According to the classification scheme utilizing the spinorial geometry or the bilinears of Killing spinors, the general solution preserves one quarter of supersymmetry and is described by the Przanowski-Tod class with the self-dual Weyl tensor. We demonstrate that there exists an additional Killing spinor, provided the Przanowski-Tod metric admits a Killing vector that commutes with the principal one. The proof proceeds by recasting the metric into another Przanowski-Tod form. This formalism enables us to show that the self-dual Reissner-Nordström-Taub-NUT-AdS metric possesses a second Killing spinor, which has been missed over many years. We also address the supersymmetry when the Przanowski-Tod space is conformal to each of the self-dual ambi-toric Kähler metrics. It turns out that three classes of solutions are all reduced to the self-dual Carter family, by virtue of the nondegenerate Killing-Yano tensor.

Hidden symmetries of Eisenhart-Duval lift metrics and the Dirac equation with flux

NASA Astrophysics Data System (ADS)

Cariglia, Marco

2012-10-01

The Eisenhart-Duval lift allows embedding nonrelativistic theories into a Lorentzian geometrical setting. In this paper we study the lift from the point of view of the Dirac equation and its hidden symmetries. We show that dimensional reduction of the Dirac equation for the Eisenhart-Duval metric in general gives rise to the nonrelativistic Lévy-Leblond equation in lower dimension. We study in detail in which specific cases the lower dimensional limit is given by the Dirac equation, with scalar and vector flux, and the relation between lift, reduction, and the hidden symmetries of the Dirac equation. While there is a precise correspondence in the case of the lower dimensional massive Dirac equation with no flux, we find that for generic fluxes it is not possible to lift or reduce all solutions and hidden symmetries. As a by-product of this analysis, we construct new Lorentzian metrics with special tensors by lifting Killing-Yano and closed conformal Killing-Yano tensors and describe the general conformal Killing-Yano tensor of the Eisenhart-Duval lift metrics in terms of lower dimensional forms. Last, we show how, by dimensionally reducing the higher dimensional operators of the massless Dirac equation that are associated with shared hidden symmetries, it is possible to recover hidden symmetry operators for the Dirac equation with flux.

Transverse conformal Killing forms on Kähler foliations

NASA Astrophysics Data System (ADS)

Jung, Seoung Dal

2015-04-01

On a closed, connected Riemannian manifold with a Kähler foliation of codimension q = 2 m, any transverse Killing r(≥ 2) -form is parallel (Jung and Jung, 2012). In this paper, we study transverse conformal Killing forms on Kähler foliations. In fact, if the foliation is minimal, then for any transverse conformal Killing r-form ϕ(2 ≤ r ≤ q - 2), Jϕ is parallel. Here J is defined in Section 4.

Stationary metrics and optical Zermelo-Randers-Finsler geometry

NASA Astrophysics Data System (ADS)

Gibbons, G. W.; Herdeiro, C. A. R.; Warnick, C. M.; Werner, M. C.

2009-02-01

We consider a triality between the Zermelo navigation problem, the geodesic flow on a Finslerian geometry of Randers type, and spacetimes in one dimension higher admitting a timelike conformal Killing vector field. From the latter viewpoint, the data of the Zermelo problem are encoded in a (conformally) Painlevé-Gullstrand form of the spacetime metric, whereas the data of the Randers problem are encoded in a stationary generalization of the usual optical metric. We discuss how the spacetime viewpoint gives a simple and physical perspective on various issues, including how Finsler geometries with constant flag curvature always map to conformally flat spacetimes and that the Finsler condition maps to either a causality condition or it breaks down at an ergo surface in the spacetime picture. The gauge equivalence in this network of relations is considered as well as the connection to analogue models and the viewpoint of magnetic flows. We provide a variety of examples.

Conformal Killing horizons and their thermodynamics

NASA Astrophysics Data System (ADS)

Nielsen, Alex B.; Shoom, Andrey A.

2018-05-01

Certain dynamical black hole solutions can be mapped to static spacetimes by conformal metric transformations. This mapping provides a physical link between the conformal Killing horizon of the dynamical black hole and the Killing horizon of the static spacetime. Using the Vaidya spacetime as an example, we show how this conformal relation can be used to derive thermodynamic properties of such dynamical black holes. Although these horizons are defined quasi-locally and can be located by local experiments, they are distinct from other popular notions of quasi-local horizons such as apparent horizons. Thus in the dynamical Vaidya spacetime describing constant accretion of null dust, the conformal Killing horizon, which is null by construction, is the natural horizon to describe the black hole.

Conserved charges of black holes in Weyl and Einstein-Gauss-Bonnet gravities

NASA Astrophysics Data System (ADS)

Peng, Jun-Jin

2014-11-01

An off-shell generalization of the Abbott-Deser-Tekin (ADT) conserved charge was recently proposed by Kim et al. They achieved this by introducing off-shell Noether currents and potentials. In this paper, we construct the crucial off-shell Noether current by the variation of the Bianchi identity for the expression of EOM, with the help of the property of Killing vector. Our Noether current, which contains an additional term that is just one half of the Lie derivative of a surface term with respect to the Killing vector, takes a different form in comparison with the one in their work. Then we employ the generalized formulation to calculate the quasi-local conserved charges for the most general charged spherically symmetric and the dyonic rotating black holes with AdS asymptotics in four-dimensional conformal Weyl gravity, as well as the charged spherically symmetric black holes in arbitrary dimensional Einstein-Gauss-Bonnet gravity coupled to Maxwell or nonlinear electrodynamics in AdS spacetime. Our results confirm those obtained through other methods in the literature.

Killing spinors are Killing vector fields in Riemannian supergeometry

NASA Astrophysics Data System (ADS)

Alekseevsky, D. V.; Cortés, V.; Devchand, C.; Semmelmann, U.

1998-06-01

A supermanifold M is canonically associated to any pseudo-Riemannian spin manifold ( M0, g0). Extending the metric g0 to a field g of bilinear forms g( p) on TpM, pɛM0, the pseudo-Riemannian supergeometry of ( M, g) is formulated as G-structure on M, where G is a supergroup with even part G 0 ≊ Spin(k, l); (k, l) the signature of ( M0, go). Killing vector fields on ( M, g) are, by definition, infinitesimal automorphisms of this G-structure. For every spinor field s there exists a corresponding odd vector field Xs on M. Our main result is that Xs is a Killing vector field on ( M, g) if and only if s is a twistor spinor. In particular, any Killing spinor s defines a Killing vector field Xs.

Stability of marginally outer trapped surfaces and symmetries

NASA Astrophysics Data System (ADS)

Carrasco, Alberto; Mars, Marc

2009-09-01

We study the properties of stable, strictly stable and locally outermost marginally outer trapped surfaces in spacelike hypersurfaces of spacetimes possessing certain symmetries such as isometries, homotheties and conformal Killings. We first obtain results for general diffeomorphisms in terms of the so-called metric deformation tensor and then particularize to different types of symmetries. In particular, we find restrictions at the surfaces on the vector field generating the symmetry. Some consequences are discussed. As an application, we present a result on non-existence of stable marginally outer trapped surfaces in slices of FLRW.

Killing vector fields in three dimensions: a method to solve massive gravity field equations

NASA Astrophysics Data System (ADS)

Gürses, Metin

2010-10-01

Killing vector fields in three dimensions play an important role in the construction of the related spacetime geometry. In this work we show that when a three-dimensional geometry admits a Killing vector field then the Ricci tensor of the geometry is determined in terms of the Killing vector field and its scalars. In this way we can generate all products and covariant derivatives at any order of the Ricci tensor. Using this property we give ways to solve the field equations of topologically massive gravity (TMG) and new massive gravity (NMG) introduced recently. In particular when the scalars of the Killing vector field (timelike, spacelike and null cases) are constants then all three-dimensional symmetric tensors of the geometry, the Ricci and Einstein tensors, their covariant derivatives at all orders, and their products of all orders are completely determined by the Killing vector field and the metric. Hence, the corresponding three-dimensional metrics are strong candidates for solving all higher derivative gravitational field equations in three dimensions.

Spacetimes with Killing tensors. [for Einstein-Maxwell fields with certain spinor indices

NASA Technical Reports Server (NTRS)

Hughston, L. P.; Sommers, P.

1973-01-01

The characteristics of the Killing equation and the Killing tensor are discussed. A conformal Killing tensor is of interest inasmuch as it gives rise to a quadratic first integral for null geodesic orbits. The Einstein-Maxwell equations are considered together with the Bianchi identity and the conformal Killing tensor. Two examples for the application of the considered relations are presented, giving attention to the charged Kerr solution and the charged C-metric.

Invariant solutions to the conformal Killing-Yano equation on Lie groups

NASA Astrophysics Data System (ADS)

Andrada, A.; Barberis, M. L.; Dotti, I. G.

2015-08-01

We search for invariant solutions of the conformal Killing-Yano equation on Lie groups equipped with left invariant Riemannian metrics, focusing on 2-forms. We show that when the Lie group is compact equipped with a bi-invariant metric or 2-step nilpotent, the only invariant solutions occur on the 3-dimensional sphere or on a Heisenberg group. We classify the 3-dimensional Lie groups with left invariant metrics carrying invariant conformal Killing-Yano 2-forms.

On hidden symmetries of extremal Kerr-NUT-AdS-dS black holes

NASA Astrophysics Data System (ADS)

Rasmussen, Jørgen

2011-05-01

It is well known that the Kerr-NUT-AdS-dS black hole admits two linearly independent Killing vectors and possesses a hidden symmetry generated by a rank-2 Killing tensor. The near-horizon geometry of an extremal Kerr-NUT-AdS-dS black hole admits four linearly independent Killing vectors, and we show how the hidden symmetry of the black hole itself is carried over by means of a modified Killing-Yano potential which is given explicitly. We demonstrate that the corresponding Killing tensor of the near-horizon geometry is reducible as it can be expressed in terms of the Casimir operators formed by the four Killing vectors.

Timelike Killing vectors and ergo surfaces in non-asymptotically flat spacetimes

NASA Astrophysics Data System (ADS)

Pelavas, N.

2005-02-01

Ergo surfaces are investigated in spacetimes with a cosmological constant. We find the existence of multiple timelike Killing vectors, each corresponding to a distinct ergo surface, with no one being preferred. Using a kinematic invariant, which provides a measure of hypersurface orthogonality, we explore its potential role in selecting a preferred timelike Killing vector and consequently a unique ergo surface.

On Finsler spacetimes with a timelike Killing vector field

NASA Astrophysics Data System (ADS)

Caponio, Erasmo; Stancarone, Giuseppe

2018-04-01

We study Finsler spacetimes and Killing vector fields taking care of the fact that the generalised metric tensor associated to the Lorentz–Finsler function L is in general well defined only on a subset of the slit tangent bundle. We then introduce a new class of Finsler spacetimes endowed with a timelike Killing vector field that we call stationary splitting Finsler spacetimes. We characterize when a Finsler spacetime with a timelike Killing vector field is locally a stationary splitting. Finally, we show that the causal structure of a stationary splitting is the same of one of two Finslerian static spacetimes naturally associated to the stationary splitting.

Commuting symmetry operators of the Dirac equation, Killing-Yano and Schouten-Nijenhuis brackets

NASA Astrophysics Data System (ADS)

Cariglia, Marco; Krtouš, Pavel; Kubizňák, David

2011-07-01

In this paper we derive the most general first-order symmetry operator commuting with the Dirac operator in all dimensions and signatures. Such an operator splits into Clifford even and Clifford odd parts which are given in terms of odd Killing-Yano and even closed conformal Killing-Yano inhomogeneous forms, respectively. We study commutators of these symmetry operators and give necessary and sufficient conditions under which they remain of the first-order. In this specific setting we can introduce a Killing-Yano bracket, a bilinear operation acting on odd Killing-Yano and even closed conformal Killing-Yano forms, and demonstrate that it is closely related to the Schouten-Nijenhuis bracket. An important nontrivial example of vanishing Killing-Yano brackets is given by Dirac symmetry operators generated from the principal conformal Killing-Yano tensor [hep-th/0612029]. We show that among these operators one can find a complete subset of mutually commuting operators. These operators underlie separability of the Dirac equation in Kerr-NUT-(A)dS spacetimes in all dimensions [arXiv:0711.0078].

Conformal Yano-Killing Tensors for Space-times with Cosmological Constant

NASA Astrophysics Data System (ADS)

Czajka, P.; Jezierski, J.

We present a new method for constructing conformal Yano-Killing tensors in five-di\\-men\\-sio\\-nal Anti-de Sitter space-time. The found tensors are represented in two different coordinate systems. We also discuss, in terms of CYK tensors, global charges which are well defined for asymptotically (five-dimensional) Anti-de Sitter space-time. Additionally in Appendix we present our own derivation of conformal Killing one-forms in four-dimensional Anti-de Sitter space-time as an application of the Theorem presented in the paper.

Separability of black holes in string theory

NASA Astrophysics Data System (ADS)

Keeler, Cynthia; Larsen, Finn

2012-10-01

We analyze the origin of separability for rotating black holes in string theory, considering both massless and massive geodesic equations as well as the corresponding wave equations. We construct a conformal Killing-Stackel tensor for a general class of black holes with four independent charges, then identify two-charge configurations where enhancement to an exact Killing-Stackel tensor is possible. We show that further enhancement to a conserved Killing-Yano tensor is possible only for the special case of Kerr-Newman black holes. We construct natural null congruences for all these black holes and use the results to show that only the Kerr-Newman black holes are algebraically special in the sense of Petrov. Modifying the asymptotic behavior by the subtraction procedure that induces an exact SL(2)2 also preserves only the conformal Killing-Stackel tensor. Similarly, we find that a rotating Kaluza-Klein black hole possesses a conformal Killing-Stackel tensor but has no further enhancements.

Light cone thermodynamics

NASA Astrophysics Data System (ADS)

De Lorenzo, Tommaso; Perez, Alejandro

2018-02-01

We show that null surfaces defined by the outgoing and infalling wave fronts emanating from and arriving at a sphere in Minkowski spacetime have thermodynamical properties that are in strict formal correspondence with those of black hole horizons in curved spacetimes. Such null surfaces, made of pieces of light cones, are bifurcate conformal Killing horizons for suitable conformally stationary observers. They can be extremal and nonextremal depending on the radius of the shining sphere. Such conformal Killing horizons have a constant light cone (conformal) temperature, given by the standard expression in terms of the generalization of surface gravity for conformal Killing horizons. Exchanges of conformally invariant energy across the horizon are described by a first law where entropy changes are given by 1 /(4 ℓp2) of the changes of a geometric quantity with the meaning of horizon area in a suitable conformal frame. These conformal horizons satisfy the zeroth to the third laws of thermodynamics in an appropriate way. In the extremal case they become light cones associated with a single event; these have vanishing temperature as well as vanishing entropy.

Hidden symmetries and Lie algebra structures from geometric and supergravity Killing spinors

NASA Astrophysics Data System (ADS)

Açık, Özgür; Ertem, Ümit

2016-08-01

We consider geometric and supergravity Killing spinors and the spinor bilinears constructed out of them. The spinor bilinears of geometric Killing spinors correspond to the antisymmetric generalizations of Killing vector fields which are called Killing-Yano forms. They constitute a Lie superalgebra structure in constant curvature spacetimes. We show that the Dirac currents of geometric Killing spinors satisfy a Lie algebra structure up to a condition on 2-form spinor bilinears. We propose that the spinor bilinears of supergravity Killing spinors give way to different generalizations of Killing vector fields to higher degree forms. It is also shown that those supergravity Killing forms constitute a Lie algebra structure in six- and ten-dimensional cases. For five- and eleven-dimensional cases, the Lie algebra structure depends on an extra condition on supergravity Killing forms.

Closed Conformal Killing-Yano Tensor and Uniqueness of Generalized Kerr-NUT-de Sitter Spacetime

NASA Astrophysics Data System (ADS)

Houri, Tsuyoshi

We classify all spacetimes with a rank-2 closed conformal Killing-Yano tensor. They give a generalization of Kerr-NUT-de Sitter spacetime. The Einstein condition is explicitly solved. The Kerr-NUT-de Sitter spacetime is obtained as a spacetime with a non-degenerate CKY tensor.

A note on φ-analytic conformal vector fields

NASA Astrophysics Data System (ADS)

Deshmukh, Sharief; Bin Turki, Nasser

2017-09-01

Taking clue from the analytic vector fields on a complex manifold, φ-analytic conformal vector fields are defined on a Riemannian manifold (Deshmukh and Al-Solamy in Colloq. Math. 112(1):157-161, 2008). In this paper, we use φ-analytic conformal vector fields to find new characterizations of the n-sphere Sn(c) and the Euclidean space (Rn,<,> ).

Classification of the Lie and Noether point symmetries for the Wave and the Klein-Gordon equations in pp-wave spacetimes

NASA Astrophysics Data System (ADS)

Paliathanasis, A.; Tsamparlis, M.; Mustafa, M. T.

2018-02-01

A complete classification of the Lie and Noether point symmetries for the Klein-Gordon and the wave equation in pp-wave spacetimes is obtained. The classification analysis is carried out by reducing the problem of the determination of the point symmetries to the problem of existence of conformal killing vectors on the pp-wave spacetimes. Employing the existing results for the isometry classes of the pp-wave spacetimes, the functional form of the potential is determined for which the Klein-Gordon equation admits point symmetries and Noetherian conservation law. Finally the Lie and Noether point symmetries of the wave equation are derived.

Asymptotic symmetries on Killing horizons

NASA Astrophysics Data System (ADS)

Koga, Jun-Ichirou

2001-12-01

We investigate asymptotic symmetries regularly defined on spherically symmetric Killing horizons in Einstein theory with or without the cosmological constant. These asymptotic symmetries are described by asymptotic Killing vectors, along which the Lie derivatives of perturbed metrics vanish on a Killing horizon. We derive the general form of the asymptotic Killing vectors and find that the group of asymptotic symmetries consists of rigid O(3) rotations of a horizon two-sphere and supertranslations along the null direction on the horizon, which depend arbitrarily on the null coordinate as well as the angular coordinates. By introducing the notion of asymptotic Killing horizons, we also show that local properties of Killing horizons are preserved not only under diffeomorphisms but also under nontrivial transformations generated by the asymptotic symmetry group. Although the asymptotic symmetry group contains the Diff(S1) subgroup, which results from supertranslations dependent only on the null coordinate, it is shown that the Poisson brackets algebra of the conserved charges conjugate to asymptotic Killing vectors does not acquire nontrivial central charges. Finally, by considering extended symmetries, we discuss the fact that unnatural reduction of the symmetry group is necessary in order to obtain the Virasoro algebra with nontrivial central charges, which is not justified when we respect the spherical symmetry of Killing horizons.

Asymptotically spacelike warped anti-de Sitter spacetimes in generalized minimal massive gravity

NASA Astrophysics Data System (ADS)

Setare, M. R.; Adami, H.

2017-06-01

In this paper we show that warped AdS3 black hole spacetime is a solution of the generalized minimal massive gravity (GMMG) and introduce suitable boundary conditions for asymptotically warped AdS3 spacetimes. Then we find the Killing vector fields such that transformations generated by them preserve the considered boundary conditions. We calculate the conserved charges which correspond to the obtained Killing vector fields and show that the algebra of the asymptotic conserved charges is given as the semi direct product of the Virasoro algebra with U(1) current algebra. We use a particular Sugawara construction to reconstruct the conformal algebra. Thus, we are allowed to use the Cardy formula to calculate the entropy of the warped black hole. We demonstrate that the gravitational entropy of the warped black hole exactly coincides with what we obtain via Cardy’s formula. As we expect, the warped Cardy formula also gives us exactly the same result as we obtain from the usual Cardy’s formula. We calculate mass and angular momentum of the warped black hole and then check that obtained mass, angular momentum and entropy to satisfy the first law of the black hole mechanics. According to the results of this paper we believe that the dual theory of the warped AdS3 black hole solution of GMMG is a warped CFT.

Reviving the shear-free perfect fluid conjecture in general relativity

NASA Astrophysics Data System (ADS)

Sikhonde, Muzikayise E.; Dunsby, Peter K. S.

2017-12-01

Employing a Mathematica symbolic computer algebra package called xTensor, we present (1+3) -covariant special case proofs of the shear-free perfect fluid conjecture in general relativity. We first present the case where the pressure is constant, and where the acceleration is parallel to the vorticity vector. These cases were first presented in their covariant form by Senovilla et al. We then provide a covariant proof for the case where the acceleration and vorticity vectors are orthogonal, which leads to the existence of a Killing vector along the vorticity. This Killing vector satisfies the new constraint equations resulting from the vanishing of the shear. Furthermore, it is shown that in order for the conjecture to be true, this Killing vector must have a vanishing spatially projected directional covariant derivative along the velocity vector field. This in turn implies the existence of another basic vector field along the direction of the vorticity for the conjecture to hold. Finally, we show that in general, there exists a basic vector field parallel to the acceleration for which the conjecture is true.

Conformal Yano-Killing Tensors in General Relativity

NASA Astrophysics Data System (ADS)

Jezierski, Jacek

2011-09-01

How CYK tensors appear in General Relativity? Geometric definition of the asymptotic flat spacetime: strong asymptotic flatness, which guarantees well defined total angular momentum [2, 3, 4] Conserved quantities - asymptotic charges (ℐ, 𝓲0) [2, 3, 4, 5, 6, 9] Quasi-local mass and "rotational energy" for Kerr black hole [5] Constants of motion along geodesics and symmetric Killing tensors [5, 6] Spacetimes possessing CYK tensor [10]: Minkowski (quadratic polynomials) [5] (Anti-)deSitter (natural construction) [7, 8, 9] Kerr (type D spacetime) [5] Taub-NUT (new symmetric conformal Killing tensors) [6] Other applications: Symmetries of Dirac operator Symmetries of Maxwell equations

Killing approximation for vacuum and thermal stress-energy tensor in static space-times

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

Frolov, V.P.; Zel'nikov, A.I.

1987-05-15

The problem of the vacuum polarization of conformal massless fields in static space-times is considered. A tensor T/sub ..mu..//sub ..nu../ constructed from the curvature, the Killing vector, and their covariant derivatives is proposed which can be used to approximate the average value of the stress-energy tensor /sup ren/ in such spaces. It is shown that if (i) its trace T /sub epsilon//sup epsilon/ coincides with the trace anomaly /sup ren/, (ii) it satisfies the conservation law T/sup ..mu..//sup epsilon/ /sub ;//sub epsilon/ = 0, and (iii) it has the correct behavior under the scale transformations, then it is uniquely definedmore » up to a few arbitrary constants. These constants must be chosen to satisfy the boundary conditions. In the case of a static black hole in a vacuum these conditions single out the unique tensor T/sub ..mu..//sub ..nu../ which provides a good approximation for /sup ren/ in the Hartle-Hawking vacuum. The relation between this approach and the Page-Brown-Ottewill approach is discussed.« less

9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus...

9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus...

9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus...

9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus...

No more CKY two-forms in the NHEK

NASA Astrophysics Data System (ADS)

Mitsuka, Yoshihiro; Moutsopoulos, George

2012-02-01

We show that in the near-horizon limit of a Kerr-NUT-AdS black hole, the space of conformal Killing-Yano two-forms does not enhance and remains of dimension 2. The same holds for an analogous polar limit in the case of extremal NUT charge. We also derive the conformal Killing-Yano p-form equation for any background in an arbitrary dimension in the form of parallel transport.

Gauged twistor spinors and symmetry operators

NASA Astrophysics Data System (ADS)

Ertem, Ümit

2017-03-01

We consider gauged twistor spinors which are supersymmetry generators of supersymmetric and superconformal field theories in curved backgrounds. We show that the spinor bilinears of gauged twistor spinors satisfy the gauged conformal Killing-Yano equation. We prove that the symmetry operators of the gauged twistor spinor equation can be constructed from ordinary conformal Killing-Yano forms in constant curvature backgrounds. This provides a way to obtain gauged twistor spinors from ordinary twistor spinors.

Combining Synthetic Human Odours and Low-Cost Electrocuting Grids to Attract and Kill Outdoor-Biting Mosquitoes: Field and Semi-Field Evaluation of an Improved Mosquito Landing Box

PubMed Central

Matowo, Nancy S.; Koekemoer, Lizette L.; Moore, Sarah J.; Mmbando, Arnold S.; Mapua, Salum A.; Coetzee, Maureen; Okumu, Fredros O.

2016-01-01

Background On-going malaria transmission is increasingly mediated by outdoor-biting vectors, especially where indoor insecticidal interventions such as long-lasting insecticide treated nets (LLINs) are widespread. Often, the vectors are also physiologically resistant to insecticides, presenting major obstacles for elimination. We tested a combination of electrocuting grids with synthetic odours as an alternative killing mechanism against outdoor-biting mosquitoes. Methods An odour-baited device, the Mosquito Landing Box (MLB), was improved by fitting it with low-cost electrocuting grids to instantly kill mosquitoes attracted to the odour lure, and automated photo switch to activate attractant-dispensing and mosquito-killing systems between dusk and dawn. MLBs fitted with one, two or three electrocuting grids were compared outdoors in a malaria endemic village in Tanzania, where vectors had lost susceptibility to pyrethroids. MLBs with three grids were also tested in a large semi-field cage (9.6×9.6×4.5m), to assess effects on biting-densities of laboratory-reared Anopheles arabiensis on volunteers sitting near MLBs. Results Significantly more mosquitoes were killed when MLBs had two or three grids, than one grid in wet and dry seasons (P<0.05). The MLBs were highly efficient against Mansonia species and malaria vector, An. arabiensis. Of all mosquitoes, 99% were non-blood fed, suggesting host-seeking status. In the semi-field, the MLBs reduced mean number of malaria mosquitoes attempting to bite humans fourfold. Conclusion The improved odour-baited MLBs effectively kill outdoor-biting malaria vector mosquitoes that are behaviourally and physiologically resistant to insecticidal interventions e.g. LLINs. The MLBs reduce human-biting vector densities even when used close to humans, and are insecticide-free, hence potentially antiresistance. The devices could either be used as surveillance tools or complementary mosquito control interventions to accelerate malaria elimination where outdoor transmission is significant. PMID:26789733

Hidden symmetry in the presence of fluxes

NASA Astrophysics Data System (ADS)

Kubizňák, David; Warnick, Claude M.; Krtouš, Pavel

2011-03-01

We derive the most general first-order symmetry operator for the Dirac equation coupled to arbitrary fluxes. Such an operator is given in terms of an inhomogeneous form ω which is a solution to a coupled system of first-order partial differential equations which we call the generalized conformal Killing-Yano system. Except trivial fluxes, solutions of this system are subject to additional constraints. We discuss various special cases of physical interest. In particular, we demonstrate that in the case of a Dirac operator coupled to the skew symmetric torsion and U(1) field, the system of generalized conformal Killing-Yano equations decouples into the homogeneous conformal Killing-Yano equations with torsion introduced in D. Kubiznak et al. (2009) [8] and the symmetry operator is essentially the one derived in T. Houri et al. (2010) [9]. We also discuss the Dirac field coupled to a scalar potential and in the presence of 5-form and 7-form fluxes.

Symmetries, holography, and quantum phase transition in two-dimensional dilaton AdS gravity

NASA Astrophysics Data System (ADS)

Cadoni, Mariano; Ciulu, Matteo; Tuveri, Matteo

2018-05-01

We revisit the Almheiri-Polchinski dilaton gravity model from a two-dimensional (2D) bulk perspective. We describe a peculiar feature of the model, namely the pattern of conformal symmetry breaking using bulk Killing vectors, a covariant definition of mass and the flow between different vacua of the theory. We show that the effect of the symmetry breaking is both the generation of an infrared scale (a mass gap) and to make local the Goldstone modes associated with the asymptotic symmetries of the 2D spacetime. In this way a nonvanishing central charge is generated in the dual conformal theory, which accounts for the microscopic entropy of the 2D black hole. The use of covariant mass allows to compare energetically the two different vacua of the theory and to show that at zero temperature the vacuum with a constant dilaton is energetically preferred. We also translate in the bulk language several features of the dual CFT discussed by Maldacena et al. The uplifting of the 2D model to (d +2 )-dimensional theories exhibiting hyperscaling violation is briefly discussed.

Baby de Sitter black holes and dS3/CFT2

NASA Astrophysics Data System (ADS)

de Buyl, Sophie; Detournay, Stéphane; Giribet, Gaston; Ng, Gim Seng

2014-02-01

Unlike three-dimensional Einstein gravity, three-dimensional massive gravity admits asymptotically de Sitter space (dS) black hole solutions. These black holes present interesting features and provide us with toy models to study the dS/CFT correspondence. A remarkable property of these black holes is that they are always in thermal equilibrium with the cosmological horizon of the space that hosts them. This invites us to study the thermodynamics of these solutions within the context of dS/CFT. We study the asymptotic symmetry group of the theory and find that it indeed coincides with the local two-dimensional conformal algebra. The charge algebra associated to the asymptotic Killing vectors consists of two copies of the Virasoro algebra with non-vanishing central extension. We compute the mass and angular momentum of the dS black holes and verify that a naive application of Cardy's formula exactly reproduces the entropy of both the black hole and the cosmological horizon. By adapting the holographic renormalization techniques to the case of dS space, we define the boundary stress tensor of the dual Euclidean conformal field theory.

Integrability of spinning particle motion in higher-dimensional rotating black hole spacetimes.

PubMed

Kubizňák, David; Cariglia, Marco

2012-02-03

We study the motion of a classical spinning particle (with spin degrees of freedom described by a vector of Grassmann variables) in higher-dimensional general rotating black hole spacetimes with a cosmological constant. In all dimensions n we exhibit n bosonic functionally independent integrals of spinning particle motion, corresponding to explicit and hidden symmetries generated from the principal conformal Killing-Yano tensor. Moreover, we demonstrate that in 4-, 5-, 6-, and 7-dimensional black hole spacetimes such integrals are in involution, proving the bosonic part of the motion integrable. We conjecture that the same conclusion remains valid in all higher dimensions. Our result generalizes the result of Page et al. [Phys. Rev. Lett. 98, 061102 (2007)] on complete integrability of geodesic motion in these spacetimes.

9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Hepatitis and Canine Adenovirus...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus...

The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

PubMed Central

Smith, Ryan C; Vega-Rodríguez, Joel; Jacobs-Lorena, Marcelo

2014-01-01

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission. PMID:25185005

9 CFR 113.207 - Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Encephalomyelitis Vaccine, Eastern... PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.207 Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus. Encephalomyelitis Vaccine, Eastern, Western, and...

9 CFR 113.207 - Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Encephalomyelitis Vaccine, Eastern... PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.207 Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus. Encephalomyelitis Vaccine, Eastern, Western, and...

9 CFR 113.207 - Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Encephalomyelitis Vaccine, Eastern... PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.207 Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus. Encephalomyelitis Vaccine, Eastern, Western, and...

9 CFR 113.207 - Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Encephalomyelitis Vaccine, Eastern... PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.207 Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus. Encephalomyelitis Vaccine, Eastern, Western, and...

Integrability conditions for Killing-Yano tensors and maximally symmetric spaces in the presence of torsion

NASA Astrophysics Data System (ADS)

Batista, Carlos

2015-04-01

The integrability conditions for the existence of Killing-Yano tensors or, equivalently, covariantly closed conformal Killing-Yano tensors, in the presence of torsion are worked out. As an application, all metrics and torsions compatible with the existence of a Killing-Yano tensor of order n -1 are obtained. Finally, the issue of defining a maximally symmetric space with respect to connections with torsion is addressed.

Binary black hole spacetimes with a helical Killing vector

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

Klein, Christian

Binary black hole spacetimes with a helical Killing vector, which are discussed as an approximation for the early stage of a binary system, are studied in a projection formalism. In this setting the four-dimensional Einstein equations are equivalent to a three-dimensional gravitational theory with a SL(2,R)/SO(1,1) sigma model as the material source. The sigma model is determined by a complex Ernst equation. 2+1 decompositions of the three-metric are used to establish the field equations on the orbit space of the Killing vector. The two Killing horizons of spherical topology which characterize the black holes, the cylinder of light where themore » Killing vector changes from timelike to spacelike, and infinity are singular points of the equations. The horizon and the light cylinder are shown to be regular singularities, i.e., the metric functions can be expanded in a formal power series in the vicinity. The behavior of the metric at spatial infinity is studied in terms of formal series solutions to the linearized Einstein equations. It is shown that the spacetime is not asymptotically flat in the strong sense to have a smooth null infinity under the assumption that the metric tends asymptotically to the Minkowski metric. In this case the metric functions have an oscillatory behavior in the radial coordinate in a nonaxisymmetric setting, the asymptotic multipoles are not defined. The asymptotic behavior of the Weyl tensor near infinity shows that there is no smooth null infinity.« less

Selective killing of Helicobacter pylori with pH-responsive helix–coil conformation transitionable antimicrobial polypeptides

PubMed Central

Xiong, Menghua; Bao, Yan; Xu, Xin; Wang, Hua; Han, Zhiyuan; Wang, Zhiyu; Liu, Yeqing; Huang, Songyin; Song, Ziyuan; Chen, Jinjing; Peek, Richard M.; Yin, Lichen; Chen, Lin-Feng; Cheng, Jianjun

2017-01-01

Current clinical treatment of Helicobacter pylori infection, the main etiological factor in the development of gastritis, gastric ulcers, and gastric carcinoma, requires a combination of at least two antibiotics and one proton pump inhibitor. However, such triple therapy suffers from progressively decreased therapeutic efficacy due to the drug resistance and undesired killing of the commensal bacteria due to poor selectivity. Here, we report the development of antimicrobial polypeptide-based monotherapy, which can specifically kill H. pylori under acidic pH in the stomach while inducing minimal toxicity to commensal bacteria under physiological pH. Specifically, we designed a class of pH-sensitive, helix–coil conformation transitionable antimicrobial polypeptides (HCT-AMPs) (PGA)m-r-(PHLG-MHH)n, bearing randomly distributed negatively charged glutamic acid and positively charged poly(γ-6-N-(methyldihexylammonium)hexyl-l-glutamate) (PHLG-MHH) residues. The HCT-AMPs showed unappreciable toxicity at physiological pH when they adopted random coiled conformation. Under acidic condition in the stomach, they transformed to the helical structure and exhibited potent antibacterial activity against H. pylori, including clinically isolated drug-resistant strains. After oral gavage, the HCT-AMPs afforded comparable H. pylori killing efficacy to the triple-therapy approach while inducing minimal toxicity against normal tissues and commensal bacteria, in comparison with the remarkable killing of commensal bacteria by 65% and 86% in the ileal contents and feces, respectively, following triple therapy. This strategy renders an effective approach to specifically target and kill H. pylori in the stomach while not harming the commensal bacteria/normal tissues. PMID:29133389

Killing spinors and related symmetries in six dimensions

NASA Astrophysics Data System (ADS)

Batista, Carlos

2016-03-01

Benefiting from the index spinorial formalism, the Killing spinor equation is integrated in six-dimensional spacetimes. The integrability conditions for the existence of a Killing spinor are worked out and the Killing spinors are classified into two algebraic types; in the first type the scalar curvature of the spacetime must be negative, while in the second type the spacetime must be an Einstein manifold. In addition, the equations that define Killing-Yano (KY) and closed conformal Killing-Yano (CCKY) tensors are expressed in the index notation and, as consequence, all nonvanishing KY and CCKY tensors that can be generated from a Killing spinor are made explicit.

Integrability of Spinning Particle Motion in Higher-Dimensional Rotating Black Hole Spacetimes

NASA Astrophysics Data System (ADS)

Kubizňák, David; Cariglia, Marco

2012-02-01

We study the motion of a classical spinning particle (with spin degrees of freedom described by a vector of Grassmann variables) in higher-dimensional general rotating black hole spacetimes with a cosmological constant. In all dimensions n we exhibit n bosonic functionally independent integrals of spinning particle motion, corresponding to explicit and hidden symmetries generated from the principal conformal Killing-Yano tensor. Moreover, we demonstrate that in 4-, 5-, 6-, and 7-dimensional black hole spacetimes such integrals are in involution, proving the bosonic part of the motion integrable. We conjecture that the same conclusion remains valid in all higher dimensions. Our result generalizes the result of Page et al. [Phys. Rev. Lett. 98, 061102 (2007)PRLTAO0031-900710.1103/PhysRevLett.98.061102] on complete integrability of geodesic motion in these spacetimes.

Extrema of mass, first law of black hole mechanics, and a staticity theorem in Einstein-Maxwell-axion-dilaton gravity

NASA Astrophysics Data System (ADS)

Rogatko, Marek

1998-08-01

Using the ADM formulation of the Einstein-Maxwell axion-dilaton gravity we derive the formulas for the variation of mass and other asymptotic conserved quantities in the theory under consideration. Generalizing this kind of reasoning to the initial data for the manifold with an interior boundary we get the generalized first law of black hole mechanics. We consider an asymptotically flat solution to the Einstein-Maxwell axion-dilaton gravity describing a black hole with a Killing vector field timelike at infinity, the horizon of which comprises a bifurcate Killing horizon with a bifurcate surface. Supposing that the Killing vector field is asymptotically orthogonal to the static hypersurface with boundary S and a compact interior, we find that the solution is static in the exterior world, when the timelike vector field is normal to the horizon and has vanishing electric and axion-electric fields on static slices.

Maximal analytic extension and hidden symmetries of the dipole black ring

NASA Astrophysics Data System (ADS)

Armas, Jay

2011-12-01

We construct analytic extensions across the Killing horizons of non-extremal and extremal dipole black rings in Einstein-Maxwell’s theory using different methods. We show that these extensions are non-globally hyperbolic, have multiple asymptotically flat regions and, in the non-extremal case, are also maximal and timelike complete. Moreover, we find that in both cases, the causal structure of the maximally extended spacetime resembles that of the four-dimensional Reissner-Nordström black hole. Furthermore, motivated by the physical interpretation of one of these extensions, we find a separable solution to the Hamilton-Jacobi equation corresponding to zero energy null geodesics and relate it to the existence of a conformal Killing tensor and a conformal Killing-Yano tensor in a specific dimensionally reduced spacetime.

Conserved charges for black holes in Einstein-Gauss-Bonnet gravity coupled to nonlinear electrodynamics in AdS space

NASA Astrophysics Data System (ADS)

Mišković, Olivera; Olea, Rodrigo

2011-01-01

Motivated by possible applications within the framework of anti-de Sitter gravity/conformal field theory correspondence, charged black holes with AdS asymptotics, which are solutions to Einstein-Gauss-Bonnet gravity in D dimensions, and whose electric field is described by nonlinear electrodynamics are studied. For a topological static black hole ansatz, the field equations are exactly solved in terms of the electromagnetic stress tensor for an arbitrary nonlinear electrodynamic Lagrangian in any dimension D and for arbitrary positive values of Gauss-Bonnet coupling. In particular, this procedure reproduces the black hole metric in Born-Infeld and conformally invariant electrodynamics previously found in the literature. Altogether, it extends to D>4 the four-dimensional solution obtained by Soleng in logarithmic electrodynamics, which comes from vacuum polarization effects. Falloff conditions for the electromagnetic field that ensure the finiteness of the electric charge are also discussed. The black hole mass and vacuum energy as conserved quantities associated to an asymptotic timelike Killing vector are computed using a background-independent regularization of the gravitational action based on the addition of counterterms which are a given polynomial in the intrinsic and extrinsic curvatures.

Conserved charges for black holes in Einstein-Gauss-Bonnet gravity coupled to nonlinear electrodynamics in AdS space

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

Miskovic, Olivera; Olea, Rodrigo; Instituto de Fisica, Pontificia Universidad Catolica de Valparaiso, Casilla 4059, Valparaiso

2011-01-15

Motivated by possible applications within the framework of anti-de Sitter gravity/conformal field theory correspondence, charged black holes with AdS asymptotics, which are solutions to Einstein-Gauss-Bonnet gravity in D dimensions, and whose electric field is described by nonlinear electrodynamics are studied. For a topological static black hole ansatz, the field equations are exactly solved in terms of the electromagnetic stress tensor for an arbitrary nonlinear electrodynamic Lagrangian in any dimension D and for arbitrary positive values of Gauss-Bonnet coupling. In particular, this procedure reproduces the black hole metric in Born-Infeld and conformally invariant electrodynamics previously found in the literature. Altogether, itmore » extends to D>4 the four-dimensional solution obtained by Soleng in logarithmic electrodynamics, which comes from vacuum polarization effects. Falloff conditions for the electromagnetic field that ensure the finiteness of the electric charge are also discussed. The black hole mass and vacuum energy as conserved quantities associated to an asymptotic timelike Killing vector are computed using a background-independent regularization of the gravitational action based on the addition of counterterms which are a given polynomial in the intrinsic and extrinsic curvatures.« less

An exact conformal symmetry Ansatz on Kaluza-Klein reduced TMG

NASA Astrophysics Data System (ADS)

Moutsopoulos, George; Ritter, Patricia

2011-11-01

Using a Kaluza-Klein dimensional reduction, and further imposing a conformal Killing symmetry on the reduced metric generated by the dilaton, we show an Ansatz that yields many of the known stationary axisymmetric solutions to TMG.

The 3 + 1 decomposition of conformal Yano-Killing tensors and ‘momentary’ charges for the spin-2 field

NASA Astrophysics Data System (ADS)

Jezierski, Jacek; Migacz, Szymon

2015-02-01

The ‘fully charged’ spin-2 field solution is presented. This is an analog of the Coulomb solution in electrodynamics and represents the ‘non-waving’ part of the spin-2 field theory. Basic facts and definitions of the spin-2 field and conformal Yano-Killing tensors are introduced. Application of those two objects provides a precise definition of quasi-local gravitational charge. Next, the 3 + 1 decomposition leads to the construction of the momentary gravitational charges on the initial surface, which is applicable for Schwarzschild-like spacetimes.

Innovative Techniques for Estimating Illegal Activities in a Human-Wildlife-Management Conflict

PubMed Central

Cross, Paul; St. John, Freya A. V.; Khan, Saira; Petroczi, Andrea

2013-01-01

Effective management of biological resources is contingent upon stakeholder compliance with rules. With respect to disease management, partial compliance can undermine attempts to control diseases within human and wildlife populations. Estimating non-compliance is notoriously problematic as rule-breakers may be disinclined to admit to transgressions. However, reliable estimates of rule-breaking are critical to policy design. The European badger (Meles meles) is considered an important vector in the transmission and maintenance of bovine tuberculosis (bTB) in cattle herds. Land managers in high bTB prevalence areas of the UK can cull badgers under license. However, badgers are also known to be killed illegally. The extent of illegal badger killing is currently unknown. Herein we report on the application of three innovative techniques (Randomized Response Technique (RRT); projective questioning (PQ); brief implicit association test (BIAT)) for investigating illegal badger killing by livestock farmers across Wales. RRT estimated that 10.4% of farmers killed badgers in the 12 months preceding the study. Projective questioning responses and implicit associations relate to farmers' badger killing behavior reported via RRT. Studies evaluating the efficacy of mammal vector culling and vaccination programs should incorporate estimates of non-compliance. Mitigating the conflict concerning badgers as a vector of bTB requires cross-disciplinary scientific research, departure from deep-rooted positions, and the political will to implement evidence-based management. PMID:23341973

Innovative techniques for estimating illegal activities in a human-wildlife-management conflict.

PubMed

Cross, Paul; St John, Freya A V; Khan, Saira; Petroczi, Andrea

2013-01-01

Effective management of biological resources is contingent upon stakeholder compliance with rules. With respect to disease management, partial compliance can undermine attempts to control diseases within human and wildlife populations. Estimating non-compliance is notoriously problematic as rule-breakers may be disinclined to admit to transgressions. However, reliable estimates of rule-breaking are critical to policy design. The European badger (Meles meles) is considered an important vector in the transmission and maintenance of bovine tuberculosis (bTB) in cattle herds. Land managers in high bTB prevalence areas of the UK can cull badgers under license. However, badgers are also known to be killed illegally. The extent of illegal badger killing is currently unknown. Herein we report on the application of three innovative techniques (Randomized Response Technique (RRT); projective questioning (PQ); brief implicit association test (BIAT)) for investigating illegal badger killing by livestock farmers across Wales. RRT estimated that 10.4% of farmers killed badgers in the 12 months preceding the study. Projective questioning responses and implicit associations relate to farmers' badger killing behavior reported via RRT. Studies evaluating the efficacy of mammal vector culling and vaccination programs should incorporate estimates of non-compliance. Mitigating the conflict concerning badgers as a vector of bTB requires cross-disciplinary scientific research, departure from deep-rooted positions, and the political will to implement evidence-based management.

The potential for fungal biopesticides to reduce malaria transmission under diverse environmental conditions.

PubMed

Heinig, R L; Paaijmans, Krijn P; Hancock, Penelope A; Thomas, Matthew B

2015-12-01

The effectiveness of conventional malaria vector control is being threatened by the spread of insecticide resistance. One promising alternative to chemicals is the use of naturally-occurring insect-killing fungi. Numerous laboratory studies have shown that isolates of fungal pathogens such as Beauveria bassiana can infect and kill adult mosquitoes, including those resistant to chemical insecticides.Unlike chemical insecticides, fungi may take up to a week or more to kill mosquitoes following exposure. This slow kill speed can still reduce malaria transmission because the malaria parasite itself takes at least eight days to complete its development within the mosquito. However, both fungal virulence and parasite development rate are strongly temperature-dependent, so it is possible that biopesticide efficacy could vary across different transmission environments.We examined the virulence of a candidate fungal isolate against two key malaria vectors at temperatures from 10-34 °C. Regardless of temperature, the fungus killed more than 90% of exposed mosquitoes within the predicted duration of the malarial extrinsic incubation period, a result that was robust to realistic diurnal temperature variation.We then incorporated temperature sensitivities of a suite of mosquito, parasite and fungus life-history traits that are important determinants of malaria transmission into a stage-structured malaria transmission model. The model predicted that, at achievable daily fungal infection rates, fungal biopesticides have the potential to deliver substantial reductions in the density of malaria-infectious mosquitoes across all temperatures representative of malaria transmission environments. Synthesis and applications . Our study combines empirical data and theoretical modelling to prospectively evaluate the potential of fungal biopesticides to control adult malaria vectors. Our results suggest that Beauveria bassiana could be a potent tool for malaria control and support further development of fungal biopesticides to manage infectious disease vectors.

AGT, N-Burge partitions and {{W}}_N minimal models

NASA Astrophysics Data System (ADS)

Belavin, Vladimir; Foda, Omar; Santachiara, Raoul

2015-10-01

Let {B}_{N,n}^{p,p', H} be a conformal block, with n consecutive channels χ ι , ι = 1, ⋯ n, in the conformal field theory {M}_N^{p,p'× {M}^{H} , where {M}_N^{p,p' } is a {W}_N minimal model, generated by chiral spin-2, ⋯ spin- N currents, and labeled by two co-prime integers p and p', 1 < p < p', while {M}^{H} is a free boson conformal field theory. {B}_{N,n}^{p,p', H} is the expectation value of vertex operators between an initial and a final state. Each vertex operator is labelled by a charge vector that lives in the weight lattice of the Lie algebra A N - 1, spanned by weight vectors {overrightarrow{ω}}_1,\\cdots, {overrightarrow{ω}}_{N-1} . We restrict our attention to conformal blocks with vertex operators whose charge vectors point along {overrightarrow{ω}}_1 . The charge vectors that label the initial and final states can point in any direction.

Integrability of geodesics and action-angle variables in Sasaki-Einstein space T^{1,1}

NASA Astrophysics Data System (ADS)

Visinescu, Mihai

2016-09-01

We briefly describe the construction of Stäkel-Killing and Killing-Yano tensors on toric Sasaki-Einstein manifolds without working out intricate generalized Killing equations. The integrals of geodesic motions are expressed in terms of Killing vectors and Killing-Yano tensors of the homogeneous Sasaki-Einstein space T^{1,1}. We discuss the integrability of geodesics and construct explicitly the action-angle variables. Two pairs of frequencies of the geodesic motions are resonant giving way to chaotic behavior when the system is perturbed.

Infinite-Dimensional Symmetry Algebras as a Help Toward Solutions of the Self-Dual Field Equations with One Killing Vector

NASA Astrophysics Data System (ADS)

Finley, Daniel; McIver, John K.

2002-12-01

The sDiff(2) Toda equation determines all self-dual, vacuum solutions of the Einstein field equations with one rotational Killing vector. Some history of the searches for non-trivial solutions is given, including those that begin with the limit as n → ∞ of the An Toda lattice equations. That approach is applied here to the known prolongation structure for the Toda lattice, hoping to use Bäcklund transformations to generate new solutions. Although this attempt has not yet succeeded, new faithful (tangent-vector) realizations of A∞ are described, and a direct approach via the continuum Lie algebras of Saveliev and Leznov is given.

Inactivated- or killed-virus HIV/AIDS vaccines.

PubMed

Sheppard, Haynes W

2005-06-01

Inactivated or "killed" virus (KV) is a "classical" approach that has produced safe and effective human and veterinary vaccines but has received relatively little attention in the effort to develop an HIV/AIDS vaccine. Initially, KV and rgp120 subunit vaccines were the two most obvious approaches but, unfortunately, rgp120 has not been efficacious and the KV approach has been limited by a variety of scientific, technical, and sociological factors. For example, when responses to cellular antigens, present on SIV grown in human cells, proved to be largely responsible for efficacy, the KV approach was widely discounted. Similarly, when lab-adapted HIV-1 appeared to lose envelope glycoprotein during preparation (not the case for primary isolates), this was viewed as a fundamental barrier to the KV concept. Also, a preference for "safer", genetically-engineered vaccines, and emphasis on cellular immunity, have left KV low on the priority list for funding agencies and investigators. The recent suggestion that "native" trimeric gp120 displays conserved conformational neutralization epitopes, along with the failure of rgp120, and difficulties in raising strong cellular responses with DNA or vectored vaccines, has restored some interest in the KV concept. In the past 15 years, several groups have initiated pre-clinical development of KV candidates for SIV or HIV and promising, albeit limited, information has been produced. In this chapter we discuss the rationale (including pros and cons) for producing and testing killed-HIV vaccines, the prospects for success, the nature and scope of research needed to test the KV concept, what has been learned to date, and what remains undone.

Note on the Noether charge and holographic transports

NASA Astrophysics Data System (ADS)

Fan, Zhong-Ying

2018-03-01

We clarify the relation between the Noether charge associated to an arbitrary vector field and the equations of motion by revisiting Wald formalism. For a timelike Killing vector, aspects of the Noether charge suggest that it is dual to the heat current in the boundary for general holographic theories. For a spacelike Killing vector, we interpret the Noether charge (at the transverse direction) as shear stress of the dual fluid so we can compute the ratio of shear viscosity to entropy density by simply using the infrared data on the black hole event horizon. We test the new method for Einstein gravity and Gauss-Bonnet gravity and find that it produces correct results for both cases even in the presence of additional matter fields.

Proper projective symmetry in LRS Bianchi type V spacetimes

NASA Astrophysics Data System (ADS)

Shabbir, Ghulam; Mahomed, K. S.; Mahomed, F. M.; Moitsheki, R. J.

2018-04-01

In this paper, we investigate proper projective vector fields of locally rotationally symmetric (LRS) Bianchi type V spacetimes using direct integration and algebraic techniques. Despite the non-degeneracy in the Riemann tensor eigenvalues, we classify proper Bianchi type V spacetimes and show that the above spacetimes do not admit proper projective vector fields. Here, in all the cases projective vector fields are Killing vector fields.

Blocking transmission of vector-borne diseases.

PubMed

Schorderet-Weber, Sandra; Noack, Sandra; Selzer, Paul M; Kaminsky, Ronald

2017-04-01

Vector-borne diseases are responsible for significant health problems in humans, as well as in companion and farm animals. Killing the vectors with ectoparasitic drugs before they have the opportunity to pass on their pathogens could be the ideal way to prevent vector borne diseases. Blocking of transmission might work when transmission is delayed during blood meal, as often happens in ticks. The recently described systemic isoxazolines have been shown to successfully prevent disease transmission under conditions of delayed pathogen transfer. However, if the pathogen is transmitted immediately at bite as it is the case with most insects, blocking transmission becomes only possible if ectoparasiticides prevent the vector from landing on or, at least, from biting the host. Chemical entities exhibiting repellent activity in addition to fast killing, like pyrethroids, could prevent pathogen transmission even in cases of immediate transfer. Successful blocking depends on effective action in the context of the extremely diverse life-cycles of vectors and vector-borne pathogens of medical and veterinary importance which are summarized in this review. This complexity leads to important parameters to consider for ectoparasiticide research and when considering the ideal drug profile for preventing disease transmission. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Killing-Yano symmetry of Kaluza-Klein black holes in five dimensions

NASA Astrophysics Data System (ADS)

Houri, Tsuyoshi; Yamamoto, Kei

2013-04-01

Using a generalized Killing-Yano equation in the presence of torsion, spacetime metrics admitting a rank-2 generalized Killing-Yano tensor are investigated in five dimensions under the assumption that its eigenvector associated with the zero eigenvalue is a Killing vector field. It is shown that such metrics are classified into three types and the corresponding local expressions are given explicitly. It is also shown that they cover some classes of charged, rotating Kaluza-Klein black hole solutions of minimal supergravity and Abelian heterotic supergravity.

Conformal Transformations and Conformal Killing Fields

NASA Astrophysics Data System (ADS)

Definition 1.1 A semi-Riemannian manifold is a pair (M,g) consisting of a differentiate (i.e. C∞) manifold M and a differentiable tensor field g which assigns to each point a ∈ M a non-degenerate and symmetric bilinear form on the tangent space TaM: g_a :T_a M × T_a M to R.

Control of Malaria Vector Mosquitoes by Insecticide-Treated Combinations of Window Screens and Eave Baffles.

PubMed

Killeen, Gerry F; Masalu, John P; Chinula, Dingani; Fotakis, Emmanouil A; Kavishe, Deogratius R; Malone, David; Okumu, Fredros

2017-05-01

We assessed window screens and eave baffles (WSEBs), which enable mosquitoes to enter but not exit houses, as an alternative to indoor residual spraying (IRS) for malaria vector control. WSEBs treated with water, the pyrethroid lambda-cyhalothrin, or the organophosphate pirimiphos-methyl, with and without a binding agent for increasing insecticide persistence on netting, were compared with IRS in experimental huts. Compared with IRS containing the same insecticide, WSEBs killed similar proportions of Anopheles funestus mosquitoes that were resistant to pyrethroids, carbamates and organochlorines and greater proportions of pyrethroid-resistant, early exiting An. arabiensis mosquitoes. WSEBs with pirimiphos-methyl killed greater proportions of both vectors than lambda-cyhalothrin or lambda-cyhalothrin plus pirimiphos-methyl and were equally efficacious when combined with binding agent. WSEBs required far less insecticide than IRS, and binding agents might enhance durability. WSEBs might enable affordable deployment of insecticide combinations to mitigate against physiologic insecticide resistance and improve control of behaviorally resistant, early exiting vectors.

Twistor Geometry of Null Foliations in Complex Euclidean Space

NASA Astrophysics Data System (ADS)

Taghavi-Chabert, Arman

2017-01-01

We give a detailed account of the geometric correspondence between a smooth complex projective quadric hypersurface Q^n of dimension n ≥ 3, and its twistor space PT, defined to be the space of all linear subspaces of maximal dimension of Q^n. Viewing complex Euclidean space CE^n as a dense open subset of Q^n, we show how local foliations tangent to certain integrable holomorphic totally null distributions of maximal rank on CE^n can be constructed in terms of complex submanifolds of PT. The construction is illustrated by means of two examples, one involving conformal Killing spinors, the other, conformal Killing-Yano 2-forms. We focus on the odd-dimensional case, and we treat the even-dimensional case only tangentially for comparison.

Conformal Galilei algebras, symmetric polynomials and singular vectors

NASA Astrophysics Data System (ADS)

Křižka, Libor; Somberg, Petr

2018-01-01

We classify and explicitly describe homomorphisms of Verma modules for conformal Galilei algebras cga_ℓ (d,C) with d=1 for any integer value ℓ \\in N. The homomorphisms are uniquely determined by singular vectors as solutions of certain differential operators of flag type and identified with specific polynomials arising as coefficients in the expansion of a parametric family of symmetric polynomials into power sum symmetric polynomials.

Lentiviral vectors in cancer immunotherapy.

PubMed

Oldham, Robyn Aa; Berinstein, Elliot M; Medin, Jeffrey A

2015-01-01

Basic science advances in cancer immunotherapy have resulted in various treatments that have recently shown success in the clinic. Many of these therapies require the insertion of genes into cells to directly kill them or to redirect the host's cells to induce potent immune responses. Other analogous therapies work by modifying effector cells for improved targeting and enhanced killing of tumor cells. Initial studies done using γ-retroviruses were promising, but safety concerns centered on the potential for insertional mutagenesis have highlighted the desire to develop other options for gene delivery. Lentiviral vectors (LVs) have been identified as potentially more effective and safer alternative delivery vehicles. LVs are now in use in clinical trials for many different types of inherited and acquired disorders, including cancer. This review will discuss current knowledge of LVs and the applications of this viral vector-based delivery vehicle to cancer immunotherapy.

The natural dietary genistein boosts bacteriophage-mediated cancer cell killing by improving phage-targeted tumor cell transduction.

PubMed

Tsafa, Effrosyni; Al-Bahrani, Mariam; Bentayebi, Kaoutar; Przystal, Justyna; Suwan, Keittisak; Hajitou, Amin

2016-08-09

Gene therapy has long been regarded as a promising treatment for cancer. However, cancer gene therapy is still facing the challenge of targeting gene delivery vectors specifically to tumors when administered via clinically acceptable non-invasive systemic routes (i.e. intravenous). The bacteria virus, bacteriophage (phage), represents a new generation of promising vectors in systemic gene delivery since their targeting can be achieved through phage capsid display ligands, which enable them to home to specific tumor receptors without the need to ablate any native eukaryotic tropism. We have previously reported a tumor specific bacteriophage vector named adeno-associated virus/phage, or AAVP, in which gene expression is under a recombinant human rAAV2 virus genome targeted to tumors via a ligand-directed phage capsid. However, cancer gene therapy with this tumor-targeted vector achieved variable outcomes ranging from tumor regression to no effect in both experimental and natural preclinical models. Herein, we hypothesized that combining the natural dietary genistein, with proven anticancer activity, would improve bacteriophage anticancer safe therapy. We show that combination treatment with genistein and AAVP increased targeted cancer cell killing by AAVP carrying the gene for Herpes simplex virus thymidine kinase (HSVtk) in 2D tissue cultures and 3D tumor spheroids. We found this increased tumor cell killing was associated with enhanced AAVP-mediated gene expression. Next, we established that genistein protects AAVP against proteasome degradation and enhances vector genome accumulation in the nucleus. Combination of genistein and phage-guided virotherapy is a safe and promising strategy that should be considered in anticancer therapy with AAVP.

LETTER TO THE EDITOR: Anti-self-dual Riemannian metrics without Killing vectors: can they be realized on K3?

NASA Astrophysics Data System (ADS)

Malykh, A. A.; Nutku, Y.; Sheftel, M. B.

2003-11-01

Explicit Riemannian metrics with Euclidean signature and anti-self-dual curvature that do not admit any Killing vectors are presented. The metric and the Riemann curvature scalars are homogeneous functions of degree zero in a single real potential and its derivatives. The solution for the potential is a sum of exponential functions which suggests that for the choice of a suitable domain of coordinates and parameters it can be the metric on a compact manifold. Then, by the theorem of Hitchin, it could be a class of metrics on K3, or on surfaces whose universal covering is K3.

Electron in higher-dimensional weakly charged rotating black hole spacetimes

NASA Astrophysics Data System (ADS)

Cariglia, Marco; Frolov, Valeri P.; Krtouš, Pavel; Kubizňák, David

2013-03-01

We demonstrate separability of the Dirac equation in weakly charged rotating black hole spacetimes in all dimensions. The electromagnetic field of the black hole is described by a test field approximation, with the vector potential proportional to the primary Killing vector field. It is shown that the demonstrated separability can be intrinsically characterized by the existence of a complete set of mutually commuting first-order symmetry operators generated from the principal Killing-Yano tensor. The presented results generalize the results on integrability of charged particle motion and separability of charged scalar field studied in V. P. Frolov and P. Krtous [Phys. Rev. D 83, 024016 (2011)].

A 1-D Simulation Analysis of the Development and Maintenance of the 2001 Red Tide of the Ichthyotoxic Dinoflagellate Karenia brevis on the West Florida Shelf

DTIC Science & Technology

2012-04-26

subsequent fish kills supplied additional organic nutrients for utilization by these opportunistic toxic algae. Both nutrient vectors represented organic non...ichthyotoxic levels, rapid decay of subsequent fish kills supplied additional organic nutrients for utilization by these opportunistic toxic algae. Both...HABSIM model (Fig. 2) a positive feedback of the recycled organic nutrients (DON and DOP) from decaying fish , killed by K. brevis. Note that dissolved

A Projective-to-Conformal Fefferman-Type Construction

NASA Astrophysics Data System (ADS)

Hammerl, Matthias; Sagerschnig, Katja; Šilhan, Josef; Taghavi-Chabert, Arman; Zádník, Vojtĕch

2017-10-01

We study a Fefferman-type construction based on the inclusion of Lie groups SL(n+1) into Spin(n+1,n+1). The construction associates a split-signature (n,n)-conformal spin structure to a projective structure of dimension n. We prove the existence of a canonical pure twistor spinor and a light-like conformal Killing field on the constructed conformal space. We obtain a complete characterisation of the constructed conformal spaces in terms of these solutions to overdetermined equations and an integrability condition on the Weyl curvature. The Fefferman-type construction presented here can be understood as an alternative approach to study a conformal version of classical Patterson-Walker metrics as discussed in recent works by Dunajski-Tod and by the authors. The present work therefore gives a complete exposition of conformal Patterson-Walker metrics from the viewpoint of parabolic geometry.

Static models with conformal symmetry

NASA Astrophysics Data System (ADS)

Manjonjo, A. M.; Maharaj, S. D.; Moopanar, S.

2018-02-01

We study static spherically symmetric spacetimes with a spherical conformal symmetry and a nonstatic conformal factor associated with the conformal Killing field. With these assumptions we find an explicit relationship relating two metric components of the metric tensor field. This leads to the general solution of the Einstein field equations with a conformal symmetry in a static spherically symmetric spacetime. For perfect fluids we can find all metrics explicitly and show that the models always admit a barotropic equation of state. Contained within this class of spacetimes are the well known metrics of (interior) Schwarzschild, Tolman, Kuchowicz, Korkina and Orlyanskii, Patwardhan and Vaidya, and Buchdahl and Land. The isothermal metric of Saslaw et al also admits a conformal symmetry. For imperfect fluids an infinite family of exact solutions to the field equations can be generated.

Vector Galileon and inflationary magnetogenesis

NASA Astrophysics Data System (ADS)

Nandi, Debottam; Shankaranarayanan, S.

2018-01-01

Cosmological inflation provides the initial conditions for the structure formation. However, the origin of large-scale magnetic fields can not be addressed in this framework. The key issue for this long-standing problem is the conformal invariance of the electromagnetic (EM) field in 4-D. While many approaches have been proposed in the literature for breaking conformal invariance of the EM action, here, we provide a completely new way of looking at the modifications to the EM action and generation of primordial magnetic fields during inflation. We explicitly construct a higher derivative EM action that breaks conformal invariance by demanding three conditions—theory be described by vector potential Aμ and its derivatives, Gauge invariance be satisfied, and equations of motion be linear in second derivatives of vector potential. The unique feature of our model is that appreciable magnetic fields are generated at small wavelengths while tiny magnetic fields are generated at large wavelengths that are consistent with current observations.

Separability of massive field equations for spin-0 and spin-1/2 charged particles in the general nonextremal rotating charged black hole spacetimes in minimal five-dimensional gauged supergravity

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

Wu Shuangqing

We continue to investigate the separability of massive field equations for spin-0 and spin-1/2 charged particles in the general, nonextremal, rotating, charged, Chong-Cvetic-Lue-Pope black holes with two independent angular momenta and a nonzero cosmological constant in minimal D=5 gauged supergravity theory. We show that the complex Klein-Gordon equation and the modified Dirac equation with the inclusion of an extra counterterm can be separated by variables into purely radial and purely angular parts in this general Einstein-Maxwell-Chern-Simons background spacetime. A second-order symmetry operator that commutes with the complex Laplacian operator is constructed from the separated solutions and expressed compactly in termsmore » of a rank-2 Staeckel-Killing tensor which admits a simple diagonal form in the chosen pentad one-forms so that it can be understood as the square of a rank-3 totally antisymmetric tensor. A first-order symmetry operator that commutes with the modified Dirac operator is expressed in terms of a rank-3 generalized Killing-Yano tensor and its covariant derivative. The Hodge dual of this generalized Killing-Yano tensor is a generalized principal conformal Killing-Yano tensor of rank-2, which can generate a 'tower' of generalized (conformal) Killing-Yano and Staeckel-Killing tensors that are responsible for the whole hidden symmetries of this general, rotating, charged, Kerr-anti-de Sitter black hole geometry. In addition, the first laws of black hole thermodynamics have been generalized to the case that the cosmological constant can be viewed as a thermodynamical variable.« less

The natural dietary genistein boosts bacteriophage-mediated cancer cell killing by improving phage-targeted tumor cell transduction

PubMed Central

Tsafa, Effrosyni; Al-Bahrani, Mariam; Bentayebi, Kaoutar; Przystal, Justyna; Suwan, Keittisak; Hajitou, Amin

2016-01-01

Gene therapy has long been regarded as a promising treatment for cancer. However, cancer gene therapy is still facing the challenge of targeting gene delivery vectors specifically to tumors when administered via clinically acceptable non-invasive systemic routes (i.e. intravenous). The bacteria virus, bacteriophage (phage), represents a new generation of promising vectors in systemic gene delivery since their targeting can be achieved through phage capsid display ligands, which enable them to home to specific tumor receptors without the need to ablate any native eukaryotic tropism. We have previously reported a tumor specific bacteriophage vector named adeno-associated virus/phage, or AAVP, in which gene expression is under a recombinant human rAAV2 virus genome targeted to tumors via a ligand-directed phage capsid. However, cancer gene therapy with this tumor-targeted vector achieved variable outcomes ranging from tumor regression to no effect in both experimental and natural preclinical models. Herein, we hypothesized that combining the natural dietary genistein, with proven anticancer activity, would improve bacteriophage anticancer safe therapy. We show that combination treatment with genistein and AAVP increased targeted cancer cell killing by AAVP carrying the gene for Herpes simplex virus thymidine kinase (HSVtk) in 2D tissue cultures and 3D tumor spheroids. We found this increased tumor cell killing was associated with enhanced AAVP-mediated gene expression. Next, we established that genistein protects AAVP against proteasome degradation and enhances vector genome accumulation in the nucleus. Combination of genistein and phage-guided virotherapy is a safe and promising strategy that should be considered in anticancer therapy with AAVP. PMID:27437775

In vivo marking of spontaneous or vaccine-induced fibrosarcomas in the domestic house cat, using an adenoviral vector containing a bifunctional fusion protein, GAL-TEK.

PubMed

Marini, F C; Cannon, J P; Belmont, J W; Shillitoe, E J; Lapeyre, J N

1995-09-01

We evaluated the ability of a replication-deficient, recombinant adenoviral vector to transfer the bifunctional gene GAL-TEK, which expresses a marking/therapeutic gene product, to naturally occurring cat fibrosarcomas in situ. GAL-TEK contains an in-frame fusion of the bacterial LacZ gene for histochemical marking of tumors with beta-galactosidase (beta-Gal) and the HSV tk gene for enzyme-prodrug activation of the prodrug ganciclovir (GCV) to induce selective tumor cell killing. GAL-TEK bifunctional marking and cell killing activities were tested in vitro after adenoviral vector infection of HT1080 human fibrosarcoma cells. The tk activity of GAL-TEK is shown to be almost as potent as HSV tk to catalyze conversion of GCV to GCV nucleotides and promote selective cell killing. Using 8 cats with recurring 2.5-cm2 fibrosarcomas that either arose spontaneously or were induced by vaccine, we determined experimentally the administration routes and times required for optimum GAL-TEK gene transfer by beta-Gal histological staining and reverse transcriptase polymerase chain reaction to the multiple compartments of the growing fibrosarcomas consonant with minimizing collateral infection of neighboring tissues and other unwanted side effects.

Vectors, viscin, and Viscaceae: mistletoes as parasites, mutualists, and resources.

Treesearch

Juliann E. Aukema

2003-01-01

Mistletoes are aerial, hemiparasitic plants found on trees throughout the world. They have unique ecological arrangements with the host plants they parasitize and the birds that disperse their seeds. Similar in many respects to vector-borne macroparasites, mistletoes are often detrimental to their hosts, and can even kill them. Coevolution has led to resistance...

Oral, Slow-Release Ivermectin: Biting Back at Malaria Vectors.

PubMed

Chaccour, Carlos J; Rabinovich, N Regina

2017-03-01

Bellinger and colleagues offer an elegant twist for a promising new tool against malaria. This formulation is designed to release ivermectin, a mosquito-killing drug for 10 days after a single oral dose. This could reduce the vector population and serve as a complementary tool for malaria elimination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is California bay laurel a suitable host for the non-native redbay ambrosia beetle, vector of laurel wilt disease?

USDA-ARS?s Scientific Manuscript database

Laurel wilt is a deadly vascular disease of trees in the Lauraceae that kills healthy redbay (Persea borbonia), sassafras (Sassafras albidum), and other related hosts. The fungal pathogen (Raffaelea lauricola) and it vector, the redbay ambrosia beetle (Xyleborus glabratus) are native to Asia and ha...

Intertwined Hamiltonians in two-dimensional curved spaces

NASA Astrophysics Data System (ADS)

Aghababaei Samani, Keivan; Zarei, Mina

2005-04-01

The problem of intertwined Hamiltonians in two-dimensional curved spaces is investigated. Explicit results are obtained for Euclidean plane, Minkowski plane, Poincaré half plane (AdS2), de Sitter plane (dS2), sphere, and torus. It is shown that the intertwining operator is related to the Killing vector fields and the isometry group of corresponding space. It is shown that the intertwined potentials are closely connected to the integral curves of the Killing vector fields. Two problems are considered as applications of the formalism presented in the paper. The first one is the problem of Hamiltonians with equispaced energy levels and the second one is the problem of Hamiltonians whose spectrum is like the spectrum of a free particle.

Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery

PubMed Central

Chauchet, Xavier; Hannani, Dalil; Djebali, Sophia; Laurin, David; Polack, Benoit; Marvel, Jacqueline; Buffat, Laurent; Toussaint, Bertrand; Le Gouëllec, Audrey

2016-01-01

Live-attenuated bacterial vectors for antigens delivery have aroused growing interest in the field of cancer immunotherapy. Their potency to stimulate innate immunity and to promote intracellular antigen delivery into antigen-presenting cells could be exploited to elicit a strong and specific cellular immune response against tumor cells. We previously described genetically-modified and attenuated Pseudomonas aeruginosa vectors able to deliver in vivo protein antigens into antigen-presenting cells, through Type 3 secretion system of the bacteria. Using this approach, we managed to protect immunized mice against aggressive B16 melanoma development in both a prophylactic and therapeutic setting. In this study, we further investigated the antigen-specific CD8+ T cell response, in terms of phenotypic and functional aspects, obtained after immunizations with a killed but metabolically active P. aeruginosa attenuated vector. We demonstrated that P. aeruginosa vaccine induces a highly functional pool of antigen-specific CD8+ T cell able to infiltrate the tumor. Furthermore, multiple immunizations allowed the development of a long-lasting immune response, represented by a pool of predominantly effector memory cells which protected mice against late tumor challenge. Overall, killed but metabolically active P. aeruginosa vector is a safe and promising approach for active and specific antitumor immunotherapy. PMID:28035332

Universal properties from a local geometric structure of a Killing horizon

NASA Astrophysics Data System (ADS)

Koga, Jun-ichirou

2007-06-01

We consider universal properties that arise from a local geometric structure of a Killing horizon, and analyse whether such universal properties give rise to degeneracy of classical configurations. We first introduce a non-perturbative definition of such a local geometric structure, which we call an asymptotic Killing horizon. It is then shown that infinitely many asymptotic Killing horizons reside on a common null hypersurface, once there exists one asymptotic Killing horizon, which is thus considered as degeneracy. In order to see how this degeneracy is physically meaningful, we analyse also the acceleration of the orbits of the vector that generates an asymptotic Killing horizon. It is shown that there exists the diff(S1) or diff(R1) sub-algebra on an asymptotic Killing horizon universally, which is picked out naturally, based on the behaviour of the acceleration. We argue that the discrepancy between string theory and the Euclidean approach in the entropy of an extreme black hole may be resolved, if the microscopic states responsible for black hole thermodynamics are connected with asymptotic Killing horizons.

Different Vaccine Vectors Delivering the Same Antigen Elicit CD8plus T Cell Responses with Distinct Clonotype and Epitope Specificity

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

M Honda; R Wang; W Kong

Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8{sup +} cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8{sup +} T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2D{sup d} better than the native sequences, and clones with distinct specificities were elicited by alternativemore » vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8{sup +} T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination.« less

Different Vaccine Vectors Delivering the Same Antigen Elicit CD8+ T Cell Responses with Distinct Clonotype and Epitope Specificity

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

Honda, M.; Robinson, H.; Wang, R.

Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8{sup +} cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8{sup +} T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2D{sup d} better than the native sequences, and clones with distinct specificities were elicited by alternativemore » vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8{sup +} T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination.« less

Curved manifolds with conserved Runge-Lenz vectors

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

Ngome, J.-P.

2009-12-15

van Holten's algorithm is used to construct Runge-Lenz-type conserved quantities, induced by Killing tensors, on curved manifolds. For the generalized Taub-Newman-Unti-Tamburino metric, the most general external potential such that the combined system admits a conserved Runge-Lenz-type vector is found. In the multicenter case, the subclass of two-center metric exhibits a conserved Runge-Lenz-type scalar.

Curved manifolds with conserved Runge-Lenz vectors

NASA Astrophysics Data System (ADS)

Ngome, J.-P.

2009-12-01

van Holten's algorithm is used to construct Runge-Lenz-type conserved quantities, induced by Killing tensors, on curved manifolds. For the generalized Taub-Newman-Unti-Tamburino metric, the most general external potential such that the combined system admits a conserved Runge-Lenz-type vector is found. In the multicenter case, the subclass of two-center metric exhibits a conserved Runge-Lenz-type scalar.

Simplified Models of Vector Control Impact upon Malaria Transmission by Zoophagic Mosquitoes

PubMed Central

Kiware, Samson S.; Chitnis, Nakul; Moore, Sarah J.; Devine, Gregor J.; Majambere, Silas; Merrill, Stephen; Killeen, Gerry F.

2012-01-01

Background High coverage of personal protection measures that kill mosquitoes dramatically reduce malaria transmission where vector populations depend upon human blood. However, most primary malaria vectors outside of sub-Saharan Africa can be classified as “very zoophagic,” meaning they feed occasionally (<10% of blood meals) upon humans, so personal protection interventions have negligible impact upon their survival. Methods and Findings We extended a published malaria transmission model to examine the relationship between transmission, control, and the baseline proportion of bloodmeals obtained from humans (human blood index). The lower limit of the human blood index enables derivation of simplified models for zoophagic vectors that (1) Rely on only three field-measurable parameters. (2) Predict immediate and delayed (with and without assuming reduced human infectivity, respectively) impacts of personal protection measures upon transmission. (3) Illustrate how appreciable indirect communal-level protection for non-users can be accrued through direct personal protection of users. (4) Suggest the coverage and efficacy thresholds required to attain epidemiological impact. The findings suggest that immediate, indirect, community-wide protection of users and non-users alike may linearly relate to the efficacy of a user’s direct personal protection, regardless of whether that is achieved by killing or repelling mosquitoes. High protective coverage and efficacy (≥80%) are important to achieve epidemiologically meaningful impact. Non-users are indirectly protected because the two most common species of human malaria are strict anthroponoses. Therefore, the small proportion of mosquitoes that are killed or diverted while attacking humans can represent a large proportion of those actually transmitting malaria. Conclusions Simplified models of malaria transmission by very zoophagic vectors may be used by control practitioners to predict intervention impact interventions using three field-measurable parameters; the proportion of human exposure to mosquitoes occurring when an intervention can be practically used, its protective efficacy when used, and the proportion of people using it. PMID:22701527

Chapter 11 - Progression of Laurel Wilt Disease in Georgia: 2009–11 (Project SC-EM-08-02)

Treesearch

R. Scott Cameron; Chip Bates; James Johnson

2014-01-01

Laurel wilt disease (LWD) is caused by the fungus Raffaelea lauricola and vectored by the redbay ambrosia beetle (RAB), Xyleborus glabratus (Fraedrich and others 2008). The pathogen and vector were apparently introduced from Asia through the Port of Savannah, and the disease has spread rapidly throughout the lower coastal plains forests in Georgia, killing nearly all...

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination

PubMed Central

Brady, Oliver J.; Godfray, H. Charles J.; Tatem, Andrew J.; Gething, Peter W.; Cohen, Justin M.; McKenzie, F. Ellis; Perkins, T. Alex; Reiner, Robert C.; Tusting, Lucy S.; Sinka, Marianne E.; Moyes, Catherine L.; Eckhoff, Philip A.; Scott, Thomas W.; Lindsay, Steven W.; Hay, Simon I.; Smith, David L.

2016-01-01

Background Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria. Methods and Results Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention. Conclusions Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions. PMID:26822603

The Maxwell and Navier-Stokes equations that follow from Einstein equation in a spacetime containing a Killing vector field

NASA Astrophysics Data System (ADS)

Rodrigues, Fabio Grangeiro; Rodrigues, Waldyr Alves, Jr.; da Rocha, Roldão

2012-10-01

In this paper we are concerned to reveal that any spacetime structure , which is a model of a gravitational field in General Relativity generated by an energy-momentum tensor T - and which contains at least one nontrivial Killing vector field A - is such that the 2-form field F = dA (where A = g(A,)) satisfies a Maxwell like equation - with a well determined current that contains a term of the superconducting type- which follows directly from Einstein equation. Moreover, we show that the resulting Maxwell like equations, under an additional condition imposed to the Killing vector field, may be written as a Navier-Stokes like equation as well. As a result, we have a set consisting of Einstein, Maxwell and Navier-Stokes equations, that follows sequentially from the first one under precise mathematical conditions and once some identifications about field variables are evinced, as explained in details throughout the text. We compare and emulate our results with others on the same subject appearing in the literature. In Appendix A we fix our notation and recall some necessary material concerning the theory of differential forms, Lie derivatives and the Clifford bundle formalism used in this paper. Moreover, we comment in Appendix B on some analogies (and main differences) between our results to the ones obtained long ago by Bergmann and Kommar which are reviewed and briefly criticized.

Predicting the impact of insecticide-treated bed nets on malaria transmission: the devil is in the detail.

PubMed

Gu, Weidong; Novak, Robert J

2009-11-16

Insecticide-treated bed nets (ITNs), including long-lasting insecticidal nets (LLINs), play a primary role in global campaigns to roll back malaria in tropical Africa. Effectiveness of treated nets depends on direct impacts on individual mosquitoes including killing and excite-repellency, which vary considerably among vector species due to variations in host-seeking behaviours. While monitoring and evaluation programmes of ITNs have focuses on morbidity and all-cause mortality in humans, local entomological context receives little attention. Without knowing the dynamics of local vector species and their responses to treated nets, it is difficult to predict clinical outcomes when ITN applications are scaled up across African continent. Sound model frameworks incorporating intricate interactions between mosquitoes and treated nets are needed to develop the predictive capacity for scale-up applications of ITNs. An established agent-based model was extended to incorporate the direct outcomes, e.g. killing and avoidance, of individual mosquitoes exposing to ITNs in a hypothetical village setting with 50 houses and 90 aquatic habitats. Individual mosquitoes were tracked throughout the life cycle across the landscape. Four levels of coverage, i.e. 40, 60, 80 and 100%, were applied at the household level with treated houses having only one bed net. By using Latin hypercube sampling scheme, parameters governing killing, diverting and personal protection of net users were evaluated for their relative roles in containing mosquito populations, entomological inoculation rates (EIRs) and malaria incidence. There were substantial gaps in coverage between households and individual persons, and 100% household coverage resulted in circa 50% coverage of the population. The results show that applications of ITNs could give rise to varying impacts on population-level metrics depending on values of parameters governing interactions of mosquitoes and treated nets at the individual level. The most significant factor in determining effectiveness was killing capability of treated nets. Strong excito-repellent effect of impregnated nets might lead to higher risk exposure to non-bed net users. With variabilities of vector mosquitoes in host-seeking behaviours and the responses to treated nets, it is anticipated that scale-up applications of INTs might produce varying degrees of success dependent on local entomological and epidemiological contexts. This study highlights that increased ITN coverage led to significant reduction in risk exposure and malaria incidence only when treated nets yielded high killing effects. It is necessary to test efficacy of treated nets on local dominant vector mosquitoes, at least in laboratory, for monitoring and evaluation of ITN programmes.

Spacetime symmetries and Kepler's third law

NASA Astrophysics Data System (ADS)

Le Tiec, Alexandre

2012-11-01

The curved spacetime geometry of a system of two point masses moving on a circular orbit has a helical symmetry. We show how Kepler’s third law for circular motion, and its generalization in post-Newtonian theory, can be recovered from a simple, covariant condition on the norm of the associated helical Killing vector field. This unusual derivation can be used to illustrate some concepts of prime importance in a general relativity course, including those of Killing field, covariance, coordinate dependence and gravitational redshift.

Anomaly-corrected supersymmetry algebra and supersymmetric holographic renormalization

NASA Astrophysics Data System (ADS)

An, Ok Song

2017-12-01

We present a systematic approach to supersymmetric holographic renormalization for a generic 5D N=2 gauged supergravity theory with matter multiplets, including its fermionic sector, with all gauge fields consistently set to zero. We determine the complete set of supersymmetric local boundary counterterms, including the finite counterterms that parameterize the choice of supersymmetric renormalization scheme. This allows us to derive holographically the superconformal Ward identities of a 4D superconformal field theory on a generic background, including the Weyl and super-Weyl anomalies. Moreover, we show that these anomalies satisfy the Wess-Zumino consistency condition. The super-Weyl anomaly implies that the fermionic operators of the dual field theory, such as the supercurrent, do not transform as tensors under rigid supersymmetry on backgrounds that admit a conformal Killing spinor, and their anticommutator with the conserved supercharge contains anomalous terms. This property is explicitly checked for a toy model. Finally, using the anomalous transformation of the supercurrent, we obtain the anomaly-corrected supersymmetry algebra on curved backgrounds admitting a conformal Killing spinor.

The value of muscular and skeletal scores in the live animal and carcass classification scores as indicators of carcass composition in cattle.

PubMed

Drennan, M J; McGee, M; Keane, M G

2008-05-01

The objective was to determine the relationship of muscular and skeletal scores taken on the live animal and carcass conformation and fat scores with carcass composition and value. Bulls (n = 48) and heifers (n = 37) of 0.75 to 1.0 late-maturing breed genotypes slaughtered at 16 and 20 months of age, respectively, were used. At 8 months of age (weaning) and immediately pre-slaughter, visual muscular scores were recorded for each animal and additionally skeletal scores were recorded pre-slaughter. Carcass weight, kidney and channel fat weight, carcass conformation and fat scores, fat depth over the longissimus dorsi muscle at the 12th (bulls) or 10th (heifers) rib and carcass length were recorded post-slaughter. Each carcass was subsequently dissected into meat, fat and bone using a commercial dissection procedure. Muscular scores taken pre-slaughter showed positive correlations with killing-out rate (r ≈ 0.65), carcass meat proportion (r ≈ 0.60), value (r ≈ 0.55) and conformation score (r ≈ 0.70), and negative correlations with carcass bone (r ≈ -0.60) and fat (r ≈ -0.4) proportions. Corresponding correlations with muscular scores at weaning were lower. Correlations of skeletal scores taken pre-slaughter, carcass length and carcass weight with killing-out rate and the various carcass traits were mainly not significant. Carcass fat depth and kidney and channel fat weight were negatively correlated with carcass meat proportion and value, and positively correlated with fat proportion. Correlations of carcass conformation score were positive (r = 0.50 to 0.68) with killing-out rate, carcass meat proportion and carcass value and negative with bone (r ≈ -0.56) and fat (r ≈ -0.40) proportions. Corresponding correlations with carcass fat score were mainly negative except for carcass fat proportion (r ≈ 0.79). A one-unit (scale 1 to 15) increase in carcass conformation score increased carcass meat proportion by 8.9 and 8.1 g/kg, decreased fat proportion by 4.0 and 2.9 g/kg and decreased bone proportion by 4.9 and 5.2 g/kg in bulls and heifers, respectively. Corresponding values per unit increase in carcass fat score were -11.9 and -9.7 g/kg, 12.4 and 9.9 g/kg, and -0.5 and -0.2 g/kg. Carcass conformation and fat scores explained 0.70 and 0.55 of the total variation in meat yield for bulls and heifers, respectively. It is concluded that live animal muscular scores, and carcass conformation and fat scores, are useful indicators of carcass meat proportion and value.

Vector and axial-vector decomposition of Einstein's gravitational action

NASA Astrophysics Data System (ADS)

Soh, Kwang S.

1991-08-01

Vector and axial-vector gravitational fields are introduced to express the Einstein action in the manner of electromagnetism. Their conformal scaling properties are examined, and the resemblance between the general coordinate and electromagnetic gauge transformation is elucidated. The chiral formulation of the gravitational action is constructed. I am deeply grateful to Professor S. Hawking, and Professor G. Lloyd for warm hospitality at DAMTP, and Darwin College, University of Cambridge, respectively. I also appreciate much help received from Dr. Q.-H. Park.

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination.

PubMed

Brady, Oliver J; Godfray, H Charles J; Tatem, Andrew J; Gething, Peter W; Cohen, Justin M; McKenzie, F Ellis; Perkins, T Alex; Reiner, Robert C; Tusting, Lucy S; Sinka, Marianne E; Moyes, Catherine L; Eckhoff, Philip A; Scott, Thomas W; Lindsay, Steven W; Hay, Simon I; Smith, David L

2016-02-01

Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria. Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention. Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Increasing the Efficacy of Oncolytic Adenovirus Vectors

PubMed Central

Toth, Karoly; Wold, William S. M.

2010-01-01

Oncolytic adenovirus (Ad) vectors present a new modality to treat cancer. These vectors attack tumors via replicating in and killing cancer cells. Upon completion of the vector replication cycle, the infected tumor cell lyses and releases progeny virions that are capable of infecting neighboring tumor cells. Repeated cycles of vector replication and cell lysis can destroy the tumor. Numerous Ad vectors have been generated and tested, some of them reaching human clinical trials. In 2005, the first oncolytic Ad was approved for the treatment of head-and-neck cancer by the Chinese FDA. Oncolytic Ads have been proven to be safe, with no serious adverse effects reported even when high doses of the vector were injected intravenously. The vectors demonstrated modest anti-tumor effect when applied as a single agent; their efficacy improved when they were combined with another modality. The efficacy of oncolytic Ads can be improved using various approaches, including vector design, delivery techniques, and ancillary treatment, which will be discussed in this review. PMID:21994711

Using a new odour-baited device to explore options for luring and killing outdoor-biting malaria vectors: a report on design and field evaluation of the Mosquito Landing Box

PubMed Central

2013-01-01

Background Mosquitoes that bite people outdoors can sustain malaria transmission even where effective indoor interventions such as bednets or indoor residual spraying are already widely used. Outdoor tools may therefore complement current indoor measures and improve control. We developed and evaluated a prototype mosquito control device, the ‘Mosquito Landing Box’ (MLB), which is baited with human odours and treated with mosquitocidal agents. The findings are used to explore technical options and challenges relevant to luring and killing outdoor-biting malaria vectors in endemic settings. Methods Field experiments were conducted in Tanzania to assess if wild host-seeking mosquitoes 1) visited the MLBs, 2) stayed long or left shortly after arrival at the device, 3) visited the devices at times when humans were also outdoors, and 4) could be killed by contaminants applied on the devices. Odours suctioned from volunteer-occupied tents were also evaluated as a potential low-cost bait, by comparing baited and unbaited MLBs. Results There were significantly more Anopheles arabiensis, An. funestus, Culex and Mansonia mosquitoes visiting baited MLB than unbaited controls (P≤0.028). Increasing sampling frequency from every 120 min to 60 and 30 min led to an increase in vector catches of up to 3.6 fold (P≤0.002), indicating that many mosquitoes visited the device but left shortly afterwards. Outdoor host-seeking activity of malaria vectors peaked between 7:30 and 10:30pm, and between 4:30 and 6:00am, matching durations when locals were also outdoors. Maximum mortality of mosquitoes visiting MLBs sprayed or painted with formulations of candidate mosquitocidal agent (pirimiphos-methyl) was 51%. Odours from volunteer occupied tents attracted significantly more mosquitoes to MLBs than controls (P<0.001). Conclusion While odour-baited devices such as the MLBs clearly have potential against outdoor-biting mosquitoes in communities where LLINs are used, candidate contaminants must be those that are effective at ultra-low doses even after short contact periods, since important vector species such as An. arabiensis make only brief visits to such devices. Natural human odours suctioned from occupied dwellings could constitute affordable sources of attractants to supplement odour baits for the devices. The killing agents used should be environmentally safe, long lasting, and have different modes of action (other than pyrethroids as used on LLINs), to curb the risk of physiological insecticide resistance. PMID:23642306

Rigidly rotating zero-angular-momentum observer surfaces in the Kerr spacetime

NASA Astrophysics Data System (ADS)

Frolov, Andrei V.; Frolov, Valeri P.

2014-12-01

A stationary observer in the Kerr spacetime has zero angular momentum if their angular velocity ω has a particular value, which depends on the position of the observer. Worldlines of such zero-angular-momentum observers (ZAMOs) with the same value of the angular velocity ω form a three-dimensional surface, which has the property that the Killing vectors generating time translation and rotation are tangent to it. We call such a surface a rigidly rotating ZAMO surface. This definition allows for a natural generalization to the surfaces inside the black hole, where ZAMO trajectories formally become spacelike. A general property of such a surface is that there exist linear combinations of the Killing vectors with constant coefficients which make them orthogonal on it. In this paper we discuss properties of the rigidly rotating ZAMO surfaces both outside and inside the black hole and the relevance of these objects to a couple of interesting physical problems.

FRW and domain walls in higher spin gravity

NASA Astrophysics Data System (ADS)

Aros, R.; Iazeolla, C.; Noreña, J.; Sezgin, E.; Sundell, P.; Yin, Y.

2018-03-01

We present exact solutions to Vasiliev's bosonic higher spin gravity equations in four dimensions with positive and negative cosmological constant that admit an interpretation in terms of domain walls, quasi-instantons and Friedman-Robertson-Walker (FRW) backgrounds. Their isometry algebras are infinite dimensional higher-spin extensions of spacetime isometries generated by six Killing vectors. The solutions presented are obtained by using a method of holomorphic factorization in noncommutative twistor space and gauge functions. In interpreting the solutions in terms of Fronsdal-type fields in space-time, a field-dependent higher spin transformation is required, which is implemented at leading order. To this order, the scalar field solves Klein-Gordon equation with conformal mass in ( A) dS 4 . We interpret the FRW solution with de Sitter asymptotics in the context of inflationary cosmology and we expect that the domain wall and FRW solutions are associated with spontaneously broken scaling symmetries in their holographic description. We observe that the factorization method provides a convenient framework for setting up a perturbation theory around the exact solutions, and we propose that the nonlinear completion of particle excitations over FRW and domain wall solutions requires black hole-like states.

Particle definitions and the information loss paradox

NASA Astrophysics Data System (ADS)

Venditti, Alex

An investigation of information loss in black hole spacetimes is performed. We demonstrate that the definition of particles as energy levels of the Harmonic oscillator will not have physical significance in general and is thus not a good instrument to study the radiation of black holes. This is due to the ambiguity of the choice of coordinates on the phase space of the quantum field. We demonstrate how to identify quantum states in the functional Schrodinger picture. We demonstrate that information is truly lost in the case of a Vaidya black hole (a black hole formed from null dust) if we neglect back reaction. This is done by quantizing the constrained classical system of a Klein-Gordon field in a Vaidya background. The interaction picture of quantum mechanics can be applied to this system. We find a physically well motivated vacuum state for a spherically symmetric spacetime with an extra conformal Killing vector. We also demonstrate how to calculate the response of a particle detector in the a LeMaitre-Tolman-Bondi spacetime with a selfsimilarity. Finally, some of the claims and confusion surrounding Unruh radiation, Hawking radiation and the equivalence principle are investigated and shown to be false.

Thermodynamic integration of the free energy along a reaction coordinate in Cartesian coordinates

NASA Astrophysics Data System (ADS)

den Otter, W. K.

2000-05-01

A generalized formulation of the thermodynamic integration (TI) method for calculating the free energy along a reaction coordinate is derived. Molecular dynamics simulations with a constrained reaction coordinate are used to sample conformations. These are then projected onto conformations with a higher value of the reaction coordinate by means of a vector field. The accompanying change in potential energy plus the divergence of the vector field constitute the derivative of the free energy. Any vector field meeting some simple requirements can be used as the basis of this TI expression. Two classes of vector fields are of particular interest here. The first recovers the conventional TI expression, with its cumbersome dependence on a full set of generalized coordinates. As the free energy is a function of the reaction coordinate only, it should in principle be possible to derive an expression depending exclusively on the definition of the reaction coordinate. This objective is met by the second class of vector fields to be discussed. The potential of mean constraint force (PMCF) method, after averaging over the unconstrained momenta, falls in this second class. The new method is illustrated by calculations on the isomerization of n-butane, and is compared with existing methods.

Conformal supergravity in five dimensions: new approach and applications

NASA Astrophysics Data System (ADS)

Butter, Daniel; Kuzenko, Sergei M.; Novak, Joseph; Tartaglino-Mazzucchelli, Gabriele

2015-02-01

We develop a new off-shell formulation for five-dimensional (5D) conformal supergravity obtained by gauging the 5D superconformal algebra in superspace. An important property of the conformal superspace introduced is that it reduces to the super-conformal tensor calculus (formulated in the early 2000's) upon gauging away a number of superfluous fields. On the other hand, a different gauge fixing reduces our formulation to the SU(2) superspace of arXiv:0802.3953, which is suitable to describe the most general off-shell supergravity-matter couplings. Using the conformal superspace approach, we show how to reproduce practically all off-shell constructions derived so far, including he supersymmetric extensions of R 2 terms, thus demonstrating the power of our formulation. Furthermore, we construct for the first time a supersymmetric completion of the Ricci tensor squared term using the standard Weyl multiplet coupled to an off-shell vector multiplet. In addition, we present several procedures to generate higher-order off-shell invariants in supergravity, including higher-derivative ones. The covariant projective multiplets proposed in arXiv:0802.3953 are lifted to conformal superspace, and a manifestly superconformal action principle is given. We also introduce unconstrained prepotentials for the vector multiplet, the multiplet (i.e., the linear multiplet without central charge) and multiplets, with n = 0 , 1 , . . . Superform formulations are given for the BF action and the non-abelian Chern-Simons action. Finally, we describe locally supersymmetric theories with gauged central charge in conformal superspace.

Evaluating the Vector Control Potential of the In2Care® Mosquito Trap Against Aedes aegypti and Aedes albopictus Under Semifield Conditions in Manatee County, Florida.

PubMed

Buckner, Eva A; Williams, Katie F; Marsicano, Ambyr L; Latham, Mark D; Lesser, Christopher R

2017-09-01

Successful integrated vector management programs may need new strategies in addition to conventional larviciding and adulticiding strategies to target Aedes aegypti and Ae. albopictus, which can develop in small, often cryptic, artificial and natural containers. The In2Care® mosquito trap was recently developed to target and kill larval and adult stages of these invasive container-inhabiting Aedes mosquitoes by utilizing autodissemination. Gravid females that visit the trap pick up pyriproxyfen (PPF) that they later transfer to nearby larval habitats as well as Beauveria bassiana spores that slowly kill them. We assessed the efficacy of the In2Care mosquito trap in a semifield setting against locally sourced strains of Ae. aegypti and Ae. albopictus. We found that the In2Care mosquito trap is attractive to gravid Ae. aegypti and Ae. albopictus females and serves as an egg sink, preventing any adult emergence from the trap (P = 0.0053 for both species). Adult females successfully autodisseminated PPF to surrounding water-filled containers, leading to a statistically significant reduction in new mosquito emergence (P ≤ 0.0002 for both species). Additionally, we found effective contamination with Beauveria bassiana spores, which significantly reduced the survivorship of exposed Ae. aegypti and Ae. albopictus (P ≤ 0.008 for both species in all experimental setups). In summary, the In2Care mosquito trap successfully killed multiple life stages of 2 main mosquito vector species found in Florida under semifield conditions.

How to Kill Creativity--Ten Easy Steps

ERIC Educational Resources Information Center

Moore, E. M

2007-01-01

A cursory review of academic headlines would suggest that educational institutions can be perceived as formalized, regimented and systematic--intellectual factories that reward those staff and students who conform best to rigid systems which ensure the efficient processing of quantity. Is this the reality? Do prevailing economic and bureaucratic…

A lentiviral vector that activates latent human immunodeficiency virus-1 proviruses by the overexpression of tat and that kills the infected cells.

PubMed

Macías, David; Oya, Ricardo; Saniger, Luisa; Martín, Francisco; Luque, Francisco

2009-11-01

Despite the efficient HIV-1 replication blockage achieved with current highly active antiretroviral therapy (HAART) therapies, HIV-1 persists in the body and survives in a latent state that can last for the entire life of the patient. A long-lived reservoir of latently infected CD4(+) memory T cells represents the most important sanctuary for the virus and the greatest obstacle for viral eradication. In this work, we present an initial step toward a gene therapy approach aimed at the activation of latent provirus to induce the death of latently infected T cells. Latent HIV-1 infection is characterized by the failure of viral gene expression as a consequence of uninitiated or aborted transcription. We have constructed an HIV-1-based lentiviral vector (p5p53RTAT3) that expresses the viral trans-activating protein Tat in a drug-regulated manner and p53 in a Rev-dependent manner. We have demonstrated that the Tat-expressed protein from p5p53RTAT3 vector reactivates latent HIV-1 proviruses in J1.1 and ACH-2 cell lines and promotes p53-induced apoptosis in the presence of Rev. Our system was able to trigger the trans-activation of the provirus 5' long terminal repeat (LTR), stimulate the expression of the Rev protein from a tat-defective provirus, and provoke apoptosis selectively in the cells transfected with a tat-defective HIV-1 provirus in contrast to those with no HIV-1 provirus. However, the Rev-dependent p53 killing of latently infected cells was not effective enough for complete elimination of the awakened HIV-1 viruses. In summary, we have developed a vector system that is efficient in activating latent HIV-1 proviruses but that needs further improvement to kill infected cells.

Human Lipooligosaccharide IGG That Prevents Endemic Meningococcal Disease Recognizes an Internal Lacto-N-neotetraose Structure*

PubMed Central

Cheng, Hui; Yang, Zhijie; Estabrook, Michele M.; John, Constance M.; Jarvis, Gary A.; McLaughlin, Stephanie; Griffiss, J. McLeod

2011-01-01

Antibodies that initiate complement-mediated killing of Neisseria meningitidis as they enter the bloodstream from the oropharynx protect against disseminated disease. Human IgGs that bind the neisserial L7 lipooligosaccharide (LOS) are bactericidal for L3,7 and L2,4 meningococci in the presence of human complement. These strains share a lacto-N-neotetraose (nLc4) LOS α chain. We used a set of mutants that have successive saccharide deletions from the nLc4 α chain to characterize further the binding and bactericidal activity of nLc4 LOS IgG. We found that the nLc4 α chain conforms at least four different antigens. We separately purified IgG that required the nLc4 (non-reducing) terminal galactose (Gal) for binding and IgG that bound the truncated nLc3 α chain that lacks this Gal residue. IgG that bound the internal nLc3 α chain killed both L3,7 and L2,4 strains, whereas IgG that required the nLc4 terminal Gal residue for binding killed L2,4 stains but not L3,7 strains. These results show that the diversity of LOS antibodies in human serum is as much a function of the conformation of multiple antigens by a single glycoform as of the production of multiple glycoforms. Differences in sensitivity to killing by human nLc4 LOS IgG may account for the fact that fully two-thirds of endemic group B meningococcal disease in infants and children is caused by L3,7 strains, but only 20% is caused by L2,4 stains. PMID:22027827

Targeted application of an organophosphate-based paint applied on windows and doors against Anopheles coluzzii resistant to pyrethroids under real life conditions in Vallée du Kou, Burkina Faso (West Africa).

PubMed

Poda, Serge B; Soma, Dieudonné D; Hien, Aristide; Namountougou, Moussa; Gnankiné, Olivier; Diabaté, Abdoulaye; Fournet, Florence; Baldet, Thierry; Mas-Coma, Santiago; Mosqueira, Beatriz; Dabiré, Roch K

2018-04-02

A novel strategy applying an organophosphate-based insecticide paint on doors and windows in combination with long-lasting insecticide-treated nets (LLINs) was tested for the control of pyrethroid-resistant malaria vectors in a village setting in Vallée du Kou, a rice-growing area west of Burkina Faso. Insecticide Paint Inesfly 5A IGR™, comprised of two organophosphates and an insect growth regulator, was applied to doors and windows and tested in combination with pyrethroid-treated LLINs. The killing effect was monitored for 5 months by early morning collections of anophelines and other culicids. The residual efficacy was evaluated monthly by WHO bioassays using Anopheles gambiae 'Kisumu' and local populations of Anopheles coluzzii resistant to pyrethroids. The spatial mortality efficacy (SME) at distances of 1 m was also assessed against pyrethroid-susceptible and -resistant malaria vectors. The frequency of L1014F kdr and Ace-1 R G119S mutations was, respectively, reported throughout the study. The Insecticide Paint Inesfly 5A IGR had been tested in past studies yielding a long-term mortality rate of 80% over 12 months against An. coluzzii, the local pyrethroid-resistant malaria vector. The purpose of the present study is to test if treating smaller, targeted surfaces (e.g. doors and windows) was also efficient in killing malaria vectors. Treating windows and doors alone yielded a killing efficacy of 100% for 1 month against An. coluzzii resistant to pyrethroids, but efficacy reduced quickly afterwards. Likewise, WHO cone bioassays yielded mortalities of 80-100% for 2 months but declined to 90 and 40% 2 and 3 months after treatment, respectively. Mosquitoes exposed to insecticide paint-treated surfaces at distances of 1 m, yielded mortality rates of about 90-80% against local pyrethroids-resistant An. coluzzii during the first 2 months, but decreased to 30% afterwards. Anopheles coluzzii was reported to be exclusively the local malaria vector and resistant to pyrethroids with high L1014 kdr frequency. The combination of insecticide paint on doors and windows with LLINs yielded high mortality rates in the short term against wild pyrethroid-resistant malaria vector populations. A high SME was observed against laboratory strains of pyrethroid-resistant malaria vectors placed for 30 min at 1 m from the treated/control walls. The application of the insecticide paint on doors and windows led to high but short-lasting mortality rates. The strategy may be an option in a context where low cost, rapid responses need to be implemented in areas where malaria vectors are resistant to pyrethroids.

Conformal symmetries of Einstein's field equations and initial data

NASA Astrophysics Data System (ADS)

Sharma, Ramesh

2005-04-01

This paper examines the initial data for the evolution of the space-time solution of Einstein's equations admitting a conformal symmetry. Under certain conditions on the extrinsic curvature of the initial complete spacelike hypersurface and sectional curvature of the space-time with respect to sections containing the normal vector field, we have shown that the initial hypersurface is conformally diffeomorphic to a sphere or a flat space or a hyperbolic space or the product of an open real interval and a complete 2-manifold. It has been further shown that if the initial hypersurface is compact, then it is conformally diffeomorphic to a sphere. Finally, the conformal symmetries of a generalized Robertson-Walker space-time have been described.

Conformal invariance of (0, 2) sigma models on Calabi-Yau manifolds

NASA Astrophysics Data System (ADS)

Jardine, Ian T.; Quigley, Callum

2018-03-01

Long ago, Nemeschansky and Sen demonstrated that the Ricci-flat metric on a Calabi-Yau manifold could be corrected, order by order in perturbation theory, to produce a conformally invariant (2, 2) nonlinear sigma model. Here we extend this result to (0, 2) sigma models for stable holomorphic vector bundles over Calabi-Yaus.

Optical trapping of core-shell magnetic microparticles by cylindrical vector beams

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

Zhong, Min-Cheng; Gong, Lei; Li, Di

2014-11-03

Optical trapping of core-shell magnetic microparticles is experimentally demonstrated by using cylindrical vector beams. Second, we investigate the optical trapping efficiencies. The results show that radially and azimuthally polarized beams exhibit higher axial trapping efficiencies than the Gaussian beam. Finally, a trapped particle is manipulated to kill a cancer cell. The results make possible utilizing magnetic particles for optical manipulation, which is an important advantage for magnetic particles as labeling agent in targeted medicine and biological analysis.

LETTER TO THE EDITOR: A theorem on topologically massive gravity

NASA Astrophysics Data System (ADS)

Aliev, A. N.; Nutku, Y.

1996-03-01

We show that for three dimensional spacetimes admitting a hypersurface orthogonal Killing vector field, Deser, Jackiw and Templeton's vacuum field equations of topologically massive gravity allow only the trivial flat spacetime solution. Thus spin is necessary to support topological mass.

Conformal collineations and anisotropic fluids in general relativity

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

Duggal, K.L.; Sharma, R.

1986-10-01

Recently, Herrera et al. (L. Herrera, J. Jimenez, L. Leal, J. Ponce de Leon, M. Esculpi, and V. Galino, J. Math. Phys. 25, 3274 (1984)) studied the consequences of the existence of a one-parameter group of conformal motions for anisotropic matter. They concluded that for special conformal motions, the stiff equation of state (p = ..mu..) is singled out in a unique way, provided the generating conformal vector field is orthogonal to the four-velocity. In this paper, the same problem is studied by using conformal collineations (which include conformal motions as subgroups). It is shown that, for a special conformalmore » collineation, the stiff equation of state is not singled out. Non-Einstein Ricci-recurrent spaces are considered as physical models for the fluid matter.« less

Conformational and functional analysis of molecular dynamics trajectories by Self-Organising Maps

PubMed Central

2011-01-01

Background Molecular dynamics (MD) simulations are powerful tools to investigate the conformational dynamics of proteins that is often a critical element of their function. Identification of functionally relevant conformations is generally done clustering the large ensemble of structures that are generated. Recently, Self-Organising Maps (SOMs) were reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data mining problems. We present a novel strategy to analyse and compare conformational ensembles of protein domains using a two-level approach that combines SOMs and hierarchical clustering. Results The conformational dynamics of the α-spectrin SH3 protein domain and six single mutants were analysed by MD simulations. The Cα's Cartesian coordinates of conformations sampled in the essential space were used as input data vectors for SOM training, then complete linkage clustering was performed on the SOM prototype vectors. A specific protocol to optimize a SOM for structural ensembles was proposed: the optimal SOM was selected by means of a Taguchi experimental design plan applied to different data sets, and the optimal sampling rate of the MD trajectory was selected. The proposed two-level approach was applied to single trajectories of the SH3 domain independently as well as to groups of them at the same time. The results demonstrated the potential of this approach in the analysis of large ensembles of molecular structures: the possibility of producing a topological mapping of the conformational space in a simple 2D visualisation, as well as of effectively highlighting differences in the conformational dynamics directly related to biological functions. Conclusions The use of a two-level approach combining SOMs and hierarchical clustering for conformational analysis of structural ensembles of proteins was proposed. It can easily be extended to other study cases and to conformational ensembles from other sources. PMID:21569575

Diffeomorphism invariance and black hole entropy

NASA Astrophysics Data System (ADS)

Huang, Chao-Guang; Guo, Han-Ying; Wu, Xiaoning

2003-11-01

The Noether-charge and the Hamiltonian realizations for the diff(M) algebra in diffeomorphism-invariant gravitational theories without a cosmological constant in any dimension are studied in a covariant formalism. We analyze how the Hamiltonian functionals form the diff(M) algebra under the Poisson brackets and show how the Noether charges with respect to the diffeomorphism generated by the vector fields and their variations in n-dimensional general relativity form this algebra. The asymptotic behaviors of vector fields generating diffeomorphism of the manifold with boundaries are discussed. It is shown that the “central extension” for a large class of vector fields is always zero on the Killing horizon. We also check whether choosing the vector fields near the horizon may pick up the Virasoro algebra. The conclusion is unfortunately negative in any dimension.

Potentialities of Mermithid Nematodes for the Biocontrol of Blackflies (Diptera: Simuliidae)--A Review,

DTIC Science & Technology

biocontrol agents of agricultural insect pests and medically important insect vectors. More specifically, mermithid nematodes appear to regulate natural...Mermithids comprise a family of nematodes which invariably kill/sterilize their insect host(s). These nematodes have considerable potential as

Classical aspects of higher spin topologically massive gravity

NASA Astrophysics Data System (ADS)

Chen, Bin; Long, Jiang; Zhang, Jian-Dong

2012-10-01

We study the classical solutions of three-dimensional topologically massive gravity (TMG) and its higher spin generalization, in the first-order formulation. The action of higher spin TMG has been proposed by Chen and Long (2011 J. High Energy Phys. JHEP12(2011)114) to be of a Chern-Simons-like form. The equations of motion are more complicated than the ones in pure higher spin AdS3 gravity, but are still tractable. As all the solutions in higher spin gravity are automatically the solutions of higher spin TMG, we focus on other solutions. We manage to find the AdS pp-wave solutions with higher spin hair and find that the non-vanishing higher spin fields may or may not modify the pp-wave geometry. In order to discuss the warped spacetime, we introduce the notion of a special Killing vector, which is defined to be the symmetry on the frame-like fields. We reproduce various warped spacetimes of TMG in our framework, with the help of special Killing vectors.

Is drought helping or killing dengue? Investigation of spatiotemporal relationship between dengue fever and drought

NASA Astrophysics Data System (ADS)

Lee, Chieh-Han; Yu, Hwa-Lung

2015-04-01

Dengue Fever is a vector-borne disease that is transmitted between human and mosquitos in tropical and sub-tropical regions. Previous studies have found significant relationship between the epidemic of dengue cases and climate variables, especially temperature and precipitation. Besides, the natural phenomena (e.g., drought) are considered that significantly drop the number of dengue cases by killing vector's breeding environment. However, in Kaohsiung City, Taiwan, there are evidences that the temporal pattern of dengue is correlated to drought events. Kaohsiung City experienced two main dengue outbreaks in 2002 and 2014 that both years were confirmed with serious drought. Especially in 2014, Kaohsiung City was suffered from extremely dengue outbreak in 2014 that reported the highest number of dengue cases in the history. This study constructs the spatiotemporal model of dengue incidences and index of drought events (Standardized Precipitation Index, SPI) based on the distributed lag nonlinear model (DLNM). Other meteorological measures are also included in the analysis.

Use of vectors in sequence analysis.

PubMed

Ishikawa, T; Yamamoto, K; Yoshikura, H

1987-10-01

Applications of the vector diagram, a new type of representation of protein structure, in homology search of various proteins including oncogene products are presented. The method takes account of various kinds of information concerning the properties of amino acids, such as Chou and Fasman's probability data. The method can detect conformational similarities of proteins which may not be detected by the conventional programs.

Mesonic spectroscopy of minimal walking technicolor

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

Del Debbio, Luigi; Lucini, Biagio; Patella, Agostino

2010-07-01

We investigate the structure and the novel emerging features of the mesonic nonsinglet spectrum of the minimal walking technicolor theory. Precision measurements in the nonsinglet pseudoscalar and vector channels are compared to the expectations for an IR-conformal field theory and a QCD-like theory. Our results favor a scenario in which minimal walking technicolor is (almost) conformal in the infrared, while spontaneous chiral symmetry breaking seems less plausible.

[Climate change - a pioneer for the expansion of canine vector-borne diseases?].

PubMed

Krämer, F; Mencke, N

2011-01-01

Vector-transmitted diseases are one of the major contributors to the global burden of disease in humans and animals. Climate change is consistently held responsible for the spread of parasitic acarid and insect vectors such as ticks, fleas, sand flies and mosquitoes, and their transmitted pathogens (in the case of the dog the so-called canine vector-borne diseases [CVBD]). Currently, there is only insufficient data available to prove whether climate change is a major driving force for vector and disease expansion, but the evidence is growing. Other reasons, such as ecological, demographic and socio-economic factors, e.g. pet travel into and pet import from endemic areas, also play a role in this development. Apart from all the controversial discussion of the factors leading to vector and disease expansion, preventative measures should include dog owners' education as they are responsible for individual parasite protection as well as for the minimisation of adverse risk behaviour, e.g. regarding pet travel. Broad-spectrum vector control should be practised by using parasiticides that repel and kill blood feeders in order to minimize the risk of CVBD-pathogen transmission.

Sildenafil (Viagra) sensitizes prostate cancer cells to doxorubicin-mediated apoptosis through CD95

PubMed Central

Das, Anindita; Durrant, David; Mitchell, Clint; Dent, Paul; Batra, Surinder K.; Kukreja, Rakesh C.

2016-01-01

We previously reported that Sildenafil enhances apoptosis and antitumor efficacy of doxorubicin (DOX) while attenuating its cardiotoxic effect in prostate cancer. In the present study, we investigated the mechanism by which sildenafil sensitizes DOX in killing of prostate cancer (PCa) cells, DU145. The death receptor Fas (APO-1 or CD95) induces apoptosis in many carcinoma cells, which is negatively regulated by anti-apoptotic molecules such as FLIP (Fas-associated death domain (FADD) interleukin-1-converting enzyme (FLICE)-like inhibitory protein). Co-treatment of PCa cells with sildenafil and DOX for 48 hours showed reduced expression of both long and short forms of FLIP (FLIP-L and -S) as compared to individual drug treatment. Over-expression of FLIP-s with an adenoviral vector attentuated the enhanced cell-killing effect of DOX and sildenafil. Colony formation assays also confirmed that FLIP-S over-expression inhibited the DOX and sildenafil-induced synergistic killing effect as compared to the cells infected with an empty vector. Moreover, siRNA knock-down of CD95 abolished the effect of sildenafil in enhancing DOX lethality in cells, but had no effect on cell killing after treatment with a single agent. Sildenafil co-treatment with DOX inhibited DOX-induced NF-κB activity by reducing phosphorylation of IκB and nuclear translocation of the p65 subunit, in addition to down regulation of FAP-1 (Fas associated phosphatase-1, a known inhibitor of CD95-mediated apoptosis) expression. This data provides evidence that the CD95 is a key regulator of sildenafil and DOX mediated enhanced cell death in prostate cancer. PMID:26716643

Insecticide-impregnated netting as a potential tool for long-lasting control of the leishmaniasis vector Lutzomyia longipalpis in animal shelters

PubMed Central

2013-01-01

Background Leishmaniasis remains a serious neglected disease, with more than 350 million people potentially at risk worldwide. Control strategies often rely on spraying residual insecticides to target populations of the sand fly vectors that transmit Leishmania parasites when blood-feeding. These programmes are often difficult to sustain effectively, as sand fly resting sites must be resprayed on a regular basis. Here, we investigate whether application of insecticide-impregnated netting to a surface could act as an alternative to residual spraying for controlling the American visceral leishmaniasis vector Lutzomyia longipalpis. Methods Female L. longipalpis from our laboratory colony were exposed for 1 h to three treatments applied to plywood surfaces: 2% permethrin-impregnated netting (Olyset®), 20 mg a.i.m-2 micro-encapsulated lambda-cyhalothrin (Demand CS®) and a no-treatment control. We compared the speed at which these treatments acted, by measuring the percentage of sand flies killed both immediately after exposure to the treatment for 1 hour, as well as the number that had died 24 h after the 1 hour exposure. We repeated the experiment at 6 and 12 months following application to test the effectiveness of each treatment over time. Results When first applied, the lambda-cyhalothrin killed more sand flies in the first hour than the permethrin-impregnated netting. However, the effectiveness of the lambda-cyhalothrin diminished over time, so that there was no difference between the two treatments at 12 months. Both killed more sand flies than the control. When measured 24 h following exposure, both test treatments had killed close to 100% of sand flies when first applied, but while the lethal effect of the netting was maintained at close to 100% over 12 months, the effectiveness of the residual insecticide diminished to approximately 80% after 6 months. Conclusions The results of these initial laboratory experiments indicate that covering surfaces with insecticide impregnated netting material may provide a longer-lasting solution for killing sand flies than residual spraying. Field trials are needed to identify the feasibility of treating surfaces with netting or similar impregnated materials as part of a control program. In targeting L. longipalpis, the greatest benefits may be seen in treating animal sheds with netting, where these sand flies aggregate in large numbers, and which can be difficult to treat repeatedly by conventional spraying. PMID:23642213

From spinning conformal blocks to matrix Calogero-Sutherland models

NASA Astrophysics Data System (ADS)

Schomerus, Volker; Sobko, Evgeny

2018-04-01

In this paper we develop further the relation between conformal four-point blocks involving external spinning fields and Calogero-Sutherland quantum mechanics with matrix-valued potentials. To this end, the analysis of [1] is extended to arbitrary dimensions and to the case of boundary two-point functions. In particular, we construct the potential for any set of external tensor fields. Some of the resulting Schrödinger equations are mapped explicitly to the known Casimir equations for 4-dimensional seed conformal blocks. Our approach furnishes solutions of Casimir equations for external fields of arbitrary spin and dimension in terms of functions on the conformal group. This allows us to reinterpret standard operations on conformal blocks in terms of group-theoretic objects. In particular, we shall discuss the relation between the construction of spinning blocks in any dimension through differential operators acting on seed blocks and the action of left/right invariant vector fields on the conformal group.

A geometric description of Maxwell field in a Kerr spacetime

NASA Astrophysics Data System (ADS)

Jezierski, Jacek; Smołka, Tomasz

2016-06-01

We consider the Maxwell field in the exterior of a Kerr black hole. For this system, we propose a geometric construction of generalized Klein-Gordon equation called Fackerell-Ipser equation. Our model is based on conformal Yano-Killing tensor (CYK tensor). We present non-standard properties of CYK tensors in the Kerr spacetime which are useful in electrodynamics.

Complete integrability of geodesic motion in Sasaki-Einstein toric Yp,q spaces

NASA Astrophysics Data System (ADS)

Babalic, Elena Mirela; Visinescu, Mihai

2015-09-01

We construct explicitly the constants of motion for geodesics in the five-dimensional Sasaki-Einstein spaces Yp,q. To carry out this task, we use the knowledge of the complete set of Killing vectors and Killing-Yano tensors on these spaces. In spite of the fact that we generate a multitude of constants of motion, only five of them are functionally independent implying the complete integrability of geodesic flow on Yp,q spaces. In the particular case of the homogeneous Sasaki-Einstein manifold T1,1 the integrals of motion have simpler forms and the relations between them are described in detail.

A 3D-Engineered Conformal Implant Releases DNA Nanocomplexs for Eradicating the Postsurgery Residual Glioblastoma.

PubMed

Yang, Yuan; Du, Ting; Zhang, Jiumeng; Kang, Tianyi; Luo, Li; Tao, Jie; Gou, Zhiyuan; Chen, Shaochen; Du, Yanan; He, Jiankang; Jiang, Shu; Mao, Qing; Gou, Maling

2017-08-01

Gene therapy has great promise for glioblastoma treatment; however, it remains a great challenge to efficiently deliver genes to the brain. The incomplete resection of glioblastoma always leads to poor prognosis. Here, a 3D-engineered conformal implant for eradicating the postsurgery residual glioblastoma is designed. This implant is constructed by 3D-printing technology to match the tumor cavity and release an oncolytic virus-inspired DNA nanocomplex to kill glioblastoma cells through apoptosis induction. Meanwhile, a 3D-engineered subcutaneous glioblastoma xenograft is built to mimic the resection tumor cavity in mice. Insertion of the implant into the glioblastoma resection cavity efficiently delays tumor recurrence and significantly prolongs overall survival. This study provides a proof-of-concept of glioblastoma therapy using a conformal implant that releases oncolytic DNA nanocomplexs. This strategy can lead to the development of future precision therapy for eradicating postsurgery residual tumors.

Consistent compactification of double field theory on non-geometric flux backgrounds

NASA Astrophysics Data System (ADS)

Hassler, Falk; Lüst, Dieter

2014-05-01

In this paper, we construct non-trivial solutions to the 2 D-dimensional field equations of Double Field Theory (DFT) by using a consistent Scherk-Schwarz ansatz. The ansatz identifies 2( D - d) internal directions with a twist U M N which is directly connected to the covariant fluxes ABC . It exhibits 2( D - d) linear independent generalized Killing vectors K I J and gives rise to a gauged supergravity in d dimensions. We analyze the covariant fluxes and the corresponding gauged supergravity with a Minkowski vacuum. We calculate fluctuations around such vacua and show how they gives rise to massive scalars field and vectors field with a non-abelian gauge algebra. Because DFT is a background independent theory, these fields should directly correspond the string excitations in the corresponding background. For ( D - d) = 3 we perform a complete scan of all allowed covariant fluxes and find two different kinds of backgrounds: the single and the double elliptic case. The later is not T-dual to a geometric background and cannot be transformed to a geometric setting by a field redefinition either. While this background fulfills the strong constraint, it is still consistent with the Killing vectors depending on the coordinates and the winding coordinates, thereby giving a non-geometric patching. This background can therefore not be described in Supergravity or Generalized Geometry.

Wingnut (Juglandaceae) as a new generic host for Pityophthorus juglandis (Coleoptera: Curculionidae) and the thousand cankers disease pathogen, Geosmithia morbida (Ascomycota: Hypocreales)

Treesearch

Stacy M. Hishinuma; Paul L. Dallara; Mohammad A. Yaghmour; Marcelo M. Zerillo; Corwin M. Parker; Tatiana V. Roubtsova; Tivonne L. Nguyen; Ned A. Tisserat; Richard M. Bostock; Mary L. Flint; Steven J. Seybold

2016-01-01

The walnut twig beetle (WTB), Pityophthorus juglandis Blackman (Coleoptera: Curculionidae), vectors a fungus, Geosmithia morbida Kolarík, Freeland, Utley, and Tisserat (Ascomycota: Hypocreales), which colonises and kills the phloem of walnut and butternut trees, Juglans Linnaeus (Juglandaceae). Over the...

Influence of temperature and humidity on the viability of Ophiognomonia clavigignenti-juglandacearum Conidia

Treesearch

M.J. Moore; M.E. Ostry

2015-01-01

Butternut canker, caused by the fungus Ophiognomonia clavigignenti-juglandacearum, primarily kills butternut (Juglans cinerea). Rain splash and local air currents are the primary means of conidia dispersal but that does not explain its long-distance spread and infection of isolated trees. Dispersal by insect or animal vectors...

Population trends of the redbay ambrosia beetle (Coleoptera: Curculionidae: Scolytinae): does utilization of small diameter redbay trees allow populations to persist?

Treesearch

M. Lake Maner; James Hanula; Scott Horn

2014-01-01

The redbay ambrosia beetle, Xyleborus glabratus Eichhoff, vectors laurel wilt, Raffaelea lauricola T.C. Harr., Fraedrich & Aghayeva, that quickly kills all large diam (> 2.5cm) redbay trees [Persea borbonia (L.) Sprengel] in an area but smaller diam trees (

Invasive Bark Beetles, Forest Insect& Disease Leaflet 176

Treesearch

J.C. Lee; R.A. Haack; J.F. Negron; J.J. Witcosky; S.J. Seybold

2007-01-01

Bark beetles (Scolytidae) are among the most damaging insects in Northern Hemisphere forests, killing trees by direct feeding and by vectoring fungal pathogens. In addition to an already formidable native bark beetle complex, the number of exotic scolytids in U.S. forests has increased rapidly, with 53 known species established as of June 2007.

Global structure of five-dimensional fuzzballs

NASA Astrophysics Data System (ADS)

Gibbons, G. W.; Warner, N. P.

2014-01-01

We describe and study families of BPS microstate geometries, namely, smooth, horizonless asymptotically flat solutions to supergravity. We examine these solutions from the perspective of earlier attempts to find solitonic solutions in gravity and show how the microstate geometries circumvent the earlier ‘no-go’ theorems. In particular, we re-analyze the Smarr formula and show how it must be modified in the presence of non-trivial second homology. This, combined with the supergravity Chern-Simons terms, allows the existence of rich classes of BPS, globally hyperbolic, asymptotically flat, microstate geometries whose spatial topology is the connected sum of N copies of S2 × S2 with a ‘point at infinity’ removed. These solutions also exhibit ‘evanescent ergo-regions,’ that is, the non-space-like Killing vector guaranteed by supersymmetry is time-like everywhere except on time-like hypersurfaces (ergo-surfaces) where the Killing vector becomes null. As a by-product of our work, we are able to resolve the puzzle of why some regular soliton solutions violate the BPS bound: their spacetimes do not admit a spin structure.

Sterculia guttata seeds extractives--an effective mosquito larvicide.

PubMed

Katade, Sushama R; Pawar, Pushpa V; Wakharkar, Radhika D; Deshpande, Nirmala R

2006-08-01

The larvicidal activity of ethanol, chloroform and hexane soxhlet extracts obtained from S. guttata seeds was investigated against the IVth instar larvae of Dengue fever vector, Aedes aegypti and filarial vector, Culex quinquefasciatus. All extracts including fractions of ethanol extract exhibited 100% larval kill within 24 hr exposure period at 500 ppm concentration. Fraction A1 of ethanol was found to be most promising; its LC50 was 21.552 and 35.520 ppm against C. quinquefasciatus and A. aegypti respectively. Naturally occurring S. guttata seed derived fractions merit further study as potential mosquito larval control agents or lead compounds.

Isolation of fungi from dead arthropods and identification of a new mosquito natural pathogen.

PubMed

Jaber, Sana; Mercier, Alex; Knio, Khouzama; Brun, Sylvain; Kambris, Zakaria

2016-09-05

Insects are well known vectors of human and animal pathogens and millions of people are killed by mosquito-borne diseases every year. The use of insecticides to target insect vectors has been hampered by the issues of toxicity to the environment and by the selection of resistant insects. Therefore, biocontrol strategies based on naturally occurring microbial pathogens emerged as a promising control alternative. The entomopathogenic fungus Beauveria bassiana is well characterized and have been approved by the United States Environmental Protection Agency as a pest biological control method. However, thousands of other fungi are unexploited and it is important to identify and use different fungi for biocontrol with possibly some vector specific strains. The aim of this study was to identify new fungal entomopathogens that may be used as potential mosquito biocontrol agents. Cadavers of arthropods were collected from pesticide free areas and the fungi associated isolated, cultured and identified. Then the ability of each isolate to kill laboratory insects was assayed and compared to that of B. bassiana. In total we have isolated and identified 42 fungal strains from 17 different arthropod cadavers. Twenty four fungal isolates were cultivated in the laboratory and were able to induce sporulation. When fungal spores were microinjected into Drosophila melanogaster, eight isolates proved to be highly pathogenic while the remaining strains showed moderate or no pathogenicity. Then a selection of isolates was tested against Aedes mosquitoes in a model mimicking natural infections. Only one fungus (Aspergillus nomius) was as pathogenic as B. bassiana and able to kill 100 % of the mosquitoes. The obtained results are encouraging and demonstrate the feasibility of this simple approach for the identification of new potential mosquito killers. Indeed, it is essential to anticipate and prepare biocontrol methods to fight the expansion of mosquitoes' habitat predicted in certain geographical areas in association with the occurring climatic changes.

Ebola virus vaccine: benefit and risks of adenovirus-based vectors.

PubMed

Mennechet, Franck J D; Tran, Thi Thu Phuong; Eichholz, Karsten; van de Perre, Philippe; Kremer, Eric J

2015-01-01

In 2014, an outbreak of Ebola virus spread rapidly in West Africa. The epidemic killed more than 10,000 people and resulted in transmissions outside the endemic countries. WHO hopes for effective vaccines by the end of 2015. Numerous vaccine candidates have been proposed, and several are currently being evaluated in humans. Among the vaccine candidates are vectors derived from adenovirus (Ad). Despite previous encouraging preclinical and Phase I/II trials, Ad vectors used in three Phase II trials targeting HIV were prematurely interrupted because of the lack of demonstrated efficacy. The vaccine was not only ineffective but also led to a higher rate of HIV acquisition. In this context, the authors discuss the potential benefits, risks and impact of using Ad-derived vaccines to control Ebola virus disease.

Complete affine connection in the causal boundary: static, spherically symmetric spacetimes

NASA Astrophysics Data System (ADS)

Harris, Steven (Stacey) G.

2017-02-01

The boundary at I^+, future null infinity, for a standard static, spherically symmetric spactime is examined for possible linear connections. Two independent methods are employed, one for treating I^+ as the future causal boundary, and one for treating it as a conformal boundary (the latter is subsumed in the former, which is of greater generality). Both methods provide the same result: a constellation of various possible connections, depending on an arbitrary choice of a certain function, a sort of gauge freedom in obtaining a natural connection on I^+; choosing that function to be constant (for instance) results in a complete connection. Treating I^+ as part of the future causal boundary, the method is to impute affine connections on null hypersurfaces going out to I^+, in terms of a transverse vector field on each null hypersurface (there is much gauge freedom on choice of the transverse vector fields). Treating I^+ as part of a conformal boundary, the method is to make a choice of conformal factor that makes the boundary totally geodesic in the enveloping manifold (there is much gauge freedom in choice of that conformal factor). Similar examination is made of other boundaries, such as timelike infinity and timelike and spacelike singularities. These are much simpler, as they admit a unique connection from a similar limiting process (i.e., no gauge freedom); and that connection is complete.

Conformal invariance and the metrication of the fundamental forces

NASA Astrophysics Data System (ADS)

Mannheim, Philip D.

2016-07-01

We revisit Weyl’s metrication (geometrization) of electromagnetism. We show that by making Weyl’s proposed geometric connection be pure imaginary, not only are we able to metricate electromagnetism, an underlying local conformal invariance makes the geometry be strictly Riemannian and prevents observational gravity from being complex. Via torsion, we achieve an analogous metrication for axial-vector fields. We generalize our procedure to Yang-Mills theories, and achieve a metrication of all the fundamental forces. Only in the gravity sector does our approach differ from the standard picture of fundamental forces, with our approach requiring that standard Einstein gravity be replaced by conformal gravity. We show that quantum conformal gravity is a consistent and unitary quantum gravitational theory, one that, unlike string theory, only requires four spacetime dimensions.

Biology and host associations of redbay ambrosia beetle (Coleoptera: Curculionidae: Scolytinae), exotic vector of laurel wilt killing redbay trees in the Southeastern United States

Treesearch

James L. Hanula; Albert E. Mayfield; Stephen W. Fraedrich; Robert J. Babaglia

2008-01-01

The redbay ambrosia beetle, Xyleborus glabratus Eichhoff (Coleoptera: Curculionidae: Scolyhnae), and its fungal symbiont, Rafaelea sp., are new introductions to the southeastern United States responsible for the wilt of mature redbay, Persea borbonia (L) Spreng., trees. In 2006 and 2007, we investigated the...

WORKING WITH ALKALINE MATERIALS TO ACHIEVE A CLASS B, CLASS A, AND/OR A BIOSOLIDS THAT DOES NOT ATTRACT VECTORS

EPA Science Inventory

This workshop presentation begins with a discussion of the use of lime and other alkaline materials from the very earliest times to the present for killing bacteria, viruses and parasites and for controlling odors in wastewaters and sludge. It answers the question "How did EPA ar...

Conservation laws and evolution schemes in geodesic, hydrodynamic, and magnetohydrodynamic flows

NASA Astrophysics Data System (ADS)

Markakis, Charalampos; Uryū, Kōji; Gourgoulhon, Eric; Nicolas, Jean-Philippe; Andersson, Nils; Pouri, Athina; Witzany, Vojtěch

2017-09-01

Carter and Lichnerowicz have established that barotropic fluid flows are conformally geodesic and obey Hamilton's principle. This variational approach can accommodate neutral, or charged and poorly conducting, fluids. We show that, unlike what has been previously thought, this approach can also accommodate perfectly conducting magnetofluids, via the Bekenstein-Oron description of ideal magnetohydrodynamics. When Noether symmetries associated with Killing vectors or tensors are present in geodesic flows, they lead to constants of motion polynomial in the momenta. We generalize these concepts to hydrodynamic flows. Moreover, the Hamiltonian descriptions of ideal magnetohydrodynamics allow one to cast the evolution equations into a hyperbolic form useful for evolving rotating or binary compact objects with magnetic fields in numerical general relativity. In this framework, Ertel's potential vorticity theorem for baroclinic fluids arises as a special case of a conservation law valid for any Hamiltonian system. Moreover, conserved circulation laws, such as those of Kelvin, Alfvén and Bekenstein-Oron, emerge simply as special cases of the Poincaré-Cartan integral invariant of Hamiltonian systems. We use this approach to obtain an extension of Kelvin's theorem to baroclinic (nonisentropic) fluids, based on a temperature-dependent time parameter. We further extend this result to perfectly or poorly conducting baroclinic magnetoflows. Finally, in the barotropic case, such magnetoflows are shown to also be geodesic, albeit in a Finsler (rather than Riemann) space.

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

Sergyeyev, Artur; Krtous, Pavel; Institute of Theoretical Physics, Faculty of Mathematics and Physics, Charles University in Prague, V Holesovickach 2, Prague

We consider the Klein-Gordon equation in generalized higher-dimensional Kerr-NUT-(A)dS spacetime without imposing any restrictions on the functional parameters characterizing the metric. We establish commutativity of the second-order operators constructed from the Killing tensors found in [J. High Energy Phys. 02 (2007) 004] and show that these operators, along with the first-order operators originating from the Killing vectors, form a complete set of commuting symmetry operators (i.e., integrals of motion) for the Klein-Gordon equation. Moreover, we demonstrate that the separated solutions of the Klein-Gordon equation obtained in [J. High Energy Phys. 02 (2007) 005] are joint eigenfunctions for all of thesemore » operators. We also present an explicit form of the zero mode for the Klein-Gordon equation with zero mass. In the semiclassical approximation we find that the separated solutions of the Hamilton-Jacobi equation for geodesic motion are also solutions for a set of Hamilton-Jacobi-type equations which correspond to the quadratic conserved quantities arising from the above Killing tensors.« less

General minimal surface solution for gravitational instantons

NASA Astrophysics Data System (ADS)

Aliev, A. N.; Kalaycı, J.; Nutku, Y.

1997-07-01

We construct the general instanton metric obtained from Weierstrass' general local solution for minimal surfaces using the correspondence between minimal surfaces in three-dimensional Euclidean space and gravitational instantons admitting two Killing vectors. The resulting metric contains one arbitrary analytic function and we show that it can be transformed to the Gibbons-Hawking form of an instanton metric that was reported earlier.

Does myxomatosis still regulate numbers of rabbits (Oryctolagus cuniculus Linnaeus, 1758) in the United Kingdom?

PubMed

Trout, R C; Ross, J; Fox, A P

1993-03-01

Myxomatosis now kills a much smaller proportion of rabbit populations than in the past, while remaining an important regulatory factor, as shown experimentally. On two separate occasions, experimental reduction of the prevalence of the disease (by reducing infestations of the main vector, the rabbit flea) led to significant increases in numbers of rabbits surviving the winter.

40 CFR 180.1154 - CryIA(c) and CryIC derived delta-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated...

Code of Federal Regulations, 2010 CFR

2010-07-01

...-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated in killed Pseudomonas fluorescens, and the... RESIDUES IN FOOD Exemptions From Tolerances § 180.1154 CryIA(c) and CryIC derived delta-endotoxins of... plasmid and cloning vector genetic constructs. CryIA(c) and CryIC derived delta-endotoxins of Bacillus...

40 CFR 180.1154 - CryIA(c) and CryIC derived delta-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated...

Code of Federal Regulations, 2011 CFR

2011-07-01

...-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated in killed Pseudomonas fluorescens, and the... RESIDUES IN FOOD Exemptions From Tolerances § 180.1154 CryIA(c) and CryIC derived delta-endotoxins of... plasmid and cloning vector genetic constructs. CryIA(c) and CryIC derived delta-endotoxins of Bacillus...

Prallethrin-induced excitation increases contact between sprayed ultra-low-volume droplets and flying mosquitoes (Diptera: Culicidae) in a wind tunnel

USDA-ARS?s Scientific Manuscript database

Mosquitoes are important in the United States due to their roles as pestiferous biters and vectors of diseases such as West Nile Virus and Dengue. Conventional applications of pesticides in spray clouds are often limited by their ability to contact and kill mosquitoes that may be resting or hiding ...

40 CFR 180.1154 - CryIA(c) and CryIC derived delta-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated...

Code of Federal Regulations, 2013 CFR

2013-07-01

...-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated in killed Pseudomonas fluorescens, and the... RESIDUES IN FOOD Exemptions From Tolerances § 180.1154 CryIA(c) and CryIC derived delta-endotoxins of... plasmid and cloning vector genetic constructs. CryIA(c) and CryIC derived delta-endotoxins of Bacillus...

40 CFR 180.1154 - CryIA(c) and CryIC derived delta-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated...

Code of Federal Regulations, 2012 CFR

2012-07-01

...-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated in killed Pseudomonas fluorescens, and the... RESIDUES IN FOOD Exemptions From Tolerances § 180.1154 CryIA(c) and CryIC derived delta-endotoxins of... plasmid and cloning vector genetic constructs. CryIA(c) and CryIC derived delta-endotoxins of Bacillus...

40 CFR 180.1154 - CryIA(c) and CryIC derived delta-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated...

Code of Federal Regulations, 2014 CFR

2014-07-01

...-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated in killed Pseudomonas fluorescens, and the... RESIDUES IN FOOD Exemptions From Tolerances § 180.1154 CryIA(c) and CryIC derived delta-endotoxins of... plasmid and cloning vector genetic constructs. CryIA(c) and CryIC derived delta-endotoxins of Bacillus...

Mutation in the sodium channel gene corresponds with phenotypic resistance of Rhipicephalus sanguineus sensu lato (Acari: Ixodidae) to pyrethroids

USDA-ARS?s Scientific Manuscript database

The brown dog tick, Rhipicephalus sanguineus sensu lato, is a cosmopolitan ectoparasite and vector of pathogens that kill humans and animals. Pyrethroids represent a class of synthetic acaricides that have been used intensely to try to control the brown dog tick and mitigate the risk of tick-borne d...

[Retroviral-mediated transfer of a hygromycin phosphotransferase-thymidine kinase fusion gene into human bladder carcinoma cell].

PubMed

Ye, C; Chen, S; Pei, X; Li, L; Feng, K

1999-08-01

To evaluate the therapeutic efficacy of retroviral-mediated hygromycin phosphotransferase-thymidine kinase fusion gene (HyTK)/GCV on human bladder carcinoma cell. A retroviral expression vector pL (HyTK) SN was constructed. By using FuGENE 6-mediated transfection and "ping-pong effect" technique, high-titer of retroviral supernatant was obtained and HyTK gene was transferred into EJ cells. A retroviral vector encoding, enhanced green fluorescent protein, EGFP was used to rapidly detect the transduction efficiency. Antitumor effects were observed after GCV treatment. In vitro experiments demonstrated the EJ cells transferred by HyTK gene were killed in the GCV treatment. Non-transduced parental cells were not sensitive to GCV, but they were dead by the bystander killing of neighboring cells when mixed with EJ/HyTK cells at various ratios. In addition, this not only affect wild-type EJ cells but also cells from different bladder carcinoma cell lines. Retroviral-mediated HyTK/GCV systems were a promising suicide gene therapy for bladder carcinoma. EGFP may act as a convenient and rapid reporter to monitor retroviral-mediated gene transfer and expression in bladder carcinoma cells.

An Impossible Journey? The Development of Plasmodium falciparum NF54 in Culex quinquefasciatus

PubMed Central

Knöckel, Julia; Molina-Cruz, Alvaro; Fischer, Elizabeth; Muratova, Olga; Haile, Ashley; Barillas-Mury, Carolina; Miller, Louis H.

2013-01-01

Although Anopheles mosquitoes are the vectors for human Plasmodium spp., there are also other mosquito species–among them culicines (Culex spp., Aedes spp.)–present in malaria-endemic areas. Culicine mosquitoes transmit arboviruses and filarial worms to humans and are vectors for avian Plasmodium spp., but have never been observed to transmit human Plasmodium spp. When ingested by a culicine mosquito, parasites could either face an environment that does not allow development due to biologic incompatibility or be actively killed by the mosquito’s immune system. In the latter case, the molecular mechanism of killing must be sufficiently powerful that Plasmodium is not able to overcome it. To investigate how human malaria parasites develop in culicine mosquitoes, we infected Culex quinquefasciatus with Plasmodium falciparum NF54 and monitored development of parasites in the blood bolus and midgut epithelium at different time points. Our results reveal that ookinetes develop in the midgut lumen of C. quinquefasciatus in slightly lower numbers than in Anopheles gambiae G3. After 30 hours, parasites have invaded the midgut and can be observed on the basal side of the midgut epithelium by confocal and transmission electron microscopy. Very few of the parasites in C. quinquefasciatus are alive, most of them are lysed. Eight days after the mosquito’s blood meal, no oocysts can be found in C. quinquefasciatus. Our results suggest that the mosquito immune system could be involved in parasite killing early in development after ookinetes have crossed the midgut epithelium and come in contact with the mosquito hemolymph. PMID:23658824

Apoptin towards safe and efficient anticancer therapies.

PubMed

Backendorf, Claude; Noteborn, Mathieu H M

2014-01-01

The chicken anemia virus derived protein apoptin harbors cancer-selective cell killing characteristics, essentially based on phosphorylation-mediated nuclear transfer in cancer cells and efficient cytoplasmic degradation in normal cells. Here, we describe a growing set of preclinical experiments underlying the promises of the anti-cancer potential of apoptin. Various non-replicative oncolytic viral vector systems have revealed the safety and efficacy of apoptin. In addition, apoptin enhanced the oncolytic potential of adenovirus, parvovirus and Newcastle disease virus vectors. Intratumoral injection of attenuated Salmonella typhimurium bacterial strains and plasmid-based systems expressing apoptin resulted in significant tumor regression. In-vitro and in-vivo experiments showed that recombinant membrane-transferring PTD4- or TAT-apoptin proteins have potential as a future anticancer therapeutics. In xenografted hepatoma and melanoma mouse models PTD4-apoptin protein entered both cancer and normal cells, but only killed cancer cells. Combinatorial treatment of PTD4-apoptin with various (chemo)therapeutic compounds revealed an additive or even synergistic effect, reducing the side effects of the single (chemo)therapeutic treatment. Degradable polymeric nanocapsules harboring MBP-apoptin fusion-protein induced tumor-selective cell killing in-vitro and in-vivo and revealed the potential of polymer-apoptin protein vehicles as an anticancer agent.Besides its direct use as an anticancer therapeutic, apoptin research has also generated novel possibilities for drug design. The nuclear location domains of apoptin are attractive tools for targeting therapeutic compounds into the nucleus of cancer cells. Identification of cancer-related processes targeted by apoptin can potentially generate novel drug targets. Recent breakthroughs important for clinical applications are reported inferring apoptin-based clinical trials as a feasible reality.

Magnetic resonance image guided transurethral ultrasound prostate ablation: a preclinical safety and feasibility study with 28-day followup.

PubMed

Burtnyk, Mathieu; Hill, Tracy; Cadieux-Pitre, Heather; Welch, Ian

2015-05-01

We determine the safety and feasibility of magnetic resonance image guided transurethral ultrasound prostate ablation using active temperature feedback control in a preclinical canine model with 28-day followup. After a long acclimatization period we performed ultrasound treatment in 8 subjects using the magnetic resonance image guided TULSA-PRO™ transurethral ultrasound prostate ablation system. Comprehensive examinations and observations were done before and throughout the 28-day followup, including assessment of clinically significant treatment related adverse events. In addition to gross pathology evaluation, extensive histopathological analysis was done to assess cell kill inside and outside the prostate. We evaluated prostate conformal heating by comparing the spatial difference between the treatment plan and the 55C isotherm measured on magnetic resonance imaging thermometry acquired during treatment. These findings were confirmed on contrast enhanced magnetic resonance imaging immediately after treatment and at 28 days. Clinically there were no adverse events in any of the 8 subjects throughout the 28-day followup. All subjects had normal urinary and bowel function. Gross necropsy and histology confirmed that the intended thermal cell kill was confined to the prostate. No surrounding tissue was damaged, including the rectum and the external urinary sphincter. Conformal heating was achieved with an average -0.9 mm accuracy and 0.9 mm precision. Contrast enhanced magnetic resonance imaging and histological analysis confirmed tissue ablation in targeted areas of the prostate. Urethral tissue was spared from thermal damage. Magnetic resonance image guided transurethral ultrasound is a safe, feasible procedure for accurate and precise conformal thermal ablation of prostate tissue, as demonstrated in a preclinical model with 28-day followup. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

What does not kill them makes them stronger: larval environment and infectious dose alter mosquito potential to transmit filarial worms.

PubMed

Breaux, Jennifer A; Schumacher, Molly K; Juliano, Steven A

2014-07-07

For organisms with complex life cycles, larval environments can modify adult phenotypes. For mosquitoes and other vectors, when physiological impacts of stressors acting on larvae carry over into the adult stage they may interact with infectious dose of a vector-borne pathogen, producing a range of phenotypes for vector potential. Investigation of impacts of a common source of stress, larval crowding and intraspecific competition, on adult vector interactions with pathogens may increase our understanding of the dynamics of pathogen transmission by mosquito vectors. Using Aedes aegypti and the nematode parasite Brugia pahangi, we demonstrate dose dependency of fitness effects of B. pahangi infection on the mosquito, as well as interactions between competitive stress among larvae and infectious dose for resulting adults that affect the physiological and functional ability of mosquitoes to act as vectors. Contrary to results from studies on mosquito-arbovirus interactions, our results suggest that adults from crowded larvae may limit infection better than do adults from uncrowded controls, and that mosquitoes from high-quality larval environments are more physiologically and functionally capable vectors of B. pahangi. Our results provide another example of how the larval environment can have profound effects on vector potential of resulting adults. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Equilibrium and Dynamics Properties of Poly(oxyethylene) Melts and Related Poly(alkylethers) from Simulations and Ab Initio Calculations

NASA Technical Reports Server (NTRS)

Smith, Grant D.; Jaffe, R. L.; Yoon, D. Y.; Arnold, James O. (Technical Monitor)

1994-01-01

Molecular dynamics simulations of POE melts have been performed utilizing a potential force field parameterized to reproduce conformer energies and rotational energy barriers in dimethoxyethane as determined from ab initio electronic structure calculations. Chain conformations and dimensions of POE from the simulations were found to be in good agreement with predictions of a rotational isomeric state (RIS) model based upon the ab initio conformational. energies. The melt chains were found to be somewhat extended relative to chains at theta conditions. This effect will be discussed in light of neutron scattering experiments which indicate that POE chains are extended in the melt relative to theta solutions. The conformational characteristics of POE chains will also be compared with those of other poly (alkylethers), namely poly(oxymethylene), poly(oxytrimethylene) and poly(oxytetramethylene). Local conformational dynamics were found to be more rapid than in polymethylene. Calculated C-H vector correlation times were found to be in reasonable agreement with experimental values from C-13 NMR spin-lattice relaxation times. The influence of ionic salts on local conformations and dynamics will also be discussed.

Inhalation of Nebulized Perfluorochemical Enhances Recombinant Adenovirus and Adeno-Associated Virus-Mediated Gene Expression in Lung Epithelium

PubMed Central

Beckett, Travis; Bonneau, Laura; Howard, Alan; Blanchard, James; Borda, Juan; Weiner, Daniel J.; Wang, Lili; Gao, Guang Ping; Kolls, Jay K.; Bohm, Rudolf; Liggitt, Denny

2012-01-01

Abstract Use of perfluorochemical liquids during intratracheal vector administration enhances recombinant adenovirus and adeno-associated virus (AAV)-mediated lung epithelial gene expression. We hypothesized that inhalation of nebulized perfluorochemical vapor would also enhance epithelial gene expression after subsequent intratracheal vector administration. Freely breathing adult C57BL/6 mice were exposed for selected times to nebulized perflubron or sterile saline in a sealed Plexiglas chamber. Recombinant adenoviral vector was administered by transtracheal puncture at selected times afterward and mice were killed 3 days after vector administration to assess transgene expression. Mice tolerated the nebulized perflubron without obvious ill effects. Vector administration 6 hr after nebulized perflubron exposure resulted in an average 540% increase in gene expression in airway and alveolar epithelium, compared with that with vector alone or saline plus vector control (p<0.05). However, vector administration 1 hr, 1 day, or 3 days after perflubron exposure was not different from either nebulized saline with vector or vector alone and a 60-min exposure to nebulized perflubron is required. In parallel pilot studies in macaques, inhalation of nebulized perflubron enhanced recombinant AAV2/5 vector expression throughout the lung. Serial chest radiographs, bronchoalveolar lavages, and results of complete blood counts and serum biochemistries demonstrated no obvious adverse effects of nebulized perflubron. Further, one macaque receiving nebulized perflubron only was monitored for 1 year with no obvious adverse effects of exposure. These results demonstrate that inhalation of nebulized perflubron, a simple, clinically more feasible technique than intratracheal administration of liquid perflubron, safely enhances lung gene expression. PMID:22568624

Molecular Detection of Breast Cancer

DTIC Science & Technology

1998-02-01

treatment-resistant cancer cells. Clearly new approaches are needed to treat these diseases. This project is designed to develop novel approaches to...detect breast cancer cells that contaminate peripheral blood and bone marrow, and to remove such contaminating cells. An RT-PCR assay has been developed ...to detect breast cancer cells, and a novel gene therapy vector has been developed to kill contaminating cancer cells. Blood and bone marrow samples

Japanese oak wilt as a newly emerged forest pest in Japan: why does a symbiotic ambrosia fungus kill host trees?

Treesearch

Naoto Kamata; Koujiro Esaki; Kenryu Kato; Hisahito Oana; Yutaka Igeta; Ryotaro Komura

2007-01-01

Japanese oak wilt (JOW) has been known since the 1930s, but in the last 15 years epidemics have intensified and spread to the island's western coastal areas. The symbiotic ambrosia fungus Raffaelea quercivora is the causal agent of oak dieback, and is vectored by Platypus quercivorus (Murayama). This is the first example of an...

Holography for Schrödinger backgrounds

NASA Astrophysics Data System (ADS)

Guica, Monica; Skenderis, Kostas; Taylor, Marika; van Rees, Balt C.

2011-02-01

We discuss holography for Schrödinger solutions of both topologically massive gravity in three dimensions and massive vector theories in ( d + 1) dimensions. In both cases the dual field theory can be viewed as a d-dimensional conformal field theory (two dimensional in the case of TMG) deformed by certain operators that respect the Schrödinger symmetry. These operators are irrelevant from the viewpoint of the relativistic conformal group but they are exactly marginal with respect to the non-relativistic conformal group. The spectrum of linear fluctuations around the background solutions corresponds to operators that are labeled by their scaling dimension and the lightcone momentum k v . We set up the holographic dictionary and compute 2-point functions of these operators both holographically and in field theory using conformal perturbation theory and find agreement. The counterterms needed for holographic renormalization are non-local in the v lightcone direction.

A Safe Bacterial Microsyringe for In Vivo Antigen Delivery and Immunotherapy

PubMed Central

Le Gouëllec, Audrey; Chauchet, Xavier; Laurin, David; Aspord, Caroline; Verove, Julien; Wang, Yan; Genestet, Charlotte; Trocme, Candice; Ahmadi, Mitra; Martin, Sandrine; Broisat, Alexis; Cretin, François; Ghezzi, Catherine; Polack, Benoit; Plumas, Joël; Toussaint, Bertrand

2013-01-01

The industrial development of active immunotherapy based on live-attenuated bacterial vectors has matured. We developed a microsyringe for antigen delivery based on the type III secretion system (T3SS) of P. aeruginosa. We applied the “killed but metabolically active” (KBMA) attenuation strategy to make this bacterial vector suitable for human use. We demonstrate that attenuated P. aeruginosa has the potential to deliver antigens to human antigen-presenting cells in vitro via T3SS with considerable attenuated cytotoxicity as compared with the wild-type vector. In a mouse model of cancer, we demonstrate that this KBMA strain, which cannot replicate in its host, efficiently disseminates into lymphoid organs and delivers its heterologous antigen. The attenuated strain effectively induces a cellular immune response to the cancerous cells while lowering the systemic inflammatory response. Hence, a KBMA P. aeruginosa microsyringe is an efficient and safe tool for in vivo antigen delivery. PMID:23531551

Supersymmetric solutions of N =(1 ,1 ) general massive supergravity

NASA Astrophysics Data System (ADS)

Deger, N. S.; Nazari, Z.; Sarıoǧlu, Ö.

2018-05-01

We construct supersymmetric solutions of three-dimensional N =(1 ,1 ) general massive supergravity (GMG). Solutions with a null Killing vector are, in general, pp-waves. We identify those that appear at critical points of the model, some of which do not exist in N =(1 ,1 ) new massive supergravity (NMG). In the timelike case, we find that many solutions are common with NMG, but there is a new class that is genuine to GMG, two members of which are stationary Lifshitz and timelike squashed AdS spacetimes. We also show that in addition to the fully supersymmetric AdS vacuum, there is a second AdS background with a nonzero vector field that preserves 1 /4 supersymmetry.

3D hydrophobic moment vectors as a tool to characterize the surface polarity of amphiphilic peptides.

PubMed

Reißer, Sabine; Strandberg, Erik; Steinbrecher, Thomas; Ulrich, Anne S

2014-06-03

The interaction of membranes with peptides and proteins is largely determined by their amphiphilic character. Hydrophobic moments of helical segments are commonly derived from their two-dimensional helical wheel projections, and the same is true for β-sheets. However, to the best of our knowledge, there exists no method to describe structures in three dimensions or molecules with irregular shape. Here, we define the hydrophobic moment of a molecule as a vector in three dimensions by evaluating the surface distribution of all hydrophilic and lipophilic regions over any given shape. The electrostatic potential on the molecular surface is calculated based on the atomic point charges. The resulting hydrophobic moment vector is specific for the instantaneous conformation, and it takes into account all structural characteristics of the molecule, e.g., partial unfolding, bending, and side-chain torsion angles. Extended all-atom molecular dynamics simulations are then used to calculate the equilibrium hydrophobic moments for two antimicrobial peptides, gramicidin S and PGLa, under different conditions. We show that their effective hydrophobic moment vectors reflect the distribution of polar and nonpolar patches on the molecular surface and the calculated electrostatic surface potential. A comparison of simulations in solution and in lipid membranes shows how the peptides undergo internal conformational rearrangement upon binding to the bilayer surface. A good correlation with solid-state NMR data indicates that the hydrophobic moment vector can be used to predict the membrane binding geometry of peptides. This method is available as a web application on http://www.ibg.kit.edu/HM/. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Long-term modulation of cosmic rays during solar cycle 21

NASA Technical Reports Server (NTRS)

Fenton, A. G.; Fenton, K. B.; Humble, J. E.

1985-01-01

A preliminary result concerning the rigidity dependence of the longer-term solar cycle modulation is reported. The long-term modulation, using monthly mean intensities and referred to November 1977 as a normalizing level, appear to be in accordance with the exponent gamma = 1, provided only Brisbane and Hobart data are used. Darwin data do not conform to this pattern except perhaps during the early years of the cycle until about the end of 1980, since when the Darwin long-term intensity has been largely steady, apart from Forbush-type decreases and the as yet unidentified vector from the observed SI vector. The true SI vector of galactic origin can be obtained. The resultant vector has the amplitude of 0.031% and the phase of 2.3h. The present result seems to be consistent with those so far reported.

[Construction, expression and characterization of the fusion gene of super-antigen SEA and single chain Fv of the ND-1 monoclonal antibody against human colorectal cancer].

PubMed

Chen, Hang; Li, Li; Fang, Jin

2012-04-01

To construct and express the recombinant ND-1-scFv/SEA, a fusion protein of superantigen (staphylococcal enterotoxinA, SEA) and single-chain variable fragment of monoclonal antibody ND-1 against human clolorectal carcinoma, and to enhance the targeted killing effect of SEA. The expression of the fusion protein was induced in E.coli M15 by IPTG. Ni-NTA resin affinity chromatography was used to separate and purify the expressed product. The specific binding activity of the purified ND-1-scFv/SEA protein was examined by indirect immunofluorescence assay and the targeted-cytotoxicity was determined using MTT assay. The expressing vector of fusion gene ND-1scFv/SEA was constructed successfully. ND-1-scFv/SEA protein retained a high binding affinity to antigen-positive human colorectal cancer cell CCL-187 and had a stronger capability to activate PBMC and kill the target cells compared to SEA alone, with a killing rate of 91% at 4 μg/mL. ND-1-scFv/SEA fusion protein could specifically target colorectal cancer cell, enhance the activity of kill tumor cell and has potential applications in the targeted therapy of colorectal cancer.

A FRET-Based Method for Probing the Conformational Behavior of an Intrinsically Disordered Repeat Domain from Bordetella pertussis Adenylate Cyclase

DTIC Science & Technology

2009-10-22

ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES...MONITORING AGENCY NAME( S ) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM( S ) 11. SPONSOR/MONITOR’S REPORT NUMBER( S ) 12. DISTRIBUTION/AVAILABILITY STATEMENT...fusion protein C*-BR( S )-Y* expression vector pET/C*-CyaA1488-1680-Y*, nonfluorescent CFP expression vector pET/CFP*, and the maltose binding protein-RTX

Oviposition Site Selection by the Dengue Vector Aedes aegypti and Its Implications for Dengue Control

PubMed Central

Wong, Jacklyn; Stoddard, Steven T.; Astete, Helvio; Morrison, Amy C.; Scott, Thomas W.

2011-01-01

Background Because no dengue vaccine or antiviral therapy is commercially available, controlling the primary mosquito vector, Aedes aegypti, is currently the only means to prevent dengue outbreaks. Traditional models of Ae. aegypti assume that population dynamics are regulated by density-dependent larval competition for food and little affected by oviposition behavior. Due to direct impacts on offspring survival and development, however, mosquito choice in oviposition site can have important consequences for population regulation that should be taken into account when designing vector control programs. Methodology/Principal Findings We examined oviposition patterns by Ae. aegypti among 591 naturally occurring containers and a set of experimental containers in Iquitos, Peru. Using larval starvation bioassays as an indirect measure of container food content, we assessed whether females select containers with the most food for their offspring. Our data indicate that choice of egg-laying site is influenced by conspecific larvae and pupae, container fill method, container size, lid, and sun exposure. Although larval food positively influenced oviposition, our results did not support the hypothesis that females act primarily to maximize food for larvae. Females were most strongly attracted to sites containing immature conspecifics, even when potential competitors for their progeny were present in abundance. Conclusion/Significance Due to strong conspecific attraction, egg-laying behavior may contribute more to regulating Ae. aegypti populations than previously thought. If highly infested containers are targeted for removal or larvicide application, females that would have preferentially oviposited in those sites may instead distribute their eggs among other suitable, previously unoccupied containers. Strategies that kill mosquitoes late in their development (i.e., insect growth regulators that kill pupae rather than larvae) will enhance vector control by creating “egg sinks,” treated sites that exploit conspecific attraction of ovipositing females, but reduce emergence of adult mosquitoes via density-dependent larval competition and late acting insecticide. PMID:21532736

Synergy between repellents and organophosphates on bed nets: efficacy and behavioural response of natural free-flying An. gambiae mosquitoes.

PubMed

Pennetier, Cédric; Costantini, Carlo; Corbel, Vincent; Licciardi, Séverine; Dabiré, Roch K; Lapied, Bruno; Chandre, Fabrice; Hougard, Jean-Marc

2009-11-19

Chemicals are used on bed nets in order to prevent infected bites and to kill aggressive malaria vectors. Because pyrethroid resistance has become widespread in the main malaria vectors, research for alternative active ingredients becomes urgent. Mixing a repellent and a non-pyrethroid insecticide seemed to be a promising tool as mixtures in the laboratory showed the same features as pyrethroids. We present here the results of two trials run against free-flying Anopheles gambiae populations comparing the effects of two insect repellents (either DEET or KBR 3023, also known as icaridin) and an organophosphate insecticide at low-doses (pirimiphos-methyl, PM) used alone and in combination on bed nets. We showed that mixtures of PM and the repellents induced higher exophily, blood feeding inhibition and mortality among wild susceptible and resistant malaria vectors than compounds used alone. Nevertheless the synergistic interactions are only involved in the high mortality induced by the two mixtures. These field trials argue in favour of the strategy of mixing repellent and organophosphate on bed nets to better control resistant malaria vectors.

Host preference of the vector beetle, host resistance, and expanding patterns of Japanese oak wilt in a stand

Treesearch

Kazuyoshi Futai; Hiroaki Kiku; Hong-ye Qi; Hagus Tarn; Yuko Takeuchi; Michimasa Yamasaki

2012-01-01

Since the early 1980s, an epidemic forest disease, Japanese Oak Wilt (JOW), has been spreading from coastal areas along the Sea of Japan to the interior of Honshu island and has been devastating huge areas of forests by killing an enormous number of oak trees in urban fringe mountains, gardens, and parks. The disease is caused by a fungus, Raffaelea...

Field tests on the residual effectiveness of deposits of malathion and Bayer 29493 against resistant Anopheles albimanus in El Salvador*

PubMed Central

Schoof, H. F.; Mathis, Willis; Austin, J. R.

1961-01-01

The appearance of resistance to both dieldrin and DDT in several malaria vectors has intensified investigations on the potential of organophosphorus compounds for residual application. This report describes the final year's activities of a three-year study on malathion. Water-wettable formulations of malathion and of Bayer 29493 were evaluated against DDT/dieldrin-resistant Anopheles albimanus in El Salvador. The results indicate that neither compound at a dosage of 0.5 g/m2 offers any promise as a residual agent. At dosages of 1.0 g/m2 or 2.0 g/m2 the two toxicants gave effective kills (70%-100%) for periods of 21/2-3 months, based on 1-hour exposure to the treated surfaces. Up to 3 months, both compounds gave similar levels of effectiveness on wood, thatch, and mud. On whitewash and plaster surfaces, Bayer 29493 was superior to malathion. The findings indicate that each insecticide has considerable potential value for residual treatment in areas where the malaria vector cannot be killed effectively by either DDT or dieldrin. In such areas, further investigation into their utility as replacements for the chlorinated hydrocarbon insecticides is warranted. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:13748489

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.

PubMed

See, Raymond H; Petric, Martin; Lawrence, David J; Mok, Catherine P Y; Rowe, Thomas; Zitzow, Lois A; Karunakaran, Karuna P; Voss, Thomas G; Brunham, Robert C; Gauldie, Jack; Finlay, B Brett; Roper, Rachel L

2008-09-01

Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.

Antitumor activity of cytotoxic T lymphocytes engineered to target vascular endothelial growth factor receptors

NASA Astrophysics Data System (ADS)

Niederman, Thomas M. J.; Ghogawala, Zoher; Carter, Bob S.; Tompkins, Hillary S.; Russell, Margaret M.; Mulligan, Richard C.

2002-05-01

The demonstration that angiogenesis is required for the growth of solid tumors has fueled an intense interest in the development of new therapeutic strategies that target the tumor vasculature. Here we report the development of an immune-based antiangiogenic strategy that is based on the generation of T lymphocytes that possess a killing specificity for cells expressing vascular endothelial growth factor receptors (VEGFRs). To target VEGFR-expressing cells, recombinant retroviral vectors were generated that encoded a chimeric T cell receptor comprised of VEGF sequences linked to intracellular signaling sequences derived from the chain of the T cell receptor. After transduction of primary murine CD8 lymphocytes by such vectors, the transduced cells were shown to possess an efficient killing specificity for cells expressing the VEGF receptor, Flk-1, as measured by in vitro cytotoxicity assays. After adoptive transfer into tumor-bearing mice, the genetically modified cytotoxic T lymphocytes strongly inhibited the growth of a variety of syngeneic murine tumors and human tumor xenografts. An increased effect on in vivo tumor growth inhibition was seen when this therapy was combined with the systemic administration of TNP-470, a conventional angiogenesis inhibitor. The utilization of the immune system to target angiogenic markers expressed on tumor vasculature may prove to be a powerful means for controlling tumor growth.

Photoacoustically-guided photothermal killing of mosquitoes targeted by nanoparticles.

PubMed

Foster, Stephen R; Galanzha, Ekaterina I; Totten, Daniel C; Beneš, Helen; Shmookler Reis, Robert J; Zharov, Vladimir P

2014-07-01

In biomedical applications, nanoparticles have demonstrated the potential to eradicate abnormal cells in small localized pathological zones associated with cancer or infections. Here, we introduce a method for nanotechnology-based photothermal (PT) killing of whole organisms considered harmful to humans or the environment. We demonstrate that laser-induced thermal, and accompanying nano- and microbubble phenomena, can injure or kill C. elegans and mosquitoes fed carbon nanotubes, gold nanospheres, gold nanoshells, or magnetic nanoparticles at laser energies that are safe for humans. In addition, a photoacoustic (PA) effect was used to control nanoparticle delivery. Through the integration of this technique with molecular targeting, nanoparticle clustering, magnetic capturing and spectral sharpening of PA and PT plasmonic resonances, our laser-based PA-PT nano-theranostic platform can be applied to detection and the physical destruction of small organisms and carriers of pathogens, such as malaria vectors, spiders, bed bugs, fleas, ants, locusts, grasshoppers, phytophagous mites, or other arthropod pests, irrespective of their resistance to conventional treatments. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhibitors Selective for Mycobacterial Versus Human Proteasomes

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

Lin, G.; Li, D; Sorio de Carvalho, L

Many anti-infectives inhibit the synthesis of bacterial proteins, but none selectively inhibits their degradation. Most anti-infectives kill replicating pathogens, but few preferentially kill pathogens that have been forced into a non-replicating state by conditions in the host. To explore these alternative approaches we sought selective inhibitors of the proteasome of Mycobacterium tuberculosis. Given that the proteasome structure is extensively conserved, it is not surprising that inhibitors of all chemical classes tested have blocked both eukaryotic and prokaryotic proteasomes, and no inhibitor has proved substantially more potent on proteasomes of pathogens than of their hosts. Here we show that certain oxathiazol-2-onemore » compounds kill non-replicating M.?tuberculosis and act as selective suicide-substrate inhibitors of the M.?tuberculosis proteasome by cyclocarbonylating its active site threonine. Major conformational changes protect the inhibitor-enzyme intermediate from hydrolysis, allowing formation of an oxazolidin-2-one and preventing regeneration of active protease. Residues outside the active site whose hydrogen bonds stabilize the critical loop before and after it moves are extensively non-conserved. This may account for the ability of oxathiazol-2-one compounds to inhibit the mycobacterial proteasome potently and irreversibly while largely sparing the human homologue.« less

Double gauge invariance and covariantly-constant vector fields in Weyl geometry

NASA Astrophysics Data System (ADS)

Kassandrov, Vladimir V.; Rizcallah, Joseph A.

2014-08-01

The wave equation and equations of covariantly-constant vector fields (CCVF) in spaces with Weyl nonmetricity turn out to possess, in addition to the canonical conformal-gauge, a gauge invariance of another type. On a Minkowski metric background, the CCVF system alone allows us to pin down the Weyl 4-metricity vector, identified herein with the electromagnetic potential. The fundamental solution is given by the ordinary Lienard-Wiechert field, in particular, by the Coulomb distribution for a charge at rest. Unlike the latter, however, the magnitude of charge is necessarily unity, "elementary", and charges of opposite signs correspond to retarded and advanced potentials respectively, thus establishing a direct connection between the particle/antiparticle asymmetry and the "arrow of time".

Asymptotic structure of the Einstein-Maxwell theory on AdS3

NASA Astrophysics Data System (ADS)

Pérez, Alfredo; Riquelme, Miguel; Tempo, David; Troncoso, Ricardo

2016-02-01

The asymptotic structure of AdS spacetimes in the context of General Relativity coupled to the Maxwell field in three spacetime dimensions is analyzed. Although the fall-off of the fields is relaxed with respect to that of Brown and Henneaux, the variation of the canonical generators associated to the asymptotic Killing vectors can be shown to be finite once required to span the Lie derivative of the fields. The corresponding surface integrals then acquire explicit contributions from the electromagnetic field, and become well-defined provided they fulfill suitable integrability conditions, implying that the leading terms of the asymptotic form of the electromagnetic field are functionally related. Consequently, for a generic choice of boundary conditions, the asymptotic symmetries are broken down to {R}⊗ U(1)⊗ U(1) . Nonetheless, requiring compatibility of the boundary conditions with one of the asymptotic Virasoro symmetries, singles out the set to be characterized by an arbitrary function of a single variable, whose precise form depends on the choice of the chiral copy. Remarkably, requiring the asymptotic symmetries to contain the full conformal group selects a very special set of boundary conditions that is labeled by a unique constant parameter, so that the algebra of the canonical generators is given by the direct sum of two copies of the Virasoro algebra with the standard central extension and U (1). This special set of boundary conditions makes the energy spectrum of electrically charged rotating black holes to be well-behaved.

Gauge Theories of Vector Particles

DOE R&D Accomplishments Database

Glashow, S. L.; Gell-Mann, M.

1961-04-24

The possibility of generalizing the Yang-Mills trick is examined. Thus we seek theories of vector bosons invariant under continuous groups of coordinate-dependent linear transformations. All such theories may be expressed as superpositions of certain "simple" theories; we show that each "simple theory is associated with a simple Lie algebra. We may introduce mass terms for the vector bosons at the price of destroying the gauge-invariance for coordinate-dependent gauge functions. The theories corresponding to three particular simple Lie algebras - those which admit precisely two commuting quantum numbers - are examined in some detail as examples. One of them might play a role in the physics of the strong interactions if there is an underlying super-symmetry, transcending charge independence, that is badly broken. The intermediate vector boson theory of weak interactions is discussed also. The so-called "schizon" model cannot be made to conform to the requirements of partial gauge-invariance.

Coherent Conformational Degrees of Freedom as a Structural Basis for Allosteric Communication

PubMed Central

Mitternacht, Simon; Berezovsky, Igor N.

2011-01-01

Conformational changes in allosteric regulation can to a large extent be described as motion along one or a few coherent degrees of freedom. The states involved are inherent to the protein, in the sense that they are visited by the protein also in the absence of effector ligands. Previously, we developed the measure binding leverage to find sites where ligand binding can shift the conformational equilibrium of a protein. Binding leverage is calculated for a set of motion vectors representing independent conformational degrees of freedom. In this paper, to analyze allosteric communication between binding sites, we introduce the concept of leverage coupling, based on the assumption that only pairs of sites that couple to the same conformational degrees of freedom can be allosterically connected. We demonstrate how leverage coupling can be used to analyze allosteric communication in a range of enzymes (regulated by both ligand binding and post-translational modifications) and huge molecular machines such as chaperones. Leverage coupling can be calculated for any protein structure to analyze both biological and latent catalytic and regulatory sites. PMID:22174669

A proposal for the molecular basis of μ and δ opiate receptor differentiation based on modeling of two types of cyclic enkephalins and a narcotic alkaloid

NASA Astrophysics Data System (ADS)

Michel, André; Villeneuve, Gérald; DiMaio, John

1991-12-01

The molecular basis underlying the divergent receptor selectivity of two cyclic opioid peptides Tyr-c[ N δ- d-Orn2-Gly-Phe-Leu-] (c-ORN) and [ d-Pen2, l-Cys5]-enkephalinamide (c-PEN) was investigated using a molecular modeling approach. Ring closure and conformational searching procedures were used to determine low-energy cyclic backbone conformers. Following reinsertion of amino acid side chains, the narcotic alkaloid 7α-[(1R)-1-methyl-1-hydroxy-3-phenylpropyl]-6,14-endoethenotetrahydro oripavine (PEO) was used as a flexible template for bimolecular superpositions with each of the determined peptide ring conformers using the coplanarity and cocentricity of the phenolic rings as the minimum constraint. A vector space of PEO, accounting for all possible orientations for the C21-aromatic ring of PEO served as a geometrical locus for the aromatic ring of the Phe4 residue in the opioid peptides. Although a vast number of polypeptide conformations satisfied the criteria of the opiate pharmacophore, they could be grouped into three classes differing in magnitude and sign of the torsional angle values of the tyrosyl side chain. Only class III conformers for both c-ORN and c-PEN, having tyramine dihedral angles χ1 =-150° ± 30° and χ2=-155° ± 20°, had significant structural and conformational properties that were mutually compatible while respecting the PEO vector space. Comparison of these properties in the context of the divergent receptor selectivity of the studied opioid peptides suggests that the increased distortion of the peptide backbone in the closure region of c-PEN together with the pendant β,β-dimethyl group, combine to generate a steric volume which is absent in c-ORN and that may be incompatible with a restrictive topography of the μ receptor. The nature and stereo-chemistry of substituents adjacent to the closure region of the peptides could also modulate receptor selection by interacting with a charged (δ) or neutral (μ) subsite.

Universal properties of the near-horizon optical geometry

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

Gibbons, G. W.; Warnick, C. M.

2009-03-15

Making use of the fact that the optical geometry near a static nondegenerate Killing horizon is asymptotically hyperbolic, we investigate some universal features of black-hole horizons. Applying the Gauss-Bonnet theorem allows us to establish some general properties of gravitational lensing, valid for all black holes. Hyperbolic geometry allows us to find rates for the loss of scalar, vector, and fermionic ''hair'' as objects fall quasistatically towards the horizon, extending previous results for Schwarzschild to all static Killing horizons. In the process we find the Lienard-Wiechert potential for hyperbolic space and calculate the force between electrons mediated by neutrinos, extending themore » flat space result of Feinberg and Sucher. We further demonstrate how these techniques allow us to derive the exact Copson-Linet potential due to a point charge in a Schwarzschild background in a simple fashion.« less

Antipathogen genes and the replacement of disease-vectoring mosquito populations: a model-based evaluation

PubMed Central

Robert, Michael A; Okamoto, Kenichi W; Gould, Fred; Lloyd, Alun L

2014-01-01

Recently, genetic strategies aimed at controlling populations of disease-vectoring mosquitoes have received considerable attention as alternatives to traditional measures. Theoretical studies have shown that female-killing (FK), antipathogen (AP), and reduce and replace (R&R) strategies can each decrease the number competent vectors. In this study, we utilize a mathematical model to evaluate impacts on competent Aedes aegypti populations of FK, AP, and R&R releases as well as hybrid strategies that result from combinations of these three approaches. We show that while the ordering of efficacy of these strategies depends upon population life history parameters, sex ratio of releases, and switch time in combination strategies, AP-only and R&R/AP releases typically lead to the greatest long-term reduction in competent vectors. R&R-only releases are often less effective at long-term reduction of competent vectors than AP-only releases or R&R/AP releases. Furthermore, the reduction in competent vectors caused by AP-only releases is easier to maintain than that caused by FK-only or R&R-only releases even when the AP gene confers a fitness cost. We discuss the roles that density dependence and inclusion of females play in the order of efficacy of the strategies. We anticipate that our results will provide added impetus to continue developing AP strategies. PMID:25558284

Purely electromagnetic spacetimes

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

Ivanov, B. V.

The Rainich's program of describing metrics induced by pure electromagnetic fields is implemented in a simpler way by using the Ernst formalism and increasing the symmetry of spacetime. Stationary metrics possessing one, two or three Killing vectors are studied and classified. Three branches of solutions exist. Electromagnetically induced mass terms appear in two of them, including a class of solutions in harmonic functions. The static subcase is discussed too. Relations to other well-known electrovacuum metrics are elucidated.

Refined human artificial chromosome vectors for gene therapy and animal transgenesis

PubMed Central

Kazuki, Y; Hoshiya, H; Takiguchi, M; Abe, S; Iida, Y; Osaki, M; Katoh, M; Hiratsuka, M; Shirayoshi, Y; Hiramatsu, K; Ueno, E; Kajitani, N; Yoshino, T; Kazuki, K; Ishihara, C; Takehara, S; Tsuji, S; Ejima, F; Toyoda, A; Sakaki, Y; Larionov, V; Kouprina, N; Oshimura, M

2011-01-01

Human artificial chromosomes (HACs) have several advantages as gene therapy vectors, including stable episomal maintenance, and the ability to carry large gene inserts. We previously developed HAC vectors from the normal human chromosomes using a chromosome engineering technique. However, endogenous genes were remained in these HACs, limiting their therapeutic applications. In this study, we refined a HAC vector without endogenous genes from human chromosome 21 in homologous recombination-proficient chicken DT40 cells. The HAC was physically characterized using a transformation-associated recombination (TAR) cloning strategy followed by sequencing of TAR-bacterial artificial chromosome clones. No endogenous genes were remained in the HAC. We demonstrated that any desired gene can be cloned into the HAC using the Cre-loxP system in Chinese hamster ovary cells, or a homologous recombination system in DT40 cells. The HAC can be efficiently transferred to other type of cells including mouse ES cells via microcell-mediated chromosome transfer. The transferred HAC was stably maintained in vitro and in vivo. Furthermore, tumor cells containing a HAC carrying the suicide gene, herpes simplex virus thymidine kinase (HSV-TK), were selectively killed by ganciclovir in vitro and in vivo. Thus, this novel HAC vector may be useful not only for gene and cell therapy, but also for animal transgenesis. PMID:21085194

Lithology and aggregate quality attributes for the digital geologic map of Colorado

USGS Publications Warehouse

Knepper, Daniel H.; Green, Gregory N.; Langer, William H.

1999-01-01

This geologic map was prepared as a part of a study of digital methods and techniques as applied to complex geologic maps. The geologic map was digitized from the original scribe sheets used to prepare the published Geologic Map of Colorado (Tweto 1979). Consequently the digital version is at 1:500,000 scale using the Lambert Conformal Conic map projection parameters of the state base map. Stable base contact prints of the scribe sheets were scanned on a Tektronix 4991 digital scanner. The scanner automatically converts the scanned image to an ASCII vector format. These vectors were transferred to a VAX minicomputer, where they were then loaded into ARC/INFO. Each vector and polygon was given attributes derived from the original 1979 geologic map.

Dip-pen patterning of poly(9,9-dioctylfluorene) chain-conformation-based nano-photonic elements.

PubMed

Perevedentsev, Aleksandr; Sonnefraud, Yannick; Belton, Colin R; Sharma, Sanjiv; Cass, Anthony E G; Maier, Stefan A; Kim, Ji-Seon; Stavrinou, Paul N; Bradley, Donal D C

2015-01-19

Metamaterials are a promising new class of materials, in which sub-wavelength physical structures, rather than variations in chemical composition, can be used to modify the nature of their interaction with electromagnetic radiation. Here we show that a metamaterials approach, using a discrete physical geometry (conformation) of the segments of a polymer chain as the vector for a substantial refractive index change, can be used to enable visible wavelength, conjugated polymer photonic elements. In particular, we demonstrate that a novel form of dip-pen nanolithography provides an effective means to pattern the so-called β-phase conformation in poly(9,9-dioctylfluorene) thin films. This can be done on length scales ≤500 nm, as required to fabricate a variety of such elements, two of which are theoretically modelled using complex photonic dispersion calculations.

The Effects of Climate Change and Globalization on Mosquito Vectors: Evidence from Jeju Island, South Korea on the Potential for Asian Tiger Mosquito (Aedes albopictus) Influxes and Survival from Vietnam Rather Than Japan

PubMed Central

Jeong, Ji Yeon; Yoo, Seung Jin; Koh, Young-Sang; Lee, Seogjae; Heo, Sang Taek; Seong, Seung-Yong; Lee, Keun Hwa

2013-01-01

Background Climate change affects the survival and transmission of arthropod vectors as well as the development rates of vector-borne pathogens. Increased international travel is also an important factor in the spread of vector-borne diseases (VBDs) such as dengue, West Nile, yellow fever, chikungunya, and malaria. Dengue is the most important vector-borne viral disease. An estimated 2.5 billion people are at risk of infection in the world and there are approximately 50 million dengue infections and an estimated 500,000 individuals are hospitalized with dengue haemorrhagic fever annually. The Asian tiger mosquito (Aedes albopictus) is one of the vectors of dengue virus, and populations already exist on Jeju Island, South Korea. Currently, colder winter temperatures kill off Asian tiger mosquito populations and there is no evidence of the mosquitos being vectors for the dengue virus in this location. However, dengue virus-bearing mosquito vectors can inflow to Jeju Island from endemic area such as Vietnam by increased international travel, and this mosquito vector's survival during colder winter months will likely occur due to the effects of climate change. Methods and Results In this section, we show the geographical distribution of medically important mosquito vectors such as Ae. albopictus, a vector of both dengue and chikungunya viruses; Culex pipiens, a vector of West Nile virus; and Anopheles sinensis, a vector of Plasmodium vivax, within Jeju Island, South Korea. We found a significant association between the mean temperature, amount of precipitation, and density of mosquitoes. The phylogenetic analyses show that an Ae. albopictus, collected in southern area of Jeju Island, was identical to specimens found in Ho Chi Minh, Vietnam, and not Nagasaki, Japan. Conclusion Our results suggest that mosquito vectors or virus-bearing vectors can transmit from epidemic regions of Southeast Asia to Jeju Island and can survive during colder winter months. Therefore, Jeju Island is no longer safe from vector borne diseases (VBDs) due to the effects of globalization and climate change, and we should immediately monitor regional climate change to identify newly emerging VBDs. PMID:23894312

The effects of climate change and globalization on mosquito vectors: evidence from Jeju Island, South Korea on the potential for Asian tiger mosquito (Aedes albopictus) influxes and survival from Vietnam rather than Japan.

PubMed

Lee, Su Hyun; Nam, Kwang Woo; Jeong, Ji Yeon; Yoo, Seung Jin; Koh, Young-Sang; Lee, Seogjae; Heo, Sang Taek; Seong, Seung-Yong; Lee, Keun Hwa

2013-01-01

Climate change affects the survival and transmission of arthropod vectors as well as the development rates of vector-borne pathogens. Increased international travel is also an important factor in the spread of vector-borne diseases (VBDs) such as dengue, West Nile, yellow fever, chikungunya, and malaria. Dengue is the most important vector-borne viral disease. An estimated 2.5 billion people are at risk of infection in the world and there are approximately 50 million dengue infections and an estimated 500,000 individuals are hospitalized with dengue haemorrhagic fever annually. The Asian tiger mosquito (Aedes albopictus) is one of the vectors of dengue virus, and populations already exist on Jeju Island, South Korea. Currently, colder winter temperatures kill off Asian tiger mosquito populations and there is no evidence of the mosquitos being vectors for the dengue virus in this location. However, dengue virus-bearing mosquito vectors can inflow to Jeju Island from endemic area such as Vietnam by increased international travel, and this mosquito vector's survival during colder winter months will likely occur due to the effects of climate change. In this section, we show the geographical distribution of medically important mosquito vectors such as Ae. albopictus, a vector of both dengue and chikungunya viruses; Culex pipiens, a vector of West Nile virus; and Anopheles sinensis, a vector of Plasmodium vivax, within Jeju Island, South Korea. We found a significant association between the mean temperature, amount of precipitation, and density of mosquitoes. The phylogenetic analyses show that an Ae. albopictus, collected in southern area of Jeju Island, was identical to specimens found in Ho Chi Minh, Vietnam, and not Nagasaki, Japan. Our results suggest that mosquito vectors or virus-bearing vectors can transmit from epidemic regions of Southeast Asia to Jeju Island and can survive during colder winter months. Therefore, Jeju Island is no longer safe from vector borne diseases (VBDs) due to the effects of globalization and climate change, and we should immediately monitor regional climate change to identify newly emerging VBDs.

CD4 mimetics sensitize HIV-1-infected cells to ADCC.

PubMed

Richard, Jonathan; Veillette, Maxime; Brassard, Nathalie; Iyer, Shilpa S; Roger, Michel; Martin, Loïc; Pazgier, Marzena; Schön, Arne; Freire, Ernesto; Routy, Jean-Pierre; Smith, Amos B; Park, Jongwoo; Jones, David M; Courter, Joel R; Melillo, Bruno N; Kaufmann, Daniel E; Hahn, Beatrice H; Permar, Sallie R; Haynes, Barton F; Madani, Navid; Sodroski, Joseph G; Finzi, Andrés

2015-05-19

HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by limiting the overall amount of Env at the cell surface. Here we report that small-molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1-infected individuals. Importantly, we identified one CD4 mimetic with the capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells to ADCC killing mediated by autologous sera and effector cells. Thus, CD4 mimetics hold the promise of therapeutic utility in preventing and controlling HIV-1 infection.

CD4 mimetics sensitize HIV-1-infected cells to ADCC

PubMed Central

Richard, Jonathan; Veillette, Maxime; Brassard, Nathalie; Iyer, Shilpa S.; Roger, Michel; Martin, Loïc; Pazgier, Marzena; Schön, Arne; Freire, Ernesto; Routy, Jean-Pierre; Smith, Amos B.; Park, Jongwoo; Jones, David M.; Courter, Joel R.; Melillo, Bruno N.; Kaufmann, Daniel E.; Hahn, Beatrice H.; Permar, Sallie R.; Haynes, Barton F.; Madani, Navid; Sodroski, Joseph G.; Finzi, Andrés

2015-01-01

HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by limiting the overall amount of Env at the cell surface. Here we report that small-molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1-infected individuals. Importantly, we identified one CD4 mimetic with the capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells to ADCC killing mediated by autologous sera and effector cells. Thus, CD4 mimetics hold the promise of therapeutic utility in preventing and controlling HIV-1 infection. PMID:25941367

Minimal unitary representation of SO∗(8)=SO(6,2) and its SU(2) deformations as massless 6D conformal fields and their supersymmetric extensions

NASA Astrophysics Data System (ADS)

Fernando, Sudarshan; Günaydin, Murat

2010-12-01

We study the minimal unitary representation (minrep) of SO(6,2) over an Hilbert space of functions of five variables, obtained by quantizing its quasiconformal realization. The minrep of SO(6,2), which coincides with the minrep of SO(8) similarly constructed, corresponds to a massless conformal scalar field in six spacetime dimensions. There exists a family of "deformations" of the minrep of SO(8) labeled by the spin t of an SU(2 subgroup of the little group SO(4) of lightlike vectors. These deformations labeled by t are positive energy unitary irreducible representations of SO(8) that describe massless conformal fields in six dimensions. The SU(2 spin t is the six-dimensional counterpart of U(1) deformations of the minrep of 4D conformal group SU(2,2) labeled by helicity. We also construct the supersymmetric extensions of the minimal unitary representation of SO(8) to minimal unitary representations of OSp(8|2N) that describe massless six-dimensional conformal supermultiplets. The minimal unitary supermultiplet of OSp(8|4) is the massless supermultiplet of (2,0) conformal field theory that is believed to be dual to M-theory on AdS×S.

Synergy between Repellents and Organophosphates on Bed Nets: Efficacy and Behavioural Response of Natural Free-Flying An. gambiae Mosquitoes

PubMed Central

Pennetier, Cédric; Costantini, Carlo; Corbel, Vincent; Licciardi, Séverine; Dabiré, Roch K.; Lapied, Bruno; Chandre, Fabrice; Hougard, Jean-Marc

2009-01-01

Background Chemicals are used on bed nets in order to prevent infected bites and to kill aggressive malaria vectors. Because pyrethroid resistance has become widespread in the main malaria vectors, research for alternative active ingredients becomes urgent. Mixing a repellent and a non-pyrethroid insecticide seemed to be a promising tool as mixtures in the laboratory showed the same features as pyrethroids. Methodology/Principal Findings We present here the results of two trials run against free-flying Anopheles gambiae populations comparing the effects of two insect repellents (either DEET or KBR 3023, also known as icaridin) and an organophosphate insecticide at low-doses (pirimiphos-methyl, PM) used alone and in combination on bed nets. We showed that mixtures of PM and the repellents induced higher exophily, blood feeding inhibition and mortality among wild susceptible and resistant malaria vectors than compounds used alone. Nevertheless the synergistic interactions are only involved in the high mortality induced by the two mixtures. Conclusion These field trials argue in favour of the strategy of mixing repellent and organophosphate on bed nets to better control resistant malaria vectors. PMID:19936249

Symmetry enhancement of extremal horizons in D  =  5 supergravity

NASA Astrophysics Data System (ADS)

Kayani, U.

2018-06-01

We consider the near-horizon geometry of supersymmetric extremal black holes in un-gauged and gauged 5-dimensional supergravity, coupled to abelian vector multiplets. By analyzing the global properties of the Killing spinors, we prove that the near-horizon geometries undergo a supersymmetry enhancement. This follows from a set of generalized Lichnerowicz-type theorems we establish, together with an index theory argument. As a consequence, these solutions always admit a symmetry group.

A Cysteine Protease Is Critical for Babesia spp. Transmission in Haemaphysalis Ticks

PubMed Central

Tsuji, Naotoshi; Miyoshi, Takeharu; Battsetseg, Badger; Matsuo, Tomohide; Xuan, Xuenan; Fujisaki, Kozo

2008-01-01

Vector ticks possess a unique system that enables them to digest large amounts of host blood and to transmit various animal and human pathogens, suggesting the existence of evolutionally acquired proteolytic mechanisms. We report here the molecular and reverse genetic characterization of a multifunctional cysteine protease, longipain, from the babesial parasite vector tick Haemaphysalis longicornis. Longipain shares structural similarity with papain-family cysteine proteases obtained from invertebrates and vertebrates. Endogenous longipain was mainly expressed in the midgut epithelium and was specifically localized at lysosomal vacuoles and possibly released into the lumen. Its expression was up-regulated by host blood feeding. Enzymatic functional assays using in vitro and in vivo substrates revealed that longipain hydrolysis occurs over a broad range of pH and temperature. Haemoparasiticidal assays showed that longipain dose-dependently killed tick-borne Babesia parasites, and its babesiacidal effect occurred via specific adherence to the parasite membranes. Disruption of endogenous longipain by RNA interference revealed that longipain is involved in the digestion of the host blood meal. In addition, the knockdown ticks contained an increased number of parasites, suggesting that longipain exerts a killing effect against the midgut-stage Babesia parasites in ticks. Our results suggest that longipain is essential for tick survival, and may have a role in controlling the transmission of tick-transmittable Babesia parasites. PMID:18483546

Development and evaluation of mosquito-electrocuting traps as alternatives to the human landing catch technique for sampling host-seeking malaria vectors.

PubMed

Maliti, Deodatus V; Govella, Nicodem J; Killeen, Gerry F; Mirzai, Nosrat; Johnson, Paul C D; Kreppel, Katharina; Ferguson, Heather M

2015-12-15

The human landing catch (HLC) is the gold standard method for sampling host-seeking malaria vectors. However, the HLC is ethically questionable because it requires exposure of humans to potentially infectious mosquito bites. Two exposure-free methods for sampling host-seeking mosquitoes were evaluated using electrocuting surfaces as potential replacements for HLC: (1) a previously evaluated, commercially available electrocuting grid (CA-EG) designed for killing flies, and (2) a custom-made mosquito electrocuting trap (MET) designed to kill African malaria vectors. The MET and the CA-EG were evaluated relative to the HLC in a Latin Square experiment conducted in the Kilombero Valley, Tanzania. The sampling consistency of the traps across the night and at varying mosquito densities was investigated. Estimates of the proportion of mosquitoes caught indoors (P(i)), proportion of human exposure occurring indoors (π(i)), and proportion of mosquitoes caught when most people are likely to be indoors (P(fl)) were compared for all traps. Whereas the CA-EG performed poorly (<10% of catch of HLC), sampling efficiency of the MET for sampling Anopheles funestus s.l. was indistinguishable from HLC indoors and outdoors. For Anopheles gambiae s.l., sampling sensitivity of MET was 20.9% (95% CI 10.3-42.2) indoors and 58.5% (95% CI 32.2-106.2) outdoors relative to HLC. There was no evidence of density-dependent sampling by the MET or CA-EG. Similar estimates of P(i) were obtained for An. gambiae s.l. and An. funestus s.l. from all trapping methods. The proportion of mosquitoes caught when people are usually indoors (P(fl)) was underestimated by the CA-EG and MET for An. gambiae s.l., but similar to the HLC for An. funestus. Estimates of the proportion of human exposure occurring indoors (π(i)) obtained from the CA-EG and MET were similar to the HLC for An. gambiae s.l., but overestimated for An. funestus. The MET showed promise as an outdoor sampling tool for malaria vectors where it achieved >50% sampling sensitivity relative to the HLC. The CA-EG had poor sampling sensitivity outdoors and inside. With further modification, the MET could provide an efficient and safer alternative to the HLC for the surveillance of mosquito vectors outdoors.

Parainfluenza Virus Infection Sensitizes Cancer Cells to DNA-Damaging Agents: Implications for Oncolytic Virus Therapy.

PubMed

Fox, Candace R; Parks, Griffith D

2018-04-01

A parainfluenza virus 5 (PIV5) with mutations in the P/V gene (P/V-CPI - ) is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burdens in mouse model systems. Here we show that P/V-CPI - infection of HEp-2 human laryngeal cancer cells results in the majority of the cells dying, but unexpectedly, over time, there is an emergence of a population of cells that survive as P/V-CPI - persistently infected (PI) cells. P/V-CPI - PI cells had elevated levels of basal caspase activation, and viability was highly dependent on the activity of cellular inhibitor-of-apoptosis proteins (IAPs) such as Survivin and XIAP. In challenge experiments with external inducers of apoptosis, PI cells were more sensitive to cisplatin-induced DNA damage and cell death. This increased cisplatin sensitivity correlated with defects in DNA damage signaling pathways such as phosphorylation of Chk1 and translocation of damage-specific DNA binding protein 1 (DDB1) to the nucleus. Cisplatin-induced killing of PI cells was sensitive to the inhibition of wild-type (WT) p53-inducible protein 1 (WIP1), a phosphatase which acts to terminate DNA damage signaling pathways. A similar sensitivity to cisplatin was seen with cells during acute infection with P/V-CPI - as well as during acute infections with WT PIV5 and the related virus human parainfluenza virus type 2 (hPIV2). Our results have general implications for the design of safer paramyxovirus-based vectors that cannot establish PI as well as the potential for combining chemotherapy with oncolytic RNA virus vectors. IMPORTANCE There is intense interest in developing oncolytic viral vectors with increased potency against cancer cells, particularly those cancer cells that have gained resistance to chemotherapies. We have found that infection with cytoplasmically replicating parainfluenza virus can result in increases in the killing of cancer cells by agents that induce DNA damage, and this is linked to alterations to DNA damage signaling pathways that balance cell survival versus death. Our results have general implications for the design of safer paramyxovirus-based vectors that cannot establish persistent infection, the repurposing of drugs that target cellular IAPs as antivirals, and the combined use of DNA-damaging chemotherapy agents in conjunction with oncolytic RNA virus vectors. Copyright © 2018 American Society for Microbiology.

Pilot study on the combination of an organophosphate-based insecticide paint and pyrethroid-treated long lasting nets against pyrethroid resistant malaria vectors in Burkina Faso.

PubMed

Mosqueira, Beatriz; Soma, Dieudonné D; Namountougou, Moussa; Poda, Serge; Diabaté, Abdoulaye; Ali, Ouari; Fournet, Florence; Baldet, Thierry; Carnevale, Pierre; Dabiré, Roch K; Mas-Coma, Santiago

2015-08-01

A pilot study to test the efficacy of combining an organophosphate-based insecticide paint and pyrethroid-treated Long Lasting Insecticide Treated Nets (LLINs) against pyrethroid-resistant malaria vector mosquitoes was performed in a real village setting in Burkina Faso. Paint Inesfly 5A IGR™, comprised of two organophosphates (OPs) and an Insect Growth Regulator (IGR), was tested in combination with pyrethroid-treated LLINs. Efficacy was assessed in terms of mortality for 12 months using Early Morning Collections of malaria vectors and 30-minute WHO bioassays. Resistance to pyrethroids and OPs was assessed by detecting the frequency of L1014F and L1014S kdr mutations and Ace-1(R)G119S mutation, respectively. Blood meal origin was identified using a direct enzyme-linked immunosorbent assay (ELISA). The combination of Inesfly 5A IGR™ and LLINs was effective in killing 99.9-100% of malaria vector populations for 6 months regardless of the dose and volume treated. After 12 months, mortality rates decreased to 69.5-82.2%. The highest mortality rates observed in houses treated with 2 layers of insecticide paint and a larger volume. WHO bioassays supported these results: mortalities were 98.8-100% for 6 months and decreased after 12 months to 81.7-97.0%. Mortality rates in control houses with LLINs were low. Collected malaria vectors consisted exclusively of Anopheles coluzzii and were resistant to pyrethroids, with a L1014 kdr mutation frequency ranging from 60 to 98% through the study. About 58% of An. coluzzii collected inside houses had bloodfed on non-human animals. Combining Inesfly 5A IGR™ and LLINs yielded a one year killing efficacy against An. coluzzii highly resistant to pyrethroids but susceptible to OPs that exhibited an anthropo-zoophilic behaviour in the study area. The results obtained in a real setting supported previous work performed in experimental huts and underscore the need to study the impact that this novel strategy may have on clinical malaria and malaria exposure in children in a similar area of high pyrethroid resistance in South-Western Burkina Faso. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Krtous, Pavel; Frolov, Valeri P.; Kubiznak, David

We prove that the most general solution of the Einstein equations with the cosmological constant which admits a principal conformal Killing-Yano tensor is the Kerr-NUT-(A)dS metric. Even when the Einstein equations are not imposed, any spacetime admitting such hidden symmetry can be written in a canonical form which guarantees the following properties: it is of the Petrov type D, it allows the separation of variables for the Hamilton-Jacobi, Klein-Gordon, and Dirac equations, the geodesic motion in such a spacetime is completely integrable. These results naturally generalize the results obtained earlier in four dimensions.

Development of recombinant adeno-associated virus vectors carrying small interfering RNA (shHec1)-mediated depletion of kinetochore Hec1 protein in tumor cells.

PubMed

Li, L; Yang, L; Scudiero, D A; Miller, S A; Yu, Z-X; Stukenberg, P T; Shoemaker, R H; Kotin, R M

2007-05-01

Transcript depletion using small interfering RNA (siRNA) technology represents a potentially valuable technique for the treatment of cancer. However, delivering therapeutic quantities of siRNA into solid tumors by chemical transfection is not feasible, whereas viral vectors efficiently transduce many human tumor cell lines. Yet producing sufficient quantities of viral vectors that elicit acute and selective cytotoxicity remains a major obstacle for preclinical and clinical trials. Using the invertebrate Spodoptera frugiperda (Sf9) cell line, we were able to produce high titer stocks of cytotoxic recombinant adeno-associated virus (rAAV) that express short hairpin RNA (shRNA) and that efficiently deplete Hec1 (highly expressed in cancer 1), or Kntc2 (kinetochore-associated protein 2), a kinetochore protein directly involved in kinetochore microtubule interactions, chromosome congression and spindle checkpoint signaling. Depletion of Hec1 protein results in persistent spindle checkpoint activation followed by cell death. Because Hec1 expression and activity are only present in mitotic cells, non-dividing cells were not affected by rAAV treatment. On the basis of the results of screening 56 human tumor cell lines with three different serotype vectors, we used a tumor xenograft model to test the effects in vivo. The effects of the shHec1 vector were evident in sectioned and stained tumors. The experiments with rAAV-shRNA vectors demonstrate the utility of producing vectors in invertebrate cells to obtain sufficient concentrations and quantities for solid tumor therapy. This addresses an important requirement for cancer gene therapy, to produce cytotoxic vectors in sufficient quantities and concentrations to enable quantitative transduction and selective killing of solid tumor cells.

Protein-driven RNA nanostructured devices that function in vitro and control mammalian cell fate.

PubMed

Shibata, Tomonori; Fujita, Yoshihiko; Ohno, Hirohisa; Suzuki, Yuki; Hayashi, Karin; Komatsu, Kaoru R; Kawasaki, Shunsuke; Hidaka, Kumi; Yonehara, Shin; Sugiyama, Hiroshi; Endo, Masayuki; Saito, Hirohide

2017-09-14

Nucleic acid nanotechnology has great potential for future therapeutic applications. However, the construction of nanostructured devices that control cell fate by detecting and amplifying protein signals has remained a challenge. Here we design and build protein-driven RNA-nanostructured devices that actuate in vitro by RNA-binding-protein-inducible conformational change and regulate mammalian cell fate by RNA-protein interaction-mediated protein assembly. The conformation and function of the RNA nanostructures are dynamically controlled by RNA-binding protein signals. The protein-responsive RNA nanodevices are constructed inside cells using RNA-only delivery, which may provide a safe tool for building functional RNA-protein nanostructures. Moreover, the designed RNA scaffolds that control the assembly and oligomerization of apoptosis-regulatory proteins on a nanometre scale selectively kill target cells via specific RNA-protein interactions. These findings suggest that synthetic RNA nanodevices could function as molecular robots that detect signals and localize target proteins, induce RNA conformational changes, and programme mammalian cellular behaviour.Nucleic acid nanotechnology has great potential for future therapeutic applications. Here the authors build protein-driven RNA nanostructures that can function within mammalian cells and regulate the cell fate.

Dark matter as a ghost free conformal extension of Einstein theory

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

Barvinsky, A.O., E-mail: barvin@td.lpi.ru

We discuss ghost free models of the recently suggested mimetic dark matter theory. This theory is shown to be a conformal extension of Einstein general relativity. Dark matter originates from gauging out its local Weyl invariance as an extra degree of freedom which describes a potential flow of the pressureless perfect fluid. For a positive energy density of this fluid the theory is free of ghost instabilities, which gives strong preference to stable configurations with a positive scalar curvature and trace of the matter stress tensor. Instabilities caused by caustics of the geodesic flow, inherent in this model, serve asmore » a motivation for an alternative conformal extension of Einstein theory, based on the generalized Proca vector field. A potential part of this field modifies the inflationary stage in cosmology, whereas its rotational part at the post inflationary epoch might simulate rotating flows of dark matter.« less

Effects of annealing and conformal alumina passivation on anisotropy and hysteresis of magneto-optical properties of cobalt slanted columnar thin films

NASA Astrophysics Data System (ADS)

Briley, Chad; Mock, Alyssa; Korlacki, Rafał; Hofmann, Tino; Schubert, Eva; Schubert, Mathias

2017-11-01

We present magneto-optical dielectric tensor data of cobalt and cobalt oxide slanted columnar thin films obtained by vector magneto-optical generalized ellipsometry. Room-temperature hysteresis magnetization measurements were performed in longitudinal and polar Kerr geometries on samples prior to and after a heat treatment process with and without a conformal Al2O3 passivation coating. The samples have been characterized by generalized ellipsometry, scanning electron microscopy, and Raman spectroscopy in conjuncture with density functional theory. We observe strongly anisotropic hysteresis behaviors, which depend on the nanocolumn and magnetizing field orientations. We find that deposited cobalt films that have been exposed to heat treatment and subsequent atmospheric oxidation into Co3O4, when not conformally passivated, reveal no measurable magneto-optical properties while cobalt films with passivation coatings retain highly anisotropic magneto-optical properties.

Population genetic structure of the dengue mosquito Aedes aegypti in Venezuela.

PubMed

Herrera, Flor; Urdaneta, Ludmel; Rivero, José; Zoghbi, Normig; Ruiz, Johanny; Carrasquel, Gabriela; Martínez, José Antonio; Pernalete, Martha; Villegas, Patricia; Montoya, Ana; Rubio-Palis, Yasmin; Rojas, Elina

2006-09-01

The mosquito Aedes aegypti is the main vector of dengue in Venezuela. The genetic structure of this vector was investigated in 24 samples collected from eight geographic regions separated by up to 1160 km. We examined the distribution of a 359-basepair region of the NADH dehydrogenase subunit 4 mitochondrial gene among 1144 Ae. aegypti from eight collections. This gene was amplified by the polymerase chain reaction and tested for variation using single strand conformation polymorphism analysis. Seven haplotypes were detected throughout Venezuela and these were sorted into two clades. Significant differentiation was detected among collections and these were genetically isolated by distance.

Discovery of Rigidified α,β-Unsaturated Imines as New Resistance-breaking Insecticides for Malaria Vector Control.

PubMed

Arlt, Alexander; Böhnke, Niels; Horstmann, Sebastian; Vermeer, Arnoldus W P; Werner, Stefan; Velten, Robert

2016-10-01

During our continuous search for new resistance-breaking insecticides applicable to malaria vector control, a new class of α,β-unsaturated imines was identified by applying the principle of conformational rigidification as a powerful tool for compound optimisation. Herein we describe the successful synthesis of these compounds and their biological test results. Our lead compound 16 from this insecticidal class outperforms market standards, notably for the control of mosquito strains that exhibit either metabolic or target-site resistance to these established insecticides. In our model system for insecticide-treated mosquito nets the compound reveals long-lasting efficacy for up to several months.

Causal structures in Gauss-Bonnet gravity

NASA Astrophysics Data System (ADS)

Izumi, Keisuke

2014-08-01

We analyze causal structures in Gauss-Bonnet gravity. It is known that Gauss-Bonnet gravity potentially has superluminal propagation of gravitons due to its noncanonical kinetic terms. In a theory with superluminal modes, an analysis of causality based on null curves makes no sense, and thus, we need to analyze them in a different way. In this paper, using the method of the characteristics, we analyze the causal structure in Gauss-Bonnet gravity. We have the result that, on a Killing horizon, gravitons can propagate in the null direction tangent to the Killing horizon. Therefore, a Killing horizon can be a causal edge as in the case of general relativity; i.e. a Killing horizon is the "event horizon" in the sense of causality. We also analyze causal structures on nonstationary solutions with (D-2)-dimensional maximal symmetry, including spherically symmetric and flat spaces. If the geometrical null energy condition, RABNANB≥0 for any null vector NA, is satisfied, the radial velocity of gravitons must be less than or equal to that of light. However, if the geometrical null energy condition is violated, gravitons can propagate faster than light. Hence, on an evaporating black hole where the geometrical null energy condition is expected not to hold, classical gravitons can escape from the "black hole" defined with null curves. That is, the causal structures become nontrivial. It may be one of the possible solutions for the information loss paradox of evaporating black holes.

Trypanosoma cruzi: partial prevention of the natural infection of guinea pigs with a killed parasite vaccine.

PubMed

Basombrio, M A

1990-07-01

Guinea pigs are natural reservoirs of Chagas' disease. Domestic breeding and local trade of these animals are common practices among andean communities in South America. Infection by Trypanosoma cruzi occurs when the animals live in triatomine-infested houses or yards. The preventive effect of a vaccine consisting of cultured T. cruzi killed by freezing and thawing plus saponin was tested both in mice and in the guinea pig ecosystem. Resistance against T. cruzi challenge in mice was improved by increasing the trypomastigote/epimastigote ratio in live attenuated vaccines but not in killed parasite vaccines. Although the killing of attenuated parasites sharply reduced their immunogenicity for mice, a protective effect against natural T. cruzi infection was detected in guinea pigs. A total of 88 guinea pigs were vaccinated in four intradermal sites on three occasions. Eighty controls received similar inoculations of culture medium plus saponin. All animals were kept in a triatomine-infested yard. Parasitemia was studied with the capillary microhematocrit method. After an exposure time averaging 4 months, natural T. cruzi infection occurred in 55% (44/80) of the controls and in 33% (29/88) of the vaccinated group (P less than 0.01). The number of highly parasitemic guinea pigs was also significantly decreased (6/80 vs 0/88, P less than 0.01). Thus, immunizing protocols which are only partially protective against artificial callenge with T. cruzi may nevertheless constrain the exchange of parasites between natural hosts and vectors.

Determination of Airborne Concentrations of Dichlorvos Over a Range of Temperatures When Using Commercially Available Pesticide Strips In a Simulated Military Guard Post

DTIC Science & Technology

2013-03-22

insects, such as mosquitoes and sand flies. Currently, in the Afghanistan area of operations (AO), there is an intermediate to high risk for vector...Agency (EPA) to kill flies, mosquitoes , gnats, bedbugs, and other arthropod pests. Available in two sizes, the strips are hung in an enclosed room with...toluamide (DEET) to repel biting insects, further assists in protecting exposed personnel. Buildings and areas are also protected from insects by

Gyroscope precession along bound equatorial plane orbits around a Kerr black hole

NASA Astrophysics Data System (ADS)

Bini, Donato; Geralico, Andrea; Jantzen, Robert T.

2016-09-01

The precession of a test gyroscope along stable bound equatorial plane orbits around a Kerr black hole is analyzed, and the precession angular velocity of the gyro's parallel transported spin vector and the increment in the precession angle after one orbital period is evaluated. The parallel transported Marck frame which enters this discussion is shown to have an elegant geometrical explanation in terms of the electric and magnetic parts of the Killing-Yano 2-form and a Wigner rotation effect.

Limit cycles and conformal invariance

NASA Astrophysics Data System (ADS)

Fortin, Jean-François; Grinstein, Benjamín; Stergiou, Andreas

2013-01-01

There is a widely held belief that conformal field theories (CFTs) require zero beta functions. Nevertheless, the work of Jack and Osborn implies that the beta functions are not actually the quantites that decide conformality, but until recently no such behavior had been exhibited. Our recent work has led to the discovery of CFTs with nonzero beta functions, more precisely CFTs that live on recurrent trajectories, e.g., limit cycles, of the beta-function vector field. To demonstrate this we study the S function of Jack and Osborn. We use Weyl consistency conditions to show that it vanishes at fixed points and agrees with the generator Q of limit cycles on them. Moreover, we compute S to third order in perturbation theory, and explicitly verify that it agrees with our previous determinations of Q. A byproduct of our analysis is that, in perturbation theory, unitarity and scale invariance imply conformal invariance in four-dimensional quantum field theories. Finally, we study some properties of these new, "cyclic" CFTs, and point out that the a-theorem still governs the asymptotic behavior of renormalization-group flows.

Hypoxia/hepatoma dual specific suicide gene expression plasmid delivery using bio-reducible polymer for hepatocellular carcinoma therapy.

PubMed

Kim, Hyun Ah; Nam, Kihoon; Lee, Minhyung; Kim, Sung Wan

2013-10-10

Gene therapy is suggested as a promising alternative strategy of hepatocellular carcinoma (HCC, also called hepatoma) therapy. To achieve a successful and safe gene therapy, tight regulation of gene expression is required to minimize side-effects in normal tissues. In this study, we developed a novel hypoxia and hepatoma dual specific gene expression vector. The constructed vectors were transfected into various cell lines using bio-reducible polymer, PAM-ABP. First, pAFPS-Luc or pAFPL-Luc vector was constructed with the alpha-fectoprotein (AFP) promoter and enhancer for hepatoma tissue specific gene expression. Then, pEpo-AFPL-Luc was constructed by insertion of the erythropoietin (Epo) enhancer for hypoxic cancer specific gene expression. In vitro transfection assay showed that pEpo-AFPL-Luc transfected hepatoma cell increased gene expression under hypoxic condition. To confirm the therapeutic effect of dual specific vector, herpes simplex virus thymidine kinase (HSV-TK) gene was introduced for cancer cell killing. The pEpo-AFPL-TK was transfected into hepatoma cell lines in the presence of ganciclovir (GCV) pro-drug. Caspase-3/7, MTT and TUNEL assays elucidated that pEpo-AFPL-TK transfected cells showed significant increasing of death rate in hypoxic hepatoma cells compared to controls. Therefore, the hypoxia/hepatoma dual specific gene expression vector with the Epo enhancer and AFP promoter may be useful for hepatoma specific gene therapy. © 2013.

Developing an expanded vector control toolbox for malaria elimination

PubMed Central

Tatarsky, Allison; Diabate, Abdoulaye; Chaccour, Carlos J; Marshall, John M; Okumu, Fredros O; Brunner, Shannon; Newby, Gretchen; Williams, Yasmin A; Malone, David; Tusting, Lucy S; Gosling, Roland D

2017-01-01

Vector control using long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) accounts for most of the malaria burden reductions achieved recently in low and middle-income countries (LMICs). LLINs and IRS are highly effective, but are insufficient to eliminate malaria transmission in many settings because of operational constraints, growing resistance to available insecticides and mosquitoes that behaviourally avoid contact with these interventions. However, a number of substantive opportunities now exist for rapidly developing and implementing more diverse, effective and sustainable malaria vector control strategies for LMICs. For example, mosquito control in high-income countries is predominantly achieved with a combination of mosquito-proofed housing and environmental management, supplemented with large-scale insecticide applications to larval habitats and outdoor spaces that kill off vector populations en masse, but all these interventions remain underused in LMICs. Programmatic development and evaluation of decentralised, locally managed systems for delivering these proactive mosquito population abatement practices in LMICs could therefore enable broader scale-up. Furthermore, a diverse range of emerging or repurposed technologies are becoming available for targeting mosquitoes when they enter houses, feed outdoors, attack livestock, feed on sugar or aggregate into mating swarms. Global policy must now be realigned to mobilise the political and financial support necessary to exploit these opportunities over the decade ahead, so that national malaria control and elimination programmes can access a much broader, more effective set of vector control interventions. PMID:28589022

Towards thermodynamics of universal horizons in Einstein-æther theory.

PubMed

Berglund, Per; Bhattacharyya, Jishnu; Mattingly, David

2013-02-15

Holography grew out of black hole thermodynamics, which relies on the causal structure and general covariance of general relativity. In Einstein-æther theory, a generally covariant theory with a dynamical timelike unit vector, every solution breaks local Lorentz invariance, thereby grossly modifying the causal structure of gravity. However, there are still absolute causal boundaries, called "universal horizons," which are not Killing horizons yet obey a first law of black hole mechanics and must have an entropy if they do not violate a generalized second law. We couple a scalar field to the timelike vector and show via the tunneling approach that the universal horizon radiates as a blackbody at a fixed temperature, even if the scalar field equations also violate local Lorentz invariance. This suggests that the class of holographic theories may be much broader than currently assumed.

Conformal gravity and time

NASA Astrophysics Data System (ADS)

Hazboun, Jeffrey Shafiq

2014-10-01

Cartan geometry provides a rich formalism from which to look at various geometrically motivated extensions to general relativity. In this manuscript, we start by motivating reasons to extend the theory of general relativity. We then introduce the reader to our technique, called the quotient manifold method, for extending the geometry of spacetime. We will specifically look at the class of theories formed from the various quotients of the conformal group. Starting with the conformal symmetries of Euclidean space, we construct a manifold where time manifests as a part of the geometry. Though there is no matter present in the geome- try studied here, geometric terms analogous to dark energy and dark matter appear when we write down the Einstein tensor. Specifically, the quotient of the conformal group of Euclidean four-space by its Weyl subgroup results in a geometry possessing many of the properties of relativistic phase space, including both a natural symplectic form and nondegenerate Killing metric. We show the general solution possesses orthogonal Lagrangian submanifolds, with the induced metric and the spin connection on the submanifolds necessarily Lorentzian, despite the Euclidean starting point. By examining the structure equations of the biconformal space in an orthonormal frame adapted to its phase space properties, we also find two new tensor fields exist in this geometry, not present in Riemannian geometry. The first is a combination of the Weyl vector with the scale factor on the metric, and determines the time-like directions on the submanifolds. The second comes from the components of the spin connection, symmetric with respect to the new metric. Though this field comes from the spin connection, it transforms ho- mogeneously. Finally, we show in the absence of Cartan curvature or sources, the configuration space has geometric terms equivalent to a perfect fluid and a cosmological constant. We complete the analysis of this homogeneous space by transforming the known, general solution of the Maurer-Cartan equations into the orthogonal, Lagrangian basis. This results in a signature-changing metric, just as in the work of Spencer and Wheeler, however without any conditions on the curvature of the momentum sector. The Riemannian curvatures of the two submanifolds are directly related. We investigate the case where the curvature on the momentum submanifold vanishes, while the curvature of the configuration submanifold gives an effective energy-momentum tensor corresponding to a perfect fluid. In the second part of this manuscript, we look at the most general curved biconformal geometry dictated by the Wehner-Wheeler action. We use the assemblage of structure equations, Bianchi identities, and field equations to show how the geometry of the manifolds self-organizes into trivial Weyl geometries, which can then be gauged to Riemannian geometries. The Bianchi identities reveal the strong relationships between the various curvatures, torsions, and cotorsions. The discussion of the curved case culminates in a number of simplifying restrictions that show general relativity as the base of the more general theory.

Anisotropic power-law inflation for a conformal-violating Maxwell model

NASA Astrophysics Data System (ADS)

Do, Tuan Q.; Kao, W. F.

2018-05-01

A set of power-law solutions of a conformal-violating Maxwell model with a non-standard scalar-vector coupling will be shown in this paper. In particular, we are interested in a coupling term of the form X^{2n} F^{μ ν }F_{μ ν } with X denoting the kinetic term of the scalar field. Stability analysis indicates that the new set of anisotropic power-law solutions is unstable during the inflationary phase. The result is consistent with the cosmic no-hair conjecture. We show, however, that a set of stable slowly expanding solutions does exist for a small range of parameters λ and n. Hence a small anisotropy can survive during the slowly expanding phase.

750 GeV diphotons: implications for supersymmetric unification II

DOE PAGES

Hall, Lawrence J.; Harigaya, Keisuke; Nomura, Yasunori

2016-07-29

Perturbative supersymmetric gauge coupling unification is possible in six theories where complete SU (5) TeV-scale multiplets of vector matter account for the size of the reported 750 GeV diphoton resonance, interpreted as a singlet multiplet S=(s+ia)/√2. One of these has a full generation of vector matter and a unified gauge coupling αG ~ 1. The diphoton signal rate is enhanced by loops of vector squarks and sleptons, especially when the trilinear A couplings are large. If the SH uH d coupling is absent, both s and a can contribute to the resonance, which may then have a large apparent widthmore » if the mass splitting from s and a arises from loops of vector matter. The width depends sensitively on A parameters and phases of the vector squark and slepton masses. Vector quarks and/or squarks are expected to be in reach of the LHC. If the SH uH d coupling is present, a leads to a narrow diphoton resonance, while a second resonance with decays s → hh, W +W – , ZZ is likely to be discovered at future LHC runs. In some of the theories a non-standard origin or running of the soft parameters is required, for example involving conformal hidden sector interactions.« less

AAV viral vector delivery to the brain by shape-conforming MR-guided infusions.

PubMed

Bankiewicz, Krystof S; Sudhakar, Vivek; Samaranch, Lluis; San Sebastian, Waldy; Bringas, John; Forsayeth, John

2016-10-28

Gene transfer technology offers great promise as a potential therapeutic approach to the brain but has to be viewed as a very complex technology. Success of ongoing clinical gene therapy trials depends on many factors such as selection of the correct genetic and anatomical target in the brain. In addition, selection of the viral vector capable of transfer of therapeutic gene into target cells, along with long-term expression that avoids immunotoxicity has to be established. As with any drug development strategy, delivery of gene therapy has to be consistent and predictable in each study subject. Failed drug and vector delivery will lead to failed clinical trials. In this article, we describe our experience with AAV viral vector delivery system, that allows us to optimize and monitor in real time viral vector administration into affected regions of the brain. In addition to discussing MRI-guided technology for administration of AAV vectors we have developed and now employ in current clinical trials, we also describe ways in which infusion cannula design and stereotactic trajectory may be used to maximize the anatomical coverage by using fluid backflow. This innovative approach enables more precise coverage by fitting the shape of the infusion to the shape of the anatomical target. Copyright © 2016 Elsevier B.V. All rights reserved.

"Lollipop-shaped" high-sensitivity Microelectromechanical Systems vector hydrophone based on Parylene encapsulation

NASA Astrophysics Data System (ADS)

Liu, Yuan; Wang, Renxin; Zhang, Guojun; Du, Jin; Zhao, Long; Xue, Chenyang; Zhang, Wendong; Liu, Jun

2015-07-01

This paper presents methods of promoting the sensitivity of Microelectromechanical Systems (MEMS) vector hydrophone by increasing the sensing area of cilium and perfect insulative Parylene membrane. First, a low-density sphere is integrated with the cilium to compose a "lollipop shape," which can considerably increase the sensing area. A mathematic model on the sensitivity of the "lollipop-shaped" MEMS vector hydrophone is presented, and the influences of different structural parameters on the sensitivity are analyzed via simulation. Second, the MEMS vector hydrophone is encapsulated through the conformal deposition of insulative Parylene membrane, which enables underwater acoustic monitoring without any typed sound-transparent encapsulation. Finally, the characterization results demonstrate that the sensitivity reaches up to -183 dB (500 Hz 0dB at 1 V/ μPa ), which is increased by more than 10 dB, comparing with the previous cilium-shaped MEMS vector hydrophone. Besides, the frequency response takes on a sensitivity increment of 6 dB per octave. The working frequency band is 20-500 Hz and the concave point depth of 8-shaped directivity is beyond 30 dB, indicating that the hydrophone is promising in underwater acoustic application.

Molecular dynamics: deciphering the data.

PubMed

Dauber-Osguthorpe, P; Maunder, C M; Osguthorpe, D J

1996-06-01

The dynamic behaviour of molecules is important in determining their activity. Molecular dynamics (MD) simulations give a detailed description of motion, from small fluctuations to conformational transitions, and can include solvent effects. However, extracting useful information about conformational motion from a trajectory is not trivial. We have used digital signal-processing techniques to characterise the motion in MD simulations, including: calculating the frequency distribution, applying filtering functions, and extraction of vectors defining the characteristic motion for each frequency in an MD simulation. We describe here some typical results obtained for peptides and proteins. The nature of the low-frequency modes of motion, as obtained from MD and normal mode (NM) analysis, of Ace-(Ala)31-Nma and of a proline mutant is discussed. Low-frequency modes extracted from the MD trajectories of Rop protein and phospholipase A2 reveal characteristic motions of secondary structure elements, as well as concerned motions that are of significance to the protein's biological activity. MD simulations are also used frequently as a tool for conformational searches and for investigating protein folding/unfolding. We have developed a novel method that uses time-domain filtering to channel energy into conformational motion and thus enhance conformational transitions. The selectively enhanced molecular dynamics method is tested on the small molecule hexane.

Molecular dynamics: Deciphering the data

NASA Astrophysics Data System (ADS)

Dauber-Osguthorpe, Pnina; Maunder, Colette M.; Osguthorpe, David J.

1996-06-01

The dynamic behaviour of molecules is important in determining their activity. Molecular dynamics (MD) simulations give a detailed description of motion, from small fluctuations to conformational transitions, and can include solvent effects. However, extracting useful information about conformational motion from a trajectory is not trivial. We have used digital signal-processing techniques to characterise the motion in MD simulations, including: calculating the frequency distribution, applying filtering functions, and extraction of vectors defining the characteristic motion for each frequency in an MD simulation. We describe here some typical results obtained for peptides and proteins. The nature of the low-frequency modes of motion, as obtained from MD and normal mode (NM) analysis, of Ace-(Ala)31-Nma and of a proline mutant is discussed. Low-frequency modes extracted from the MD trajectories of Rop protein and phospholipase A2 reveal characteristic motions of secondary structure elements, as well as concerted motions that are of significance to the protein's biological activity. MD simulations are also used frequently as a tool for conformational searches and for investigating protein folding/unfolding. We have developed a novel method that uses time-domain filtering to channel energy into conformational motion and thus enhance conformational transitions. The selectively enhanced molecular dynamics method is tested on the small molecule hexane.

Tissue-Specific Expression of Herpes Simplex Virus Thymidine Kinase Gene Delivered by Adeno-Associated Virus Inhibits the Growth of Human Hepatocellular Carcinoma in Athymic Mice

NASA Astrophysics Data System (ADS)

Su, Hua; Lu, Ronghua; Chang, Judy C.; Kan, Yuet Wai

1997-12-01

About 70% of hepatocellular carcinomas are known to express α -fetoprotein, which is normally expressed in fetal but not in adult livers. To induce herpes simplex virus-thymidine kinase expression in these cancer cells, we constructed an adeno-associated viral vector containing the HSV-TK gene under the control of the α -fetoprotein enhancer and albumin promoter. We previously demonstrated in vitro that although this vector can transduce a variety of human cells, only transduced AFP and albumin-expressing hepatocellular carcinoma cell lines were sensitive to killing by ganciclovir (GCV). In the present study, we explored the effect of this vector on hepatocellular carcinoma cells in vivo. Subcutaneous tumors generated in nude mice by implanting hepatocellular carcinoma cells previously transduced with this vector shrank dramatically after treatment with GCV. Bystander effect was also observed on the tumors generated by mixing transduced and untransduced cells. To test whether the tumor cells can be transduced by the virus in vivo, we injected the recombinant adeno-associated virus into tumors generated by untransduced hepatocarcinoma cell line. Tumor growth were retarded after treatment with GCV. These experiments demonstrate the feasibility of in vivo transduction of tumor cell with rAAV.

Progress in directed energy control of vectors for microbes and other cells

NASA Astrophysics Data System (ADS)

Kiel, Johnathan L.; Parker, Jill E.; Holwitt, Eric A.; Vivekananda, Jeeva; Sloan, Mark A.; Stribling, Lucille J. V.

2004-07-01

Biosynthetic semiconductor, diazoluminomelanin (DALM), is a polymer of tyrosine, luminol, and nitrite. DALM has a very large cross section of absorption for light from ultraviolet to radio frequencies. This polymer can be made efficiently in a genetically engineered E.coli, JM109/pIC2ORNR1.1 (ATCC# 69905). We have been pursuing ways to couple electromagnetic radiation to vectors using this polymer. DNA capture elements (DCEs; formerly aptamers) have made this possible. We incorporated DCEs into the plasmid of this E. coli to direct binding to whatever microbe or cell desired and to produce DALM attached to the plasmid DNA. Using two other vectors pSV2neoNR101 or pSV2neoNR8005 (ATCC # 69617 and 69618, respectively), both propagated in the E. coli host HB101, we have also inserted genes necessary for DALM production into animal and human cell lines (mouse monocytic leukemia: ATCC # CRL- 11771, -11772, -1173, mouse mammary adenocarcinoma: ATCC# CRL-12184, -12185; and human carcinoma of the cervix: ATCC # CRL-12510). The DCE/DALM vectors can be used to tag target cells, detectable by broad-spectrum light absorbance, luminescence, or fluorescence. DCE/DALM can further be activated with light, microwave energy, or by oxidative chemistry to kill the targeted microbes or other cells.

Approaches to utilize mesenchymal progenitor cells as cellular vehicles.

PubMed

Pereboeva, L; Komarova, S; Mikheeva, G; Krasnykh, V; Curiel, D T

2003-01-01

Mammalian cells represent a novel vector approach for gene delivery that overcomes major drawbacks of viral and nonviral vectors and couples cell therapy with gene delivery. A variety of cell types have been tested in this regard, confirming that the ideal cellular vector system for ex vivo gene therapy has to comply with stringent criteria and is yet to be found. Several properties of mesenchymal progenitor cells (MPCs), such as easy access and simple isolation and propagation procedures, make these cells attractive candidates as cellular vehicles. In the current work, we evaluated the potential utility of MPCs as cellular vectors with the intent to use them in the cancer therapy context. When conventional adenoviral (Ad) vectors were used for MPC transduction, the highest transduction efficiency of MPCs was 40%. We demonstrated that Ad primary-binding receptors were poorly expressed on MPCs, while the secondary Ad receptors and integrins presented in sufficient amounts. By employing Ad vectors with incorporated integrin-binding motifs (Ad5lucRGD), MPC transduction was augmented tenfold, achieving efficient genetic loading of MPCs with reporter and anticancer genes. MPCs expressing thymidine kinase were able to exert a bystander killing effect on the cancer cell line SKOV3ip1 in vitro. In addition, we found that MPCs were able to support Ad replication, and thus can be used as cell vectors to deliver oncolytic viruses. Our results show that MPCs can foster expression of suicide genes or support replication of adenoviruses as potential anticancer therapeutic payloads. These findings are consistent with the concept that MPCs possess key properties that ensure their employment as cellular vehicles and can be used to deliver either therapeutic genes or viruses to tumor sites.

Improved Prefusion Stability, Optimized Codon Usage, and Augmented Virion Packaging Enhance the Immunogenicity of Respiratory Syncytial Virus Fusion Protein in a Vectored-Vaccine Candidate

PubMed Central

Liang, Bo; Ngwuta, Joan O.; Surman, Sonja; Kabatova, Barbora; Liu, Xiang; Lingemann, Matthias; Liu, Xueqiao; Yang, Lijuan; Herbert, Richard; Swerczek, Joanna; Chen, Man; Moin, Syed M.; Kumar, Azad; McLellan, Jason S.; Kwong, Peter D.; Graham, Barney S.; Collins, Peter L.

2017-01-01

ABSTRACT Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory tract disease worldwide, but it lacks a licensed vaccine or suitable antiviral drug. A live attenuated chimeric bovine/human parainfluenza virus type 3 (rB/HPIV3) was developed previously as a vector expressing RSV fusion (F) protein to confer bivalent protection against RSV and HPIV3. In a previous clinical trial in virus-naive children, rB/HPIV3 was well tolerated but the immunogenicity of wild-type RSV F was unsatisfactory. We previously modified RSV F with a designed disulfide bond (DS) to increase stability in the prefusion (pre-F) conformation and to be efficiently packaged in the vector virion. Here, we further stabilized pre-F by adding both disulfide and cavity-filling mutations (DS-Cav1), and we also modified RSV F codon usage to have a lower CpG content and a higher level of expression. This RSV F open reading frame was evaluated in rB/HPIV3 in three forms: (i) pre-F without vector-packaging signal, (ii) pre-F with vector-packaging signal, and (iii) secreted pre-F ectodomain trimer. Despite being efficiently expressed, the secreted pre-F was poorly immunogenic. DS-Cav1 stabilized pre-F, with or without packaging, induced higher titers of pre-F specific antibodies in hamsters, and improved the quality of RSV-neutralizing serum antibodies. Codon-optimized RSV F containing fewer CpG dinucleotides had higher F expression, replicated more efficiently in vivo, and was more immunogenic. The combination of DS-Cav1 pre-F stabilization, optimized codon usage, reduced CpG content, and vector packaging significantly improved vector immunogenicity and protective efficacy against RSV. This provides an improved vectored RSV vaccine candidate suitable for pediatric clinical evaluation. IMPORTANCE RSV and HPIV3 are the first and second leading viral causes of severe pediatric respiratory disease worldwide. Licensed vaccines or suitable antiviral drugs are not available. We are developing a chimeric rB/HPIV3 vector expressing RSV F as a bivalent RSV/HPIV3 vaccine and have been evaluating means to increase RSV F immunogenicity. In this study, we evaluated the effects of improved stabilization of F in the pre-F conformation and of codon optimization resulting in reduced CpG content and greater pre-F expression. Reduced CpG content dampened the interferon response to infection, promoting higher replication and increased F expression. We demonstrate that improved pre-F stabilization and strategic manipulation of codon usage, together with efficient pre-F packaging into vector virions, significantly increased F immunogenicity in the bivalent RSV/HPIV3 vaccine. The improved immunogenicity included induction of increased titers of high-quality complement-independent antibodies with greater pre-F site Ø binding and greater protection against RSV challenge. PMID:28539444

General Wahlquist metrics in all dimensions

NASA Astrophysics Data System (ADS)

Hinoue, Kazuki; Houri, Tsuyoshi; Rugina, Christina; Yasui, Yukinori

2014-07-01

It is shown that the Wahlquist metric, which is a stationary, axially symmetric perfect fluid solution with ρ +3p=const, admits a rank-2 generalized closed conformal Killing-Yano tensor with a skew-symmetric torsion. Taking advantage of the presence of such a tensor, we obtain a higher-dimensional generalization of the Wahlquist metric in arbitrary dimensions, including a family of vacuum black hole solutions with spherical horizon topology such as Schwarzschild-Tangherlini, Myers-Perry and higher-dimensional Kerr-NUT-(A)dS metrics and a family of static, spherically symmetric perfect fluid solutions in higher dimensions.

Influence of Multidimensionality on Convergence of Sampling in Protein Simulation

NASA Astrophysics Data System (ADS)

Metsugi, Shoichi

2005-06-01

We study the problem of convergence of sampling in protein simulation originating in the multidimensionality of protein’s conformational space. Since several important physical quantities are given by second moments of dynamical variables, we attempt to obtain the time of simulation necessary for their sufficient convergence. We perform a molecular dynamics simulation of a protein and the subsequent principal component (PC) analysis as a function of simulation time T. As T increases, PC vectors with smaller amplitude of variations are identified and their amplitudes are equilibrated before identifying and equilibrating vectors with larger amplitude of variations. This sequential identification and equilibration mechanism makes protein simulation a useful method although it has an intrinsic multidimensional nature.

Tumor transfection after systemic injection of DNA lipid nanocapsules.

PubMed

Morille, Marie; Passirani, Catherine; Dufort, Sandrine; Bastiat, Guillaume; Pitard, Bruno; Coll, Jean-Luc; Benoit, Jean-Pierre

2011-03-01

With the goal of generating an efficient vector for systemic gene delivery, a new kind of nanocarrier consisting of lipid nanocapsules encapsulating DOTAP/DOPE lipoplexes (DNA LNCs) was pegylated by the post-insertion of amphiphilic and flexible polymers. The aim of this surface modification was to create a long-circulating vector, able to circulate in the blood stream and efficient in transfecting tumoral cells after passive targeting by enhanced permeability and retention effect (EPR effect). PEG conformation, electrostatic features, and hydrophylicity are known to be important factors able to influence the pharmacokinetic behaviour of vectors. In this context, the surface structure characteristics of the newly pegylated DNA LNCs were studied by measuring electrophoretic mobility as a function of ionic strength in order to establish a correlation between surface properties and in vivo performance of the vector. Finally, thanks to this PEGylation, gene expression was measured up to 84-fold higher in tumor compared to other tested organs after intravenous injection. The present results indicate that PEGylated DNA LNCs are promising carriers for an efficient cancer gene therapy. Copyright © 2010 Elsevier Ltd. All rights reserved.

A New Clade of African Body and Head Lice Infected by Bartonella quintana and Yersinia pestis-Democratic Republic of the Congo.

PubMed

Drali, Rezak; Shako, Jean-Christophe; Davoust, Bernard; Diatta, Georges; Raoult, Didier

2015-11-01

The human body louse is known as a vector for the transmission of three serious diseases-specifically, epidemic typhus, trench fever, and relapsing fever caused by Rickettsia prowazekii, Bartonella quintana, and Borrelia recurrentis, respectively-that have killed millions of people. It is also suspected in the transmission of a fourth pathogen, Yersinia pestis, which is the etiologic agent of plague. To date, human lice belonging to the genus Pediculus have been classified into three mitochondrial clades: A, B, and C. Here, we describe a fourth mitochondrial clade, Clade D, comprising head and body lice. Clade D may be a vector of B. quintana and Y. pestis, which is prevalent in a highly plague-endemic area near the Rethy Health District, Orientale Province, Democratic Republic of the Congo. © The American Society of Tropical Medicine and Hygiene.

Monitoring of the Conformational Space of Dipeptides by Generative Topographic Mapping.

PubMed

Horvath, Dragos; Marcou, Gilles; Varnek, Alexandre

2018-01-01

This work describes a procedure to build generative topographic maps (GTM) as 2D representation of the conformational space (CS) of dipeptides. GTMs with excellent propensities to support highly predictive landscapes of various conformational properties were reported for three dipeptides (AA, KE and KR). CS monitoring via GTMproceeds through the projection of conformer ensembles on the map, producing cumulated responsibility (CR) vectors characteristic of the CS areas covered by the ensemble. Overlap of the CS areas visited by two distinct simulations can be expressed by the Tanimoto coefficient Tc of the associated CRs. This idea was used to monitor the reproducibility of the stochastic evolutionary conformer generation process implemented in S4MPLE. It could be shown that conformers produced by <500 S4MPLE runs reproducibly cover the relevant CS zone at given setup of the driving force field. The propensity of a simulation to visit the native CS zone can thus be quantitatively estimated, as the Tc score with respect to the "native" CR, as defined by the ensemble of dipeptide geometries extracted from PDB proteins. It could be shown that low-energy CS regions were indeed found to fall within the native zone. The Tc overlap score behaved as a smooth function of force field parameters. This opens the perspective of a novel force field parameter tuning procedure, bound to simultaneously optimize the behavior of the in Silico simulations for every possible dipeptide. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

On the Solutions of Two-Extended Principal Conformal Toda Theory

NASA Astrophysics Data System (ADS)

Chao, L.; Hou, B. Y.

1994-02-01

The solutions of the two-extended principal conformal Toda theory (2-EPCT theory, also called bosonic superconformal Toda theory) are constructed in two different ways: (1) Leznov-Saveliev algebraic analysis and (2) the associated chiral embedding surface. The first approach gives rise to the general solution in terms of appropriate matrix elements in different fundamental representations of the underlying Lie algebra, whilst the second one leads to a special solution in the form of Wronski determinants and their co-minors, and it gives an explicit geometrical interpretation of the WZNW → 2-EPCT reduction. The key points of both approaches are the chiral vectors derived recently by the authors, which constitute a closed exchange algebra of the theory.

Impedance of curved rectangular spiral coils around a conductive cylinder

NASA Astrophysics Data System (ADS)

Burke, S. K.; Ditchburn, R. J.; Theodoulidis, T. P.

2008-07-01

Eddy-current induction due to a thin conformable coil wrapped around a long conductive cylinder is examined using a second-order vector potential formalism. Compact closed-form expressions are derived for the self- and mutual impedances of curved rectangular spiral coils (i) in free space and (ii) when wrapped around the surface of the cylindrical rod. The validity of these expressions was tested against the results of a systematic series of experiments using a cylindrical Al-alloy rod and conformable coils manufactured using flexible printed-circuit-board technology. The theoretical expressions were in very good agreement with the experimental measurements. The significance of the results for eddy-current nondestructive inspection using flexible coils and flexible coil arrays is discussed.

Cosmological perturbations in antigravity

NASA Astrophysics Data System (ADS)

Oltean, Marius; Brandenberger, Robert

2014-10-01

We compute the evolution of cosmological perturbations in a recently proposed Weyl-symmetric theory of two scalar fields with oppositely signed conformal couplings to Einstein gravity. It is motivated from the minimal conformal extension of the standard model, such that one of these scalar fields is the Higgs while the other is a new particle, the dilaton, introduced to make the Higgs mass conformally symmetric. At the background level, the theory admits novel geodesically complete cyclic cosmological solutions characterized by a brief period of repulsive gravity, or "antigravity," during each successive transition from a big crunch to a big bang. For simplicity, we consider scalar perturbations in the absence of anisotropies, with potential set to zero and without any radiation. We show that despite the necessarily wrong-signed kinetic term of the dilaton in the full action, these perturbations are neither ghostlike nor tachyonic in the limit of strongly repulsive gravity. On this basis, we argue—pending a future analysis of vector and tensor perturbations—that, with respect to perturbative stability, the cosmological solutions of this theory are viable.

Lift of noninvariant solutions of heavenly equations from three to four dimensions and new ultra-hyperbolic metrics

NASA Astrophysics Data System (ADS)

Malykh, A. A.; Nutku, Y.; Sheftel, M. B.

2007-08-01

We demonstrate that partner symmetries provide a lift of noninvariant solutions of the three-dimensional Boyer-Finley equation to noninvariant solutions of the four-dimensional hyperbolic complex Monge-Ampère equation. The lift is applied to noninvariant solutions of the Boyer-Finley equation, obtained earlier by the method of group foliation, to yield noninvariant solutions of the hyperbolic complex Monge-Ampère equation. Using these solutions we construct new Ricci-flat ultra-hyperbolic metrics with non-zero curvature tensor that have no Killing vectors.

Partner symmetries and non-invariant solutions of four-dimensional heavenly equations

NASA Astrophysics Data System (ADS)

Malykh, A. A.; Nutku, Y.; Sheftel, M. B.

2004-07-01

We extend our method of partner symmetries to the hyperbolic complex Monge-Ampère equation and the second heavenly equation of Plebañski. We show the existence of partner symmetries and derive the relations between them. For certain simple choices of partner symmetries the resulting differential constraints together with the original heavenly equations are transformed to systems of linear equations by an appropriate Legendre transformation. The solutions of these linear equations are generically non-invariant. As a consequence we obtain explicitly new classes of heavenly metrics without Killing vectors.

Functionally relevant protein motions: Extracting basin-specific collective coordinates from molecular dynamics trajectories

NASA Astrophysics Data System (ADS)

Pan, Patricia Wang; Dickson, Russell J.; Gordon, Heather L.; Rothstein, Stuart M.; Tanaka, Shigenori

2005-01-01

Functionally relevant motion of proteins has been associated with a number of atoms moving in a concerted fashion along so-called "collective coordinates." We present an approach to extract collective coordinates from conformations obtained from molecular dynamics simulations. The power of this technique for differentiating local structural fuctuations between classes of conformers obtained by clustering is illustrated by analyzing nanosecond-long trajectories for the response regulator protein Spo0F of Bacillus subtilis, generated both in vacuo and using an implicit-solvent representation. Conformational clustering is performed using automated histogram filtering of the inter-Cα distances. Orthogonal (varimax) rotation of the vectors obtained by principal component analysis of these interresidue distances for the members of individual clusters is key to the interpretation of collective coordinates dominating each conformational class. The rotated loadings plots isolate significant variation in interresidue distances, and these are associated with entire mobile secondary structure elements. From this we infer concerted motions of these structural elements. For the Spo0F simulations employing an implicit-solvent representation, collective coordinates obtained in this fashion are consistent with the location of the protein's known active sites and experimentally determined mobile regions.

Alpha-lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

PubMed

Svensson, Malin; Fast, Jonas; Mossberg, Ann-Kristin; Düringer, Caroline; Gustafsson, Lotta; Hallgren, Oskar; Brooks, Charles L; Berliner, Lawrence; Linse, Sara; Svanborg, Catharina

2003-12-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a complex of human alpha-lactalbumin and oleic acid (C18:1:9 cis) that kills tumor cells by an apoptosis-like mechanism. Previous studies have shown that a conformational change is required to form HAMLET from alpha-lactalbumin, and that a partially unfolded conformation is maintained in the HAMLET complex. This study examined if unfolding of alpha-lactalbumin is sufficient to induce cell death. We used the bovine alpha-lactalbumin Ca(2+) site mutant D87A, which is unable to bind Ca(2+), and thus remains partially unfolded regardless of solvent conditions. The D87A mutant protein was found to be inactive in the apoptosis assay, but could readily be converted to a HAMLET-like complex in the presence of oleic acid. BAMLET (bovine alpha-lactalbumin made lethal to tumor cells) and D87A-BAMLET complexes were both able to kill tumor cells. This activity was independent of the Ca(2+)site, as HAMLET maintained a high affinity for Ca(2+) but D87A-BAMLET was active with no Ca(2+) bound. We conclude that partial unfolding of alpha-lactalbumin is necessary but not sufficient to trigger cell death, and that the activity of HAMLET is defined both by the protein and the lipid cofactor. Furthermore, a functional Ca(2+)-binding site is not required for conversion of alpha-lactalbumin to the active complex or to cause cell death. This suggests that the lipid cofactor stabilizes the altered fold without interfering with the Ca(2+)site.

HIV envelope-mediated, CCR5/α4β7-dependent killing of CD4-negative γδ T cells which are lost during progression to AIDS.

PubMed

Li, Haishan; Pauza, C David

2011-11-24

HIV infects and replicates in CD4+ T cells but effects on host immunity and disease also involve depletion, hyper-activation, and modification of CD4-negative cell populations. In particular, the depletion of CD4-negative γδ T cells is common to all HIV+ individuals. We found that soluble or cell-associated envelope glycoproteins from CCR5-tropic strains of HIV could bind, activates the p38-caspase pathway, and induce the death of γδ cells. Envelope binding requires integrin α4β7 and chemokine receptor CCR5 which are at high levels and form a complex on the γδ T cell membrane. This receptor complex facilitated V3 loop binding to CCR5 in the absence of CD4-induced conformational changes. Cell death was increased by antigen stimulation after exposure to envelope glycoprotein. Direct signaling by envelope glycoprotein killed CD4-negative γδ T cells and reproduced a defect observed in all patients with HIV disease.

Superconformal quantum field theory in curved spacetime

NASA Astrophysics Data System (ADS)

de Medeiros, Paul; Hollands, Stefan

2013-09-01

By conformally coupling vector and hyper multiplets in Minkowski space, we obtain a class of field theories with extended rigid conformal supersymmetry on any Lorentzian 4-manifold admitting twistor spinors. We construct the conformal symmetry superalgebras which describe classical symmetries of these theories and derive an appropriate BRST operator in curved spacetime. In the process, we elucidate the general framework of cohomological algebra which underpins the construction. We then consider the corresponding perturbative quantum field theories. In particular, we examine the conditions necessary for conformal supersymmetries to be preserved at the quantum level, i.e. when the BRST operator commutes with the perturbatively defined S-matrix, which ensures superconformal invariance of amplitudes. To this end, we prescribe a renormalization scheme for time-ordered products that enter the perturbative S-matrix and show that such products obey certain Ward identities in curved spacetime. These identities allow us to recast the problem in terms of the cohomology of the BRST operator. Through a careful analysis of this cohomology, and of the renormalization group in curved spacetime, we establish precise criteria which ensure that all conformal supersymmetries are preserved at the quantum level. As a by-product, we provide a rigorous proof that the beta-function for such theories is one-loop exact. We also briefly discuss the construction of chiral rings and the role of non-perturbative effects in curved spacetime.

Temporal frequency of knockdown resistance mutations, F1534C and V1016G, in Aedes aegypti in Chiang Mai city, Thailand and the impact of the mutations on the efficiency of thermal fogging spray with pyrethroids.

PubMed

Plernsub, Suriya; Saingamsook, Jassada; Yanola, Jintana; Lumjuan, Nongkran; Tippawangkosol, Pongsri; Walton, Catherine; Somboon, Pradya

2016-10-01

In Thailand, control of dengue outbreaks is currently attained by the use of space sprays, particularly thermal fogging using pyrethroids, with the aim of killing infected Aedes mosquito vectors in epidemic areas. However, the principal dengue vector, Aedes aegypti, is resistant to pyrethroids conferred mainly by mutations in the voltage-gated sodium channel gene, F1534C and V1016G, termed knockdown resistance (kdr). The objectives of this study were to determine the temporal frequencies of F1534C and V1016G in Ae. aegypti populations in relation to pyrethroid resistance in Chiang Mai city, and to evaluate the impact of the mutations on the efficacy of thermal fogging with the pyrethroid deltamethrin. Larvae and pupae were collected from several areas around Chiang Mai city during 2011-2015 and reared to adulthood for bioassays for deltamethrin susceptibility. These revealed no trend of increasing deltamethrin resistance during the study period (mortality 58.0-69.5%, average 62.8%). This corresponded to no overall change in the frequencies of the C1534 allele (0.55-0.66, average 0.62) and G1016 allele (0.34-0.45, average 0.38), determined using allele specific amplification. Only three genotypes of kdr mutations were detected: C1534 homozygous (VV/CC); G1016/C1534 double heterozygous (VG/FC); and G1016 homozygous (GG/FF) indicating that the F1534C and V1016G mutations occurred on separate haplotypic backgrounds and a lack of recombination between them to date. The F1 progeny females were used to evaluate the efficacy of thermal fogging spray with Damthrin-SP(®) (deltamethrin+S-bioallethrin+piperonyl butoxide) using a caged mosquito bioassay. The thermal fogging spray killed 100% and 61.3% of caged mosquito bioassay placed indoors and outdoors, respectively. The outdoor spray had greater killing effect on C1534 homozygous and had partially effect on double heterozygous mosquitoes, but did not kill any G1016 homozygous mutants living outdoors. As this selection pressure would be expected to have led to an increase in frequency of the G1016 allele, it is likely that the relatively stable kdr mutation allele frequencies observed here result from balancing selection, in the form of overdominance for VG/FC genotypes and/or the effects of fluctuating environments that vary in insecticide exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

Holographic CBK relation

NASA Astrophysics Data System (ADS)

Gabadadze, Gregory; Tukhashvili, Giorgi

2018-07-01

The Crewther-Broadhurst-Kataev (CBK) relation connects the Bjorken function for deep-inelastic sum rules (or the Gross-Llewellyn Smith function) with the Adler function for electron-positron annihilation in QCD; it has been checked to hold up to four loops in perturbation theory. Here we study non-perturbative terms in the CBK relation using a holographic dual theory that is believed to capture properties of QCD. We show that for the large invariant momenta the perturbative CBK relation is exactly satisfied. For the small momenta non-perturbative corrections enter the relation and we calculate their significant effects. We also give an exact holographic expression for the Bjorken function, as well as for the entire three-point axial-vector-vector correlation function, and check their consistency in the conformal limit.

Biological Control of the Chagas Disease Vector Triatoma infestans with the Entomopathogenic Fungus Beauveria bassiana Combined with an Aggregation Cue: Field, Laboratory and Mathematical Modeling Assessment

PubMed Central

Forlani, Lucas; Pedrini, Nicolás; Girotti, Juan R.; Mijailovsky, Sergio J.; Cardozo, Rubén M.; Gentile, Alberto G.; Hernández-Suárez, Carlos M.; Rabinovich, Jorge E.; Juárez, M. Patricia

2015-01-01

Background Current Chagas disease vector control strategies, based on chemical insecticide spraying, are growingly threatened by the emergence of pyrethroid-resistant Triatoma infestans populations in the Gran Chaco region of South America. Methodology and findings We have already shown that the entomopathogenic fungus Beauveria bassiana has the ability to breach the insect cuticle and is effective both against pyrethroid-susceptible and pyrethroid-resistant T. infestans, in laboratory as well as field assays. It is also known that T. infestans cuticle lipids play a major role as contact aggregation pheromones. We estimated the effectiveness of pheromone-based infection boxes containing B. bassiana spores to kill indoor bugs, and its effect on the vector population dynamics. Laboratory assays were performed to estimate the effect of fungal infection on female reproductive parameters. The effect of insect exuviae as an aggregation signal in the performance of the infection boxes was estimated both in the laboratory and in the field. We developed a stage-specific matrix model of T. infestans to describe the fungal infection effects on insect population dynamics, and to analyze the performance of the biopesticide device in vector biological control. Conclusions The pheromone-containing infective box is a promising new tool against indoor populations of this Chagas disease vector, with the number of boxes per house being the main driver of the reduction of the total domestic bug population. This ecologically safe approach is the first proven alternative to chemical insecticides in the control of T. infestans. The advantageous reduction in vector population by delayed-action fungal biopesticides in a contained environment is here shown supported by mathematical modeling. PMID:25969989

Amelioration of murine beta-thalassemia through drug selection of hematopoietic stem cells transduced with a lentiviral vector encoding both gamma-globin and the MGMT drug-resistance gene.

PubMed

Zhao, Huifen; Pestina, Tamara I; Nasimuzzaman, Md; Mehta, Perdeep; Hargrove, Phillip W; Persons, Derek A

2009-06-04

Correction of murine models of beta-thalassemia has been achieved through high-level globin lentiviral vector gene transfer into mouse hematopoietic stem cells (HSCs). However, transduction of human HSCs is less robust and may be inadequate to achieve therapeutic levels of genetically modified erythroid cells. We therefore developed a double gene lentiviral vector encoding both human gamma-globin under the transcriptional control of erythroid regulatory elements and methylguanine methyltransferase (MGMT), driven by a constitutive cellular promoter. MGMT expression provides cellular resistance to alkylator drugs, which can be administered to kill residual untransduced, diseased HSCs, whereas transduced cells are protected. Mice transplanted with beta-thalassemic HSCs transduced with a gamma-globin/MGMT vector initially had subtherapeutic levels of red cells expressing gamma-globin. To enrich gamma-globin-expressing cells, transplanted mice were treated with the alkylator agent 1,3-bis-chloroethyl-1-nitrosourea. This resulted in significant increases in the number of gamma-globin-expressing red cells and the amount of fetal hemoglobin, leading to resolution of anemia. Selection of transduced HSCs was also obtained when cells were drug-treated before transplantation. Mice that received these cells demonstrated reconstitution with therapeutic levels of gamma-globin-expressing cells. These data suggest that MGMT-based drug selection holds promise as a modality to improve gene therapy for beta-thalassemia.

A heterotypic bystander effect for tumor cell killing after adeno-associated virus/phage-mediated, vascular-targeted suicide gene transfer.

PubMed

Trepel, Martin; Stoneham, Charlotte A; Eleftherohorinou, Hariklia; Mazarakis, Nicholas D; Pasqualini, Renata; Arap, Wadih; Hajitou, Amin

2009-08-01

Suicide gene transfer is the most commonly used cytotoxic approach in cancer gene therapy; however, a successful suicide gene therapy depends on the generation of efficient targeted systemic gene delivery vectors. We recently reported that selective systemic delivery of suicide genes such as herpes simplex virus thymidine kinase (HSVtk) to tumor endothelial cells through a novel targeted adeno-associated virus/phage vector leads to suppression of tumor growth. This marked effect has been postulated to result primarily from the death of cancer cells by hypoxia following the targeted disruption of tumor blood vessels. Here, we investigated whether an additional mechanism of action is involved. We show that there is a heterotypic "bystander" effect between endothelial cells expressing the HSVtk suicide gene and tumor cells. Treatment of cocultures of HSVtk-transduced endothelial cells and non-HSVtk-transduced tumor cells with ganciclovir results in the death of both endothelial and tumor cells. Blocking of this effect by 18alpha-glycyrrhetinic acid indicates that gap junctions between endothelial and tumor cells are largely responsible for this phenomenon. Moreover, the observed bystander killing is mediated by connexins 43 and 26, which are expressed in endothelial and tumor cell types. Finally, this heterotypic bystander effect is accompanied by a suppression of tumor growth in vivo that is independent of primary gene transfer into host-derived tumor vascular endothelium. These findings add an alternative nonmutually exclusive and potentially synergistic cytotoxic mechanism to cancer gene therapy based on targeted adeno-associated virus/phage and further support the promising role of nonmalignant tumor stromal cells as therapeutic targets.

Molecular modelling studies of kdr mutations in voltage gated sodium channel revealed significant conformational variations contributing to insecticide resistance.

PubMed

Yellapu, Nanda Kumar; Gopal, Jeyakodi; Kasinathan, Gunasekaran; Purushothaman, Jambulingam

2018-06-01

Voltage gated sodium channels (VGSC) of mosquito vectors are the primary targets of dichlorodiphenyltrichloroethane (DDT) and other synthetic pyrethroids used in public health programmes. The knockdown resistant (kdr) mutations in VGSC are associated with the insecticide resistance especially in Anophelines. The present study is aimed to emphasize and demarcate the impact of three kdr-mutations such as L1014S, L1014F and L1014H on insecticide resistance. The membrane model of sodium transport domain of VGSC (STD-VGSC) was constructed using de novo approach based on domain and trans-membrane predictions. The comparative molecular modelling studies of wild type and mutant models of STD-VGSC revealed that L1014F mutant was observed to be near native to the wild type model in all the respects, but, L1014S and L1014H mutations showed drastic variations in the energy levels, root mean square fluctuations (RMSF) that resulted in conformational variations. The predicted binding sites also showed variable cavity volumes and RMSF in L1014S and L1014H mutants. Further, DDT also found be bound in near native manner to wild type in L1014F mutant and with variable orientation and affinities in L1014S and L1014H mutants. The variations and fluctuations observed in mutant structures explained that each mutation has its specific impact on the conformation of VGSC and its binding with DDT. The study provides new insights into the structure-function-correlations of mutant STD-VGSC structures and demonstrates the role and effects of kdr mutations on insecticide resistance in mosquito vectors.

Engineered T cells for pancreatic cancer treatment

PubMed Central

Katari, Usha L; Keirnan, Jacqueline M; Worth, Anna C; Hodges, Sally E; Leen, Ann M; Fisher, William E; Vera, Juan F

2011-01-01

Objective Conventional chemotherapy and radiotherapy produce marginal survival benefits in pancreatic cancer, underscoring the need for novel therapies. The aim of this study is to develop an adoptive T cell transfer approach to target tumours expressing prostate stem cell antigen (PSCA), a tumour-associated antigen that is frequently expressed by pancreatic cancer cells. Methods Expression of PSCA on cell lines and primary tumour samples was confirmed by immunohistochemistry. Healthy donor- and patient-derived T cells were isolated, activated in vitro using CD3/CD28, and transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) targeting PSCA. The ability of these cells to kill tumour cells was analysed by chromium-51 (Cr51) release. Results Prostate stem cell antigen was expressed on >70% of the primary tumour samples screened. Activated, CAR-modified T cells could be readily generated in clinically relevant numbers and were specifically able to kill PSCA-expressing pancreatic cancer cell lines with no non-specific killing of PSCA-negative target cells, thus indicating the potential efficacy and safety of this approach. Conclusions Prostate stem cell antigen is frequently expressed on pancreatic cancer cells and can be targeted for immune-mediated destruction using CAR-modified, adoptively transferred T cells. The safety and efficacy of this approach indicate that it deserves further study and may represent a promising novel treatment for patients with pancreatic cancer. PMID:21843265

Control of invasive marine invertebrates: an experimental evaluation of the use of low salinity for managing pest corals (Tubastraea spp.).

PubMed

Moreira, Patrícia L; Ribeiro, Felipe V; Creed, Joel C

2014-01-01

This study investigated the use of low salinity as a killing agent for the invasive pest corals Tubastraea coccinea and Tubastraea tagusensis (Dendrophylliidae). Experiments investigated the efficacy of different salinities, the effect of colony size on susceptibility and the influence of length of exposure. Experimental treatments of colonies were carried out in aquaria. Colonies were then fixed onto experimental plates and monitored in the field periodically over a period of four weeks. The killing effectiveness of low salinity depended on the test salinity and the target species, but was independent of colony size. Low salinity was fast acting and prejudicial to survival: discoloration, necrosis, fragmenting and sloughing, exposure of the skeleton and cover by biofoulers occurred post treatment. For T. tagusensis, 50% mortality (LC50) after three days occurred at eight practical salinity units (PSU); for T. coccinea the LC50 was 2 PSU. Exposure to freshwater for 45-120 min resulted in 100% mortality for T. tagusensis, but only the 120 min period was 100% effective in killing T. coccinea. Freshwater is now routinely used for the post-border management of Tubastraea spp. This study also provides insights as to how freshwater may be used as a routine biosecurity management tool when applied pre-border to shipping vectors potentially transporting non-indigenous marine biofouling species.

Ribosome Display of Combinatorial Antibody Libraries Derived from Mice Immunized with Heat-Killed Xylella fastidiosa and the Selection of MopB-Specific Single-Chain Antibodies

PubMed Central

Azizi, Armaghan; Arora, Arinder; Markiv, Anatoliy; Lampe, David J.; Miller, Thomas A.

2012-01-01

Pierce's disease is a devastating lethal disease of Vitus vinifera grapevines caused by the bacterium Xylella fastidiosa. There is no cure for Pierce's disease, and control is achieved predominantly by suppressing transmission of the glassy-winged sharpshooter insect vector. We present a simple robust approach for the generation of panels of recombinant single-chain antibodies against the surface-exposed elements of X. fastidiosa that may have potential use in diagnosis and/or disease transmission blocking studies. In vitro combinatorial antibody ribosome display libraries were assembled from immunoglobulin transcripts rescued from the spleens of mice immunized with heat-killed X. fastidiosa. The libraries were used in a single round of selection against an outer membrane protein, MopB, resulting in the isolation of a panel of recombinant antibodies. The potential use of selected anti-MopB antibodies was demonstrated by the successful application of the 4XfMopB3 antibody in an enzyme-linked immunosorbent assay (ELISA), a Western blot assay, and an immunofluorescence assay (IFA). These immortalized in vitro recombinant single-chain antibody libraries generated against heat-killed X. fastidiosa are a resource for the Pierce's disease research community that may be readily accessed for the isolation of antibodies against a plethora of X. fastidiosa surface-exposed antigenic molecules. PMID:22327580

Comparative evaluation of recombinant LigB protein and heat-killed antigen-based latex agglutination test with microscopic agglutination test for diagnosis of bovine leptospirosis.

PubMed

Nagalingam, Mohandoss; Thirumalesh, Sushma Rahim Assadi; Kalleshamurthy, Triveni; Niharika, Nakkala; Balamurugan, Vinayagamurthy; Shome, Rajeswari; Sengupta, Pinaki Prasad; Shome, Bibek Ranjan; Prabhudas, Krishnamsetty; Rahman, Habibur

2015-10-01

This study aimed to develop latex agglutination test (LAT) using recombinant leptospiral immunoglobulin-like protein (LigB) (rLigB) antigen and compare its diagnostic efficacy with LAT using conventional heat-killed leptospiral antigen and microscopic agglutination test (MAT) in diagnosing bovine leptospirosis. The PCR-amplified 1053-bp ligB gene sequences from Leptospira borgpetersenii Hardjo serovar were cloned in pET 32 (a) vector at EcoRI and NotI sites and expressed in BL21 E. coli cells as fusion protein with thioredoxin (-57 kDa) and characterized by SDS-PAGE and immunoblot. Out of 390 serum samples [cattle (n = 214), buffaloes (n = 176)] subjected to MAT, 115 samples showed reciprocal titre≥100 up to 1600 against one or more serovars. For recombinant LigB protein/antigen-based LAT, agglutination was observed in the positive sample, while no agglutination was observed in the negative sample. Similarly, heat-killed leptospiral antigen was prepared from and used in LAT for comparison with MAT. A two-sided contingency table was used for analysis of LAT using both the antigens separately against MAT for 390 serum samples. The sensitivity, specificity and positive and negative predictive values of recombinant LigB LAT were found to be 75.65, 91.27, 78.38 and 89.96 %, respectively, and that of heat-killed antigen-based LAT were 72.17, 89.82, 74.77 and 88.53 %, respectively, in comparison with MAT. This developed test will be an alternative/complementary to the existing battery of diagnostic assays/tests for specific detection of pathogenic Leptospira infection in bovine population.

A collaborative filtering approach for protein-protein docking scoring functions.

PubMed

Bourquard, Thomas; Bernauer, Julie; Azé, Jérôme; Poupon, Anne

2011-04-22

A protein-protein docking procedure traditionally consists in two successive tasks: a search algorithm generates a large number of candidate conformations mimicking the complex existing in vivo between two proteins, and a scoring function is used to rank them in order to extract a native-like one. We have already shown that using Voronoi constructions and a well chosen set of parameters, an accurate scoring function could be designed and optimized. However to be able to perform large-scale in silico exploration of the interactome, a near-native solution has to be found in the ten best-ranked solutions. This cannot yet be guaranteed by any of the existing scoring functions. In this work, we introduce a new procedure for conformation ranking. We previously developed a set of scoring functions where learning was performed using a genetic algorithm. These functions were used to assign a rank to each possible conformation. We now have a refined rank using different classifiers (decision trees, rules and support vector machines) in a collaborative filtering scheme. The scoring function newly obtained is evaluated using 10 fold cross-validation, and compared to the functions obtained using either genetic algorithms or collaborative filtering taken separately. This new approach was successfully applied to the CAPRI scoring ensembles. We show that for 10 targets out of 12, we are able to find a near-native conformation in the 10 best ranked solutions. Moreover, for 6 of them, the near-native conformation selected is of high accuracy. Finally, we show that this function dramatically enriches the 100 best-ranking conformations in near-native structures.

A Collaborative Filtering Approach for Protein-Protein Docking Scoring Functions

PubMed Central

Bourquard, Thomas; Bernauer, Julie; Azé, Jérôme; Poupon, Anne

2011-01-01

A protein-protein docking procedure traditionally consists in two successive tasks: a search algorithm generates a large number of candidate conformations mimicking the complex existing in vivo between two proteins, and a scoring function is used to rank them in order to extract a native-like one. We have already shown that using Voronoi constructions and a well chosen set of parameters, an accurate scoring function could be designed and optimized. However to be able to perform large-scale in silico exploration of the interactome, a near-native solution has to be found in the ten best-ranked solutions. This cannot yet be guaranteed by any of the existing scoring functions. In this work, we introduce a new procedure for conformation ranking. We previously developed a set of scoring functions where learning was performed using a genetic algorithm. These functions were used to assign a rank to each possible conformation. We now have a refined rank using different classifiers (decision trees, rules and support vector machines) in a collaborative filtering scheme. The scoring function newly obtained is evaluated using 10 fold cross-validation, and compared to the functions obtained using either genetic algorithms or collaborative filtering taken separately. This new approach was successfully applied to the CAPRI scoring ensembles. We show that for 10 targets out of 12, we are able to find a near-native conformation in the 10 best ranked solutions. Moreover, for 6 of them, the near-native conformation selected is of high accuracy. Finally, we show that this function dramatically enriches the 100 best-ranking conformations in near-native structures. PMID:21526112

Origins of the helical wrapping of phenyleneethynylene polymers about single-walled carbon nanotubes.

PubMed

Von Bargen, Christopher D; MacDermaid, Christopher M; Lee, One-Sun; Deria, Pravas; Therien, Michael J; Saven, Jeffery G

2013-10-24

The highly charged, conjugated polymer poly[p-{2,5-bis(3-propoxysulfonicacidsodiumsalt)}phenylene]ethynylene (PPES) has been shown to wrap single-wall carbon nanotubes (SWNTs), adopting a robust helical superstructure. Surprisingly, PPES adopts a helical rather than a linear conformation when adhered to SWNTs. The complexes formed by PPES and related polymers upon helical wrapping of a SWNT are investigated using atomistic molecular dynamics (MD) simulations in the presence and absence of aqueous solvent. In simulations of the PPES/SWNT system in an aqueous environment, PPES spontaneously takes on a helical conformation. A potential of mean force, ΔA(ξ), is calculated as a function of ξ, the component of the end-to-end vector of the polymer chain projected on the SWNT axis; ξ is a monotonic function of the polymer's helical pitch. ΔA(ξ) provides a means to quantify the relative free energies of helical conformations of the polymer when wrapped about the SWNT. The aqueous system possesses a global minimum in ΔA(ξ) at the experimentally observed value of the helical pitch. The presence of this minimum is associated with preferred side chain conformations, where the side chains adopt conformations that provide van der Waals contact between the tubes and the aliphatic components of the side chains, while exposing the anionic sulfonates for aqueous solvation. The simulations provide a free energy estimate of a 0.2 kcal/mol/monomer preference for the helical over the linear conformation of the PPES/SWNT system in an aqueous environment.

Gravity dual for a model of perception

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

Nakayama, Yu, E-mail: nakayama@berkeley.edu

2011-01-15

One of the salient features of human perception is its invariance under dilatation in addition to the Euclidean group, but its non-invariance under special conformal transformation. We investigate a holographic approach to the information processing in image discrimination with this feature. We claim that a strongly coupled analogue of the statistical model proposed by Bialek and Zee can be holographically realized in scale invariant but non-conformal Euclidean geometries. We identify the Bayesian probability distribution of our generalized Bialek-Zee model with the GKPW partition function of the dual gravitational system. We provide a concrete example of the geometric configuration based onmore » a vector condensation model coupled with the Euclidean Einstein-Hilbert action. From the proposed geometry, we study sample correlation functions to compute the Bayesian probability distribution.« less

Partition function of free conformal fields in 3-plet representation

NASA Astrophysics Data System (ADS)

Beccaria, Matteo; Tseytlin, Arkady A.

2017-05-01

Simplest examples of AdS/CFT duality correspond to free CFTs in d dimensions with fields in vector or adjoint representation of an internal symmetry group dual in the large N limit to a theory of massless or massless plus massive higher spins in AdS d+1. One may also study generalizations when conformal fields belong to higher dimensional representations, i.e. carry more than two internal symmetry indices. Here we consider the case of the 3-fundamental ("3-plet") representation. One motivation is a conjectured connection to multiple M5-brane theory: heuristic arguments suggest that it may be related to an (interacting) CFT of 6d (2,0) tensor multiplets in 3-plet representation of large N symmetry group that has an AdS7 dual. We compute the singlet partition function Z on S 1 × S d-1 for a free field in 3-plet representation of U( N) and analyse its novel large N behaviour. The large N limit of the low temperature expansion of Z which is convergent in the vector and adjoint cases here is only asymptotic, reflecting the much faster growth of the number of singlet operators with dimension, indicating a phase transition at very low temperature. Indeed, while the critical temperatures in the vector ( T c ˜ N γ , γ > 0) and adjoint ( T c ˜ 1) cases are finite, we find that in the 3-plet case T c ˜ (log N)-1, i.e. it approaches zero at large N. We discuss some details of large N solution for the eigenvalue distribution. Similar conclusions apply to higher p-plet representations of U( N) or O( N) and also to the free p-tensor theories invariant under [U( N)] p or [ O( N)] p with p ≥ 3.

A novel, live-attenuated vesicular stomatitis virus vector displaying conformationally intact, functional HIV-1 envelope trimers that elicits potent cellular and humoral responses in mice.

PubMed

Rabinovich, Svetlana; Powell, Rebecca L R; Lindsay, Ross W B; Yuan, Maoli; Carpov, Alexei; Wilson, Aaron; Lopez, Mary; Coleman, John W; Wagner, Denise; Sharma, Palka; Kemelman, Marina; Wright, Kevin J; Seabrook, John P; Arendt, Heather; Martinez, Jennifer; DeStefano, Joanne; Chiuchiolo, Maria J; Parks, Christopher L

2014-01-01

Though vaccination with live-attenuated SIV provides the greatest protection from progressive disease caused by SIV challenge in rhesus macaques, attenuated HIV presents safety concerns as a vaccine; therefore, live viral vectors carrying HIV immunogens must be considered. We have designed a replication-competent vesicular stomatitis virus (VSV) displaying immunogenic HIV-1 Env trimers and attenuating quantities of the native surface glycoprotein (G). The clade B Env immunogen is an Env-VSV G hybrid (EnvG) in which the transmembrane and cytoplasmic tail regions are derived from G. Relocation of the G gene to the 5'terminus of the genome and insertion of EnvG into the natural G position induced a ∼1 log reduction in surface G, significant growth attenuation compared to wild-type, and incorporation of abundant EnvG. Western blot analysis indicated that ∼75% of incorporated EnvG was a mature proteolytically processed form. Flow cytometry showed that surface EnvG bound various conformationally- and trimer-specific antibodies (Abs), and in-vitro growth assays on CD4+CCR5+ cells demonstrated EnvG functionality. Neither intranasal (IN) or intramuscular (IM) administration in mice induced any observable pathology and all regimens tested generated potent Env-specific ELISA titers of 10(4)-10(5), with an IM VSV prime/IN VSV boost regimen eliciting the highest binding and neutralizing Ab titers. Significant quantities of Env-specific CD4+ T cells were also detected, which were augmented as much as 70-fold by priming with IM electroporated plasmids encoding EnvG and IL-12. These data suggest that our novel vector can achieve balanced safety and immunogenicity and should be considered as an HIV vaccine platform.

Hamiltonian analysis of curvature-squared gravity with or without conformal invariance

NASA Astrophysics Data System (ADS)

KlusoÅ, Josef; Oksanen, Markku; Tureanu, Anca

2014-03-01

We analyze gravitational theories with quadratic curvature terms, including the case of conformally invariant Weyl gravity, motivated by the intention to find a renormalizable theory of gravity in the ultraviolet region, yet yielding general relativity at long distances. In the Hamiltonian formulation of Weyl gravity, the number of local constraints is equal to the number of unstable directions in phase space, which in principle could be sufficient for eliminating the unstable degrees of freedom in the full nonlinear theory. All the other theories of quadratic type are unstable—a problem appearing as ghost modes in the linearized theory. We find that the full projection of the Weyl tensor onto a three-dimensional hypersurface contains an additional fully traceless component, given by a quadratic extrinsic curvature tensor. A certain inconsistency in the literature is found and resolved: when the conformal invariance of Weyl gravity is broken by a cosmological constant term, the theory becomes pathological, since a constraint required by the Hamiltonian analysis imposes the determinant of the metric of spacetime to be zero. In order to resolve this problem by restoring the conformal invariance, we introduce a new scalar field that couples to the curvature of spacetime, reminiscent of the introduction of vector fields for ensuring the gauge invariance.

Climate Change and Vector Borne Diseases: Getting A Grip on Control

NASA Astrophysics Data System (ADS)

Glass, G. E.; Ellis, H.

2011-12-01

Pathogens that are transmitted by arthropods to humans kill millions of people a year and have long been identified as systems likely affected by climate change. Despite this, there has been a long controversy of how to evaluate the responses of these infectious disease systems to climatic conditions so that meaningful programmatic dcisions can be made. We briefly review the rationale for overall expectations, using them to identify both the temporal and spatial resolution needed for decision making and then discuss progress to date, using the world global malaria eradication program as an example.

Lactococcus lactis-based vaccines: current status and future perspectives.

PubMed

Bahey-El-Din, Mohammed; Gahan, Cormac G M

2011-01-01

Lactococcus lactis offers significant potential as a platform for the delivery of vaccines especially via mucosal routes of administration. The organism has an established history of safe use in the food industry and is highly amenable to genetic manipulation, with many systems available for efficient production of secreted and surface-expressed proteins. Here we describe the benefits of using this organism as a vaccine delivery platform and outline how L. lactis based antigen delivery may be improved. Finally we discuss the safe use of L. lactis vectors and outline the potential for use of biological containment systems and killed lactococcal preparations.

Aerospace Technologies of the 21st Century: New Technologies of Experimental Research and Simulation Held in Berlin, Germany on 8-9 June 2000

DTIC Science & Technology

2000-01-01

11. Gal-Or, B., U.S. PAT. Appl .. 08/516870/1, Aug. 18, 1995 & Isr. Pat. Appl . 113636, May 7,1995 by Gal- Or, Lichtsinder and Sherbaum.. 12. Gal-Or...B., U.S. PAT. Appl . 08/516870/2, Aug. 18, 1995 & Isr. Pat. Appl . 111265, Oct. 12,94 by Gal- Or, Lichtsinder and Sherbaum. 13. Gal-Or, B., U.S. PAT... Appl . 08/554087, Nov. 6,1995. 14. Gal-Or, B., ?Proposed Flight Testing Standards for Engine Thrust Vectoring to Maximize Kill Ra- tios, Post-Stall

Natural HLA-B*2705 protein ligands with glutamine as anchor motif: implications for HLA-B27 association with spondyloarthropathy.

PubMed

Infantes, Susana; Lorente, Elena; Barnea, Eilon; Beer, Ilan; Barriga, Alejandro; Lasala, Fátima; Jiménez, Mercedes; Admon, Arie; López, Daniel

2013-04-12

The presentation of short viral peptide antigens by human leukocyte antigen (HLA) class I molecules on cell surfaces is a key step in the activation of cytotoxic T lymphocytes, which mediate the killing of pathogen-infected cells or initiate autoimmune tissue damage. HLA-B27 is a well known class I molecule that is used to study both facets of the cellular immune response. Using mass spectrometry analysis of complex HLA-bound peptide pools isolated from large amounts of HLA-B*2705(+) cells, we identified 200 naturally processed HLA-B*2705 ligands. Our analyses revealed that a change in the position (P) 2 anchor motif was detected in the 3% of HLA-B*2705 ligands identified. B*2705 class I molecules were able to bind these six GlnP2 peptides, which showed significant homology to pathogenic bacterial sequences, with a broad range of affinities. One of these ligands was able to bind with distinct conformations to HLA-B27 subtypes differentially associated with ankylosing spondylitis. These conformational differences could be sufficient to initiate autoimmune damage in patients with ankylosing spondylitis-associated subtypes. Therefore, these kinds of peptides (short, with GlnP2, and similar low affinity to all HLA-B27 subtypes tested but with unlike conformations in differentially ankylosing spondylitis-associated subtypes) must not be excluded from future researches involving potential arthritogenic peptides.

Natural HLA-B*2705 Protein Ligands with Glutamine as Anchor Motif

PubMed Central

Infantes, Susana; Lorente, Elena; Barnea, Eilon; Beer, Ilan; Barriga, Alejandro; Lasala, Fátima; Jiménez, Mercedes; Admon, Arie; López, Daniel

2013-01-01

The presentation of short viral peptide antigens by human leukocyte antigen (HLA) class I molecules on cell surfaces is a key step in the activation of cytotoxic T lymphocytes, which mediate the killing of pathogen-infected cells or initiate autoimmune tissue damage. HLA-B27 is a well known class I molecule that is used to study both facets of the cellular immune response. Using mass spectrometry analysis of complex HLA-bound peptide pools isolated from large amounts of HLA-B*2705+ cells, we identified 200 naturally processed HLA-B*2705 ligands. Our analyses revealed that a change in the position (P) 2 anchor motif was detected in the 3% of HLA-B*2705 ligands identified. B*2705 class I molecules were able to bind these six GlnP2 peptides, which showed significant homology to pathogenic bacterial sequences, with a broad range of affinities. One of these ligands was able to bind with distinct conformations to HLA-B27 subtypes differentially associated with ankylosing spondylitis. These conformational differences could be sufficient to initiate autoimmune damage in patients with ankylosing spondylitis-associated subtypes. Therefore, these kinds of peptides (short, with GlnP2, and similar low affinity to all HLA-B27 subtypes tested but with unlike conformations in differentially ankylosing spondylitis-associated subtypes) must not be excluded from future researches involving potential arthritogenic peptides. PMID:23430249

Crystal structure of phototoxic orange fluorescent proteins with α tryptophan-based chromophore

DOE PAGES

Pletneva, Nadya V.; Pletnev, Vladimir Z.; Sarkisyan, Karen S.; ...

2015-12-23

Phototoxic fluorescent proteins represent a sparse group of genetically encoded photosensitizers that could be used for precise light-induced inactivation of target proteins, DNA damage, and cell killing. Only two such GFP-based fluorescent proteins (FPs), KillerRed and its monomeric variant SuperNova, were described up to date. We present a crystallographic study of their two orange successors, dimeric KillerOrange and monomeric mKiller-Orange, at 1.81 and 1.57 Å resolution, respectively. They are the first orange-emitting protein photosensitizers with a tryptophan-based chromophore (Gln65-Trp66-Gly67). Same as their red progenitors, both orange photosensitizers have a water-filled channel connecting the chromophore to the β-barrel exterior and enablingmore » transport of ROS. In both proteins, Trp66 of the chromophore adopts an unusual trans-cis conformation stabilized by H-bond with the nearby Gln159. This trans-cis conformation along with the water channel was shown to be a key structural feature providing bright orange emission and phototoxicity of both examined orange photosensitizers.« less

Crystal Structure of Phototoxic Orange Fluorescent Proteins with a Tryptophan-Based Chromophore

PubMed Central

Pletneva, Nadya V.; Pletnev, Vladimir Z.; Sarkisyan, Karen S.; Gorbachev, Dmitry A.; Egorov, Evgeny S.; Mishin, Alexander S.; Lukyanov, Konstantin A.; Dauter, Zbigniew; Pletnev, Sergei

2015-01-01

Phototoxic fluorescent proteins represent a sparse group of genetically encoded photosensitizers that could be used for precise light-induced inactivation of target proteins, DNA damage, and cell killing. Only two such GFP-based fluorescent proteins (FPs), KillerRed and its monomeric variant SuperNova, were described up to date. Here, we present a crystallographic study of their two orange successors, dimeric KillerOrange and monomeric mKillerOrange, at 1.81 and 1.57 Å resolution, respectively. They are the first orange-emitting protein photosensitizers with a tryptophan-based chromophore (Gln65-Trp66-Gly67). Same as their red progenitors, both orange photosensitizers have a water-filled channel connecting the chromophore to the β-barrel exterior and enabling transport of ROS. In both proteins, Trp66 of the chromophore adopts an unusual trans-cis conformation stabilized by H-bond with the nearby Gln159. This trans-cis conformation along with the water channel was shown to be a key structural feature providing bright orange emission and phototoxicity of both examined orange photosensitizers. PMID:26699366

CONSTRUCTION OF SCALAR AND VECTOR FINITE ELEMENT FAMILIES ON POLYGONAL AND POLYHEDRAL MESHES

PubMed Central

GILLETTE, ANDREW; RAND, ALEXANDER; BAJAJ, CHANDRAJIT

2016-01-01

We combine theoretical results from polytope domain meshing, generalized barycentric coordinates, and finite element exterior calculus to construct scalar- and vector-valued basis functions for conforming finite element methods on generic convex polytope meshes in dimensions 2 and 3. Our construction recovers well-known bases for the lowest order Nédélec, Raviart-Thomas, and Brezzi-Douglas-Marini elements on simplicial meshes and generalizes the notion of Whitney forms to non-simplicial convex polygons and polyhedra. We show that our basis functions lie in the correct function space with regards to global continuity and that they reproduce the requisite polynomial differential forms described by finite element exterior calculus. We present a method to count the number of basis functions required to ensure these two key properties. PMID:28077939

Solution of free-boundary problems using finite-element/Newton methods and locally refined grids - Application to analysis of solidification microstructure

NASA Technical Reports Server (NTRS)

Tsiveriotis, K.; Brown, R. A.

1993-01-01

A new method is presented for the solution of free-boundary problems using Lagrangian finite element approximations defined on locally refined grids. The formulation allows for direct transition from coarse to fine grids without introducing non-conforming basis functions. The calculation of elemental stiffness matrices and residual vectors are unaffected by changes in the refinement level, which are accounted for in the loading of elemental data to the global stiffness matrix and residual vector. This technique for local mesh refinement is combined with recently developed mapping methods and Newton's method to form an efficient algorithm for the solution of free-boundary problems, as demonstrated here by sample calculations of cellular interfacial microstructure during directional solidification of a binary alloy.

CONSTRUCTION OF SCALAR AND VECTOR FINITE ELEMENT FAMILIES ON POLYGONAL AND POLYHEDRAL MESHES.

PubMed

Gillette, Andrew; Rand, Alexander; Bajaj, Chandrajit

2016-10-01

We combine theoretical results from polytope domain meshing, generalized barycentric coordinates, and finite element exterior calculus to construct scalar- and vector-valued basis functions for conforming finite element methods on generic convex polytope meshes in dimensions 2 and 3. Our construction recovers well-known bases for the lowest order Nédélec, Raviart-Thomas, and Brezzi-Douglas-Marini elements on simplicial meshes and generalizes the notion of Whitney forms to non-simplicial convex polygons and polyhedra. We show that our basis functions lie in the correct function space with regards to global continuity and that they reproduce the requisite polynomial differential forms described by finite element exterior calculus. We present a method to count the number of basis functions required to ensure these two key properties.

Conformal Collineations of the Ricci and Energy-Momentum Tensors in Static Plane Symmetric Space-Times

NASA Astrophysics Data System (ADS)

Akhtar, S. S.; Hussain, T.; Bokhari, A. H.; Khan, F.

2018-04-01

We provide a complete classification of static plane symmetric space-times according to conformal Ricci collineations (CRCs) and conformal matter collineations (CMCs) in both the degenerate and nondegenerate cases. In the case of a nondegenerate Ricci tensor, we find a general form of the vector field generating CRCs in terms of unknown functions of t and x subject to some integrability conditions. We then solve the integrability conditions in different cases depending upon the nature of the Ricci tensor and conclude that the static plane symmetric space-times have a 7-, 10- or 15-dimensional Lie algebra of CRCs. Moreover, we find that these space-times admit an infinite number of CRCs if the Ricci tensor is degenerate. We use a similar procedure to study CMCs in the case of a degenerate or nondegenerate matter tensor. We obtain the exact form of some static plane symmetric space-time metrics that admit nontrivial CRCs and CMCs. Finally, we present some physical applications of our obtained results by considering a perfect fluid as a source of the energy-momentum tensor.

Protein Conformational Entropy is Independent of Solvent

NASA Astrophysics Data System (ADS)

Nucci, Nathaniel; Moorman, Veronica; Gledhill, John; Valentine, Kathleen; Wand, A. Joshua

Proteins exhibit most of their conformational entropy in individual bond vector motions on the ps-ns timescale. These motions can be examined through determination of the Lipari-Szabo generalized squared order parameter (O2) using NMR spin relaxation measurements. It is often argued that most protein motions are intimately dependent on the nature of the solvating environment. Here the solvent dependence of the fast protein dynamics is directly assessed. Using the model protein ubiquitin, the order parameters of the backbone and methyl groups are shown to be generally unaffected by up to a six-fold increase in bulk viscosity or by encapsulation in the nanoscale interior of a reverse micelle. In addition, the reverse micelle condition permits direct comparison of protein dynamics to the mobility of the hydration layer; no correlation is observed. The dynamics of aromatic side chains are also assessed and provide an estimate of the length- and timescale of protein motions where solvent dependence is seen. These data demonstrate the solvent independence of conformational entropy, clarifying a long-held misconception in the fundamental behavior of biological macromolecules. Supported by the National Science Foundation.

Recombinant modified vaccinia virus Ankara–simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer

PubMed Central

Seth, Aruna; Ourmanov, Ilnour; Kuroda, Marcelo J.; Schmitz, Jörn E.; Carroll, Miles W.; Wyatt, Linda S.; Moss, Bernard; Forman, Meryl A.; Hirsch, Vanessa M.; Letvin, Norman L.

1998-01-01

The utility of modified vaccinia virus Ankara (MVA) as a vector for eliciting AIDS virus-specific cytotoxic T lymphocytes (CTL) was explored in the simian immunodeficiency virus (SIV)/rhesus monkey model. After two intramuscular immunizations with recombinant MVA-SIVSM gag pol, the monkeys developed a Gag epitope-specific CTL response readily detected in peripheral blood lymphocytes by using a functional killing assay. Moreover, those immunizations also elicited a population of CD8+ T lymphocytes in the peripheral blood that bound a specific major histocompatibility complex class I/peptide tetramer. These Gag epitope-specific CD8+ T lymphocytes also were demonstrated by using both functional and tetramer-binding assays in lymph nodes of the immunized monkeys. These observations suggest that MVA may prove a useful vector for an HIV-1 vaccine. They also suggest that tetramer staining may be a useful technology for monitoring CTL generation in vaccine trials in nonhuman primates and in humans. PMID:9707609

Improving the Cost-Effectiveness of Visual Devices for the Control of Riverine Tsetse Flies, the Major Vectors of Human African Trypanosomiasis

PubMed Central

Esterhuizen, Johan; Rayaisse, Jean Baptiste; Tirados, Inaki; Mpiana, Serge; Solano, Philippe; Vale, Glyn A.; Lehane, Michael J.; Torr, Stephen J.

2011-01-01

Control of the Riverine (Palpalis) group of tsetse flies is normally achieved with stationary artificial devices such as traps or insecticide-treated targets. The efficiency of biconical traps (the standard control device), 1×1 m black targets and small 25×25 cm targets with flanking nets was compared using electrocuting sampling methods. The work was done on Glossina tachinoides and G. palpalis gambiensis (Burkina Faso), G. fuscipes quanzensis (Democratic Republic of Congo), G. f. martinii (Tanzania) and G. f. fuscipes (Kenya). The killing effectiveness (measured as the catch per m2 of cloth) for small targets plus flanking nets is 5.5–15X greater than for 1 m2 targets and 8.6–37.5X greater than for biconical traps. This has important implications for the costs of control of the Riverine group of tsetse vectors of sleeping sickness. PMID:21829743

Identification of the ENT1 antagonists dipyridamole and dilazep as amplifiers of oncolytic herpes simplex virus-1 replication.

PubMed

Passer, Brent J; Cheema, Tooba; Zhou, Bingsen; Wakimoto, Hiroaki; Zaupa, Cecile; Razmjoo, Mani; Sarte, Jason; Wu, Shulin; Wu, Chin-lee; Noah, James W; Li, Qianjun; Buolamwini, John K; Yen, Yun; Rabkin, Samuel D; Martuza, Robert L

2010-05-15

Oncolytic herpes simplex virus-1 (oHSV) vectors selectively replicate in tumor cells, where they kill through oncolysis while sparing normal cells. One of the drawbacks of oHSV vectors is their limited replication and spread to neighboring cancer cells. Here, we report the outcome of a high-throughput chemical library screen to identify small-molecule compounds that augment the replication of oHSV G47Delta. Of the 2,640-screened bioactives, 6 compounds were identified and subsequently validated for enhanced G47Delta replication. Two of these compounds, dipyridamole and dilazep, interfered with nucleotide metabolism by potently and directly inhibiting the equilibrative nucleoside transporter-1 (ENT1). Replicative amplification promoted by dipyridamole and dilazep were dependent on HSV mutations in ICP6, the large subunit of ribonucleotide reductase. Our results indicate that ENT1 antagonists augment oHSV replication in tumor cells by increasing cellular ribonucleoside activity. (c)2010 AACR.

Investigation of spatiotemporal relationship between dengue fever and drought

NASA Astrophysics Data System (ADS)

Lee, Chieh-Han; Yu, Hwa-Lung

2016-04-01

Dengue Fever is a vector-borne disease that is transmitted between human and mosquitos in tropical and sub-tropical regions. Previous studies have found significant relationship between the epidemic of dengue cases and climate variables, especially temperature and precipitation. Besides, the natural phenomena (e.g., drought) are considered that significantly drop the number of dengue cases by killing vector's breeding environment. However, in Kaohsiung City, Taiwan, there are evidences that the temporal pattern of dengue is correlated to drought events. Kaohsiung City experienced two main dengue outbreaks in 2002 and 2014 that both years were confirmed with serious drought. Especially in 2014, Kaohsiung City was suffered from extremely dengue outbreak in 2014 that reported the highest number of dengue cases in the history. Otherwise, another nearby city, Tainan City, had reported the biggest outbreak in 2015. This study constructs the spatiotemporal model of dengue incidences and index of drought events (Standardized Precipitation Index, SPI) based on the distributed lag nonlinear model (DLNM). Other meteorological measures are also included in the analysis.

Spin-dependent post-Newtonian parameters from EMRI computation in Kerr background

NASA Astrophysics Data System (ADS)

Friedman, John; Le Tiec, Alexandre; Shah, Abhay

2013-04-01

Because the extreme mass-ratio inspiral (EMRI) approximation is accurate to all orders in v/c, it can be used to find high order post-Newtonian parameters that are not yet analytically accessible. We report here on progress in computing spin-dependent, conservative, post-Newtonian parameters from a radiation-gauge computation for a particle in circular orbit in a family of Kerr geometries. For a particle with 4-velocity u^α= U k^α, with k^α the helical Killing vector of the perturbed spacetime, the renormalized perturbation δU, when written as a function of the particle's angular velocity, is invariant under gauge transformations generated by helically symmetric vectors. The EMRI computations are done in a modified radiation gauge. Extracted parameters are compared to previously known and newly computed spin-dependent post-Newtonian terms. This work is modeled on earlier computations by Blanchet, Detweiler, Le Tiec and Whiting of spin-independent terms for a particle in circular orbit in a Schwarzschild geometry.

Dynamics of a fluctuating semi-flexible membrane

NASA Astrophysics Data System (ADS)

Tukdarian, Nathaniel; Huang, Aiqun; Adhikari, Ramesh; Bhattacharya, Aniket

2015-03-01

We report our preliminary studies of conformations and dynamics of a fluctuating semi-flexible membrane. Our model of membrane with linear dimension L consists of N2 (L = Nbl) excluded volume beads connected by anharmonic springs. The stiffness of the membrane is controlled by adjusting the strength κb of the bending potential Ubend =κb(1-n̂i .n̂j) between adjacent elementary plaquettes consisting of three beads at the corners connected by bonds and characterized by normal unit vectors n̂i and n̂j. We study the conformations and dynamic fluctuations of the membrane using Brownian dynamics simulation. We show how the radius of gyration scales with N and κb, and study characteristics of the transverse fluctuations, the root-mean-square displacement of the center of mass, and the dynamics of the end monomers at each corner.

Duality of force laws and conformal transformations

NASA Astrophysics Data System (ADS)

Kothawala, Dawood

2011-06-01

As was first noted by Isaac Newton, the two most famous ellipses of classical mechanics, arising from the force laws F ∝r and F ∝1/r2, can be mapped onto each other by changing the location of the center of force. Less well known is that this mapping can also be achieved by the complex transformation, z →z2. We derive this result and its generalization by writing the Gaussian curvature in its covariant form, and then changing the metric by a conformal transformation which mimics this mapping of the curves. We indicate how the conserved Laplace-Runge-Lenz vector for the 1/r2 force law transforms under this transformation, and compare it with the corresponding quantities for the linear force law. Our main aim is to present this duality by introducing concepts from differential geometry.

Potential for entomopathogenic fungi to control Triatoma dimidiata (Hemiptera: Reduviidae), a vector of Chagas disease in Mexico.

PubMed

Vázquez-Martínez, María Guadalupe; Cirerol-Cruz, Blanca Elva; Torres-Estrada, José Luis; López, Mario Henry Rodríguez

2014-01-01

The use of entomopathogenic fungi to control disease vectors has become relevant because traditional chemical control methods have caused damage to the environment and led to the development of resistance among vectors. Thus, this study assessed the pathogenicity of entomopathogenic fungi in Triatoma dimidiata. Preparations of 108 conidia/ml of Gliocladium virens, Talaromyces flavus, Beauveria bassiana and Metarhizium anisopliae were applied topically on T. dimidiata nymphs and adults. Controls were treated with the 0.0001% Tween-80 vehicle. Mortality was evaluated and recorded daily for 30 days. The concentration required to kill 50% of T. dimidiata (LC50) was then calculated for the most pathogenic isolate. Pathogenicity in adults was similar among B. bassiana, G. virens and T. flavus (p>0.05) and differed from that in triatomine nymphs (p=0.009). The most entomopathogenic strains in adult triatomines were B. bassiana and G. virens, which both caused 100% mortality. In nymphs, the most entomopathogenic strain was B. bassiana, followed by G. virens. The native strain with the highest pathogenicity was G. virens, for which the LC50 for T. dimidiata nymphs was 1.98 x108 conidia/ml at 13 days after inoculation. Beauveria bassiana and G. virens showed entomopathogenic potential in T. dimidiata nymphs and adults. However, the native G. virens strain presents a higher probability of success in the field, and G. virens should thus be considered a potential candidate for the biological control of triatomine Chagas disease vectors.

A Multiscale Model for the World's First Parasitic Disease Targeted for Eradication: Guinea Worm Disease

PubMed Central

Netshikweta, Rendani

2017-01-01

Guinea worm disease (GWD) is both a neglected tropical disease and an environmentally driven infectious disease. Environmentally driven infectious diseases remain one of the biggest health threats for human welfare in developing countries and the threat is increased by the looming danger of climate change. In this paper we present a multiscale model of GWD that integrates the within-host scale and the between-host scale. The model is used to concurrently examine the interactions between the three organisms that are implicated in natural cases of GWD transmission, the copepod vector, the human host, and the protozoan worm parasite (Dracunculus medinensis), and identify their epidemiological roles. The results of the study (through sensitivity analysis of R0) show that the most efficient elimination strategy for GWD at between-host scale is to give highest priority to copepod vector control by killing the copepods in drinking water (the intermediate host) by applying chemical treatments (e.g., temephos, an organophosphate). This strategy should be complemented by health education to ensure that greater numbers of individuals and communities adopt behavioural practices such as voluntary reporting of GWD cases, prevention of GWD patients from entering drinking water bodies, regular use of water from safe water sources, and, in the absence of such water sources, filtering or boiling water before drinking. Taking into account the fact that there is no drug or vaccine for GWD (interventions which operate at within-host scale), the results of our study show that the development of a drug that kills female worms at within-host scale would have the highest impact at this scale domain with possible population level benefits that include prevention of morbidity and prevention of transmission. PMID:28808479

The Long and Winding Road: From the High-Affinity Choline Uptake Site to Clinical Trials for Malignant Brain Tumors.

PubMed

Lowenstein, P R; Castro, M G

2016-01-01

Malignant brain tumors are one of the most lethal cancers. They originate from glial cells which infiltrate throughout the brain. Current standard of care involves surgical resection, radiotherapy, and chemotherapy; median survival is currently ~14-20 months postdiagnosis. Given that the brain immune system is deficient in priming systemic immune responses to glioma antigens, we proposed to reconstitute the brain immune system to achieve immunological priming from within the brain. Two adenoviral vectors are injected into the resection cavity or remaining tumor. One adenoviral vector expresses the HSV-1-derived thymidine kinase which converts ganciclovir into a compound only cytotoxic to dividing glioma cells. The second adenovirus expresses the cytokine fms-like tyrosine kinase 3 ligand (Flt3L). Flt3L differentiates precursors into dendritic cells and acts as a chemokine that attracts dendritic cells to the brain. HSV-1/ganciclovir killing of tumor cells releases tumor antigens that are taken up by dendritic cells within the brain tumor microenvironment. Tumor killing also releases HMGB1, an endogenous TLR2 agonist that activates dendritic cells. HMGB1-activated dendritic cells, loaded with glioma antigens, migrate to cervical lymph nodes to stimulate a systemic CD8+ T cells cytotoxic immune response against glioma. This immune response is specific to glioma tumors, induces immunological memory, and does neither cause brain toxicity nor autoimmune responses. An IND was granted by the FDA on 4/7/2011. A Phase I, first in person trial, to test whether reengineering the brain immune system is potentially therapeutic is ongoing. © 2016 Elsevier Inc. All rights reserved.

Conserved charge of a gravity theory with p -form gauge fields and its property under Kaluza-Klein reduction

NASA Astrophysics Data System (ADS)

Peng, Jun-Jin

2017-05-01

In this paper, we investigate the conserved charges of generally diffeomorphism invariant gravity theories with a wide variety of matter fields, particularly of the theories with multiple scalar fields and p -form potentials, in the context of the off-shell generalized Abbott-Deser-Tekin (ADT) formalism. We first construct a new off-shell ADT current that consists of the terms for the variation of a Killing vector and expressions of the field equations as well as the Lie derivative of a surface term with respect to the Killing vector within the framework of generally diffeomorphism invariant gravity theories involving various matter fields. After deriving the off-shell ADT potential corresponding to this current, we propose a formula of conserved charges for these theories. Next, we derive the off-shell ADT potential associated with the generic Lagrangian that describes a large range of gravity theories with a number of scalar fields and p -form potentials. Finally, the properties of the off-shell generalized ADT charges for the theory of Einstein gravity and the gravity theories with a single p -form potential are investigated by performing Kaluza-Klein dimensional reduction along a compactified direction. The results indicate that the charge contributed by all the fields in the lower-dimensional theory is equal to that of the higher-dimensional one at mathematical level with the hypothesis that the higher-dimensional spacetime allows for the existence of the compactified dimension. In order to illustrate our calculations, the mass and angular momentum for the five-dimensional rotating Kaluza-Klein black holes are explicitly evaluated as an example.

What befalls the proteins and water in a living cell when the cell dies?

PubMed

Ling, Gilbert N; Fu, Ya-zhen

2005-01-01

The solvency of solutes of varying molecular size in the intracellular water of freshly-killed Ehrlich carcinoma cells fits the same theoretical curve that describes the solvency of similar solutes in a 36% solution of native bovine hemoglobin--a protein found only in red blood cells and making up 97.3% of the red cell's total intracellular proteins. The merging of the two sets of data confirms the prediction of the AI Hypothesis that key intracellular protein(s) in dying cells undergo(es) a transition from: (1) one in which the polypeptide NHCO groups assume a fully-extended conformation with relatively strong power of polarizing and orienting the bulk-phase water in multilayers; to (2) one in which most of the polypeptide NHCO groups are engaged in alpha-helical and other "introvert" conformations (see below for definition) with much weaker power in polarizing-orienting multilayers of bulk-phase water. This concordance of the two sets of data also shows that what we now call native hemoglobin--supposedly denoting hemoglobin found in its natural state in living red blood cells--, in fact, more closely resembles the water-polarizing, and -orienting intracellular proteins in dead cells. Although in the dead Ehrlich carcinoma cells as well as in the 36% solution of native hemoglobin, much of the protein's polypeptide NHCO groups are engaged in alpha-helical and other "introvert" conformation (Perutz 1969; Weissbluth 1974), both systems produce a weak but nonetheless pervasive and "long-range" water polarization and orientation. It is suggested that in both the dead Ehrlich carcinoma ascites cells and in the 36% native bovine hemoglobin solution, enough polypeptide NHCO groups assume the fully-extended conformation to produce the weak but far-reaching multilayer water polarization and orientation observed.

Black Holes, Hidden Symmetry and Complete Integrability: Brief Review

NASA Astrophysics Data System (ADS)

Frolov, Valeri P.

This chapter contains a brief review of the remarkable properties of higher dimensional rotating black holes with the spherical topology of the horizon. We demonstrate that these properties are connected with and generated by a special geometrical object, the Principal Conformal Killing-Yano tensor (PCKYT). The most general solution, describing such black holes, Kerr-NUT-ADS metric, admits this structure. Moreover a solution of the Einstein Equations with (or without) a cosmological constant which possesses PCKYT is the Kerr-NUT-ADS metric. This object (PCKYT) is responsible for such remarkable properties of higher dimensional rotating black holes as: (i) complete integrability of geodesic equations and (ii) complete separation of variables of the important field equations.

On the Chern-Gauss-Bonnet theorem for the noncommutative 4-sphere

NASA Astrophysics Data System (ADS)

Arnlind, Joakim; Wilson, Mitsuru

2017-01-01

We construct a differential calculus over the noncommutative 4-sphere in the framework of pseudo-Riemannian calculi, and show that for every metric in a conformal class of perturbations of the round metric, there exists a unique metric and torsion-free connection. Furthermore, we find a localization of the projective module corresponding to the space of vector fields, which allows us to formulate a Chern-Gauss-Bonnet type theorem for the noncommutative 4-sphere.

The crystal structures of two salivary cystatins from the tick Ixodes scapularis and the effect of these inhibitors on the establishment of Borrelia burgdorferi infection in a murine model

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

Kotsyfakis, Michalis; Horka, Helena; Salat, Jiri

2010-11-17

We have previously demonstrated that two salivary cysteine protease inhibitors from the Borrelia burgdorferi (Lyme disease) vector Ixodes scapularis - namely sialostatins L and L2 - play an important role in tick biology, as demonstrated by the fact that silencing of both sialostatins in tandem results in severe feeding defects. Here we show that sialostatin L2 - but not sialostatin L - facilitates the growth of B. burgdorferi in murine skin. To examine the structural basis underlying these differential effects of the two sialostatins, we have determined the crystal structures of both sialostatin L and L2. This is the firstmore » structural analysis of cystatins from an invertebrate source. Sialostatin L2 crystallizes as a monomer with an 'unusual' conformation of the N-terminus, while sialostatin L crystallizes as a domain-swapped dimer with an N-terminal conformation similar to other cystatins. Deletion of the 'unusual' N-terminal five residues of sialostatin L2 results in marked changes in its selectivity, suggesting that this region is a particularly important determinant of the biochemical activity of sialostatin L2. Collectively, our results reveal the structure of two tick salivary components that facilitate vector blood feeding and that one of them also supports pathogen transmission to the vertebrate host.« less

Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus.

PubMed

Di Mario, Giuseppina; Soprana, Elisa; Gubinelli, Francesco; Panigada, Maddalena; Facchini, Marzia; Fabiani, Concetta; Garulli, Bruno; Basileo, Michela; Cassone, Antonio; Siccardi, Antonio; Donatelli, Isabella; Castrucci, Maria R

2017-03-01

Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses. Modified vaccinia virus Ankara (MVA) expressing a headless HA (hlHA) of A/California/4/09 (CA/09) virus was used as a vaccine to immunize C57BL/6 mice. Specific antibody and cell-mediated immune responses were determined, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus. Immunization of mice with CA/09-derived hlHA, vectored by MVA, was able to elicit influenza-specific broad cross-reactive antibodies and cell-mediated immune responses, but failed to induce neutralizing antibodies and did not protect mice against virus challenge. Although highly immunogenic, our vaccine was unable to induce a protective immunity against influenza. A misfolded and unstable conformation of the hlHA molecule may have affected its capacity of inducing neutralizing antiviral, conformational antibodies. Design of stable hlHA-based immunogens and their delivery by recombinant MVA-based vectors has the potential of improving this promising approach for a universal influenza vaccine.

Conditional Cytotoxic Anti-HIV Gene Therapy for Selectable Cell Modification

PubMed Central

Garg, Himanshu; Joshi, Anjali

2016-01-01

Gene therapy remains one of the potential strategies to achieve a cure for HIV infection. One of the major limitations of anti-HIV gene therapy concerns recovering an adequate number of modified cells to generate an HIV-proof immune system. Our study addresses this issue by developing a methodology that can mark conditional vector-transformed cells for selection and subsequently target HIV-infected cells for elimination by treatment with ganciclovir (GCV). We used the herpes simplex virus thymidine kinase (TK) mutant SR39, which is highly potent at killing cells at low GCV concentrations. This gene was cloned into a conditional HIV vector, pNL-GFPRRESA, which expresses the gene of interest as well as green fluorescent protein (GFP) in the presence of HIV Tat protein. We show here that TK-SR39 was more potent that wild-type TK (TK-WT) at eliminating infected cells at lower concentrations of GCV. As the vector expresses GFP in the presence of Tat, transient expression of Tat either by Tat RNA transfection or transduction by a nonintegrating lentiviral (NIL) vector marked the cells with GFP for selection. In cells selected by this strategy, TK-SR39 was more potent at limiting virus replication than TK-WT. Finally, in Jurkat cells modified and selected by this approach, infection with CXCR4-tropic Lai virus could be suppressed by treatment with GCV. GCV treatment limited the number of HIV-infected cells, virus production, as well as virus-induced cytopathic effects in this model. We provide proof of principle that TK-SR39 in a conditional HIV vector can provide a safe and effective anti-HIV strategy. PMID:26800572

The abundance of the Lyme disease pathogen Borrelia afzelii declines over time in the tick vector Ixodes ricinus.

PubMed

Jacquet, Maxime; Genné, Dolores; Belli, Alessandro; Maluenda, Elodie; Sarr, Anouk; Voordouw, Maarten J

2017-05-25

The population dynamics of vector-borne pathogens inside the arthropod vector can have important consequences for vector-to-host transmission. Tick-borne spirochete bacteria of the Borrelia burgdorferi (sensu lato) species complex cause Lyme borreliosis in humans and spend long periods of time (>12 months) in their Ixodes tick vectors. To date, few studies have investigated the dynamics of Borrelia spirochete populations in unfed Ixodes nymphal ticks. Larval ticks from our laboratory colony of I. ricinus were experimentally infected with B. afzelii, and killed at 1 month and 4 months after the larva-to-nymph moult. The spirochete load was also compared between engorged larval ticks and unfed nymphs (from the same cohort) and between unfed nymphs and unfed adult ticks (from the same cohort). The spirochete load of B. afzelii in each tick was estimated using qPCR. The mean spirochete load in the 1-month-old nymphs (~14,000 spirochetes) was seven times higher than the 4-month-old nymphs (~2000 spirochetes). Thus, the nymphal spirochete load declined by 80% over a period of 3 months. An engorged larval tick acquired ~100 spirochetes, and this population was 20 times larger in a young, unfed nymph. The spirochete load also appeared to decline in adult ticks. Comparison between wild and laboratory populations found that lab ticks were more susceptible to acquiring B. afzelii. The spirochete load of B. afzelii declines dramatically over time in domesticated I. ricinus nymphs under laboratory conditions. Future studies should investigate whether temporal declines in spirochete load occur in wild Ixodes ticks under natural conditions and whether these declines influence the tick-to-host transmission of Borrelia.

Conditional Cytotoxic Anti-HIV Gene Therapy for Selectable Cell Modification.

PubMed

Garg, Himanshu; Joshi, Anjali

2016-05-01

Gene therapy remains one of the potential strategies to achieve a cure for HIV infection. One of the major limitations of anti-HIV gene therapy concerns recovering an adequate number of modified cells to generate an HIV-proof immune system. Our study addresses this issue by developing a methodology that can mark conditional vector-transformed cells for selection and subsequently target HIV-infected cells for elimination by treatment with ganciclovir (GCV). We used the herpes simplex virus thymidine kinase (TK) mutant SR39, which is highly potent at killing cells at low GCV concentrations. This gene was cloned into a conditional HIV vector, pNL-GFPRRESA, which expresses the gene of interest as well as green fluorescent protein (GFP) in the presence of HIV Tat protein. We show here that TK-SR39 was more potent that wild-type TK (TK-WT) at eliminating infected cells at lower concentrations of GCV. As the vector expresses GFP in the presence of Tat, transient expression of Tat either by Tat RNA transfection or transduction by a nonintegrating lentiviral (NIL) vector marked the cells with GFP for selection. In cells selected by this strategy, TK-SR39 was more potent at limiting virus replication than TK-WT. Finally, in Jurkat cells modified and selected by this approach, infection with CXCR4-tropic Lai virus could be suppressed by treatment with GCV. GCV treatment limited the number of HIV-infected cells, virus production, as well as virus-induced cytopathic effects in this model. We provide proof of principle that TK-SR39 in a conditional HIV vector can provide a safe and effective anti-HIV strategy.

Targeting male mosquito swarms to control malaria vector density

PubMed Central

Sawadogo, Simon Peguedwinde; Niang, Abdoulaye; Bilgo, Etienne; Millogo, Azize; Maïga, Hamidou; Dabire, Roch K.; Tripet, Frederic; Diabaté, Abdoulaye

2017-01-01

Malaria control programs are being jeopardized by the spread of insecticide resistance in mosquito vector populations. It has been estimated that the spread of resistance could lead to an additional 120000 deaths per year, and interfere with the prospects for sustained control or the feasibility of achieving malaria elimination. Another complication for the development of resistance management strategies is that, in addition to insecticide resistance, mosquito behavior evolves in a manner that diminishes the impact of LLINs and IRS. Mosquitoes may circumvent LLIN and IRS control through preferential feeding and resting outside human houses and/or being active earlier in the evening before people go to sleep. Recent developments in our understanding of mosquito swarming suggest that new tools targeting mosquito swarms can be designed to cut down the high reproductive rate of malaria vectors. Targeting swarms of major malaria vectors may provide an effective control method to counteract behavioral resistance developed by mosquitoes. Here, we evaluated the impact of systematic spraying of swarms of Anopheles gambiae s.l. using a mixed carbamate and pyrethroid aerosol. The impact of this intervention on vector density, female insemination rates and the age structure of males was measured. We showed that the resulting mass killing of swarming males and some mate-seeking females resulted in a dramatic 80% decrease in population size compared to a control population. A significant decrease in female insemination rate and a significant shift in the age structure of the male population towards younger males incapable of mating were observed. This paradigm-shift study therefore demonstrates that targeting primarily males rather than females, can have a drastic impact on mosquito population. PMID:28278212

Hemangiosarcoma and its cancer stem cell subpopulation are effectively killed by a toxin targeted through epidermal growth factor and urokinase receptors.

PubMed

Schappa, Jill T; Frantz, Aric M; Gorden, Brandi H; Dickerson, Erin B; Vallera, Daniel A; Modiano, Jaime F

2013-10-15

Targeted toxins have the potential to overcome intrinsic or acquired resistance of cancer cells to conventional cytotoxic agents. Here, we hypothesized that EGFuPA-toxin, a bispecific ligand-targeted toxin (BLT) consisting of a deimmunized Pseudomonas exotoxin (PE) conjugated to epidermal growth factor and urokinase, would efficiently target and kill cells derived from canine hemangiosarcoma (HSA), a highly chemotherapy resistant tumor, as well as cultured hemangiospheres, used as a surrogate for cancer stem cells (CSC). EGFuPA-toxin showed cytotoxicity in four HSA cell lines (Emma, Frog, DD-1 and SB) at a concentration of ≤100 nM, and the cytotoxicity was dependent on specific ligand-receptor interactions. Monospecific targeted toxins also killed these chemoresistant cells; in this case, a "threshold" level of EGFR expression appeared to be required to make cells sensitive to the monospecific EGF-toxin, but not to the monospecific uPA-toxin. The IC₅₀ of CSCs was higher by approximately two orders of magnitude as compared to non-CSCs, but these cells were still sensitive to EGFuPA-toxin at nanomolar (i.e., pharmacologically relevant) concentrations, and when targeted by EGFuPA-toxin, resulted in death of the entire cell population. Taken together, our results support the use of these toxins to treat chemoresistant tumors such as sarcomas, including those that conform to the CSC model. Our results also support the use of companion animals with cancer for further translational development of these cytotoxic molecules. Copyright © 2013 UICC.

Efficiency Evaluation of Nozawa-Style Black Light Trap for Control of Anopheline Mosquitoes

PubMed Central

Lee, Hee Il; Seo, Bo Youl; Shin, E-Hyun; Burkett, Douglas A.; Lee, Jong-Koo

2009-01-01

House-residual spraying and insecticide-treated bed nets have achieved some success in controlling anthropophilic and endophagic vectors. However, these methods have relatively low efficacy in Korea because Anopheles sinensis, the primary malaria vector, is highly zoophilic and exophilic. So, we focused our vector control efforts within livestock enclosures using ultraviolet black light traps as a mechanical control measure. We found that black light traps captured significantly more mosquitoes at 2 and 2.5 m above the ground (P < 0.05). We also evaluated the effectiveness of trap spacing within the livestock enclosure. In general, traps spaced between 4 and 7 m apart captured mosquitoes more efficiently than those spaced closer together (P > 0.05). Based on these findings, we concluded that each black light trap in the livestock enclosures killed 7,586 female mosquitoes per trap per night during the peak mosquito season (July-August). In May-August 2003, additional concurrent field trials were conducted in Ganghwa county. We got 74.9% reduction (P < 0.05) of An. sinensis in human dwellings and 61.5% reduction (P > 0.05) in the livestock enclosures. The black light trap operation in the livestock enclosures proved to be an effective control method and should be incorporated into existing control strategies in developed countries. PMID:19488423

Larvicidal efficacy screening of Anacardaciae crude extracts on the dengue hemorrhagic vector, Aedes aegypti.

PubMed

Zuharah, W F; Fadzly, N; Ali, Y; Zakaria, R; Juperi, S; Asyraf, M; Dieng, H

2014-06-01

Vector-borne diseases are still rife because of the re-emergence of diseases transmitted by mosquitoes. The objective of this paper is to evaluate the larvicidal efficacy of crude leaf extract of Mangifera indica, Gluta renghas, and Melanochyla fasciculiflora against vector of dengue hemorrhagic fever, Aedes aegypti. These plant species are endemic species and widely distributed in Malaysian forests. Leaves of Ma. indica, G. renghas and M. fascculiflora were collected from Teluk Bahang National Park, Penang Malaysia. Fractions of leaves were segregated, air-dried, powdered and extracted using Soxhlet with methanol. The solvent was removed by using rotary evaporator to obtain the crude extract. Using WHO standard larval bioassay test method, third instar larvae of Aedes aegypti were exposed to concentration ranging from 200- 4500 ppm of methanol extract for all plant species. Larval mortality was observed after 24 hours exposure. The highest susceptibility and toxicity was recorded by Mangifera indica with the lowest concentration at 800 ppm followed by M. fasciculiflora and G. renghas. This indicates that crude plant extract is very effective in killing Ae. aegypti mosquitoes. This finding may lead to new low cost alternative, environmentally friendly method for mosquito control programs. To our knowledge, this is the first report on larvicidal bioefficacy from endemic Malaysian plants.

EGFR-targeted granzyme B expressed in NK cells enhances natural cytotoxicity and mediates specific killing of tumor cells.

PubMed

Oberoi, Pranav; Jabulowsky, Robert A; Bähr-Mahmud, Hayat; Wels, Winfried S

2013-01-01

Natural killer (NK) cells are highly specialized effectors of the innate immune system that hold promise for adoptive cancer immunotherapy. Their cell killing activity is primarily mediated by the pro-apoptotic serine protease granzyme B (GrB), which enters targets cells with the help of the pore-forming protein perforin. We investigated expression of a chimeric GrB fusion protein in NK cells as a means to augment their antitumoral activity. For selective targeting to tumor cells, we fused the epidermal growth factor receptor (EGFR) peptide ligand transforming growth factor α (TGFα) to human pre-pro-GrB. Established human NKL natural killer cells transduced with a lentiviral vector expressed this GrB-TGFα (GrB-T) molecule in amounts comparable to endogenous wildtype GrB. Activation of the genetically modified NK cells by cognate target cells resulted in the release of GrB-T together with endogenous granzymes and perforin, which augmented the effector cells' natural cytotoxicity against NK-sensitive tumor cells. Likewise, GrB-T was released into the extracellular space upon induction of degranulation with PMA and ionomycin. Secreted GrB-T fusion protein displayed specific binding to EGFR-overexpressing tumor cells, enzymatic activity, and selective target cell killing in the presence of an endosomolytic activity. Our data demonstrate that ectopic expression of a targeted GrB fusion protein in NK cells is feasible and can enhance antitumoral activity of the effector cells.

Innate immunity is not related to the sex of adult Tree Swallows during the nestling period

USGS Publications Warehouse

Houdek, Bradley J.; Lombardo, Michael P.; Thorpe, Patrick A.; Hahn, D. Caldwell

2011-01-01

Evolutionary theory predicts that exposure to more diverse pathogens will result in the evolution of a more robust immune response. We predicted that during the breeding season the innate immune function of female Tree Swallows (Tachycineta bicolor) should be more effective than that of males because (1) the transmission of sexually transmitted microbes during copulation puts females at greater risk because ejaculates move from males to females, (2) females copulate with multiple males, exposing them to the potentially pathogenic microbes in semen, and (3) females spend more time in the nest than do males so may be more exposed to nest microbes and ectoparasites that can be vectors of bacterial and viral pathogens. In addition, elevated testosterone in males may suppress immune function. We tested our prediction during the 2009 breeding season with microbicidal assays in vitro to assess the ability of the innate immune system to kill Escherichia coli. The sexes did not differ in the ability of their whole blood to kill E. coli. We also found no significant relationships between the ability of whole blood to kill E. coli and the reproductive performance or the physical condition of males or females. These results indicate that during the nestling period there are no sexual differences in this component of the innate immune system. In addition, they suggest that there is little association between this component of innate immunity and the reproductive performance and physical condition during the nestling period of adult Tree Swallows.

Ivermectin susceptibility, sporontocidal effect, and inhibition of time to re-feed in the Amazonian malaria vector Anopheles darlingi.

PubMed

Kobylinski, Kevin C; Escobedo-Vargas, Karín S; López-Sifuentes, Victor M; Durand, Salomón; Smith, Edward S; Baldeviano, G Christian; Gerbasi, Robert V; Ballard, Sara-Blythe; Stoops, Craig A; Vásquez, Gissella M

2017-11-21

Outdoor malaria transmission hinders malaria elimination efforts in the Amazon region and novel vector control tools are needed. Ivermectin mass drug administration (MDA) to humans kills wild Anopheles, targets outdoor-feeding vectors, and can suppress malaria parasite transmission. Laboratory investigations were performed to determine ivermectin susceptibility, sporontocidal effect and inhibition of time to re-feed for the primary Amazonian malaria vector, Anopheles darlingi. To assess ivermectin susceptibility, various concentrations of ivermectin were mixed in human blood and fed to An. darlingi. Mosquito survival was monitored daily for 7 days and a non-linear mixed effects model with Probit analysis was used to calculate lethal concentrations of ivermectin that killed 50% (LC 50 ), 25% (LC 25 ) and 5% (LC 5 ) of mosquitoes. To examine ivermectin sporonticidal effect, Plasmodium vivax blood samples were collected from malaria patients and offered to mosquitoes without or with ivermectin at the LC 50 , LC 25 or LC 5 . To assess ivermectin inhibition of mosquito time to re-feed, concentrations of ivermectin predicted to occur after a single oral dose of 200 μg/kg ivermectin were fed to An. darlingi. Every day for 12 days thereafter, individual mosquitoes were given the opportunity to re-feed on a volunteer. Any mosquitoes that re-blood fed or died were removed from the study. Ivermectin significantly reduced An. darlingi survivorship: 7-day-LC 50  = 43.2 ng/ml [37.5, 48.6], -LC 25  = 27.8 ng/ml [20.4, 32.9] and -LC 5  = 14.8 ng/ml [7.9, 20.2]. Ivermectin compound was sporontocidal to P. vivax in An. darlingi at the LC 50 and LC 25 concentrations reducing prevalence by 22.6 and 17.1%, respectively, but not at the LC 5 . Oocyst intensity was not altered at any concentration. Ivermectin significantly delayed time to re-feed at the 4-h (48.7 ng/ml) and 12-h (26.9 ng/ml) concentrations but not 36-h (10.6 ng/ml) or 60-h (6.3 ng/ml). Ivermectin is lethal to An. darlingi, modestly inhibits sporogony of P. vivax, and delays time to re-feed at concentrations found in humans up to 12 h post drug ingestion. The LC 50 value suggests that a higher than standard dose (400-μg/kg) is necessary to target An. darlingi. These results suggest that ivermectin MDA has potential in the Amazon region to aid malaria elimination efforts.

Gene therapy for human ovarian cancer cells using efficient expression of Fas gene combined with γδT cells.

PubMed

Lin, Jiajing; Zeng, Dingyuan; He, Hongying; Tan, Guangping; Lan, Ying; Jiang, Fuyan; Sheng, Shuting

2017-10-01

Low tissue specificity and efficiency of exogenous gene expression are the two major obstacles in tumor‑targeted gene therapy. The Fas cell surface death receptor (Fas)/Fas ligand pathway is one of the primary pathways responsible for the regulation of cell apoptosis. The aim of the present study was to explore whether the regulation of tumor specific promoters and a two‑step transcriptional amplification system (TSTA) assured efficient, targeted expression of their downstream Fas gene in human ovarian cancer cells, and to assess the killing effect of γδT cells on these cells with high Fas expression. Three shuttle plasmids containing different control elements of the human telomerase reverse transcriptase (hTERT) promoter and/or TSTA were constructed and packaged into adenovirus 5 (Ad5) vectors for the expression of exogenous Fas gene. The human ovarian cancer cell line SKOV3 and a control human embryonic lung fibroblast cell line were transfected with Ad5‑hTERT‑Fas or Ad5‑hTERT‑TSTA‑Fas. Fas mRNA and protein expression were examined by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. γδT lymphocytes were isolated, cultured and mixed at different ratios with SKOV3 cells with Fas expression in order to assess the killing effect of γδT cells. hTERT promoter induced the specific expression of FAS gene in SKOV3 cells, and the TSTA strategy increased FAS expression by 14.2‑fold. The killing effect of γδT cells increased with the expression level of Fas and the effector‑target cell ratio. The killing rate for SKOV3 cells with high FAS expression was 72.5% at an effector‑target cell ratio of 40:1. The regulators of hTERT promoter and TSTA assure the efficient and targeted expression of their downstream Fas gene in SKOV3 cells. The killing effect of γδT cells for ovarian cancer cells with relatively high Fas expression was improved.

Spectral flow as a map between N = (2 , 0)-models

NASA Astrophysics Data System (ADS)

Athanasopoulos, P.; Faraggi, A. E.; Gepner, D.

2014-07-01

The space of (2 , 0) models is of particular interest among all heterotic-string models because it includes the models with the minimal SO (10) unification structure, which is well motivated by the Standard Model of particle physics data. The fermionic Z2 ×Z2 heterotic-string models revealed the existence of a new symmetry in the space of string configurations under the exchange of spinors and vectors of the SO (10) GUT group, dubbed spinor-vector duality. In this paper we generalize this idea to arbitrary internal rational conformal field theories (RCFTs). We explain how the spectral flow operator normally acting within a general (2 , 2) theory can be used as a map between (2 , 0) models. We describe the details, give an example and propose more simple currents that can be used in a similar way.

Taking a vector supermultiplet apart: Alternative Fayet-Iliopoulos-type terms

NASA Astrophysics Data System (ADS)

Kuzenko, Sergei M.

2018-06-01

Starting from an Abelian N = 1 vector supermultiplet V coupled to conformal supergravity, we construct from it a nilpotent real scalar Goldstino superfield V of the type proposed in arxiv:arXiv:1702.02423. It contains only two independent component fields, the Goldstino and the auxiliary D-field. The important properties of this Goldstino superfield are: (i) it is gauge invariant; and (ii) it is super-Weyl invariant. As a result, the gauge prepotential can be represented as V = V + V, where V contains only one independent component field, modulo gauge degrees of freedom, which is the gauge one-form. Making use of V allows us to introduce new Fayet-Iliopoulos-type terms, which differ from the one proposed in arxiv:arXiv:1712.08601 and share with the latter the property that gauged R-symmetry is not required.

[Hypoxia responsive element regulated herpes simplex virus-thymidine kinase system enhances killing effect of gancyclovir on Ewing's sarcoma cell line under hypoxic condition].

PubMed

Si, Ying-jian; Guang, Li-xia; Yuan, Fa-huan; Zhang, Ke-bin

2006-08-01

To find out a possible approach to improve the effectiveness of radiotherapy and chemotherapy for Ewing's sarcoma by constructing a eukaryotic expression vector expressing herpes simplex virus-thymidine kinase (HSV-TK) regulated by hypoxia responsive element (HRE) under hypoxia and to evaluate the effects of this HRE regulated HSV-TK system on killing effect of gancyclovir (GCV) on Ewing's sarcoma cell line SK-ES under hypoxic condition. The HRE was synthesized according to the literature and cloned into the enhancer site of pIRES(2)-EGFP vector to obtain the pHRE recombinant plasmid. The HSV-TK was amplified by PCR and cloned into the multiple clone site of pIRES(2)-EGFP and pHRE to obtain pTK and pHRE-TK recombinant plasmid. The human Ewing's sarcoma cell line SK-ES was transfected by pTK or pHRE-TK recombinant plasmid with liposome and then was exposed to normoxic (21% oxygen) or hypoxic (3% oxygen) condition. The expression of enhanced green fluorescent protein (EGFP) was monitored by fluorescent microscopy. The sensitivity of human Ewing's sarcoma cell line SK-ES transfected with pTK or pHRE-TK recombinant plasmid to the anti-tumour drug GCV was determined with the method of tetrazolium (MTT) after treating with GCV for five days. (1) The result of sequencing showed that the recombinant plasmid pHRE contained HRE, and that the recombinant plasmid pTK and pHRE-TK contained HSV-TK gene in the sense direction. (2) Comparison of fluorescent optical density (FOD) showed that (1) the EGFP FOD value of pHRE and pHRE-TK group cells exposed to hypoxia was significantly higher than those exposed to normoxia (P < 0.01); (2) when the cells were exposed to hypoxia, the EGFP FOD value of pHRE and pHRE-TK group cells was significantly higher than that of pTK and empty vector group (P < 0.01); (3) there was no significant difference among the four groups of cells when they were exposed to normoxia (P > 0.05). (3) Comparison of the sensitivity of four groups of cells to GCV showed that (1) the cells in pHRE-TK and pTK groups were much more sensitive to GCV than the cells in pHRE group under hypoxia condition (P < 0.01), the higher the GCV concentration, the greater the difference; (2) the cells of pHRE-TK group were more sensitive to GCV than those in pTK group under hypoxic condition (P < 0.01), but was almost equally sensitive under normoxic condition (P > 0.05); (3) the pHRE-TK group cells had higher sensitivity to GCV under hypoxia than normoxia (P < 0.01) while the pTK group cells had almost the same sensitivity to GCV under hypoxia and normoxia (P > 0.05). (1) The eukaryotic expression vector expressing herpes simplex virus-thymidine kinase (HSV-TK) regulated by hypoxia responsive element (HRE) under hypoxia was constructed successfully. (2) HRE could up-regulate expression of EGFP by SK-ES cells under hypoxia condition. (3) HRE could enhance the killing effect of HSV-TK/GCV system on human Ewing's sarcoma cell line SK-ES under hypoxic condition.

Parasite killing in malaria non-vector mosquito Anopheles culicifacies species B: implication of nitric oxide synthase upregulation.

PubMed

Vijay, Sonam; Rawat, Manmeet; Adak, Tridibes; Dixit, Rajnikant; Nanda, Nutan; Srivastava, Harish; Sharma, Joginder K; Prasad, Godavarthi B K S; Sharma, Arun

2011-04-04

Anopheles culicifacies, the main vector of human malaria in rural India, is a complex of five sibling species. Despite being phylogenetically related, a naturally selected subgroup species B of this sibling species complex is found to be a poor vector of malaria. We have attempted to understand the differences between vector and non-vector Anopheles culicifacies mosquitoes in terms of transcriptionally activated nitric oxide synthase (AcNOS) physiologies to elucidate the mechanism of refractoriness. Identification of the differences between genes and gene products that may impart refractory phenotype can facilitate development of novel malaria transmission blocking strategies. We conducted a study on phylogenetically related susceptible (species A) and refractory (species B) sibling species of An. culicifacies mosquitoes to characterize biochemical and molecular differences in AcNOS gene and gene elements and their ability to inhibit oocyst growth. We demonstrate that in species B, AcNOS specific activity and nitrite/nitrates in mid-guts and haemolymph were higher as compared to species A after invasion of the mid-gut by P. vivax at the beginning and during the course of blood feeding. Semiquantitative RT-PCR and real time PCR data of AcNOS concluded that this gene is more abundantly expressed in midgut of species B than in species A and is transcriptionally upregulated post blood meals. Dietary feeding of L-NAME along with blood meals significantly inhibited midgut AcNOS activity leading to an increase in oocyst production in An. culicifacies species B. We hypothesize that upregulation of mosquito innate cytotoxicity due to NOS in refractory strain to Plasmodium vivax infection may contribute to natural refractoriness in An. culicifacies mosquito population. This innate capacity of refractory mosquitoes could represent the ancestral function of the mosquito immune system against the parasite and could be utilized to understand the molecular basis of refractoriness in planning effective vector control strategies.

Parasite Killing in Malaria Non-Vector Mosquito Anopheles culicifacies Species B: Implication of Nitric Oxide Synthase Upregulation

PubMed Central

Vijay, Sonam; Rawat, Manmeet; Adak, Tridibes; Dixit, Rajnikant; Nanda, Nutan; Srivastava, Harish; Sharma, Joginder K.; Prasad, Godavarthi B. K. S.; Sharma, Arun

2011-01-01

Background Anopheles culicifacies, the main vector of human malaria in rural India, is a complex of five sibling species. Despite being phylogenetically related, a naturally selected subgroup species B of this sibling species complex is found to be a poor vector of malaria. We have attempted to understand the differences between vector and non-vector Anopheles culicifacies mosquitoes in terms of transcriptionally activated nitric oxide synthase (AcNOS) physiologies to elucidate the mechanism of refractoriness. Identification of the differences between genes and gene products that may impart refractory phenotype can facilitate development of novel malaria transmission blocking strategies. Methodology/Principal Findings We conducted a study on phylogenetically related susceptible (species A) and refractory (species B) sibling species of An. culicifacies mosquitoes to characterize biochemical and molecular differences in AcNOS gene and gene elements and their ability to inhibit oocyst growth. We demonstrate that in species B, AcNOS specific activity and nitrite/nitrates in mid-guts and haemolymph were higher as compared to species A after invasion of the mid-gut by P. vivax at the beginning and during the course of blood feeding. Semiquantitative RT-PCR and real time PCR data of AcNOS concluded that this gene is more abundantly expressed in midgut of species B than in species A and is transcriptionally upregulated post blood meals. Dietary feeding of L-NAME along with blood meals significantly inhibited midgut AcNOS activity leading to an increase in oocyst production in An. culicifacies species B. Conclusions/Significance We hypothesize that upregulation of mosquito innate cytotoxicity due to NOS in refractory strain to Plasmodium vivax infection may contribute to natural refractoriness in An. culicifacies mosquito population. This innate capacity of refractory mosquitoes could represent the ancestral function of the mosquito immune system against the parasite and could be utilized to understand the molecular basis of refractoriness in planning effective vector control strategies. PMID:21483693

Deciphering the details of RNA aminoglycoside interactions: from atomistic models to biotechnological applications

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

Ilgu, Muslum

A detailed study was done of the neomycin-B RNA aptamer for determining its selectivity and binding ability to both neomycin– and kanamycin-class aminoglycosides. A novel method to increase drug concentrations in cells for more efficiently killing is described. To test the method, a bacterial model system was adopted and several small RNA molecules interacting with aminoglycosides were cloned downstream of T7 RNA polymerase promoter in an expression vector. Then, the growth analysis of E. coli expressing aptamers was observed for 12-hour period. Our analysis indicated that aptamers helped to increase the intracellular concentration of aminoglycosides thereby increasing their efficacy.

Rational design of gene-based vaccines.

PubMed

Barouch, Dan H

2006-01-01

Vaccine development has traditionally been an empirical discipline. Classical vaccine strategies include the development of attenuated organisms, whole killed organisms, and protein subunits, followed by empirical optimization and iterative improvements. While these strategies have been remarkably successful for a wide variety of viruses and bacteria, these approaches have proven more limited for pathogens that require cellular immune responses for their control. In this review, current strategies to develop and optimize gene-based vaccines are described, with an emphasis on novel approaches to improve plasmid DNA vaccines and recombinant adenovirus vector-based vaccines. Copyright 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Strong Coupling Gauge Theories in LHC ERA

NASA Astrophysics Data System (ADS)

Fukaya, H.; Harada, M.; Tanabashi, M.; Yamawaki, K.

2011-01-01

AdS/QCD, light-front holography, and the nonperturbative running coupling / Stanley J. Brodsky, Guy de Teramond and Alexandre Deur -- New results on non-abelian vortices - Further insights into monopole, vortex and confinement / K. Konishi -- Study on exotic hadrons at B-factories / Toru Iijima -- Cold compressed baryonic matter with hidden local symmetry and holography / Mannque Rho -- Aspects of baryons in holographic QCD / T. Sakai -- Nuclear force from string theory / K. Hashimoto -- Integrating out holographic QCD back to hidden local symmetry / Masayasu Harada, Shinya Matsuzaki and Koichi Yamawaki -- Holographic heavy quarks and the giant Polyakov loop / Gianluca Grignani, Joanna Karczmarek and Gordon W. Semenoff -- Effect of vector-axial-vector mixing to dilepton spectrum in hot and/or dense matter / Masayasu Harada and Chihiro Sasaki -- Infrared behavior of ghost and gluon propagators compatible with color confinement in Yang-Mills theory with the Gribov horizon / Kei-Ichi Kondo -- Chiral symmetry breaking on the lattice / Hidenori Fukaya [for JLQCD and TWQCD collaborations] -- Gauge-Higgs unification: Stable Higgs bosons as cold dark matter / Yutaka Hosotani -- The limits of custodial symmetry / R. Sekhar Chivukula ... [et al.] -- Higgs searches at the tevatron / Kazuhiro Yamamoto [for the CDF and D[symbol] collaborations] -- The top triangle moose / R. S. Chivukula ... [et al.] -- Conformal phase transition in QCD like theories and beyond / V. A. Miransky -- Gauge-Higgs unification at LHC / Nobuhito Maru and Nobuchika Okada -- W[symbol]W[symbol] scattering in Higgsless models: Identifying better effective theories / Alexander S. Belyaev ... [et al.] -- Holographic estimate of Muon g - 2 / Deog Ki Hong -- Gauge-Higgs dark matter / T. Yamashita -- Topological and curvature effects in a multi-fermion interaction model / T. Inagaki and M. Hayashi -- A model of soft mass generation / J. Hosek -- TeV physics and conformality / Thomas Appelquist -- Conformal Higgs, or techni-dilaton - composite Higgs near conformality / Koichi Yamawaki -- Phase diagram of strongly interacting theories / Francesco Sannino -- Resizing conformal windows / O. Antipin and K. Tuominen -- Nearly conformal gauge theories on the lattice / Zoltan Fodor ... [et al.] -- Going beyond QCD in lattice gauge theory / G. T. Fleming -- Phases of QCD from small to large N[symbol]: (some) lattice results / A. Deuzeman, E. Pallante and M. P. Lombardo -- Lattice gauge theory and (quasi)-conformal technicolor / D. K. Sinclair and J. B. Kogut -- Study of the running coupling constant in 10-flavor QCD with the Schrodinger functional method / N. Yamada ... [et al.] -- Study of the running coupling in twisted Polyakov scheme / T. Aoyama ... [et al.].Running coupling in strong gauge theories via the lattice / Zoltan Fodor ... [et al.] -- Higgsinoless supersymmetry and hidden gravity / Michael L. Graesser, Ryuichiro Kitano and Masafumi Kurachi -- The latest status of LHC and the EWSB physics / S. Asai -- Continuum superpartners from supersymmetric unparticles / Hsin-Chia Cheng -- Review of minimal flavor constraints for technicolor / Hidenori S. Fukano and Francesco Sannino -- Standard model and high energy Lorentz violation / Damiano Anselmi -- Dynamical electroweak symmetry breaking and fourth family / Michio Hashimoto -- Holmorphic supersymmetric Nambu-Jona-Lasino model and dynamical electroweak symmetry breaking / Dong-Won Jung, Otto C. W. Kong and Jae Sik Lee -- Ratchet model of Baryogenesis / Tatsu Takeuchi, Azusa Minamizaki and Akio Sugamoto -- Classical solutions of field equations in Einstein Gauss-Bonnet gravity / P. Suranyi, C. Vaz and L. C. R. Wijewardhana -- Black holes constitute all dark matter / Paul H. Frampton -- Electroweak precision test and Z [symbol] in the three site Higgsless model / Tomohiro Abe -- Chiral symmetry and BRST symmetry breaking, quaternion reality and the lattice simulation / Sadataka Furui -- Holographic techni-dilaton, or conformal Higgs / Kazumoto Haba, Shinya Matsuzaki and Koichi Yamawaki -- Phase structure of topologically massive gauge theory with fermion / Yuichi Hoshino -- New regularization in extra dimensional model and renormalization group flow of the cosmological constant / Shoichi Ichinose -- Spectral analysis of dense two-color QCD / T. Kanazawa, T. Wettig and N. Yamamoto -- NJL model with dimensional regularization at finite temperature / T. Fujihara ... [et al.] -- A new method of evaluating the dynamical chiral symmetry breaking scale and the chiral restoration temperature in general gauge theories by using the non-perturbative renormalization group analyses with general 4-Fermi effective interaction space / Ken-Ichi Aoki, Daisuke Sato and Kazuhiro Miyashita -- The effective chiral Lagrangian with vector mesons and hadronic [symbol] decays / D. Kimura ... [et al.] -- Spontaneous SUSY breaking with anomalous U(1) symmetry in metastable vacua and moduli stabilization / Hiroyuki Nishino -- A new description of the lattice Yang-Mills theory and non-abelian magnetic monopole dominance in the string tension / Akihiro Shibata -- Thermodynamics with unbroken center symmetry in two-flavor QCD / S. Takemoto, M. Harada and C. Sasaki -- Masses of vector bosons in two-color QCD based on the hidden local symmetry / T. Yamaoka, M. Harada and C. Nonaka -- Walking dynamics from string duals / Maurizio Piai -- The quark mass dependence of the nucleon mass in AdS/QCD / Hyo Chul Ahn -- Structure of thermal quasi-fermion in QED/QCD from the Dyson-Schwinger equation / Hisao Nakkagawa -- Critical behaviors of sigma-mode and pion in holographic superconductors / Cheonsoo Park.

A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles

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

Meador, Lydia R.

Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viralmore » vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1. - Highlights: • We devised a prime/boost anti HIV-1 vaccination strategy modeled after RV144. • We used plant-derived virus-like particles (VLPs) consisting of Gag and dgp41. • We used attenuated, replicating vaccinia virus vectors expressing the same antigens. • The immunogens elicited strong cellular and humoral immune responses.« less

Ballistic Evaluation of 7056 Aluminum

DTIC Science & Technology

2017-02-01

positioned 152 mm (6 inches) behind the target to determine the outcome of each shot. An impact is regarded as a complete penetration ( CP ), or loss, if...not result in a CP , it is considered a partial penetration (PP), or win. To keep results as consistent as possible, only shots conforming to the...defined as the vector sum of the projectile’s pitch and yaw. The V50 is calculated by the arithmetic mean of an equal number of CPs and PPs within an 18

Second level semi-degenerate fields in W_3 Toda theory: matrix element and differential equation

NASA Astrophysics Data System (ADS)

Belavin, Vladimir; Cao, Xiangyu; Estienne, Benoit; Santachiara, Raoul

2017-03-01

In a recent study we considered W_3 Toda 4-point functions that involve matrix elements of a primary field with the highest-weight in the adjoint representation of sl_3 . We generalize this result by considering a semi-degenerate primary field, which has one null vector at level two. We obtain a sixth-order Fuchsian differential equation for the conformal blocks. We discuss the presence of multiplicities, the matrix elements and the fusion rules.

New classes of modified teleparallel gravity models

NASA Astrophysics Data System (ADS)

Bahamonde, Sebastian; Böhmer, Christian G.; Krššák, Martin

2017-12-01

New classes of modified teleparallel theories of gravity are introduced. The action of this theory is constructed to be a function of the irreducible parts of torsion f (Tax ,Tten ,Tvec), where Tax ,Tten and Tvec are squares of the axial, tensor and vector components of torsion, respectively. This is the most general (well-motivated) second order teleparallel theory of gravity that can be constructed from the torsion tensor. Different particular second order theories can be recovered from this theory such as new general relativity, conformal teleparallel gravity or f (T) gravity. Additionally, the boundary term B which connects the Ricci scalar with the torsion scalar via R = - T + B can also be incorporated into the action. By performing a conformal transformation, it is shown that the two unique theories which have an Einstein frame are either the teleparallel equivalent of general relativity or f (- T + B) = f (R) gravity, as expected.

Theoretical frameworks for testing relativistic gravity. IV - A compendium of metric theories of gravity and their post-Newtonian limits.

NASA Technical Reports Server (NTRS)

Ni, W.-T.

1972-01-01

Metric theories of gravity are compiled and classified according to the types of gravitational fields they contain, and the modes of interaction among those fields. The gravitation theories considered are classified as (1) general relativity, (2) scalar-tensor theories, (3) conformally flat theories, and (4) stratified theories with conformally flat space slices. The post-Newtonian limit of each theory is constructed and its Parametrized Post-Newtonian (PPN) values are obtained by comparing it with Will's version of the formalism. Results obtained here, when combined with experimental data and with recent work by Nordtvedt and Will and by Ni, show that, of all theories thus far examined by our group, the only currently viable ones are general relativity, the Bergmann-Wagoner scalar-tensor theory and its special cases (Nordtvedt; Brans-Dicke-Jordan), and a recent, new vector-tensor theory by Nordtvedt, Hellings, and Will.

Einstein’s quadrupole formula from the kinetic-conformal Hořava theory

NASA Astrophysics Data System (ADS)

Bellorín, Jorge; Restuccia, Alvaro

We analyze the radiative and nonradiative linearized variables in a gravity theory within the family of the nonprojectable Hořava theories, the Hořava theory at the kinetic-conformal point. There is no extra mode in this formulation, the theory shares the same number of degrees of freedom with general relativity. The large-distance effective action, which is the one we consider, can be given in a generally-covariant form under asymptotically flat boundary conditions, the Einstein-aether theory under the condition of hypersurface orthogonality on the aether vector. In the linearized theory, we find that only the transverse-traceless tensorial modes obey a sourced wave equation, as in general relativity. The rest of variables are nonradiative. The result is gauge-independent at the level of the linearized theory. For the case of a weak source, we find that the leading mode in the far zone is exactly Einstein’s quadrupole formula of general relativity, if some coupling constants are properly identified. There are no monopoles nor dipoles in this formulation, in distinction to the nonprojectable Horava theory outside the kinetic-conformal point. We also discuss some constraints on the theory arising from the observational bounds on Lorentz-violating theories.

Knots in electromagnetism

NASA Astrophysics Data System (ADS)

Arrayás, M.; Bouwmeester, D.; Trueba, J. L.

2017-01-01

Maxwell equations in vacuum allow for solutions with a non-trivial topology in the electric and magnetic field line configurations at any given moment in time. One example is a space filling congruence of electric and magnetic field lines forming circles lying on the surfaces of nested tori. In this example the electric, magnetic and Poynting vector fields are orthogonal everywhere. As time evolves the electric and magnetic fields expand and deform without changing the topology and energy, while the Poynting vector structure remains unchanged while propagating with the speed of light. The topology is characterized by the concept of helicity of the field configuration. Helicity is an important fundamental concept and for massless fields it is a conserved quantity under conformal transformations. We will review several methods by which linked and knotted electromagnetic (spin-1) fields can be derived. A first method, introduced by A. Rañada, uses the formulation of the Maxwell equations in terms of differential forms combined with the Hopf map from the three-sphere S3 to the two-sphere S2. A second method is based on spinor and twistor theory developed by R. Penrose in which elementary twistor functions correspond to the family of electromagnetic torus knots. A third method uses the Bateman construction of generating null solutions from complex Euler potentials. And a fourth method uses special conformal transformations, in particular conformal inversion, to generate new linked and knotted field configurations from existing ones. This fourth method is often accompanied by shifting singularities in the field to complex space-time points. Of course the various methods must be closely related to one another although they have been developed largely independently and they suggest different directions in which to expand the study of topologically non-trivial field configurations. It will be shown how the twistor formulation allows for a direct extension to massless fields of other spin values, such as spin-2 fields satisfying the linearized Einstein vacuum equation, and how the formulation by A. Rañada can be extended to fields for which the electric and magnetic fields are not orthogonal everywhere. Underlying the various methods is the fact that electric and magnetic field lines can be described as the level curves of complex functions. Compactification of R3 naturally leads to finite energy solutions because the fields at infinity in all directions should all converge towards zero. An intriguing question that is raised by the finite energy is whether there is a connection to the quantization of the classical electromagnetic field. We will review some issues related to this question. Another interesting question is why the general formulation of topologically non-trivial solutions uses the electric and magnetic fields instead of the electromagnetic vector potentials. This leads to a discussion of the Clebsch representation of the electromagnetic field strength 2-form. Finally, a topic of great interest is the possibility of experimentally generating and investigating linked and knotted field configurations. Since the non-trivial topological field solutions exploit the special conformal symmetry of the underlying vacuum wave-equations it will only be possible to approximate the solutions in an experiment, which necessarily introduces material objects that will break the special conformal symmetry. We will review the research on plasma configurations in which the magnetic field-line configuration approximates plasma torus knots leading to the prediction of topological solitons in plasma.

Tyrosine Detoxification Is an Essential Trait in the Life History of Blood-Feeding Arthropods.

PubMed

Sterkel, Marcos; Perdomo, Hugo D; Guizzo, Melina G; Barletta, Ana Beatriz F; Nunes, Rodrigo D; Dias, Felipe A; Sorgine, Marcos H F; Oliveira, Pedro L

2016-08-22

Blood-feeding arthropods are vectors of infectious diseases such as dengue, Zika, Chagas disease, and malaria [1], and vector control is essential to limiting disease spread. Because these arthropods ingest very large amounts of blood, a protein-rich meal, huge amounts of amino acids are produced during digestion. Previous work on Rhodnius prolixus, a vector of Chagas disease, showed that, among all amino acids, only tyrosine degradation enzymes were overexpressed in the midgut compared to other tissues [2]. Here we demonstrate that tyrosine detoxification is an essential trait in the life history of blood-sucking arthropods. We found that silencing Rhodnius tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD), the first two enzymes of the phenylalanine/tyrosine degradation pathway, caused the death of insects after a blood meal. This was confirmed by using the HPPD inhibitor mesotrione, which selectively killed hematophagous arthropods but did not affect non-hematophagous insects. In addition, mosquitoes and kissing bugs died after feeding on mice that had previously received a therapeutic effective oral dose (1 mg/kg) of nitisinone, another HPPD inhibitor used in humans for the treatment of tyrosinemia type I [3]. These findings indicate that HPPD (and TAT) can be a target for the selective control of blood-sucking disease vector populations. Because HPPD inhibitors are extensively used as herbicides and in medicine, these compounds may provide an alternative less toxic to humans and more environmentally friendly than the conventional neurotoxic insecticides that are currently used, with the ability to affect only hematophagous arthropods. Copyright © 2016 Elsevier Ltd. All rights reserved.

An alternative approach in regulation of expression of a transgene by endogenous miR-145 in carcinoma and normal breast cell lines.

PubMed

Ghanbari Safari, Maryam; Baesi, Kazem; Hosseinkhani, Saman

2017-03-01

MicroRNAs are small noncoding RNAs that regulate gene expression by repressing translation of target cellular transcripts. Increasing evidences indicate that miRNAs have different expression profiles and play crucial roles in numerous cellular processes. Delivery and expression of transgenes for cancer therapy must be specific for tumors to avoid killing of healthy tissues. Many investigators have shown that transgene expression can be suppressed in normal cells using vectors that are responsive to microRNA regulation. To overcome this problem, miR-145 that exhibits downregulation in many types of cancer cells was chosen for posttranscriptional regulatory systems mediated by microRNAs. In this study, a psiCHECK-145T vector carrying four tandem copies of target sequences of miR-145 into 3'-UTR of the Renilla luciferase gene was constructed. Renilla luciferase activity from the psiCHECK-145T vector was 57% lower in MCF10A cells with high miR-145 expression as compared to a control condition. Additionally, overexpression of miR-145 in MCF-7 cells with low expression level of miR-145 showed more than 76% reduction in the Renilla luciferase activity from the psiCHECK-145T vector. Inclusion of miR-145 target sequences into the 3'-UTR of the Renilla luciferase gene is a feasible strategy for restricting transgene expression in a breast cancer cell line while sparing a breast normal cell line. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

Anopheles Midgut Epithelium Evades Human Complement Activity by Capturing Factor H from the Blood Meal

PubMed Central

Khattab, Ayman; Barroso, Marta; Miettinen, Tiera; Meri, Seppo

2015-01-01

Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood. PMID:25679788

Lethal and Pre-Lethal Effects of a Fungal Biopesticide Contribute to Substantial and Rapid Control of Malaria Vectors

PubMed Central

Blanford, Simon; Shi, Wangpeng; Christian, Riann; Marden, James H.; Koekemoer, Lizette L.; Brooke, Basil D.; Coetzee, Maureen; Read, Andrew F.; Thomas, Matthew B.

2011-01-01

Rapidly emerging insecticide resistance is creating an urgent need for new active ingredients to control the adult mosquitoes that vector malaria. Biopesticides based on the spores of entomopathogenic fungi have shown considerable promise by causing very substantial mortality within 7–14 days of exposure. This mortality will generate excellent malaria control if there is a high likelihood that mosquitoes contact fungi early in their adult lives. However, where contact rates are lower, as might result from poor pesticide coverage, some mosquitoes will contact fungi one or more feeding cycles after they acquire malaria, and so risk transmitting malaria before the fungus kills them. Critics have argued that ‘slow acting’ fungal biopesticides are, therefore, incapable of delivering malaria control in real-world contexts. Here, utilizing standard WHO laboratory protocols, we demonstrate effective action of a biopesticide much faster than previously reported. Specifically, we show that transient exposure to clay tiles sprayed with a candidate biopesticide comprising spores of a natural isolate of Beauveria bassiana, could reduce malaria transmission potential to zero within a feeding cycle. The effect resulted from a combination of high mortality and rapid fungal-induced reduction in feeding and flight capacity. Additionally, multiple insecticide-resistant lines from three key African malaria vector species were completely susceptible to fungus. Thus, fungal biopesticides can block transmission on a par with chemical insecticides, and can achieve this where chemical insecticides have little impact. These results support broadening the current vector control paradigm beyond fast-acting chemical toxins. PMID:21897846

Protein receptor-independent plasma membrane remodeling by HAMLET: a tumoricidal protein-lipid complex

PubMed Central

Nadeem, Aftab; Sanborn, Jeremy; Gettel, Douglas L.; James, Ho C. S.; Rydström, Anna; Ngassam, Viviane N.; Klausen, Thomas Kjær; Pedersen, Stine Falsig; Lam, Matti; Parikh, Atul N.; Svanborg, Catharina

2015-01-01

A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ‘’protein-centric” view is increasingly challenged by evidence for the involvement of specialized membrane domains in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. We identify a ‘’receptor independent” transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET accumulates within these de novo membrane conformations and define membrane blebs as cellular compartments for direct interactions of HAMLET with essential target proteins such as the Ras family of GTPases. Finally, we demonstrate lower sensitivity of healthy cell membranes to HAMLET challenge. These features suggest that HAMLET-induced curvature-dependent membrane conformations serve as surrogate receptors for initiating signal transduction cascades, ultimately leading to cell death. PMID:26561036

Protein receptor-independent plasma membrane remodeling by HAMLET: a tumoricidal protein-lipid complex.

PubMed

Nadeem, Aftab; Sanborn, Jeremy; Gettel, Douglas L; James, Ho C S; Rydström, Anna; Ngassam, Viviane N; Klausen, Thomas Kjær; Pedersen, Stine Falsig; Lam, Matti; Parikh, Atul N; Svanborg, Catharina

2015-11-12

A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ''protein-centric" view is increasingly challenged by evidence for the involvement of specialized membrane domains in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. We identify a ''receptor independent" transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET accumulates within these de novo membrane conformations and define membrane blebs as cellular compartments for direct interactions of HAMLET with essential target proteins such as the Ras family of GTPases. Finally, we demonstrate lower sensitivity of healthy cell membranes to HAMLET challenge. These features suggest that HAMLET-induced curvature-dependent membrane conformations serve as surrogate receptors for initiating signal transduction cascades, ultimately leading to cell death.

4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.

PubMed

Puppala, Manohar; Zhao, Xinghua; Casemore, Denise; Zhou, Bo; Aridoss, Gopalakrishnan; Narayanapillai, Sreekanth; Xing, Chengguo

2016-03-15

4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization. Copyright © 2016. Published by Elsevier Ltd.

A fully vectorized numerical solution of the incompressible Navier-Stokes equations. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Patel, N.

1983-01-01

A vectorizable algorithm is presented for the implicit finite difference solution of the incompressible Navier-Stokes equations in general curvilinear coordinates. The unsteady Reynolds averaged Navier-Stokes equations solved are in two dimension and non-conservative primitive variable form. A two-layer algebraic eddy viscosity turbulence model is used to incorporate the effects of turbulence. Two momentum equations and a Poisson pressure equation, which is obtained by taking the divergence of the momentum equations and satisfying the continuity equation, are solved simultaneously at each time step. An elliptic grid generation approach is used to generate a boundary conforming coordinate system about an airfoil. The governing equations are expressed in terms of the curvilinear coordinates and are solved on a uniform rectangular computational domain. A checkerboard SOR, which can effectively utilize the computer architectural concept of vector processing, is used for iterative solution of the governing equations.

Discrete symmetries in the heterotic-string landscape

NASA Astrophysics Data System (ADS)

Athanasopoulos, P.

2015-07-01

We describe a new type of discrete symmetry that relates heterotic-string models. It is based on the spectral flow operator which normally acts within a general N = (2, 2) model and we use this operator to construct a map between N = (2, 0) models. The landscape of N = (2, 0) models is of particular interest among all heterotic-string models for two important reasons: Firstly, N =1 spacetime SUSY requires (2, 0) superconformal invariance and secondly, models with the well motivated by the Standard Model SO(10) unification structure are of this type. This idea was inspired by a new discrete symmetry in the space of fermionic ℤ2 × ℤ2 heterotic-string models that exchanges the spinors and vectors of the SO(10) GUT group, dubbed spinor-vector duality. We will describe how to generalize this to arbitrary internal rational Conformal Field Theories.

Structure, Energetics, and Dynamics of Screw Dislocations in Even n-Alkane Crystals.

PubMed

Olson, Isabel A; Shtukenberg, Alexander G; Hakobyan, Gagik; Rohl, Andrew L; Raiteri, Paolo; Ward, Michael D; Kahr, Bart

2016-08-18

Spiral hillocks on n-alkane crystal surfaces were observed immediately after Frank recognized the importance of screw dislocations for crystal growth, yet their structures and energies in molecular crystals remain ill-defined. To illustrate the structural chemistry of screw dislocations that are responsible for plasticity in organic crystals and upon which the organic electronics and pharmaceutical industries depend, molecular dynamics was used to examine heterochiral dislocation pairs with Burgers vectors along [001] in n-hexane, n-octane, and n-decane crystals. The cores were anisotropic and elongated in the (110) slip plane, with significant local changes in molecular position, orientation, conformation, and energy. This detailed atomic level picture produced a distribution of strain consistent with linear elastic theory, giving confidence in the simulations. Dislocations with doubled Burgers vectors split into pairs with elementary displacements. These results suggest a pathway to understanding the mechanical properties and failure associated with elastic and plastic deformation in soft crystals.

Quantum corrections for spinning particles in de Sitter

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

Fröb, Markus B.; Verdaguer, Enric, E-mail: mbf503@york.ac.uk, E-mail: enric.verdaguer@ub.edu

We compute the one-loop quantum corrections to the gravitational potentials of a spinning point particle in a de Sitter background, due to the vacuum polarisation induced by conformal fields in an effective field theory approach. We consider arbitrary conformal field theories, assuming only that the theory contains a large number N of fields in order to separate their contribution from the one induced by virtual gravitons. The corrections are described in a gauge-invariant way, classifying the induced metric perturbations around the de Sitter background according to their behaviour under transformations on equal-time hypersurfaces. There are six gauge-invariant modes: two scalarmore » Bardeen potentials, one transverse vector and one transverse traceless tensor, of which one scalar and the vector couple to the spinning particle. The quantum corrections consist of three different parts: a generalisation of the flat-space correction, which is only significant at distances of the order of the Planck length; a constant correction depending on the undetermined parameters of the renormalised effective action; and a term which grows logarithmically with the distance from the particle. This last term is the most interesting, and when resummed gives a modified power law, enhancing the gravitational force at large distances. As a check on the accuracy of our calculation, we recover the linearised Kerr-de Sitter metric in the classical limit and the flat-space quantum correction in the limit of vanishing Hubble constant.« less

Free (Reactionless) Torque Generation—Or Free Propulsion Concept

NASA Astrophysics Data System (ADS)

Djordjev, Bojidar

2010-01-01

The basic principle in Newtonian Mechanics is based upon equal and opposite forces. Placing the vectors of velocity, acceleration, force and momentum of interacting objects along a single line satisfies the claim it is a linear or a 1-D concept. Classical Mechanics states that there are two main kinds of motion, linear and angular motion. Similarly placing the vectors of angular velocity, angular acceleration, torque and angular momentum along a line in the case of rotation in fact brings a plane 2-D interaction to the well known 1-D Newtonian concept. This adaptation transforms Classical Mechanics into a 1-D concept as well and presents a conformation that the linear concept is the only possible one. The Laws of Conservation of Momentum and Angular Momentum are results of the 1-D concept. But the world contains 3 geometrical spatial dimensions. Within the 3-D world there can exist 1-D, 2-D and 3-D kinds of interaction. The question is how to believe that the 3-D world can really be composed of a 1-D interaction or interactions made equal to the 1-D concept only? Examine a gyroscope—the only one mechanical device that is capable of performng 3-D behavior. The problem is that a gyroscope cannot perform three permanent and unidirectional torques that are fixed in space acting about perpendicular axes. This impossibility conforms to a 1-D concept. The idea is to find a solution that can be achieved for the 3-D concept.

Comparative activity and mechanism of action of three types of bovine antimicrobial peptides against pathogenic Prototheca spp.

PubMed

Tomasinsig, Linda; Skerlavaj, Barbara; Scarsini, Michele; Guida, Filomena; Piccinini, Renata; Tossi, Alessandro; Zanetti, Margherita

2012-02-01

The yeast-like algae of the genus Prototheca are ubiquitous saprophytes causing infections in immunocompromised patients and granulomatous mastitis in cattle. Few available therapies and the rapid spread of resistant strains worldwide support the need for novel drugs against protothecosis. Host defence antimicrobial peptides inactivate a wide array of pathogens and are a rich source of leads, with the advantage of being largely unaffected by microbial resistance mechanisms. Three structurally diverse bovine peptides [BMAP-28, Bac5 and lingual antimicrobial peptide (LAP)] have thus been tested for their capacity to inactivate Prototheca spp. In minimum inhibitory concentration (MIC) assays, they were all effective in the micromolar range against clinical mastitis isolates as well as a Prototheca wickerhamii reference strain. BMAP-28 sterilized Prototheca cultures within 30-60 min at its MIC, induced cell permeabilization with near 100% release of cellular adenosine triphosphate and resulted in extensive surface blebbing and release of intracellular material as observed by scanning electron microscopy. Bac5 and LAP inactivated Prototheca following 3-6 h incubation at fourfold their MIC and did not result in detectable surface damage despite 70-90% killing, suggesting they act via non-lytic mechanisms. In circular dichroism studies, the conformation of BMAP-28, but not that of Bac5 or LAP, was affected by interaction with liposomes mimicking algal membranes. Our results indicate that BMAP-28, Bac5 and LAP kill Prototheca with distinct potencies, killing kinetics, and modes of action and may be appropriate for protothecal mastitis treatment. In addition, the ability of Bac5 and LAP to act via non-lytic mechanisms may be exploited for the development of target-selective drugs. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.

A numerical approach to finding general stationary vacuum black holes

NASA Astrophysics Data System (ADS)

Adam, Alexander; Kitchen, Sam; Wiseman, Toby

2012-08-01

The Harmonic Einstein equation is the vacuum Einstein equation supplemented by a gauge fixing term which we take to be that of DeTurck. For static black holes analytically continued to Riemannian manifolds without boundary at the horizon, this equation has previously been shown to be elliptic, and Ricci flow and Newton’s method provide good numerical algorithms to solve it. Here we extend these techniques to the arbitrary cohomogeneity stationary case which must be treated in Lorentzian signature. For stationary spacetimes with globally timelike Killing vector the Harmonic Einstein equation is elliptic. In the presence of horizons and ergo-regions it is less obviously so. Motivated by the Rigidity theorem we study a class of stationary black hole spacetimes which is general enough to include many interesting higher dimensional solutions. We argue the Harmonic Einstein equation consistently truncates to this class of spacetimes giving an elliptic problem. The Killing horizons and axes of rotational symmetry are boundaries for this problem and we determine boundary conditions there. As a simple example we numerically construct 4D rotating black holes in a cavity using Anderson’s boundary conditions. We demonstrate both Newton’s method and Ricci flow to find these Lorentzian solutions.

Differential immune responses of Monochamus alternatus against symbiotic and entomopathogenic fungi.

PubMed

Zhang, Wei; Meng, Jie; Ning, Jing; Qin, Peijun; Zhou, Jiao; Zou, Zhen; Wang, Yanhong; Jiang, Hong; Ahmad, Faheem; Zhao, Lilin; Sun, Jianghua

2017-08-01

Monochamus alternatus, the main vector beetles of invasive pinewood nematode, has established a symbiotic relationship with a native ectotrophic fungal symbiont, Sporothrix sp. 1, in China. The immune response of M. alternatus to S. sp. 1 in the coexistence of beetles and fungi is, however, unknown. Here, we report that immune responses of M. alternatus pupae to infection caused by ectotrophic symbiotic fungus S. sp. 1 and entomopathogenic fungus Beauveria bassiana differ significantly. The S. sp. 1 did not kill the beetles while B. bassiana killed all upon injection. The transcriptome results showed that the numbers of differentially expressed genes in M. alternatus infected with S. sp. 1 were 2-fold less than those infected with B. bassiana at 48 hours post infection. It was noticed that Toll and IMD pathways played a leading role in the beetle's immune system when infected by symbiotic fungus, but upon infection by entomopathogenic fungus, only the Toll pathway gets triggered actively. Furthermore, the beetles could tolerate the infection of symbiotic fungi by retracing their Toll and IMD pathways at 48 h. This study provided a comprehensive sequence resource of M. alternatus transcriptome for further study of the immune interactions between host and associated fungi.

Electroporation driven delivery of both an IL-12 expressing plasmid and cisplatin synergizes to inhibit B16 melanoma tumor growth through an NK cell mediated tumor killing mechanism.

PubMed

Kim, Ha; Sin, Jeong-Im

2012-11-01

Combined therapy using chemotherapeutic drugs and immunotherapeutics offers some promise for treating patients with cancer. In this study, we evaluated whether cisplatin delivered by intratumoral (IT)-electroporation (EP) might enhance antitumor activity against established B16 melanoma and whether further addition of intramuscular (IM)-EP of IL-12 cDNA to IT-EP of cisplatin might augment antitumor therapeutic activity, with a focus on the underlining antitumor mechanism(s). When tumor (7 mm)-bearing animals were treated locally with cisplatin by IT-EP, they showed tumor growth inhibition significantly more than those without IT-EP. Moreover, IL-12 cDNA delivered by IM-EP was also able to inhibit tumor growth significantly more than control vector delivery. This tumor growth inhibition was mediated by NK cells, but not CD4+ T or CD8+ T cells, as determined by immune cell subset depletion and IFN-γ induction. Moreover, concurrent therapy using IT-EP of cisplatin plus IM-EP of IL-12 cDNA displayed antitumor therapeutic synergy. This therapeutic synergy appeared to be mediated by increased sensitivity of cisplatin-treated tumors to NK cell-mediated tumor killing. Taken together, these data support that cisplatin delivery by IT-EP plus IL-12 gene delivery by IM-EP are more effective at inducing antitumor therapeutic responses through increased sensitivity of cisplatin-treated tumors to NK cell-mediated tumor killing. This combined approach might have some implication for treating melanoma in patients.

Occurrence of pathogenic fungi to Amblyomma cajennense in a rural area of Central Brazil and their activities against vectors of Rocky Mountain spotted fever.

PubMed

D'Alessandro, Walmirton B; Humber, Richard A; Luz, Christian

2012-08-13

Two isolates of Beauveria bassiana and one of Purpureocillium lilacinum (=Paecilomyces lilacinus) were found infecting Amblyomma cajennense engorged females collected on horses (0.15% infection rate from a total of 1982 specimens) and another two isolates of P. lilacinum and one Metarhizium anisopliae detected in soils (2.1% from 144 samples) collected in typical pasture habitats of this tick in Central Brazil from October 2009 to March 2011. Fungi were isolated from soils with Rhipicephalus sanguineus as surrogate baits. No fungi were found in ticks or soils during the driest months (May to August). Testing pathogenicity of fungi all R. sanguineus females were killed regardless of the isolate and fungi sporulated abundantly on the cadavers. A. cajennense was less susceptible to infection with P. lilacinum within 20 days than R. sanguineus. All three fungal species probably act as natural antagonists of A. cajennense particularly in the rainy season and have interest for integrate control of vectors of Rocky Mountain spotted fever. Copyright © 2012 Elsevier B.V. All rights reserved.

Experimental Vaccines against Chagas Disease: A Journey through History.

PubMed

Rodríguez-Morales, Olivia; Monteón-Padilla, Víctor; Carrillo-Sánchez, Silvia C; Rios-Castro, Martha; Martínez-Cruz, Mariana; Carabarin-Lima, Alejandro; Arce-Fonseca, Minerva

2015-01-01

Chagas disease, or American trypanosomiasis, which is caused by the protozoan parasite Trypanosoma cruzi, is primarily a vector disease endemic in 21 Latin American countries, including Mexico. Although many vector control programs have been implemented, T. cruzi has not been eradicated. The development of an anti-T. cruzi vaccine for prophylactic and therapeutic purposes may significantly contribute to the transmission control of Chagas disease. Immune protection against experimental infection with T. cruzi has been studied since the second decade of the last century, and many types of immunogens have been used subsequently, such as killed or attenuated parasites and new DNA vaccines. This primary prevention strategy appears feasible, effective, safe, and inexpensive, although problems remain. The objective of this review is to summarize the research efforts about the development of vaccines against Chagas disease worldwide. A thorough literature review was conducted by searching PubMed with the terms "Chagas disease" and "American trypanosomiasis" together with "vaccines" or "immunization". In addition, reports and journals not cited in PubMed were identified. Publications in English, Spanish, and Portuguese were reviewed.

Repellent, irritant and toxic effects of 20 plant extracts on adults of the malaria vector Anopheles gambiae mosquito.

PubMed

Deletre, Emilie; Martin, Thibaud; Campagne, Pascal; Bourguet, Denis; Cadin, Andy; Menut, Chantal; Bonafos, Romain; Chandre, Fabrice

2013-01-01

Pyrethroid insecticides induce an excito-repellent effect that reduces contact between humans and mosquitoes. Insecticide use is expected to lower the risk of pathogen transmission, particularly when impregnated on long-lasting treated bednets. When applied at low doses, pyrethroids have a toxic effect, however the development of pyrethroid resistance in several mosquito species may jeopardize these beneficial effects. The need to find additional compounds, either to kill disease-carrying mosquitoes or to prevent mosquito contact with humans, therefore arises. In laboratory conditions, the effects (i.e., repellent, irritant and toxic) of 20 plant extracts, mainly essential oils, were assessed on adults of Anopheles gambiae, a primary vector of malaria. Their effects were compared to those of DEET and permethrin, used as positive controls. Most plant extracts had irritant, repellent and/or toxic effects on An. gambiae adults. The most promising extracts, i.e. those combining the three types of effects, were from Cymbopogon winterianus, Cinnamomum zeylanicum and Thymus vulgaris. The irritant, repellent and toxic effects occurred apparently independently of each other, and the behavioural response of adult An. gambiae was significantly influenced by the concentration of the plant extracts. Mechanisms underlying repellency might, therefore, differ from those underlying irritancy and toxicity. The utility of the efficient plant extracts for vector control as an alternative to pyrethroids may thus be envisaged.

Improved vectors for transcriptional/translational signal screening in corynebacteria using the melC operon from Streptomyces glaucescens as reporter.

PubMed

Adham, Sirin A I; Rodríguez, Sonia; Ramos, Angelina; Santamaría, Ramón I; Gil, José A

2003-07-01

The tyrosinase operon ( melC) from Streptomyces glaucescens was cloned and functionally expressed in Brevibacterium lactofermentum and Corynebacterium glutamicum under the control of the promoter of the kan gene from Tn 5. Recombinant corynebacterial cells containing the tyrosinase operon produced melanin on agar plates and in liquid culture when supplemented with copper and tyrosine. A conjugative bifunctional replacement vector for transcriptional/translational signal screening (pEMel-1) was constructed using expression of the melC operon from S. glaucescens, which can be used for cloning promoter sequences as EcoRI- NdeI fragments. When the DNA fragments with promoter activity such as cspBp or trpp were inserted into pEMel-1, B. lactofermentum harboring the chimeric plasmids produced melanin at different stages of growth, allowing temporal detection of promoter activity. The vector was also used to detect the activity of a Streptomyces promoter ( xysAp), which was inactive in B. lactofermentum, after PCR mutagenesis. The melC operon can be used for the visual, inexpensive (compared to the high price of starch azure for amylase detection), and non-selective (in contrast to the kan or cat genes) screening of several thousand clones at high colony density without killing of the transformants due to the presence of iodine (as in the case of amylase assay).

Repellent, Irritant and Toxic Effects of 20 Plant Extracts on Adults of the Malaria Vector Anopheles gambiae Mosquito

PubMed Central

Deletre, Emilie; Martin, Thibaud; Campagne, Pascal; Bourguet, Denis; Cadin, Andy; Menut, Chantal; Bonafos, Romain; Chandre, Fabrice

2013-01-01

Pyrethroid insecticides induce an excito-repellent effect that reduces contact between humans and mosquitoes. Insecticide use is expected to lower the risk of pathogen transmission, particularly when impregnated on long-lasting treated bednets. When applied at low doses, pyrethroids have a toxic effect, however the development of pyrethroid resistance in several mosquito species may jeopardize these beneficial effects. The need to find additional compounds, either to kill disease-carrying mosquitoes or to prevent mosquito contact with humans, therefore arises. In laboratory conditions, the effects (i.e., repellent, irritant and toxic) of 20 plant extracts, mainly essential oils, were assessed on adults of Anopheles gambiae, a primary vector of malaria. Their effects were compared to those of DEET and permethrin, used as positive controls. Most plant extracts had irritant, repellent and/or toxic effects on An. gambiae adults. The most promising extracts, i.e. those combining the three types of effects, were from Cymbopogon winterianus, Cinnamomum zeylanicum and Thymus vulgaris. The irritant, repellent and toxic effects occurred apparently independently of each other, and the behavioural response of adult An. gambiae was significantly influenced by the concentration of the plant extracts. Mechanisms underlying repellency might, therefore, differ from those underlying irritancy and toxicity. The utility of the efficient plant extracts for vector control as an alternative to pyrethroids may thus be envisaged. PMID:24376515

Targeting cattle for malaria elimination: marked reduction of Anopheles arabiensis survival for over six months using a slow-release ivermectin implant formulation.

PubMed

Chaccour, Carlos J; Ngha'bi, Kija; Abizanda, Gloria; Irigoyen Barrio, Angel; Aldaz, Azucena; Okumu, Fredros; Slater, Hannah; Del Pozo, Jose Luis; Killeen, Gerry

2018-05-04

Mosquitoes that feed on animals can survive and mediate residual transmission of malaria even after most humans have been protected with insecticidal bednets or indoor residual sprays. Ivermectin is a widely-used drug for treating parasites of humans and animals that is also insecticidal, killing mosquitoes that feed on treated subjects. Mass administration of ivermectin to livestock could be particularly useful for tackling residual malaria transmission by zoophagic vectors that evade human-centred approaches. Ivermectin comes from a different chemical class to active ingredients currently used to treat bednets or spray houses, so it also has potential for mitigating against emergence of insecticide resistance. However, the duration of insecticidal activity obtained with ivermectin is critical to its effectiveness and affordability. A slow-release formulation for ivermectin was implanted into cattle, causing 40 weeks of increased mortality among Anopheles arabiensis that fed on them. For this zoophagic vector of residual malaria transmission across much of Africa, the proportion surviving three days after feeding (typical mean duration of a gonotrophic cycle in field populations) was approximately halved for 25 weeks. This implantable ivermectin formulation delivers stable and sustained insecticidal activity for approximately 6 months. Residual malaria transmission by zoophagic vectors could be suppressed by targeting livestock with this long-lasting formulation, which would be impractical or unacceptable for mass treatment of human populations.

Measurement of aspheric mirror by nanoprofiler using normal vector tracing

NASA Astrophysics Data System (ADS)

Kitayama, Takao; Shiraji, Hiroki; Yamamura, Kazuya; Endo, Katsuyoshi

2016-09-01

Aspheric or free-form optics with high accuracy are necessary in many fields such as third-generation synchrotron radiation and extreme-ultraviolet lithography. Therefore the demand of measurement method for aspherical or free-form surface with nanometer accuracy increases. Purpose of our study is to develop a non-contact measurement technology for aspheric or free-form surfaces directly with high repeatability. To achieve this purpose we have developed threedimensional Nanoprofiler which detects normal vectors of sample surface. The measurement principle is based on the straightness of laser light and the accurate motion of rotational goniometers. This machine consists of four rotational stages, one translational stage and optical head which has the quadrant photodiode (QPD) and laser source. In this measurement method, we conform the incident light beam to reflect the beam by controlling five stages and determine the normal vectors and the coordinates of the surface from signal of goniometers, translational stage and QPD. We can obtain three-dimensional figure from the normal vectors and their coordinates by surface reconstruction algorithm. To evaluate performance of this machine we measure a concave aspheric mirror with diameter of 150 mm. As a result we achieve to measure large area of 150mm diameter. And we observe influence of systematic errors which the machine has. Then we simulated the influence and subtracted it from measurement result.

Wash-resistance of pirimiphos-methyl insecticide treatments of window screens and eave baffles for killing indoor-feeding malaria vector mosquitoes: an experimental hut trial, South East of Zambia.

PubMed

Chinula, Dingani; Sikaala, Chadwick H; Chanda-Kapata, Pascalina; Hamainza, Busiku; Zulu, Reuben; Reimer, Lisa; Chizema, Elizabeth; Kiware, Samson; Okumu, Fredros O; Killeen, Gerry

2018-04-13

The effectiveness of long-lasting insecticidal-treated nets (LLINs) and indoor residual spraying (IRS) for malaria control is threatened by resistance to commonly used pyrethroid insecticides. Rotations, mosaics, combinations, or mixtures of insecticides from different complementary classes are recommended by the World Health Organization (WHO) for mitigating against resistance, but many of the alternatives to pyrethroids are prohibitively expensive to apply in large national IRS campaigns. Recent evaluations of window screens and eave baffles (WSEBs) treated with pirimiphos-methyl (PM), to selectively target insecticides inside houses, demonstrated malaria vector mortality rates equivalent or superior to IRS. However, the durability of efficacy when co-applied with polyacrylate-binding agents (BA) remains to be established. This study evaluated whether WSEBs, co-treated with PM and BA have comparable wash resistance to LLINs and might therefore remain insecticidal for years rather than months. WHO-recommended wire ball assays of insecticidal efficacy were applied to polyester netting treated with or without BA plus 1 or 2 g/sq m PM. They were then tested for insecticidal efficacy using fully susceptible insectary-reared Anopheles gambiae mosquitoes, following 0, 5, 10, 15, then 20 washes as per WHO-recommended protocols for accelerated ageing of LLINs. This was followed by a small-scale field trial in experimental huts to measure malaria vector mortality achieved by polyester netting WSEBs treated with BA and 2 g/sq m PM after 0, 10 and then 20 standardized washes, alongside recently applied IRS using PM. Co-treatment with BA and either dosage of PM remained insecticidal over 20 washes in the laboratory. In experimental huts, WSEBs treated with PM plus BA consistently killed similar proportions of Anopheles arabiensis mosquitoes to PM-IRS (both consistently ≥ 94%), even after 20 washes. Co-treating WSEBs with both PM and BA results in wash-resistant insecticidal activity comparable with LLINs. Insecticide treatments for WSEBs may potentially last for years rather than months, therefore, reducing insecticide consumption by an order of magnitude relative to IRS. However, durability of WSEBs will still have to be assessed in real houses under representative field conditions of exposure to wear and tear, sunlight and rain.

Field trial on a novel control method for the dengue vector, Aedes aegypti by the systematic use of Olyset® Net and pyriproxyfen in Southern Vietnam

PubMed Central

2013-01-01

Background Jars, tanks, and drums provide favorable rearing/breeding sites for Aedes aegypti in Vietnam. However, the use of insecticides to control mosquitoes at such breeding sites has not been approved in Vietnam since they are also often sources of drinking water, making larval vector control difficult. Mosquito nets pre-treated with long-lasting insecticide treated nets (LLITNs) form an effective measure for malaria control. We examined changes in the abundance of immature Aedes aegypti to evaluate the efficacy of covering ceramic jars with lids comprising one type of LLITN, Olyset® Net, in inhibiting oviposition by adult females, and to evaluate the effect of treating other breeding containers, such as flower vases, inside and around the outside of houses with a slow-release pyriproxyfen formulation to kill pupae. Methods We selected 313 households for the trial and 363 households for the control in Tan Chanh, Long An province, Vietnam. In the trial area, Olyset® Net lids were used to cover five major types of water container (ceramic jars, cylindrical concrete tanks, other concrete tanks, plastic drums, and plastic buckets), while pyriproxyfen was used to treat flower vases and ant traps. We also monitored dengue virus transmission by measuring anti-dengue IgM and IgG levels in healthy residents in both control and trial areas to estimate the effectiveness of Olyset® Net at controlling the dengue vector, Aedes aegypti. Results The container-index and house-index for immature Ae. aegypti fell steeply one month after treatment in the trial area. Lids with Olyset® Net that fit container openings clearly seemed to reduce the presence of immature Ae. aegypti as the density of pupae decreased 1 month after treatment in the trial area. Pyriproxyfen was also effective at killing pupae in the water containers in the trial area. Although the dengue seroconversion rate was not influenced by Olyset® Net, it was lower in two-five year old children when compared to older children and adults in both control and trial areas. Conclusions Our study showed that the treatment by Olyset® Net and pyriproxyfen had a strong negative effect on the prevalence of immature Ae. aegypti, which persisted for at least 5 months after treatment. PMID:23312018

Field trial on a novel control method for the dengue vector, Aedes aegypti by the systematic use of Olyset® Net and pyriproxyfen in Southern Vietnam.

PubMed

Tsunoda, Takashi; Kawada, Hitoshi; Huynh, Trang T T; Luu, Loan Le; Le, San Hoang; Tran, Huu Ngoc; Vu, Huong Thi Que; Le, Hieu Minh; Hasebe, Futoshi; Tsuzuki, Ataru; Takagi, Masahiro

2013-01-11

Jars, tanks, and drums provide favorable rearing/breeding sites for Aedes aegypti in Vietnam. However, the use of insecticides to control mosquitoes at such breeding sites has not been approved in Vietnam since they are also often sources of drinking water, making larval vector control difficult. Mosquito nets pre-treated with long-lasting insecticide treated nets (LLITNs) form an effective measure for malaria control. We examined changes in the abundance of immature Aedes aegypti to evaluate the efficacy of covering ceramic jars with lids comprising one type of LLITN, Olyset® Net, in inhibiting oviposition by adult females, and to evaluate the effect of treating other breeding containers, such as flower vases, inside and around the outside of houses with a slow-release pyriproxyfen formulation to kill pupae. We selected 313 households for the trial and 363 households for the control in Tan Chanh, Long An province, Vietnam. In the trial area, Olyset® Net lids were used to cover five major types of water container (ceramic jars, cylindrical concrete tanks, other concrete tanks, plastic drums, and plastic buckets), while pyriproxyfen was used to treat flower vases and ant traps. We also monitored dengue virus transmission by measuring anti-dengue IgM and IgG levels in healthy residents in both control and trial areas to estimate the effectiveness of Olyset® Net at controlling the dengue vector, Aedes aegypti. The container-index and house-index for immature Ae. aegypti fell steeply one month after treatment in the trial area. Lids with Olyset® Net that fit container openings clearly seemed to reduce the presence of immature Ae. aegypti as the density of pupae decreased 1 month after treatment in the trial area. Pyriproxyfen was also effective at killing pupae in the water containers in the trial area. Although the dengue seroconversion rate was not influenced by Olyset® Net, it was lower in two-five year old children when compared to older children and adults in both control and trial areas. Our study showed that the treatment by Olyset® Net and pyriproxyfen had a strong negative effect on the prevalence of immature Ae. aegypti, which persisted for at least 5 months after treatment.

Monochromatic plane-fronted waves in conformal gravity are pure gauge

NASA Astrophysics Data System (ADS)

Fabbri, Luca; Paranjape, M. B.

2011-05-01

We consider plane-fronted, monochromatic gravitational waves on a Minkowski background, in a conformally invariant theory of general relativity. By this we mean waves of the form: gμν=ημν+γμνF(k·x), where γμν is a constant polarization tensor, and kμ is a lightlike vector. We also assume the coordinate gauge condition |g|-1/4∂τ(|g|1/4gστ)=0 which is the conformal analog of the harmonic gauge condition gμνΓμνσ=-|g|-1/2∂τ(|g|1/2gστ)=0, where det⁡[gμν]≡g. Requiring additionally the conformal gauge condition g=-1 surprisingly implies that the waves are both transverse and traceless. Although the ansatz for the metric is eminently reasonable when considering perturbative gravitational waves, we show that the metric is reducible to the metric of Minkowski space-time via a sequence of coordinate transformations which respect the gauge conditions, without any perturbative approximation that γμν be small. This implies that we have, in fact, exact plane-wave solutions; however, they are simply coordinate/conformal artifacts. As a consequence, they carry no energy. Our result does not imply that conformal gravity does not have gravitational wave phenomena. A different, more generalized ansatz for the deviation, taking into account the fourth-order nature of the field equation, which has the form gμν=ημν+Bμν(n·x)G(k·x), indeed yields waves which carry energy and momentum [P. D. Mannheim, Gen. Relativ. Gravit.GRGVA80001-7701 43, 703 (2010)10.1007/s10714-010-1088-z]. It is just surprising that transverse, traceless, plane-fronted gravitational waves, those that would be used in any standard, perturbative, quantum analysis of the theory, simply do not exist.

Spacetime symmetries and topology in bimetric relativity

NASA Astrophysics Data System (ADS)

Torsello, Francesco; Kocic, Mikica; Högâs, Marcus; Mörtsell, Edvard

2018-04-01

We explore spacetime symmetries and topologies of the two metric sectors in Hassan-Rosen bimetric theory. We show that, in vacuum, the two sectors can either share or have separate spacetime symmetries. If stress-energy tensors are present, a third case can arise, with different spacetime symmetries within the same sector. This raises the question of the best definition of spacetime symmetry in Hassan-Rosen bimetric theory. We emphasize the possibility of imposing ansatzes and looking for solutions having different Killing vector fields or different isometries in the two sectors, which has gained little attention so far. We also point out that the topology of spacetime imposes a constraint on possible metric combinations.

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

Baguet, A.; Pope, Christopher N.; Samtleben, H.

We prove an old conjecture by Duff, Nilsson, Pope and Warner asserting that the NSNS sector of supergravity (and more general the bosonic string) allows for a consistent Pauli reduction on any d-dimensional group manifold G, keeping the full set of gauge bosons of the G×G isometry group of the bi-invariant metric on G. The main tool of the construction is a particular generalised Scherk–Schwarz reduction ansatz in double field theory which we explicitly construct in terms of the group's Killing vectors. Examples include the consistent reduction from ten dimensions on S3×S3 and on similar product spaces. The construction ismore » another example of globally geometric non-toroidal compactifications inducing non-geometric fluxes.« less

Smuggling across the border: how arthropod-borne pathogens evade and exploit the host defense system of the skin.

PubMed

Bernard, Quentin; Jaulhac, Benoit; Boulanger, Nathalie

2014-05-01

The skin is a critical barrier between hosts and pathogens in arthropod-borne diseases. It harbors many resident cells and specific immune cells to arrest or limit infections by secreting inflammatory molecules or by directly killing pathogens. However, some pathogens are able to use specific skin cells and arthropod saliva for their initial development, to hide from the host immune system, and to establish persistent infection in the vertebrate host. A better understanding of the initial mechanisms taking place in the skin should allow the development of new strategies to fight these vector-borne pathogens that are spread worldwide and are of major medical importance.

A geo-coded inventory of anophelines in the Afrotropical Region south of the Sahara: 1898-2016.

PubMed

Kyalo, David; Amratia, Punam; Mundia, Clara W; Mbogo, Charles M; Coetzee, Maureen; Snow, Robert W

2017-01-01

Background : Understanding the distribution of anopheline vectors of malaria is an important prelude to the design of national malaria control and elimination programmes. A single, geo-coded continental inventory of anophelines using all available published and unpublished data has not been undertaken since the 1960s. Methods : We have searched African, European and World Health Organization archives to identify unpublished reports on anopheline surveys in 48 sub-Saharan Africa countries. This search was supplemented by identification of reports that formed part of post-graduate theses, conference abstracts, regional insecticide resistance databases and more traditional bibliographic searches of peer-reviewed literature. Finally, a check was made against two recent repositories of dominant malaria vector species locations ( circa 2,500). Each report was used to extract information on the survey dates, village locations (geo-coded to provide a longitude and latitude), sampling methods, species identification methods and all anopheline species found present during the survey. Survey records were collapsed to a single site over time.    Results : The search strategy took years and resulted in 13,331 unique, geo-coded survey locations of anopheline vector occurrence between 1898 and 2016. A total of 12,204 (92%) sites reported the presence of 10 dominant vector species/sibling species; 4,473 (37%) of these sites were sampled since 2005. 4,442 (33%) sites reported at least one of 13 possible secondary vector species; 1,107 (25%) of these sites were sampled since 2005. Distributions of dominant and secondary vectors conform to previous descriptions of the ecological ranges of these vectors. Conclusion : We have assembled the largest ever geo-coded database of anophelines in Africa, representing a legacy dataset for future updating and identification of knowledge gaps at national levels. The geo-coded database is available on Harvard Dataverse as a reference source for African national malaria control programmes planning their future control and elimination strategies.

A geo-coded inventory of anophelines in the Afrotropical Region south of the Sahara: 1898-2016

PubMed Central

Kyalo, David; Amratia, Punam; Mundia, Clara W.; Mbogo, Charles M.; Coetzee, Maureen; Snow, Robert W.

2017-01-01

Background: Understanding the distribution of anopheline vectors of malaria is an important prelude to the design of national malaria control and elimination programmes. A single, geo-coded continental inventory of anophelines using all available published and unpublished data has not been undertaken since the 1960s. Methods: We have searched African, European and World Health Organization archives to identify unpublished reports on anopheline surveys in 48 sub-Saharan Africa countries. This search was supplemented by identification of reports that formed part of post-graduate theses, conference abstracts, regional insecticide resistance databases and more traditional bibliographic searches of peer-reviewed literature. Finally, a check was made against two recent repositories of dominant malaria vector species locations ( circa 2,500). Each report was used to extract information on the survey dates, village locations (geo-coded to provide a longitude and latitude), sampling methods, species identification methods and all anopheline species found present during the survey. Survey records were collapsed to a single site over time.    Results: The search strategy took years and resulted in 13,331 unique, geo-coded survey locations of anopheline vector occurrence between 1898 and 2016. A total of 12,204 (92%) sites reported the presence of 10 dominant vector species/sibling species; 4,473 (37%) of these sites were sampled since 2005. 4,442 (33%) sites reported at least one of 13 possible secondary vector species; 1,107 (25%) of these sites were sampled since 2005. Distributions of dominant and secondary vectors conform to previous descriptions of the ecological ranges of these vectors. Conclusion: We have assembled the largest ever geo-coded database of anophelines in Africa, representing a legacy dataset for future updating and identification of knowledge gaps at national levels. The geo-coded database is available on Harvard Dataverse as a reference source for African national malaria control programmes planning their future control and elimination strategies. PMID:28884158

Predicting the effect of angular momentum on the dissociation dynamics of highly rotationally excited radical intermediates.

PubMed

Brynteson, Matthew D; Butler, Laurie J

2015-02-07

We present a model which accurately predicts the net speed distributions of products resulting from the unimolecular decomposition of rotationally excited radicals. The radicals are produced photolytically from a halogenated precursor under collision-free conditions so they are not in a thermal distribution of rotational states. The accuracy relies on the radical dissociating with negligible energetic barrier beyond the endoergicity. We test the model predictions using previous velocity map imaging and crossed laser-molecular beam scattering experiments that photolytically generated rotationally excited CD2CD2OH and C3H6OH radicals from brominated precursors; some of those radicals then undergo further dissociation to CD2CD2 + OH and C3H6 + OH, respectively. We model the rotational trajectories of these radicals, with high vibrational and rotational energy, first near their equilibrium geometry, and then by projecting each point during the rotation to the transition state (continuing the rotational dynamics at that geometry). This allows us to accurately predict the recoil velocity imparted in the subsequent dissociation of the radical by calculating the tangential velocities of the CD2CD2/C3H6 and OH fragments at the transition state. The model also gives a prediction for the distribution of angles between the dissociation fragments' velocity vectors and the initial radical's velocity vector. These results are used to generate fits to the previously measured time-of-flight distributions of the dissociation fragments; the fits are excellent. The results demonstrate the importance of considering the precession of the angular velocity vector for a rotating radical. We also show that if the initial angular momentum of the rotating radical lies nearly parallel to a principal axis, the very narrow range of tangential velocities predicted by this model must be convoluted with a J = 0 recoil velocity distribution to achieve a good result. The model relies on measuring the kinetic energy release when the halogenated precursor is photodissociated via a repulsive excited state but does not include any adjustable parameters. Even when different conformers of the photolytic precursor are populated, weighting the prediction by a thermal conformer population gives an accurate prediction for the relative velocity vectors of the fragments from the highly rotationally excited radical intermediates.

The enzyme 3-hydroxykynurenine transaminase as potential target for 1,2,4-oxadiazoles with larvicide activity against the dengue vector Aedes aegypti.

PubMed

Oliveira, Vanessa S; Pimenteira, Cecília; da Silva-Alves, Diana C B; Leal, Laylla L L; Neves-Filho, Ricardo A W; Navarro, Daniela M A F; Santos, Geanne K N; Dutra, Kamilla A; dos Anjos, Janaína V; Soares, Thereza A

2013-11-15

The mosquito Aedes aegypti is the vector agent responsible for the transmission of yellow fever and dengue fever viruses to over 80 million people in tropical and subtropical regions of the world. Exhaustive efforts have lead to a vaccine candidate with only 30% effectiveness against the dengue virus and failure to protect patients against the serotype 2. Hence, vector control remains the most viable route to dengue fever control programs. We have synthesized a class of 1,2,4-oxadiazole derivatives whose most biologically active compounds exhibit potent activity against Aedes aegypti larvae (ca. of 15 ppm) and low toxicity in mammals. Exposure to these larvicides results in larvae pigmentation in a manner correlated with the LC50 measurements. Structural comparisons of the 1,2,4-oxadiazole nucleus against known inhibitors of insect enzymes allowed the identification of 3-hydroxykynurenine transaminase as a potential target for these synthetic larvicides. Molecular docking calculations indicate that 1,2,4-oxadiazole compounds can bind to 3-hydroxykynurenine transaminase with similar conformation and binding energies as its crystallographic inhibitor 4-(2-aminophenyl)-4-oxobutanoic acid. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rapid and Scalable Plant-based Production of a Cholera Toxin B Subunit Variant to Aid in Mass Vaccination against Cholera Outbreaks

PubMed Central

Bennett, Lauren J.; Baldauf, Keegan J.; Kajiura, Hiroyuki; Fujiyama, Kazuhito; Matoba, Nobuyuki

2013-01-01

Introduction Cholera toxin B subunit (CTB) is a component of an internationally licensed oral cholera vaccine. The protein induces neutralizing antibodies against the holotoxin, the virulence factor responsible for severe diarrhea. A field clinical trial has suggested that the addition of CTB to killed whole-cell bacteria provides superior short-term protection to whole-cell-only vaccines; however, challenges in CTB biomanufacturing (i.e., cost and scale) hamper its implementation to mass vaccination in developing countries. To provide a potential solution to this issue, we developed a rapid, robust, and scalable CTB production system in plants. Methodology/Principal Findings In a preliminary study of expressing original CTB in transgenic Nicotiana benthamiana, the protein was N-glycosylated with plant-specific glycans. Thus, an aglycosylated CTB variant (pCTB) was created and overexpressed via a plant virus vector. Upon additional transgene engineering for retention in the endoplasmic reticulum and optimization of a secretory signal, the yield of pCTB was dramatically improved, reaching >1 g per kg of fresh leaf material. The protein was efficiently purified by simple two-step chromatography. The GM1-ganglioside binding capacity and conformational stability of pCTB were virtually identical to the bacteria-derived original B subunit, as demonstrated in competitive enzyme-linked immunosorbent assay, surface plasmon resonance, and fluorescence-based thermal shift assay. Mammalian cell surface-binding was corroborated by immunofluorescence and flow cytometry. pCTB exhibited strong oral immunogenicity in mice, inducing significant levels of CTB-specific intestinal antibodies that persisted over 6 months. Moreover, these antibodies effectively neutralized the cholera holotoxin in vitro. Conclusions/Significance Taken together, these results demonstrated that pCTB has robust producibility in Nicotiana plants and retains most, if not all, of major biological activities of the original protein. This rapid and easily scalable system may enable the implementation of pCTB to mass vaccination against outbreaks, thereby providing better protection of high-risk populations in developing countries. PMID:23505583

Analysis of an Hp-Non-conforming Discontinuous Galerkin Spectral Element Method for Wave

DTIC Science & Technology

2011-04-01

Scientific Computing, 36 (2008), pp. 351–390. [25] Eleuterio F . Toro , Riemann Solvers and Numerical Methods for Fluid Dynamics, Springer, 1999. [26...denoted by ñ, and the contravariant flux [15] is defined as F̃i = Jeai · F , i = 1, 2, 3, with ai as the contravariant basis vectors. We now describe...wave propagation case by the following definitions, q = ( E v ) ∈ V, Q = ( I 0 0 ρI ) , g = ( 0 f ) ∈ V, with I denoting the fourth-order identity tensor

A Measure of the Conformity of a Parameter Set to a Trend: The Partially Ordered Case.

DTIC Science & Technology

1983-05-01

A-A3214 A MEASURE OF THE CONFORMIYO QAPARAMEfERSETO QA / TREND: THE PARTIAL .U) IOWA UNIV IOWA CIT DEPT OF ......STATISTICS AND ACTURIAL SCIENCE.T...and j with i o j. Such a vector 0 = (Oi,0j,.... 0k is said to be isotone (with respect to _). In studying such inference procedures it is helpful to...noticed that none of the measures studied here are applicable in alIl the situations considered. In studying locat ion pa rameter- wlhich are not

The Invisibility of Diffeomorphisms

NASA Astrophysics Data System (ADS)

De Haro, Sebastian

2017-11-01

I examine the relationship between (d+1)-dimensional Poincaré metrics and d-dimensional conformal manifolds, from both mathematical and physical perspectives. The results have a bearing on several conceptual issues relating to asymptotic symmetries in general relativity and in gauge-gravity duality, as follows: (1: Ambient Construction) I draw from the remarkable work by Fefferman and Graham (Elie Cartan et les Mathématiques d'aujourd'hui, Astérisque, 1985; The Ambient Metric. Annals of Mathematics Studies, Princeton University Press, Princeton, 2012) on conformal geometry, in order to prove two propositions and a theorem that characterise which classes of diffeomorphisms qualify as gravity-invisible. I define natural notions of gravity-invisibility (strong, weak, and simpliciter) that apply to the diffeomorphisms of Poincaré metrics in any dimension. (2: Dualities) I apply the notions of invisibility, developed in (1), to gauge-gravity dualities: which, roughly, relate Poincaré metrics in d+1 dimensions to QFTs in d dimensions. I contrast QFT-visible versus QFT-invisible diffeomorphisms: those gravity diffeomorphisms that can, respectively cannot, be seen from the QFT. The QFT-invisible diffeomorphisms are the ones which are relevant to the hole argument in Einstein spaces. The results on dualities are surprising, because the class of QFT-visible diffeomorphisms is larger than expected, and the class of QFT-invisible ones is smaller than expected, or usually believed, i.e. larger than the PBH diffeomorphisms in Imbimbo et al. (Class Quantum Gravity 17(5):1129, 2000, Eq. 2.6). I also give a general derivation of the asymptotic conformal Killing equation, which has not appeared in the literature before.

Combining indoor and outdoor methods for controlling malaria vectors: an ecological model of endectocide-treated livestock and insecticidal bed nets.

PubMed

Yakob, Laith; Cameron, Mary; Lines, Jo

2017-03-13

Malaria is spread by mosquitoes that are increasingly recognised to have diverse biting behaviours. How a mosquito in a specific environment responds to differing availability of blood-host species is largely unknown and yet critical to vector control efficacy. A parsimonious mathematical model is proposed that accounts for a diverse range of host-biting behaviours and assesses their impact on combining long-lasting insecticidal nets (LLINs) with a novel approach to malaria control: livestock treated with insecticidal compounds ('endectocides') that kill biting mosquitoes. Simulations of a malaria control programme showed marked differences across biting ecologies in the efficacy of both LLINs as a stand-alone tool and the combination of LLINs with endectocide-treated cattle. During the intervals between LLIN mass campaigns, concordant use of endectocides is projected to reduce the bounce-back in malaria prevalence that can occur as LLIN efficacy decays over time, especially if replacement campaigns are delayed. Integrating these approaches can also dramatically improve the attainability of local elimination; endectocidal treatment schedules required to achieve this aim are provided for malaria vectors with different biting ecologies. Targeting blood-feeding mosquitoes by treating livestock with endectocides offers a potentially useful complement to existing malaria control programmes centred on LLIN distribution. This approach is likely to be effective against vectors with a wide range of host-preferences and biting behaviours, with the exception of species that are so strictly anthropophilic that most blood meals are taken on humans even when humans are much less available than non-human hosts. Identifying this functional relationship in wild mosquito populations and ascertaining the extent to which it differs, within as well as between species, is a critical next step before targets can be set for employing this novel approach and combination.

Transduction of Nonhuman Primate Brain with Adeno-Associated Virus Serotype 1: Vector Trafficking and Immune Response

PubMed Central

Forsayeth, John; Mirek, Hanna; Munson, Keith; Bringas, John; Pivirotto, Phil; McBride, Jodi L; Davidson, Beverly L.; Bankiewicz, Krystof S.

2009-01-01

Abstract We used convection-enhanced delivery (CED) to characterize gene delivery mediated by adeno-associated virus type 1 (AAV1) by tracking expression of hrGFP (humanized green fluorescent protein from Renilla reniformis) into the striatum, basal forebrain, and corona radiata of monkey brain. Four cynomolgus monkeys received single infusions into corona radiata, putamen, and caudate. The other group (n = 4) received infusions into basal forebrain. Thirty days after infusion animals were killed and their brains were processed for immunohisto-chemical evaluation. Volumetric analysis of GFP-positive brain areas was performed. AAV1-hrGFP infusions resulted in approximately 550, 700, and 73 mm3 coverage after infusion into corona radiata, striatum, and basal forebrain, respectively. Aside from targeted regions, other brain structures also showed GFP signal (internal and external globus pallidus, subthalamic nucleus), supporting the idea that AAV1 is actively trafficked to regions distal from the infusion site. In addition to neuronal transduction, a significant nonneuronal cell population was transduced by AAV1 vector; for example, oligodendrocytes in corona radiata and astrocytes in the striatum. We observed a strong humoral and cell-mediated response against AAV1-hrGFP in transduced monkeys irrespective of the anatomic location of the infusion, as evidenced by induction of circulating anti-AAV1 and anti-hrGFP antibodies, as well as infiltration of CD4+ lymphocytes and upregulation of MHC-II in regions infused with vector. We conclude that transduction of antigen-presenting cells within the CNS is a likely cause of this response and that caution is warranted when foreign transgenes are used as reporters in gene therapy studies with vectors with broader tropism than AAV2. PMID:19292604

Attenuated Listeria monocytogenes vectors overcome suppressive plasma factors during HIV infection to stimulate myeloid dendritic cells to promote adaptive immunity and reactivation of latent virus.

PubMed

Miller, Elizabeth A; Spadaccia, Meredith R; Norton, Thomas; Demmler, Morgan; Gopal, Ramya; O'Brien, Meagan; Landau, Nathaniel; Dubensky, Thomas W; Lauer, Peter; Brockstedt, Dirk G; Bhardwaj, Nina

2015-01-01

HIV-1 infection is characterized by myeloid dendritic cell (DC) dysfunction, which blunts the responsiveness to vaccine adjuvants. We previously showed that nonviral factors in HIV-seropositive plasma are partially responsible for mediating this immune suppression. In this study we investigated recombinant Listeria monocytogenes (Lm) vectors, which naturally infect and potently activate DCs from seronegative donors, as a means to overcome DC dysfunction associated with HIV infection. Monocyte-derived DCs were cocultured with plasma from HIV-infected donors (HIV-moDCs) to induce a dysregulated state and infected with an attenuated, nonreplicative vaccine strain of Lm expressing full length clade B consensus gag (KBMA Lm-gag). Lm infection stimulated cytokine secretion [interleukin (IL)-12p70, tumor necrosis factor (TNF)-α, and IL-6] and Th-1 skewing of allogeneic naive CD4 T cells by HIV-moDCs, in contrast to the suppressive effects observed by HIV plasma on moDCs on toll-like receptor ligand stimulation. Upon coculture of "killed" but metabolically active (KBMA) Lm-gag-infected moDCs from HIV-infected donors with autologous cells, expansion of polyfunctional, gag-specific CD8(+) T cells was observed. Reactivation of latent proviruses by moDCs following Lm infection was also observed in models of HIV latency in a TNF-α-dependent manner. These findings reveal the unique ability of Lm vectors to contend with dysregulation of HIV-moDCs, while simultaneously possessing the capacity to activate latent virus. Concurrent stimulation of innate and adaptive immunity and disruption of latency may be an approach to reduce the pool of latently infected cells during HIV infection. Further study of Lm vectors as part of therapeutic vaccination and eradication strategies may advance this evolving field.

Rényi entropy, stationarity, and entanglement of the conformal scalar

NASA Astrophysics Data System (ADS)

Lee, Jeongseog; Lewkowycz, Aitor; Perlmutter, Eric; Safdi, Benjamin R.

2015-03-01

We extend previous work on the perturbative expansion of the Rényi entropy, S q , around q = 1 for a spherical entangling surface in a general CFT. Applied to conformal scalar fields in various spacetime dimensions, the results appear to conflict with the known conformal scalar Rényi entropies. On the other hand, the perturbative results agree with known Rényi entropies in a variety of other theories, including theories of free fermions and vector fields and theories with Einstein gravity duals. We propose a resolution stemming from a careful consideration of boundary conditions near the entangling surface. This is equivalent to a proper treatment of total-derivative terms in the definition of the modular Hamiltonian. As a corollary, we are able to resolve an outstanding puzzle in the literature regarding the Rényi entropy of super-Yang-Mills near q = 1. A related puzzle regards the question of stationarity of the renormalized entanglement entropy (REE) across a circle for a (2+1)-dimensional massive scalar field. We point out that the boundary contributions to the modular Hamiltonian shed light on the previously-observed non-stationarity. Moreover, IR divergences appear in perturbation theory about the massless fixed point that inhibit our ability to reliably calculate the REE at small non-zero mass.

Multilateral development banks and socially responsible investments--the case of tobacco.

PubMed

Lal, Pranay

2012-12-01

Globally, tobacco kills more people than HIV-related conditions or AIDS, tuberculosis and malaria combined. In 1991, The World Bank, the world's largest lender, pledged that it would no longer support tobacco-related projects. It was expected that other financial investors would follow, but most did not respond to this call. As a result, several financial institutions continue to invest in tobacco and fuel an epidemic to an unprecedented scale. Using tobacco as a case in point, this review highlights the continuing investments among financial institutions which do not conform to 'socially responsible investments' and calls for monitoring and reporting such unethical practices. The paper also underscores the need to harmonise the numerous criteria, principles and voluntary codes that govern socially responsible investing and ensure that financial institutions comply with them.

Continuum topology optimization considering uncertainties in load locations based on the cloud model

NASA Astrophysics Data System (ADS)

Liu, Jie; Wen, Guilin

2018-06-01

Few researchers have paid attention to designing structures in consideration of uncertainties in the loading locations, which may significantly influence the structural performance. In this work, cloud models are employed to depict the uncertainties in the loading locations. A robust algorithm is developed in the context of minimizing the expectation of the structural compliance, while conforming to a material volume constraint. To guarantee optimal solutions, sufficient cloud drops are used, which in turn leads to low efficiency. An innovative strategy is then implemented to enormously improve the computational efficiency. A modified soft-kill bi-directional evolutionary structural optimization method using derived sensitivity numbers is used to output the robust novel configurations. Several numerical examples are presented to demonstrate the effectiveness and efficiency of the proposed algorithm.

Atomic Force Microscopy Study of the Interactions of Indolicidin with Model Membranes and DNA.

PubMed

Fojan, Peter; Gurevich, Leonid

2017-01-01

The cell membrane is the first barrier and quite often the primary target that antimicrobial peptides (AMPs) have to destroy or penetrate to fulfill their mission. Upon penetrating through the membrane, the peptides can further attack intracellular targets, in particular DNA. Studying the interaction of an antimicrobial peptide with a cell membrane and DNA holds keys to understanding its killing mechanisms. Commonly, these interactions are studied by using optical or scanning electron microscopy and appropriately labeled peptides. However, labeling can significantly affect the hydrophobicity, conformation, and size of the peptide, hence altering the interaction significantly. Here, we describe the use of atomic force microscopy (AFM) for a label-free study of the interactions of peptides with model membranes under physiological conditions and DNA as a possible intracellular target.

A Two-Locus Model of the Evolution of Insecticide Resistance to Inform and Optimise Public Health Insecticide Deployment Strategies

PubMed Central

2017-01-01

We develop a flexible, two-locus model for the spread of insecticide resistance applicable to mosquito species that transmit human diseases such as malaria. The model allows differential exposure of males and females, allows them to encounter high or low concentrations of insecticide, and allows selection pressures and dominance values to differ depending on the concentration of insecticide encountered. We demonstrate its application by investigating the relative merits of sequential use of insecticides versus their deployment as a mixture to minimise the spread of resistance. We recover previously published results as subsets of this model and conduct a sensitivity analysis over an extensive parameter space to identify what circumstances favour mixtures over sequences. Both strategies lasted more than 500 mosquito generations (or about 40 years) in 24% of runs, while in those runs where resistance had spread to high levels by 500 generations, 56% favoured sequential use and 44% favoured mixtures. Mixtures are favoured when insecticide effectiveness (their ability to kill homozygous susceptible mosquitoes) is high and exposure (the proportion of mosquitoes that encounter the insecticide) is low. If insecticides do not reliably kill homozygous sensitive genotypes, it is likely that sequential deployment will be a more robust strategy. Resistance to an insecticide always spreads slower if that insecticide is used in a mixture although this may be insufficient to outperform sequential use: for example, a mixture may last 5 years while the two insecticides deployed individually may last 3 and 4 years giving an overall ‘lifespan’ of 7 years for sequential use. We emphasise that this paper is primarily about designing and implementing a flexible modelling strategy to investigate the spread of insecticide resistance in vector populations and demonstrate how our model can identify vector control strategies most likely to minimise the spread of insecticide resistance. PMID:28095406

Confusion, knock-down and kill of Aedes aegypti using metofluthrin in domestic settings: a powerful tool to prevent dengue transmission?

PubMed Central

2013-01-01

Background Dengue control methods are reliant upon control of the vector, primarily Aedes aegypti. Current adulticiding methods in North Queensland include treating premises with residual synthetic pyrethroid insecticides (interior residual spraying; IRS), a laborious, intrusive task. The vapor active synthetic pyrethroid metofluthrin might offer an efficient alternative as some studies indicate that it prevents biting and has strong knockdown effects. However, its expellant and/or irritant effects, longevity, residual activity and the speed with which biting behavior is disrupted have not yet been characterized. Methods We exposed cohorts of Cairns colony (F2-4) Ae. aegypti to rooms (17–24 m3) treated with 5% and 10% AI metofluthrin emanators. Using free-flying and caged populations we measured biting (human landing rate), expulsion through unscreened windows, knockdown and death over periods ranging between a few minutes and 24 hrs. Observations of the behavior of single female Ae. aegypti exposed to metofluthrin were also made. Results Female Ae. aegypti exposed to 5% or 10% metofluthrin formulations were almost entirely inhibited from biting. This was the result of rapid knockdown and mortality (80-90% in less than one hour) and to the behavioral impacts of exposure that, within minutes, caused female Ae. aegypti to become disoriented, stop landing on hosts, and seek resting sites. Exposed mosquitoes did not exhibit any increased propensity to exit treated rooms and the 10% AI resin remained fully active for at least 20 days. Conclusion The new, high-dose, resin formulations of metofluthrin act quickly to prevent biting and to knockdown and kill free-flying female Ae. aegypti in our experimental rooms. There was no evidence that metofluthrin induced escape from treated areas. Resin-based metofluthrin emanators show great potential as a replacement for labor intensive IRS for dengue vector control. PMID:24025232

A high-risk Zika and dengue transmission hub: virus detections in mosquitoes at a Brazilian university campus.

PubMed

Eiras, Alvaro E; Pires, Simone F; Staunton, Kyran M; Paixão, Kelly S; Resende, Marcelo C; Silva, Hilcielly A; Rocha, Isadora G; Oliveira, Bruna A; Peres, Anderson M; Drumond, Betânia P; Ritchie, Scott A

2018-06-22

Zika virus (ZIKV) and dengue virus (DENV) are mosquito-borne flaviviruses prevalent throughout tropical regions. Currently, management of ZIKV and DENV centers on control of the primary vector Aedes aegypti. This vector is highly anthropophilic and is therefore prevalent throughout densely urbanised landscapes. A new passive trap for gravid Ae. aegypti (Gravid Aedes Trap - GAT) was developed for mosquito surveillance. Here the different killing agents and the level of transmission of arboviruses that may occur in mosquitoes sampled by GATs are assessed for the first time. Gravid Aedes traps (GATs) were deployed at the Federal University of Minas Gerais campus, in Belo Horizonte, Brazil to sample Ae. aegypti. Three different killing agents were evaluated within the GATs: sticky cards, long-lasting insecticide-impregnated nets (LLINs) and canola oil. Traps were monitored weekly for 14 weeks then mosquito specimens were identified to the species level and Ae. aegypti catches were pooled and submitted to qRT-PCR assays for to DENV and ZIKV virus detection, followed by Bayesian phylogenetic analysis of the ZIKV. Additionally, comparisons of means were performed on transformed weekly catch data (P = 0.05, t-tests) with the stats package of the R statistical software. In total, 1506 female Ae. aegypti were captured using GATs, with traps using sticky cards catching more mosquito than those using either LLINs or canola oil. Both ZIKV and DENV were detected in Ae. aegypti females captured over several weeks suggesting that this highly populated university campus may have served as a significant transmission hub. The infection rate for ZIKV was present in seven (8.5%) pools from four weeks while DENV was detected in four (4.9%) pools from four weeks. Phylogenetic analysis of ZIKV classified the strain as Asian genotype. The Federal University of Minas Gerais and similar organizations must strongly consider monitoring Ae. aegypti populations and reinforcing personal protection of staff and students during seasons of high mosquito activity.

Most outdoor malaria transmission by behaviourally-resistant Anopheles arabiensis is mediated by mosquitoes that have previously been inside houses.

PubMed

Killeen, Gerry F; Govella, Nicodem J; Lwetoijera, Dickson W; Okumu, Fredros O

2016-04-19

Anopheles arabiensis is stereotypical of diverse vectors that mediate residual malaria transmission globally, because it can feed outdoors upon humans or cattle, or enter but then rapidly exit houses without fatal exposure to insecticidal nets or sprays. Life histories of a well-characterized An. arabiensis population were simulated with a simple but process-explicit deterministic model and relevance to other vectors examined through sensitivity analysis. Where most humans use bed nets, two thirds of An. arabiensis blood feeds and half of malaria transmission events were estimated to occur outdoors. However, it was also estimated that most successful feeds and almost all (>98 %) transmission events are preceded by unsuccessful attempts to attack humans indoors. The estimated proportion of vector blood meals ultimately obtained from humans indoors is dramatically attenuated by availability of alternative hosts, or partial ability to attack humans outdoors. However, the estimated proportion of mosquitoes old enough to transmit malaria, and which have previously entered a house at least once, is far less sensitive to both variables. For vectors with similarly modest preference for cattle over humans and similar ability to evade fatal indoor insecticide exposure once indoors, >80 % of predicted feeding events by mosquitoes old enough to transmit malaria are preceded by at least one house entry event, so long as ≥40 % of attempts to attack humans occur indoors and humans outnumber cattle ≥4-fold. While the exact numerical results predicted by such a simple deterministic model should be considered only approximate and illustrative, the derived conclusions are remarkably insensitive to substantive deviations from the input parameter values measured for this particular An. arabiensis population. This life-history analysis, therefore, identifies a clear, broadly-important opportunity for more effective suppression of residual malaria transmission by An. arabiensis in Africa and other important vectors of residual transmission across the tropics. Improved control of predominantly outdoor residual transmission by An. arabiensis, and other modestly zoophagic vectors like Anopheles darlingi, which frequently enter but then rapidly exit from houses, may be readily achieved by improving existing technology for killing mosquitoes indoors.

Interactions in higher-spin gravity: a holographic perspective

NASA Astrophysics Data System (ADS)

Sleight, Charlotte

2017-09-01

This review is an elaboration of recent results on the holographic re-construction of metric-like interactions in higher-spin gauge theories on anti-de Sitter space (AdS), employing their conjectured duality with free conformal field theories (CFTs). After reviewing the general approach and establishing the necessary intermediate results, we extract explicit expressions for the complete cubic action on AdSd+1 and the quartic self-interaction of the scalar on AdS4 for the type A minimal bosonic higher-spin theory from the three- and four- point correlation functions of single-trace operators in the free scalar O(N) vector model. For this purpose tools were developed to evaluate tree-level three-point Witten diagrams involving totally symmetric fields of arbitrary integer spin and mass, and the conformal partial wave expansions of their tree-level four-point Witten diagrams. We also discuss the implications of the holographic duality on the locality properties of interactions in higher-spin gauge theories.

Improved Killing of Ovarian Cancer Stem Cells by Combining a Novel Chimeric Antigen Receptor-Based Immunotherapy and Chemotherapy.

PubMed

Klapdor, Rüdiger; Wang, Shuo; Hacker, Ulrich; Büning, Hildegard; Morgan, Michael; Dörk, Thilo; Hillemanns, Peter; Schambach, Axel

2017-10-01

Ovarian cancer represents the most lethal gynecological cancer. Although cytoreductive chemotherapy and surgery lead to complete macroscopic tumor removal, most of the patients in advanced stages suffer from recurrent disease and subsequently die. This may be explained by the activity of cancer stem cells (CSC), which are a subpopulation of cells with an elevated chemoresistance and an increased capacity for self-renewal and metastatic spread. Specifically targeting these cells by adoptive immunotherapy represents a promising strategy to reduce the risk for recurrent disease. This study selected the widely accepted CSC marker CD133 as a target for a chimeric antigen receptor (CAR)-based immunotherapeutic approach to treat ovarian cancer. A lentiviral vector was generated encoding a third-generation anti-CD133-CAR, and clinically used NK92 cells were transduced. These engineered natural killer (NK) cells showed specific killing against CD133-positive ovarian cancer cell lines and primary ovarian cancer cells cultured from sequential ascites harvests. Additionally, specific activation of these engineered NK cells was demonstrated via interferon-gamma secretion assays. To improve clinical efficacy of ovarian cancer treatment, the effect of the chemotherapeutic agent cisplatin was evaluated together with CAR-transduced NK cell treatment. It was demonstrated that NK cells remain cytotoxic and active under cisplatin treatment and, importantly, that sequential treatment with cisplatin followed by CAR-NK cells led to the strongest killing effect. The specific eradication of ovarian CSCs by anti-CD133-CAR expressing NK92 cells represents a promising strategy and, when confirmed in vivo, shall be the basis of future clinical studies with the aim to prevent recurrent disease.

Natural variation in virulence of the entomopathogenic fungus Beauveria bassiana against malaria mosquitoes.

PubMed

Valero-Jiménez, Claudio A; Debets, Alfons J M; van Kan, Jan A L; Schoustra, Sijmen E; Takken, Willem; Zwaan, Bas J; Koenraadt, Constantianus J M

2014-12-06

Insecticide resistance is greatly hampering current efforts to control malaria and therefore alternative methods are needed. Entomopathogenic fungi have been proposed as an alternative with a special focus on the cosmopolitan species Beauveria bassiana. However, few studies have analysed the effects of natural variation within fungal isolates on mosquito survival, and the implications and possible exploitation for malaria control. Laboratory bioassays were performed on adult female mosquitoes (Anopheles coluzzii) with spores from 29 isolates of B. bassiana, originating from different parts of the world. In addition, phenotypic characteristics of the fungal isolates such as sporulation, spore size and growth rate were studied to explore their relationship with virulence. All tested isolates of B. bassiana killed An. coluzzii mosquitoes, and the rate at which this happened differed significantly among the isolates. The risk of mosquitoes dying was around ten times higher when they were exposed to the most virulent as compared to the least virulent isolate. There was significant variation among isolates in spore size, growth rate and sporulation, but none of these morphological characteristics were correlated, and thus predictive, for the ability of the fungal isolate to kill malaria mosquitoes. This study shows that there is a wide natural variation in virulence of isolates of B. bassiana, and that selecting an appropriate fungal isolate is highly relevant in killing and thus controlling malaria mosquitoes, particularly if used as part of an integrated vector management strategy. Also, the wide variation observed in virulence offers the opportunity to better understand the molecular and genetic mechanisms that drive this variation and thus to address the potential development of resistance against entomopathogenic fungi.

Protein receptor-independent plasma membrane remodeling by HAMLET: A tumoricidal protein-lipid complex

DOE PAGES

Nadeem, Aftab; Sanborn, Jeremy; Gettel, Douglas L.; ...

2015-11-12

A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ‘’protein-centric” view is increasingly challenged by evidence for the involvement of specialized membrane domains in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. Wemore » identify a ‘’receptor independent” transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET accumulates within these de novo membrane conformations and define membrane blebs as cellular compartments for direct interactions of HAMLET with essential target proteins such as the Ras family of GTPases. In conclusion, we demonstrate lower sensitivity of healthy cell membranes to HAMLET challenge. These features suggest that HAMLET-induced curvature-dependent membrane conformations serve as surrogate receptors for initiating signal transduction cascades, ultimately leading to cell death.« less

AAV-mediated RLBP1 gene therapy improves the rate of dark adaptation in Rlbp1 knockout mice

PubMed Central

Choi, Vivian W; Bigelow, Chad E; McGee, Terri L; Gujar, Akshata N; Li, Hui; Hanks, Shawn M; Vrouvlianis, Joanna; Maker, Michael; Leehy, Barrett; Zhang, Yiqin; Aranda, Jorge; Bounoutas, George; Demirs, John T; Yang, Junzheng; Ornberg, Richard; Wang, Yu; Martin, Wendy; Stout, Kelly R; Argentieri, Gregory; Grosenstein, Paul; Diaz, Danielle; Turner, Oliver; Jaffee, Bruce D; Police, Seshidhar R; Dryja, Thaddeus P

2015-01-01

Recessive mutations in RLBP1 cause a form of retinitis pigmentosa in which the retina, before its degeneration leads to blindness, abnormally slowly recovers sensitivity after exposure to light. To develop a potential gene therapy for this condition, we tested multiple recombinant adeno-associated vectors (rAAVs) composed of different promoters, capsid serotypes, and genome conformations. We generated rAAVs in which sequences from the promoters of the human RLBP1, RPE65, or BEST1 genes drove the expression of a reporter gene (green fluorescent protein). A promoter derived from the RLBP1 gene mediated expression in the retinal pigment epithelium and Müller cells (the intended target cell types) at qualitatively higher levels than in other retinal cell types in wild-type mice and monkeys. With this promoter upstream of the coding sequence of the human RLBP1 gene, we compared the potencies of vectors with an AAV2 versus an AAV8 capsid in transducing mouse retinas, and we compared vectors with a self-complementary versus a single-stranded genome. The optimal vector (scAAV8-pRLBP1-hRLBP1) had serotype 8 capsid and a self-complementary genome. Subretinal injection of scAAV8-pRLBP1-hRLBP1 in Rlbp1 nullizygous mice improved the rate of dark adaptation based on scotopic (rod-plus-cone) and photopic (cone) electroretinograms (ERGs). The effect was still present after 1 year. PMID:26199951

Integrated description of protein dynamics from room-temperature X-ray crystallography and NMR

PubMed Central

Fenwick, R. Bryn; van den Bedem, Henry; Fraser, James S.; Wright, Peter E.

2014-01-01

Detailed descriptions of atomic coordinates and motions are required for an understanding of protein dynamics and their relation to molecular recognition, catalytic function, and allostery. Historically, NMR relaxation measurements have played a dominant role in the determination of the amplitudes and timescales (picosecond–nanosecond) of bond vector fluctuations, whereas high-resolution X-ray diffraction experiments can reveal the presence of and provide atomic coordinates for multiple, weakly populated substates in the protein conformational ensemble. Here we report a hybrid NMR and X-ray crystallography analysis that provides a more complete dynamic picture and a more quantitative description of the timescale and amplitude of fluctuations in atomic coordinates than is obtainable from the individual methods alone. Order parameters (S2) were calculated from single-conformer and multiconformer models fitted to room temperature and cryogenic X-ray diffraction data for dihydrofolate reductase. Backbone and side-chain order parameters derived from NMR relaxation experiments are in excellent agreement with those calculated from the room-temperature single-conformer and multiconformer models, showing that the picosecond timescale motions observed in solution occur also in the crystalline state. These motions are quenched in the crystal at cryogenic temperatures. The combination of NMR and X-ray crystallography in iterative refinement promises to provide an atomic resolution description of the alternate conformational substates that are sampled through picosecond to nanosecond timescale fluctuations of the protein structure. The method also provides insights into the structural heterogeneity of nonmethyl side chains, aromatic residues, and ligands, which are less commonly analyzed by NMR relaxation measurements. PMID:24474795

Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells

PubMed Central

Kasashima, Katsumi; Sezutsu, Hideki; Matsuoka, Hiroyuki

2016-01-01

Malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. The salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. Moreover, salivary gland cells express a large number of molecules that facilitate blood feeding and parasite transmission to hosts. In the present study, we adapted a functional deficiency system in specific tissues by inducing cell death using the mouse Bcl-2-associated X protein (Bax) to the Asian malaria vector mosquito, Anopheles stephensi. We applied this technique to salivary gland cells, and produced a transgenic strain containing extremely low amounts of saliva. Although probing times for feeding on mice were longer in transgenic mosquitoes than in wild-type mosquitoes, transgenic mosquitoes still successfully ingested blood. Transgenic mosquitoes also exhibited a significant reduction in oocyst formation in the midgut in a rodent malaria model. These results indicate that mosquito saliva plays an important role in malaria infection in the midgut of anopheline mosquitoes. The dysfunction in the salivary glands enabled the inhibition of malaria transmission from hosts to mosquito midguts. Therefore, salivary components have potential in the development of new drugs or genetically engineered mosquitoes for malaria control. PMID:27598328

Conformational Entropy from NMR Relaxation in Proteins: The SRLS Perspective.

PubMed

Tchaicheeyan, Oren; Meirovitch, Eva

2017-02-02

Conformational entropy changes associated with bond-vector motions in proteins contribute to the free energy of ligand-binding. To derive such contributions, we apply the slowly relaxing local structure (SRLS) approach to NMR relaxation from 15 N-H bonds or C-CDH 2 moieties of several proteins in free and ligand-bound form. The spatial restraints on probe motion, which determine the extent of local order, are expressed in SRLS by a well-defined potential, u(θ). The latter yields the orientational probability density, P eq  = exp(-u(θ)), and hence the related conformational entropy, Ŝ = -∫P eq (θ) ln[P eq (θ)] sin θ dθ (Ŝ is "entropy" in units of k B T, and θ represents the bond-vector orientation in the protein). SRLS is applied to 4-oxalocrotonate tautomerase (4-OT), the acyl-coenzyme A binding protein (ACBP), the C-terminal SH2 domain of phospholipase C γ 1 (PLC γ 1C SH2), the construct dihydrofolate reductase-E:folate (DHFR-E:folate), and their complexes with appropriate ligands, to determine ΔŜ. Eglin C and its V18A and V34A mutants are also studied. Finally, SRLS is applied to the structurally homologous proteins TNfn3 and FNfn10 to characterize within its scope the unusual "dynamics" of the TNfn3 core. Upon ligand-binding, the backbones of 4-OT, ACBP, and PLC γ 1C SH2 show limited, increased, and decreased order, respectively; the cores of DHFR-E:folate and PLC γ 1C SH2 become more ordered. The V18A (V34A) mutation increases (decreases) the order within the eglin C core. The core of TNfn3 is less ordered structurally and more mobile kinetically. Secondary structure versus loops, surface-binding versus core insertion, and ligand size emerged as being important in rationalizing ΔŜ. The consistent and general tool developed herein is expected to provide further insights in future work.

Separation of variables in Maxwell equations in Plebański-Demiański spacetime

NASA Astrophysics Data System (ADS)

Frolov, Valeri P.; Krtouš, Pavel; KubizÅák, David

2018-05-01

A new method for separating variables in the Maxwell equations in four- and higher-dimensional Kerr-(A)dS spacetimes proposed recently by Lunin is generalized to any off-shell metric that admits a principal Killing-Yano tensor. The key observation is that Lunin's ansatz for the vector potential can be formulated in a covariant form—in terms of the principal tensor. In particular, focusing on the four-dimensional case we demonstrate separability of Maxwell's equations in the Kerr-NUT-(A)dS and the Plebański-Demiański family of spacetimes. The new method of separation of variables is quite different from the standard approach based on the Newman-Penrose formalism.

Dynamical boson stars.

PubMed

Liebling, Steven L; Palenzuela, Carlos

2017-01-01

The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s, John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called geons , but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name boson stars . Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single Killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.

Catenotaenia dendritica (Cestoda: Catenotaeniidae) and Three Ectoparasite Species in the Red Squirrel, Sciurus vulgaris, from Cheongju, Korea

PubMed Central

Choe, Seongjun; Lee, Dongmin; Park, Hansol; Jeon, Hyeong-Kyu; Lee, Youngsun; Na, Ki-Jeong; Lee, In-Yong; Eom, Keeseon S.

2016-01-01

Parasites are recorded from the red squirrel, Sciurus vulgaris, from Cheongju, the Republic of Korea. A total of 5 road-killed squirrels were thoroughly examined for internal and external parasites from November 2011 to May 2014. Total 4 parasite species, including 1 tapeworm and 3 ectoparasite species were recovered. They were morphologically identified as Catenotaenia dendritica (Cestoda: Catenotaeniidae), Hirstionyssus sciurinus, Leptotrombidium pallidum, and Ceratophyllus (Monopsyllus) indages. Among them, C. dendritica and H. sciurinus are recorded for the first time in the Korean parasite fauna. In addition, the possibility that the red squirrel could act as a reservoir host for a zoonotic disease like tsutsugamushi disease with L. pallidum as its vector has been raised. PMID:27658604

Rhodococcus equi (Prescottella equi) vaccines; the future of vaccine development.

PubMed

Giles, C; Vanniasinkam, T; Ndi, S; Barton, M D

2015-09-01

For decades researchers have been targeting prevention of Rhodococcus equi (Rhodococcus hoagui/Prescottella equi) by vaccination and the horse breeding industry has supported the ongoing efforts by researchers to develop a safe and cost effective vaccine to prevent disease in foals. Traditional vaccines including live, killed and attenuated (physical and chemical) vaccines have proved to be ineffective and more modern molecular-based vaccines including the DNA plasmid, genetically attenuated and subunit vaccines have provided inadequate protection of foals. Newer, bacterial vector vaccines have recently shown promise for R. equi in the mouse model. This article describes the findings of key research in R. equi vaccine development and looks at alternative methods that may potentially be utilised. © 2014 EVJ Ltd.

Catenotaenia dendritica (Cestoda: Catenotaeniidae) and Three Ectoparasite Species in the Red Squirrel, Sciurus vulgaris, from Cheongju, Korea.

PubMed

Choe, Seongjun; Lee, Dongmin; Park, Hansol; Jeon, Hyeong-Kyu; Lee, Youngsun; Na, Ki-Jeong; Lee, In-Yong; Eom, Keeseon S

2016-08-01

Parasites are recorded from the red squirrel, Sciurus vulgaris, from Cheongju, the Republic of Korea. A total of 5 road-killed squirrels were thoroughly examined for internal and external parasites from November 2011 to May 2014. Total 4 parasite species, including 1 tapeworm and 3 ectoparasite species were recovered. They were morphologically identified as Catenotaenia dendritica (Cestoda: Catenotaeniidae), Hirstionyssus sciurinus, Leptotrombidium pallidum, and Ceratophyllus (Monopsyllus) indages. Among them, C. dendritica and H. sciurinus are recorded for the first time in the Korean parasite fauna. In addition, the possibility that the red squirrel could act as a reservoir host for a zoonotic disease like tsutsugamushi disease with L. pallidum as its vector has been raised.

Microbial pathogens in raw pork, chicken, and beef: benefit estimates for control using irradiation

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

Roberts, T.

1985-12-01

Various control procedures have been suggested for reducing foodborne infectious diseases. Receiving considerable attention is irradiation. This report estimates the medical and wage (or productivity) benefits associated with prevention of five human diseases transmitted by beef, pork, and chicken. (These diseases can also be transmitted by other vectors, such as eggs, milk, and pets. But these sources are not included in the analysis.) All of these foodborne infectious diseases - salmonellosis, campylobacteriosis, trichinosis, tapeworm, and toxoplasmosis - could be significantly reduced by irradiating meat and poultry. The Food and Drug Administration (FDA) has just approved irradiation of pork to preventmore » trichinosis (50FR 29658-59) and is considering approval of irradiation of chicken to kill Salmonella. 22 references.« less

Bacteriophages encode factors required for protection in a symbiotic mutualism.

PubMed

Oliver, Kerry M; Degnan, Patrick H; Hunter, Martha S; Moran, Nancy A

2009-08-21

Bacteriophages are known to carry key virulence factors for pathogenic bacteria, but their roles in symbiotic bacteria are less well understood. The heritable symbiont Hamiltonella defensa protects the aphid Acyrthosiphon pisum from attack by the parasitoid Aphidius ervi by killing developing wasp larvae. In a controlled genetic background, we show that a toxin-encoding bacteriophage is required to produce the protective phenotype. Phage loss occurs repeatedly in laboratory-held H. defensa-infected aphid clonal lines, resulting in increased susceptibility to parasitism in each instance. Our results show that these mobile genetic elements can endow a bacterial symbiont with benefits that extend to the animal host. Thus, phages vector ecologically important traits, such as defense against parasitoids, within and among symbiont and animal host lineages.

Consistent Pauli reduction on group manifolds

DOE PAGES

Baguet, A.; Pope, Christopher N.; Samtleben, H.

2016-01-01

We prove an old conjecture by Duff, Nilsson, Pope and Warner asserting that the NSNS sector of supergravity (and more general the bosonic string) allows for a consistent Pauli reduction on any d-dimensional group manifold G, keeping the full set of gauge bosons of the G×G isometry group of the bi-invariant metric on G. The main tool of the construction is a particular generalised Scherk–Schwarz reduction ansatz in double field theory which we explicitly construct in terms of the group's Killing vectors. Examples include the consistent reduction from ten dimensions on S3×S3 and on similar product spaces. The construction ismore » another example of globally geometric non-toroidal compactifications inducing non-geometric fluxes.« less

New frontiers in oncolytic viruses: optimizing and selecting for virus strains with improved efficacy

PubMed Central

2018-01-01

Oncolytic viruses have demonstrated selective replication and killing of tumor cells. Different types of oncolytic viruses – adenoviruses, alphaviruses, herpes simplex viruses, Newcastle disease viruses, rhabdoviruses, Coxsackie viruses, and vaccinia viruses – have been applied as either naturally occurring or engineered vectors. Numerous studies in animal-tumor models have demonstrated substantial tumor regression and prolonged survival rates. Moreover, clinical trials have confirmed good safety profiles and therapeutic efficacy for oncolytic viruses. Most encouragingly, the first cancer gene-therapy drug – Gendicine, based on oncolytic adenovirus type 5 – was approved in China. Likewise, a second-generation oncolytic herpes simplex virus-based drug for the treatment of melanoma has been registered in the US and Europe as talimogene laherparepvec. PMID:29445265

Prevention of communicable diseases after disaster: A review

PubMed Central

Jafari, Najmeh; Shahsanai, Armindokht; Memarzadeh, Mehrdad; Loghmani, Amir

2011-01-01

Natural disasters are tragic incidents originating from atmospheric, geologic and hydrologic changes. In recent decades, millions of people have been killed by natural disasters, resulting in economic damages. Natural and complex disasters dramatically increase the mortality and morbidity due to communicable diseases. The major causes of communicable disease in disasters are categorized into four sections: Infections due to contaminated food and water, respiratory infections, vector and insect-borne diseases, and infections due to wounds and injuries. With appropriate intervention, high morbidity and mortality resulting from communicable diseases can be avoided to a great deal. This review article tries to provide the best recommendations for planning and preparing to prevent communicable disease after disaster in two phases: before disaster and after disaster. PMID:22279466

Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas.

PubMed

Sangiolo, Dario; Mesiano, Giulia; Gammaitoni, Loretta; Leuci, Valeria; Todorovic, Maja; Giraudo, Lidia; Cammarata, Cristina; Dell'Aglio, Carmine; D'Ambrosio, Lorenzo; Pisacane, Alberto; Sarotto, Ivana; Miano, Sara; Ferrero, Ivana; Carnevale-Schianca, Fabrizio; Pignochino, Ymera; Sassi, Francesco; Bertotti, Andrea; Piacibello, Wanda; Fagioli, Franca; Aglietta, Massimo; Grignani, Giovanni

2014-01-01

Unresectable metastatic bone sarcoma and soft-tissue sarcomas (STS) are incurable due to the inability to eradicate chemoresistant cancer stem-like cells (sCSC) that are likely responsible for relapses and drug resistance. In this study, we investigated the preclinical activity of patient-derived cytokine-induced killer (CIK) cells against autologous bone sarcoma and STS, including against putative sCSCs. Tumor killing was evaluated both in vitro and within an immunodeficient mouse model of autologous sarcoma. To identify putative sCSCs, autologous bone sarcoma and STS cells were engineered with a CSC detector vector encoding eGFP under the control of the human promoter for OCT4, a stem cell gene activated in putative sCSCs. Using CIK cells expanded from 21 patients, we found that CIK cells efficiently killed allogeneic and autologous sarcoma cells in vitro. Intravenous infusion of CIK cells delayed autologous tumor growth in immunodeficient mice. Further in vivo analyses established that CIK cells could infiltrate tumors and that tumor growth inhibition occurred without an enrichment of sCSCs relative to control-treated animals. These results provide preclinical proof-of-concept for an effective strategy to attack autologous sarcomas, including putative sCSCs, supporting the clinical development of CIK cells as a novel class of immunotherapy for use in settings of untreatable metastatic disease.

Entomopathogenic fungi for mosquito control: A review

PubMed Central

Scholte, Ernst-Jan; Knols, Bart G.J.; Samson, Robert A.; Takken, Willem

2004-01-01

Fungal diseases in insects are common and widespread and can decimate their populations in spectacular epizootics. Virtually all insect orders are susceptible to fungal diseases, including Dipterans. Fungal pathogens such as Lagenidium, Coelomomyces and Culicinomyces are known to affect mosquito populations, and have been studied extensively. There are, however, many other fungi that infect and kill mosquitoes at the larval and/or adult stage. The discovery, in 1977, of the selective mosquito-pathogenic bacterium Bacillus thuringiensis Berliner israelensis (Bti) curtailed widespread interest in the search for other suitable biological control agents. In recent years interest in mosquito-killing fungi is reviving, mainly due to continuous and increasing levels of insecticide resistance and increasing global risk of mosquito-borne diseases. This review presents an update of published data on mosquito-pathogenic fungi and mosquito-pathogen interactions, covering 13 different fungal genera. Notwithstanding the potential of many fungi as mosquito control agents, only a handful have been commercialized and are marketed for use in abatement programs. We argue that entomopathogenic fungi, both new and existing ones with renewed/improved efficacies may contribute to an expansion of the limited arsenal of effective mosquito control tools, and that they may contribute in a significant and sustainable manner to the control of vector-borne diseases such as malaria, dengue and filariasis. PMID:15861235

Correction of both spontaneous and DEB-induced chromosome instability in Fanconi anemia FA-C cells by FACC cDNA

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

Stavropoulos, D.J.; Tomkins, D.J.; Allingham-Hawkins, D.J.

1994-09-01

Cells from all four Fanconi anemia complementation groups show hypersensitivity to cell-killing by mitomycin C (MMC), diepoxybutane (DEB) and other DNA cross-linking agents, and increased spontaneous and DEB-induced chromosome aberrations (CA). The extent of these phenotypes varies between lymphoblastoid cell lines from different complementation groups. Our data showed that the difference in MMC hypersensitivity and DEB-CA was not always coupled. While 230N (FA-B) had higher DEB-induced CA/cell than 536N (FA-C) (7.42 vs. 4.46 respectively), that latter was much more sensitive to cell-killing by MMC (dose at 10% survival, D{sub 10}: 5.2 vs. 1.2 ng/ml respectively). Strathdes et al. (1992) clonedmore » a cDNA Fanconi anemia complementation group C (FACC) which complemented the hypersensitivity to MMC and DEB cell-killing of FA-C cells (536N) but not cells from the other three complementation groups. The present study was initiated to determine whether chromosome instability in 536N is also complemented by the FACC (FAC3) cDNA. The pREP4-FAC3 vector was transfected into 536N and transfectants selected with hygromycin B. The DEB D{sub 10} of 536N (1.0 {mu}M) was corrected to the control level (16.2 {mu}M for 3TO) by FACC (15.1 {mu}M for 536N-FACC), as previously demonstrated. Chromosome instability (cab, cse, ctb, cte) was determined without and with 0.1 {mu}g/ml DEB treatment. Spontaneous CA of 536N (0.30 aberrations/cell) was corrected to the control level (0.04 for 3TO) by FACC (0.06 for 536N-FACC). Similarly, the DEB-induced CA was corrected (2.74 for 536N vs. 0.06 and 0.02 for 3TO and 536N-FACC respectively). Thus, at least for FA complementation group C, hypersensitivity to cell-killing and chromosome instability are not dissociated and are most likely caused by the same gene defect.« less

Higher spin gravitational couplings: Ghosts in the Yang-Mills detour complex

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

Gover, A. R.; Hallowell, K.; Waldron, A.

2007-01-15

Gravitational interactions of higher spin fields are generically plagued by inconsistencies. There exists however, a simple framework that couples higher spins to a broad class of gravitational backgrounds (including Ricci flat and Einstein) consistently at the classical level. The model is the simplest example of a Yang-Mills detour complex and has broad mathematical applications, especially to conformal geometry. Even the simplest version of the theory, which couples gravitons, vectors and scalar fields in a flat background is rather rich, providing an explicit setting for detailed analysis of ghost excitations. Its asymptotic scattering states consist of a physical massless graviton, scalar,more » and massive vector along with a degenerate pair of zero norm photon excitations. Coherent states of the unstable sector do have positive norms, but their evolution is no longer unitary and amplitudes grow with time. The class of models proposed is extremely general and of considerable interest for ghost condensation and invariant theory.« less

SU(3) sextet model with Wilson fermions

NASA Astrophysics Data System (ADS)

Hansen, Martin; Pica, Claudio

2018-03-01

We present our final results for the SU(3) sextet model with the non-improved Wilson fermion discretization. We find evidence for several phases of the lattice model, including a bulk phase with broken chiral symmetry. We study the transition between the bulk and weak coupling phase which corresponds to a significant change in the qualitative behavior of spectral and scale setting observables. In particular the t0 and w0 observables seem to diverge in the chiral limit in the weak coupling phase. We then focus on the study of spectral observables in the chiral limit in the weak coupling phase at infinite volume. We consider the masses and decay constants for the pseudoscalar and vector mesons, the mass of the axial vector meson and the spin-1/2 baryon as a function of the quark mass, while controlling finite volume effects. We then test our data against both the IR conformal and the chirally broken hypotheses. Preprint: CP3-Origins-2017-49 DNRF90

Nearly extremal apparent horizons in simulations of merging black holes

NASA Astrophysics Data System (ADS)

Lovelace, Geoffrey; Scheel, Mark; Owen, Robert; Giesler, Matthew; Katebi, Reza; Szilagyi, Bela; Chu, Tony; Demos, Nicholas; Hemberger, Daniel; Kidder, Lawrence; Pfeiffer, Harald; Afshari, Nousha; SXS Collaboration

2015-04-01

The spin S of a Kerr black hole is bounded by the surface area A of its apparent horizon: 8 πS <= A . We present recent results (arXiv:1411.7297) for the extremality of apparent horizons for merging, rapidly rotating black holes with equal masses and equal spins aligned with the orbital angular momentum. Measuring the area and (using approximate Killing vectors) the spin on the individual and common apparent horizons, we find that the inequality 8 πS < A is satisfied but is very close to equality on the common apparent horizon at the instant it first appears--even for initial spins as large as S /M2 = 0 . 994 . We compute the smallest value e0 that Booth and Fairhurst's extremality parameter can take for any scaling of the horizon's null normal vectors, concluding that the common horizons are at least moderately close to extremal just after they appear. We construct binary-black-hole initial data with marginally trapped surfaces with 8 πS > A and e0 > 1 , but these surfaces are always surrounded by apparent horizons with 8 πS < A and e0 < 1 .

Transfer of a gene encoding the anticandidal protein histatin 3 to salivary glands.

PubMed

O'Connell, B C; Xu, T; Walsh, T J; Sein, T; Mastrangeli, A; Crystal, R G; Oppenheim, F G; Baum, B J

1996-12-01

Mucosal candidiasis, the most common opportunistic fungal infection in human immunodeficiency virus (HIV)-infected patients, is an early sign of clinically overt acquired immunodeficiency syndrome (AIDS) and an important cause of morbidity, particularly in HIV-infected children. The appearance of azole-resistant strains of Candida albicans had made clinical management of candidiasis increasingly difficult. We propose a novel approach to the management of candidal infections that involves the use of naturally occurring antifungal proteins, such as the histatins. Histatins are a family of small proteins that are secreted in human saliva. We have constructed recombinant adenovirus vectors that contain the histatin 3 cDNA. These vectors are capable of directing the expression of histatin 3 in the saliva of rats at up to 1,045 micrograms/ml, well above the levels found in normal human saliva. The adenovirus-directed histatin demonstrated a 90% candidacidal effect in the timed-kill assay against both fluconazole-susceptible and fluconazole-resistant strains of C. albicans and inhibited germination by 45% in the same strains. These studies suggest that a gene transfer approach to overexpress naturally occurring antifungal proteins may be useful in the management of mucosal candidiasis.

Developing live vaccines against Yersinia pestis

PubMed Central

Sun, Wei; Roland, Kenneth L.; Curtiss, Roy

2014-01-01

Three great plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people and it has been linked to biowarfare in the past. Plague is endemic in many parts of the world. In addition, the risk of plague as a bioweapon has prompted increased research to develop plague vaccines against this disease. Injectable subunit vaccines are being developed in the United States and United Kingdom. However, the live attenuated Y. pestis-EV NIIEG strain has been used as a vaccine for more than 70 years in the former Soviet Union and in some parts of Asia and provides a high degree of efficacy against plague. This vaccine has not gained general acceptance because of safety concerns. In recent years, modern molecular biological techniques have been applied to Y. pestis to construct strains with specific defined mutations designed to create safe, immunogenic vaccines with potential for use in humans and as bait vaccines to reduce the load of Y. pestis in the environment. In addition, a number of live, vectored vaccines have been reported using attenuated viral vectors or attenuated Salmonella strains to deliver plague antigens. Here we summarize the progress of live attenuated vaccines against plague. PMID:21918302

Flatspace chiral supergravity

NASA Astrophysics Data System (ADS)

Bagchi, Arjun; Basu, Rudranil; Detournary, Stéphane; Parekh, Pulastya

2018-05-01

We propose a holographic duality between a 2 dimensional (2d) chiral superconformal field theory and a certain theory of supergravity in 3d with flatspace boundary conditions that is obtained as a double scaling limit of a parity breaking theory of supergravity. We show how the asymptotic symmetries of the bulk theory reduce from the "despotic" super Bondi-Metzner-Sachs algebra (or equivalently the inhomogeneous super Galilean conformal algebra) to a single copy of the super-Virasoro algebra in this limit and also reproduce the same reduction from a study of null vectors in the putative 2d dual field theory.

The Masked Sample Covariance Estimator: An Analysis via the Matrix Laplace Transform

DTIC Science & Technology

2012-02-01

Variables: Suppose that we divide the stock market into disjoint sectors, and we would like to study the interactions among the monthly returns for...vector to conform with the market sectors, and we estimate only the entries in the diagonal blocks. Spatial or Temporal Localization: A simple random model...eαW1A c ] ≤ 4p e−B/2κ 2 = 1 n . Introduce this expression into (4.11) to conclude that E[exp(2θεM xx∗)1A c ] 4 1 n · I. (4.17) 20 RICHARD Y. CHEN

HAMLET kills tumor cells by an apoptosis-like mechanism--cellular, molecular, and therapeutic aspects.

PubMed

Svanborg, Catharina; Agerstam, Helena; Aronson, Annika; Bjerkvig, Rolf; Düringer, Caroline; Fischer, Walter; Gustafsson, Lotta; Hallgren, Oskar; Leijonhuvud, Irene; Linse, Sara; Mossberg, Ann-Kristin; Nilsson, Hanna; Pettersson, Jenny; Svensson, Malin

2003-01-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex that induces apoptosis-like death in tumor cells, but leaves fully differentiated cells unaffected. This review summarizes the information on the in vivo effects of HAMLET in patients and tumor models on the tumor cell biology, and on the molecular characteristics of the complex. HAMLET limits the progression of human glioblastomas in a xenograft model and removes skin papillomas in patients. This broad anti-tumor activity includes >40 different lymphomas and carcinomas and apoptosis is independent of p53 or bcl-2. In tumor cells HAMLET enters the cytoplasm, translocates to the perinuclear area, and enters the nuclei where it accumulates. HAMLET binds strongly to histones and disrupts the chromatin organization. In the cytoplasm, HAMLET targets ribosomes and activates caspases. The formation of HAMLET relies on the propensity of alpha-lactalbumin to alter its conformation when the strongly bound Ca2+ ion is released and the protein adopts the apo-conformation that exposes a new fatty acid binding site. Oleic acid (C18:1,9 cis) fits this site with high specificity, and stabilizes the altered protein conformation. The results illustrate how protein folding variants may be beneficial, and how their formation in peripheral tissues may depend on the folding change and the availability of the lipid cofactor. One example is the acid pH in the stomach of the breast-fed child that promotes the formation of HAMLET. This mechanism may contribute to the protective effect of breastfeeding against childhood tumors. We propose that HAMLET should be explored as a novel approach to tumor therapy.

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

Connell, Patrick; Frolov, Valeri P.; Kubiznak, David

We obtain and study the equations describing the parallel transport of orthonormal frames along geodesics in a spacetime admitting a nondegenerate, principal, conformal Killing-Yano tensor h. We demonstrate that the operator F, obtained by a projection of h to a subspace orthogonal to the velocity, has in a generic case eigenspaces of dimension not greater than 2. Each of these eigenspaces is independently parallel propagated. This allows one to reduce the parallel transport equations to a set of first order, ordinary, differential equations for the angles of rotation in the 2D eigenspaces. General analysis is illustrated by studying the equationsmore » of the parallel transport in the Kerr-NUT-(A)dS metrics. Examples of three-, four-, and five-dimensional Kerr-NUT-(A)dS are considered, and it is shown that the obtained first order equations can be solved by a separation of variables.« less

Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate

PubMed Central

Liang, Bo; Surman, Sonja; Amaro-Carambot, Emerito; Kabatova, Barbora; Mackow, Natalie; Lingemann, Matthias; Yang, Lijuan; McLellan, Jason S.; Graham, Barney S.; Kwong, Peter D.; Schaap-Nutt, Anne; Collins, Peter L.

2015-01-01

ABSTRACT Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. Vaccines are not available, and an RSV vaccine is particularly needed. A live attenuated chimeric recombinant bovine/human PIV3 (rB/HPIV3) vector expressing the RSV fusion (F) glycoprotein from an added gene has been under development as a bivalent vaccine against RSV and HPIV3. Previous clinical evaluation of this vaccine candidate suggested that increased genetic stability and immunogenicity of the RSV F insert were needed. This was investigated in the present study. RSV F expression was enhanced 5-fold by codon optimization and by modifying the amino acid sequence to be identical to that of an early passage of the original clinical isolate. This conferred a hypofusogenic phenotype that presumably reflects the original isolate. We then compared vectors expressing stabilized prefusion and postfusion versions of RSV F. In a hamster model, prefusion F induced increased quantity and quality of RSV-neutralizing serum antibodies and increased protection against wild-type (wt) RSV challenge. In contrast, a vector expressing the postfusion F was less immunogenic and protective. The genetic stability of the RSV F insert was high and was not affected by enhanced expression or the prefusion or postfusion conformation of RSV F. These studies provide an improved version of the previously well-tolerated rB/HPIV3-RSV F vaccine candidate that induces a superior RSV-neutralizing serum antibody response. IMPORTANCE Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are two major causes of pediatric pneumonia and bronchiolitis. The rB/HPIV3 vector expressing RSV F protein is a candidate bivalent live vaccine against HPIV3 and RSV. Previous clinical evaluation indicated the need to increase the immunogenicity and genetic stability of the RSV F insert. Here, we increased RSV F expression by codon optimization and by modifying the RSV F amino acid sequence to conform to that of an early passage of the original isolate. This resulted in a hypofusogenic phenotype, which likely represents the original phenotype before adaptation to cell culture. We also included stabilized versions of prefusion and postfusion RSV F protein. Prefusion RSV F induced a larger quantity and higher quality of RSV-neutralizing serum antibodies and was highly protective. This provides an improved candidate for further clinical evaluation. PMID:26157122

Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate.

PubMed

Liang, Bo; Surman, Sonja; Amaro-Carambot, Emerito; Kabatova, Barbora; Mackow, Natalie; Lingemann, Matthias; Yang, Lijuan; McLellan, Jason S; Graham, Barney S; Kwong, Peter D; Schaap-Nutt, Anne; Collins, Peter L; Munir, Shirin

2015-09-01

Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. Vaccines are not available, and an RSV vaccine is particularly needed. A live attenuated chimeric recombinant bovine/human PIV3 (rB/HPIV3) vector expressing the RSV fusion (F) glycoprotein from an added gene has been under development as a bivalent vaccine against RSV and HPIV3. Previous clinical evaluation of this vaccine candidate suggested that increased genetic stability and immunogenicity of the RSV F insert were needed. This was investigated in the present study. RSV F expression was enhanced 5-fold by codon optimization and by modifying the amino acid sequence to be identical to that of an early passage of the original clinical isolate. This conferred a hypofusogenic phenotype that presumably reflects the original isolate. We then compared vectors expressing stabilized prefusion and postfusion versions of RSV F. In a hamster model, prefusion F induced increased quantity and quality of RSV-neutralizing serum antibodies and increased protection against wild-type (wt) RSV challenge. In contrast, a vector expressing the postfusion F was less immunogenic and protective. The genetic stability of the RSV F insert was high and was not affected by enhanced expression or the prefusion or postfusion conformation of RSV F. These studies provide an improved version of the previously well-tolerated rB/HPIV3-RSV F vaccine candidate that induces a superior RSV-neutralizing serum antibody response. Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are two major causes of pediatric pneumonia and bronchiolitis. The rB/HPIV3 vector expressing RSV F protein is a candidate bivalent live vaccine against HPIV3 and RSV. Previous clinical evaluation indicated the need to increase the immunogenicity and genetic stability of the RSV F insert. Here, we increased RSV F expression by codon optimization and by modifying the RSV F amino acid sequence to conform to that of an early passage of the original isolate. This resulted in a hypofusogenic phenotype, which likely represents the original phenotype before adaptation to cell culture. We also included stabilized versions of prefusion and postfusion RSV F protein. Prefusion RSV F induced a larger quantity and higher quality of RSV-neutralizing serum antibodies and was highly protective. This provides an improved candidate for further clinical evaluation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Visceral organ weights, digestion and carcass characteristics of beef bulls differing in residual feed intake offered a high concentrate diet.

PubMed

Fitzsimons, C; Kenny, D A; McGee, M

2014-06-01

This study examined the relationship of residual feed intake (RFI) with digestion, body composition, carcass traits and visceral organ weights in beef bulls offered a high concentrate diet. Individual dry matter (DM) intake (DMI) and growth were measured in a total of 67 Simmental bulls (mean initial BW 431 kg (s.d.=63.7)) over 3 years. Bulls were offered concentrates (860 g/kg rolled barley, 60 g/kg soya bean meal, 60 g/kg molasses and 20 g/kg minerals per vitamins) ad libitum plus 0.8 kg grass silage DM daily for 105 days pre-slaughter. Ultrasonic muscle and fat depth, body condition score (BCS), muscularity score, skeletal measurements, blood metabolites, rumen fermentation and total tract digestibility (indigestible marker) were determined. After slaughter, carcasses and perinephric and retroperitoneal fat were weighed, carcasses were graded for conformation and fat score and weight of non-carcass organs, liver, heart, kidneys, lungs, gall bladder, spleen, reticulo-rumen full and empty and intestines full, were determined. The residuals of the regression of DMI on average daily gain (ADG), mid-test metabolic BW (BW0.75) and the fixed effect of year, using all animals, were used to compute individual RFI coefficients. Animals were ranked on RFI and assigned to high (inefficient), medium or low groupings. Overall mean ADG and daily DMI were 1.6 kg (s.d.=0.36) and 9.4 kg (s.d.=1.16), respectively. High RFI bulls consumed 7 and 14% more DM than medium and low RFI bulls, respectively (P<0.001). No differences between high and low RFI bulls were detected (P>0.05) for ADG, BW, BCS, skeletal measurements, muscularity scores, ultrasonic measurements, carcass weight, perinephric and retroperitoneal fat weight, kill-out proportion and carcass conformation and fat score. However, regression analysis indicated that a 1 kg DM/day increase in RFI was associated with a decrease in kill-out proportion of 20 g/kg (P<0.05) and a decrease in carcass conformation of 0.74 units (P<0.05). Weight of non-carcass organs did not differ (P>0.05) between RFI groups except for the empty weight of reticulo-rumen, which was 8% lighter (P=0.05) in low RFI compared with high RFI bulls. Regression analysis indicated that a 1 kg DM/day increase in RFI was associated with a 1 kg increase in reticulo-rumen empty weight (P<0.05). Of the visceral organs measured, the reticulo-rumen may be a biologically significant contributory factor to variation in RFI in beef bulls finished on a high concentrate diet.

The conformation of myosin head domains in rigor muscle determined by X-ray interference.

PubMed

Reconditi, M; Koubassova, N; Linari, M; Dobbie, I; Narayanan, T; Diat, O; Piazzesi, G; Lombardi, V; Irving, M

2003-08-01

In the absence of adenosine triphosphate, the head domains of myosin cross-bridges in muscle bind to actin filaments in a rigor conformation that is expected to mimic that following the working stroke during active contraction. We used x-ray interference between the two head arrays in opposite halves of each myosin filament to determine the rigor head conformation in single fibers from frog skeletal muscle. During isometric contraction (force T(0)), the interference effect splits the M3 x-ray reflection from the axial repeat of the heads into two peaks with relative intensity (higher angle/lower angle peak) 0.76. In demembranated fibers in rigor at low force (<0.05 T(0)), the relative intensity was 4.0, showing that the center of mass of the heads had moved 4.5 nm closer to the midpoint of the myosin filament. When rigor fibers were stretched, increasing the force to 0.55 T(0), the heads' center of mass moved back by 1.1-1.6 nm. These motions can be explained by tilting of the light chain domain of the head so that the mean angle between the Cys(707)-Lys(843) vector and the filament axis increases by approximately 36 degrees between isometric contraction and low-force rigor, and decreases by 7-10 degrees when the rigor fiber is stretched to 0.55 T(0).

Two Intense Decades of 19th Century Whaling Precipitated Rapid Decline of Right Whales around New Zealand and East Australia

PubMed Central

Carroll, Emma L.; Jackson, Jennifer A.; Paton, David; Smith, Tim D.

2014-01-01

Right whales (Eubalaena spp.) were the focus of worldwide whaling activities from the 16th to the 20th century. During the first part of the 19th century, the southern right whale (E. australis) was heavily exploited on whaling grounds around New Zealand (NZ) and east Australia (EA). Here we build upon previous estimates of the total catch of NZ and EA right whales by improving and combining estimates from four different fisheries. Two fisheries have previously been considered: shore-based whaling in bays and ship-based whaling offshore. These were both improved by comparison with primary sources and the American offshore whaling catch record was improved by using a sample of logbooks to produce a more accurate catch record in terms of location and species composition. Two fisheries had not been previously integrated into the NZ and EA catch series: ship-based whaling in bays and whaling in the 20th century. To investigate the previously unaddressed problem of offshore whalers operating in bays, we identified a subset of vessels likely to be operating in bays and read available extant logbooks. This allowed us to estimate the total likely catch from bay-whaling by offshore whalers from the number of vessels seasons and whales killed per season: it ranged from 2,989 to 4,652 whales. The revised total estimate of 53,000 to 58,000 southern right whales killed is a considerable increase on the previous estimate of 26,000, partly because it applies fishery-specific estimates of struck and loss rates. Over 80% of kills were taken between 1830 and 1849, indicating a brief and intensive fishery that resulted in the commercial extinction of southern right whales in NZ and EA in just two decades. This conforms to the global trend of increasingly intense and destructive southern right whale fisheries over time. PMID:24690918

Two intense decades of 19th century whaling precipitated rapid decline of right whales around New Zealand and East Australia.

PubMed

Carroll, Emma L; Jackson, Jennifer A; Paton, David; Smith, Tim D

2014-01-01

Right whales (Eubalaena spp.) were the focus of worldwide whaling activities from the 16th to the 20th century. During the first part of the 19th century, the southern right whale (E. australis) was heavily exploited on whaling grounds around New Zealand (NZ) and east Australia (EA). Here we build upon previous estimates of the total catch of NZ and EA right whales by improving and combining estimates from four different fisheries. Two fisheries have previously been considered: shore-based whaling in bays and ship-based whaling offshore. These were both improved by comparison with primary sources and the American offshore whaling catch record was improved by using a sample of logbooks to produce a more accurate catch record in terms of location and species composition. Two fisheries had not been previously integrated into the NZ and EA catch series: ship-based whaling in bays and whaling in the 20th century. To investigate the previously unaddressed problem of offshore whalers operating in bays, we identified a subset of vessels likely to be operating in bays and read available extant logbooks. This allowed us to estimate the total likely catch from bay-whaling by offshore whalers from the number of vessels seasons and whales killed per season: it ranged from 2,989 to 4,652 whales. The revised total estimate of 53,000 to 58,000 southern right whales killed is a considerable increase on the previous estimate of 26,000, partly because it applies fishery-specific estimates of struck and loss rates. Over 80% of kills were taken between 1830 and 1849, indicating a brief and intensive fishery that resulted in the commercial extinction of southern right whales in NZ and EA in just two decades. This conforms to the global trend of increasingly intense and destructive southern right whale fisheries over time.

A novel transferrin receptor-targeted hybrid peptide disintegrates cancer cell membrane to induce rapid killing of cancer cells

PubMed Central

2011-01-01

Background Transferrin receptor (TfR) is a cell membrane-associated glycoprotein involved in the cellular uptake of iron and the regulation of cell growth. Recent studies have shown the elevated expression levels of TfR on cancer cells compared with normal cells. The elevated expression levels of this receptor in malignancies, which is the accessible extracellular protein, can be a fascinating target for the treatment of cancer. We have recently designed novel type of immunotoxin, termed "hybrid peptide", which is chemically synthesized and is composed of target-binding peptide and lytic peptide containing cationic-rich amino acids components that disintegrates the cell membrane for the cancer cell killing. The lytic peptide is newly designed to induce rapid killing of cancer cells due to conformational change. In this study, we designed TfR binding peptide connected with this novel lytic peptide and assessed the cytotoxic activity in vitro and in vivo. Methods In vitro: We assessed the cytotoxicity of TfR-lytic hybrid peptide for 12 cancer and 2 normal cell lines. The specificity for TfR is demonstrated by competitive assay using TfR antibody and siRNA. In addition, we performed analysis of confocal fluorescence microscopy and apoptosis assay by Annexin-V binding, caspase activity, and JC-1 staining to assess the change in mitochondria membrane potential. In vivo: TfR-lytic was administered intravenously in an athymic mice model with MDA-MB-231 cells. After three weeks tumor sections were histologically analyzed. Results The TfR-lytic hybrid peptide showed cytotoxic activity in 12 cancer cell lines, with IC50 values as low as 4.0-9.3 μM. Normal cells were less sensitive to this molecule, with IC50 values > 50 μM. Competition assay using TfR antibody and knockdown of this receptor by siRNA confirmed the specificity of the TfR-lytic hybrid peptide. In addition, it was revealed that this molecule can disintegrate the cell membrane of T47D cancer cells just in 10 min, to effectively kill these cells and induce approximately 80% apoptotic cell death but not in normal cells. The intravenous administration of TfR-lytic peptide in the athymic mice model significantly inhibited tumor progression. Conclusions TfR-lytic peptide might provide a potent and selective anticancer therapy for patients. PMID:21849092

Complex formation and vectorization of a phosphorothioate oligonucleotide with an amphipathic leucine- and lysine-rich peptide: study at molecular and cellular levels.

PubMed

Boukhalfa-Heniche, Fatima-Zohra; Hernández, Belén; Gaillard, Stéphane; Coïc, Yves-Marie; Huynh-Dinh, Tam; Lecouvey, Marc; Seksek, Olivier; Ghomi, Mahmoud

2004-04-15

Optical spectroscopic techniques such as CD, Raman scattering, and fluorescence imaging allowed us to analyze the complex formation and vectorization of a single-stranded 20-mer phosphorothioate oligodeoxynucleotide with a 15-mer amphipathic peptide at molecular and cellular levels. Different solvent mixtures (methanol and water) and molecular ratios of peptide/oligodeoxynucleotide complexes were tested in order to overcome the problems related to solubility. Optimal conditions for both spectroscopic and cellular experiments were obtained with the molecular ratio peptide/oligodeoxynucleotide equal to 21:4, corresponding to a 7:5 ratio for their respective +/- charge ratio. At the molecular level, CD and Raman spectra were consistent with a alpha-helix conformation of the peptide in water or in a methanol-water mixture. The presence of methanol increased considerably the solubility of the peptide without altering its alpha-helix conformation, as evidenced by CD and Raman spectroscopies. UV absorption melting profile of the oligodeoxynucleotide gave rise to a flat melting profile, corresponding to its random structure in solution. Raman spectra of oligodeoxynucleotide/peptide complexes could only be studied in methanol/water mixture solutions. Drastic changes observed in Raman spectra have undoubtedly shown: (a) the perturbation occurred in the peptide secondary structure, and (b) possible interaction between the lysine residues of the peptide and the oligodeoxynucleotide. At the cellular level, the complex was prepared in a mixture of 10% methanol and 90% cell medium. Cellular uptake in optimal conditions for the oligodeoxynucleotide delivery with low cytotoxicity was controlled by fluorescence imaging allowing to specifically locate the compacted oligonucleotide labeled with fluorescein at its 5'-terminus with the peptide into human glioma cells after 1 h of incubation at 37 degrees C. Copyright 2004 Wiley Periodicals, Inc.

Conformal complex singlet extension of the Standard Model: scenario for dark matter and a second Higgs boson

NASA Astrophysics Data System (ADS)

Wang, Zhi-Wei; Steele, T. G.; Hanif, T.; Mann, R. B.

2016-08-01

We consider a conformal complex singlet extension of the Standard Model with a Higgs portal interaction. The global U(1) symmetry of the complex singlet can be either broken or unbroken and we study each scenario. In the unbroken case, the global U(1) symmetry protects the complex singlet from decaying, leading to an ideal cold dark matter candidate with approximately 100 GeV mass along with a significant proportion of thermal relic dark matter abundance. In the broken case, we have developed a renormalization-scale optimization technique to significantly narrow the parameter space and in some situations, provide unique predictions for all the model's couplings and masses. We have found there exists a second Higgs boson with a mass of approximately 550 GeV that mixes with the known 125 GeV Higgs with a large mixing angle sin θ ≈ 0.47 consistent with current experimental limits. The imaginary part of the complex singlet in the broken case could provide axion dark matter for a wide range of models. Upon including interactions of the complex scalar with an additional vector-like fermion, we explore the possibility of a diphoton excess in both the unbroken and the broken cases. In the unbroken case, the model can provide a natural explanation for diphoton excess if extra terms are introduced providing extra contributions to the singlet mass. In the broken case, we find a set of coupling solutions that yield a second Higgs boson of mass 720 GeV and an 830 GeV extra vector-like fermion F , which is able to address the 750 GeV LHC diphoton excess. We also provide criteria to determine the symmetry breaking pattern in both the Higgs and hidden sectors.

Study on relationship between expression level and molecular conformations of gene drugs targeting to hepatoma cells in vitro

PubMed Central

Yang, Dong-Ye; Lu, Fang-Gen; Tang, Xi-Xiang; Zhao, Shui-Ping; Ouyang, Chun-Hui; Wu, Xiao-Ping; Liu, Xiao-Wei; Wu, Xiao-Ying

2003-01-01

AIM: To increase exogenous gene expression level by modulating molecular conformations of targeting gene drugs. METHODS: The full length cDNAs of both P40 and P35 subunits of human interleukin 12 were amplified through polymerase chain reaction (PCR) and cloned into eukaryotic expressing vectors pcDNA3.1 (±) to construct plasmids of P (+)/IL-12, P (+)/P40 and P (-)/P35. These plasmids were combined with ASOR-PLL to form two targeting gene drugs [ASOR-PLL-P (+)/IL-12 and ASOR-PLL-P (+)/P40 + ASOR-PLL-P (-)/P35] in optimal ratios. The conformations of these two drugs at various concentrations adjuvant were examined under electron microscope (EM) and the drugs were transfected into HepG2 (ASGr+) cells. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed with total RNA extracted from the transfected cells to determine the hIL12 mRNA transcript level. The hIL12 protein in the cultured supernatant was measured with enzyme-linked immunosorbent assay (ELISA) 48 hours after transfection. RESULTS: Targeting gene drugs, whose structures were granular and circle-like and diameters ranged from 25 nm to 150 nm, had the highest hIL-12 expression level. The hIL-12 expression level in the group co-transfected with ASOR-PLL-P (+)/P40 and ASOR-PLL-P (-)/P35 was higher than that of ASOR-PLL-P (+)/IL-12 transfected group. CONCLUSION: The molecular conformations of targeting gene drugs play an important role in exogenous gene expression level, the best structures are granular and circle-like and their diameters range from 25 nm to 150 nm. The sizes and linking styles of exogenous genes also have some effects on their expression level. PMID:12970883

Feature extraction using molecular planes for fuzzy relational clustering of a flexible dopamine reuptake inhibitor.

PubMed

Banerjee, Amit; Misra, Milind; Pai, Deepa; Shih, Liang-Yu; Woodley, Rohan; Lu, Xiang-Jun; Srinivasan, A R; Olson, Wilma K; Davé, Rajesh N; Venanzi, Carol A

2007-01-01

Six rigid-body parameters (Shift, Slide, Rise, Tilt, Roll, Twist) are commonly used to describe the relative displacement and orientation of successive base pairs in a nucleic acid structure. The present work adapts this approach to describe the relative displacement and orientation of any two planes in an arbitrary molecule-specifically, planes which contain important pharmacophore elements. Relevant code from the 3DNA software package (Nucleic Acids Res. 2003, 31, 5108-5121) was generalized to treat molecular fragments other than DNA bases as input for the calculation of the corresponding rigid-body (or "planes") parameters. These parameters were used to construct feature vectors for a fuzzy relational clustering study of over 700 conformations of a flexible analogue of the dopamine reuptake inhibitor, GBR 12909. Several cluster validity measures were used to determine the optimal number of clusters. Translational (Shift, Slide, Rise) rather than rotational (Tilt, Roll, Twist) features dominate clustering based on planes that are relatively far apart, whereas both types of features are important to clustering when the pair of planes are close by. This approach was able to classify the data set of molecular conformations into groups and to identify representative conformers for use as template conformers in future Comparative Molecular Field Analysis studies of GBR 12909 analogues. The advantage of using the planes parameters, rather than the combination of atomic coordinates and angles between molecular planes used in our previous fuzzy relational clustering of the same data set (J. Chem. Inf. Model. 2005, 45, 610-623), is that the present clustering results are independent of molecular superposition and the technique is able to identify clusters in the molecule considered as a whole. This approach is easily generalizable to any two planes in any molecule.

Predicting disulfide connectivity from protein sequence using multiple sequence feature vectors and secondary structure.

PubMed

Song, Jiangning; Yuan, Zheng; Tan, Hao; Huber, Thomas; Burrage, Kevin

2007-12-01

Disulfide bonds are primary covalent crosslinks between two cysteine residues in proteins that play critical roles in stabilizing the protein structures and are commonly found in extracy-toplasmatic or secreted proteins. In protein folding prediction, the localization of disulfide bonds can greatly reduce the search in conformational space. Therefore, there is a great need to develop computational methods capable of accurately predicting disulfide connectivity patterns in proteins that could have potentially important applications. We have developed a novel method to predict disulfide connectivity patterns from protein primary sequence, using a support vector regression (SVR) approach based on multiple sequence feature vectors and predicted secondary structure by the PSIPRED program. The results indicate that our method could achieve a prediction accuracy of 74.4% and 77.9%, respectively, when averaged on proteins with two to five disulfide bridges using 4-fold cross-validation, measured on the protein and cysteine pair on a well-defined non-homologous dataset. We assessed the effects of different sequence encoding schemes on the prediction performance of disulfide connectivity. It has been shown that the sequence encoding scheme based on multiple sequence feature vectors coupled with predicted secondary structure can significantly improve the prediction accuracy, thus enabling our method to outperform most of other currently available predictors. Our work provides a complementary approach to the current algorithms that should be useful in computationally assigning disulfide connectivity patterns and helps in the annotation of protein sequences generated by large-scale whole-genome projects. The prediction web server and Supplementary Material are accessible at http://foo.maths.uq.edu.au/~huber/disulfide

Formulation and delivery of vaccines: Ongoing challenges for animal management

PubMed Central

Sharma, Sameer; Hinds, Lyn A.

2012-01-01

Development of a commercially successful animal vaccine is not only influenced by various immunological factors, such as type of antigen but also by formulation and delivery aspects. The latter includes the need for a vector or specific delivery system, the choice of route of administration and the nature of the target animal population and their habitat. This review describes the formulation and delivery aspects of various types of antigens such as killed microorganisms, proteins and nucleic acids for the development of efficacious and safe animal vaccines. It also focuses on the challenges associated with the different approaches that might be required for formulating and delivering species specific vaccines, particularly if their intended use is for improved animal management with respect to disease and/or reproductive control. PMID:23248557

Primed for death: Law enforcement-citizen homicides, social media, and retaliatory violence.

PubMed

Bejan, Vladimir; Hickman, Matthew; Parkin, William S; Pozo, Veronica F

2018-01-01

We examine whether retaliatory violence exists between law enforcement and citizens while controlling for any social media contagion effect related to prior fatal encounters. Analyzed using a trivariate dynamic structural vector-autoregressive model, daily time-series data over a 21-month period captured the frequencies of police killed in the line of duty, police deadly use of force incidents, and social media coverage. The results support a significant retaliatory violence effect against minorities by police, yet there is no evidence of retaliatory violence against law enforcement officers by minorities. Also, social media coverage of the Black Lives Matter movement increases the risk of fatal victimization to both law enforcement officers and minorities. Possible explanations for these results are based in rational choice and terror management theories.

Bianchi class B spacetimes with electromagnetic fields

NASA Astrophysics Data System (ADS)

Yamamoto, Kei

2012-02-01

We carry out a thorough analysis on a class of cosmological space-times which admit three spacelike Killing vectors of Bianchi class B and contain electromagnetic fields. Using dynamical system analysis, we show that a family of electro-vacuum plane-wave solutions of the Einstein-Maxwell equations is the stable attractor for expanding universes. Phase dynamics are investigated in detail for particular symmetric models. We integrate the system exactly for some special cases to confirm the qualitative features. Some of the obtained solutions have not been presented previously to the best of our knowledge. Finally, based on those analyses, we discuss the relation between those homogeneous models and perturbations of open Friedmann-Lemaitre-Robertson-Walker universes. We argue that the electro-vacuum plane-wave modes correspond to a certain long-wavelength limit of electromagnetic perturbations.

Primed for death: Law enforcement-citizen homicides, social media, and retaliatory violence

PubMed Central

Bejan, Vladimir; Hickman, Matthew; Pozo, Veronica F.

2018-01-01

We examine whether retaliatory violence exists between law enforcement and citizens while controlling for any social media contagion effect related to prior fatal encounters. Analyzed using a trivariate dynamic structural vector-autoregressive model, daily time-series data over a 21-month period captured the frequencies of police killed in the line of duty, police deadly use of force incidents, and social media coverage. The results support a significant retaliatory violence effect against minorities by police, yet there is no evidence of retaliatory violence against law enforcement officers by minorities. Also, social media coverage of the Black Lives Matter movement increases the risk of fatal victimization to both law enforcement officers and minorities. Possible explanations for these results are based in rational choice and terror management theories. PMID:29320548

Antibody-functionalized porous silicon nanoparticles for vectorization of hydrophobic drugs.

PubMed

Secret, Emilie; Smith, Kevin; Dubljevic, Valentina; Moore, Eli; Macardle, Peter; Delalat, Bahman; Rogers, Mary-Louise; Johns, Terrance G; Durand, Jean-Olivier; Cunin, Frédérique; Voelcker, Nicolas H

2013-05-01

We describe the preparation of biodegradable porous silicon nanoparticles (pSiNP) functionalized with cancer cell targeting antibodies and loaded with the hydrophobic anti-cancer drug camptothecin. Orientated immobilization of the antibody on the pSiNP is achieved using novel semicarbazide based bioconjugate chemistry. To demonstrate the generality of this targeting approach, the three antibodies MLR2, mAb528 and Rituximab are used, which target neuroblastoma, glioblastoma and B lymphoma cells, respectively. Successful targeting is demonstrated by means of flow cytometry and immunocytochemistry both with cell lines and primary cells. Cell viability assays after incubation with pSiNPs show selective killing of cells expressing the receptor corresponding to the antibody attached on the pSiNP. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The field efficacy of garlic extract against Dermanyssus gallinae in layer farms of Babol, Iran.

PubMed

Faghihzadeh Gorji, Shohreh; Faghihzadeh Gorji, Sina; Rajabloo, Mohammad

2014-03-01

Dermanyssus gallinae (Acari: Mesostigmata) is the most important hematophagous ectoparasite in layer farms in many countries. The reproduction rate of the parasite is rapid and can be completed in a week under favorable conditions. The parasite has direct and indirect effects on birds. It can also act as a vector for some important pathogens. Many researchers have investigated the effects of essential oils, plant extracts, oriental medicinal plant extracts, and silica against red mite. They can be used as killing agents or repellents. In the present study, the effect of garlic (Allium sativum) extract was investigated for controlling red mite infestation in a layer farm in Babol, North of Iran. Our results showed that the extract was effective and we obtained a 96% success after two successive sprays.

Delivery of chemotherapeutic drugs in tumour cell-derived microparticles.

PubMed

Tang, Ke; Zhang, Yi; Zhang, Huafeng; Xu, Pingwei; Liu, Jing; Ma, Jingwei; Lv, Meng; Li, Dapeng; Katirai, Foad; Shen, Guan-Xin; Zhang, Guimei; Feng, Zuo-Hua; Ye, Duyun; Huang, Bo

2012-01-01

Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100-1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.

Modulation of extracellular matrix in cancer is associated with enhanced tumor cell targeting by bacteriophage vectors.

PubMed

Yata, Teerapong; Lee, Eugene L Q; Suwan, Keittisak; Syed, Nelofer; Asavarut, Paladd; Hajitou, Amin

2015-06-03

Gene therapy has been an attractive paradigm for cancer treatment. However, cancer gene therapy has been challenged by the inherent limitation of vectors that are able to deliver therapeutic genes to tumors specifically and efficiently following systemic administration. Bacteriophage (phage) are viruses that have shown promise for targeted systemic gene delivery. Yet, they are considered poor vectors for gene transfer. Recently, we generated a tumor-targeted phage named adeno-associated virus/phage (AAVP), which is a filamentous phage particle whose genome contains the adeno-associated virus genome. Its effectiveness in delivering therapeutic genes to tumors specifically both in vitro and in vivo has been shown in numerous studies. Despite being a clinically useful vector, a multitude of barriers impede gene transduction to tumor cells. We hypothesized that one such factor is the tumor extracellular matrix (ECM). We used a number of tumor cell lines from different species and histological types in 2D monolayers or 3D multicellular tumor spheroid (MCTS) models. To assess whether the ECM is a barrier to tumor cell targeting by AAVP, we depleted the ECM using collagenase, hyaluronidase, or combination of both. We employed multiple techniques to investigate and quantify the effect of ECM depletion on ECM composition (including collagen type I, hyaluronic acid, fibronectin and laminin), and how AAVP adsorption, internalisation, gene expression and therapeutic efficacy are subsequently affected. Data were analyzed using a student's t test when comparing two groups or one-way ANOVA and post hoc Tukey tests when using more than two groups. We demonstrate that collagenase and hyaluronidase-mediated degradation of tumor ECM affects the composition of collagen, hyaluronic acid and fibronectin. Consequently, AAVP diffusion, internalisation, gene expression and tumor cell killing were enhanced after enzymatic treatment. Our data suggest that enhancement of gene transfer by the AAVP is solely attributed to ECM depletion. We provide substantial evidence that ECM modulation is relevant in clinically applicable settings by using 3D MCTS, which simulates in vivo environments more accurately. Our findings suggest that ECM depletion is an effective strategy to enhance the efficiency of viral vector-guided gene therapy.

Modelling the impact of vector control interventions on Anopheles gambiae population dynamics

PubMed Central

2011-01-01

Background Intensive anti-malaria campaigns targeting the Anopheles population have demonstrated substantial reductions in adult mosquito density. Understanding the population dynamics of Anopheles mosquitoes throughout their whole lifecycle is important to assess the likely impact of vector control interventions alone and in combination as well as to aid the design of novel interventions. Methods An ecological model of Anopheles gambiae sensu lato populations incorporating a rainfall-dependent carrying capacity and density-dependent regulation of mosquito larvae in breeding sites is developed. The model is fitted to adult mosquito catch and rainfall data from 8 villages in the Garki District of Nigeria (the 'Garki Project') using Bayesian Markov Chain Monte Carlo methods and prior estimates of parameters derived from the literature. The model is used to compare the impact of vector control interventions directed against adult mosquito stages - long-lasting insecticide treated nets (LLIN), indoor residual spraying (IRS) - and directed against aquatic mosquito stages, alone and in combination on adult mosquito density. Results A model in which density-dependent regulation occurs in the larval stages via a linear association between larval density and larval death rates provided a good fit to seasonal adult mosquito catches. The effective mosquito reproduction number in the presence of density-dependent regulation is dependent on seasonal rainfall patterns and peaks at the start of the rainy season. In addition to killing adult mosquitoes during the extrinsic incubation period, LLINs and IRS also result in less eggs being oviposited in breeding sites leading to further reductions in adult mosquito density. Combining interventions such as the application of larvicidal or pupacidal agents that target the aquatic stages of the mosquito lifecycle with LLINs or IRS can lead to substantial reductions in adult mosquito density. Conclusions Density-dependent regulation of anopheline larvae in breeding sites ensures robust, stable mosquito populations that can persist in the face of intensive vector control interventions. Selecting combinations of interventions that target different stages in the vector's lifecycle will result in maximum reductions in mosquito density. PMID:21798055

Possibilities and challenges for developing a successful vaccine for leishmaniasis.

PubMed

Srivastava, Saumya; Shankar, Prem; Mishra, Jyotsna; Singh, Sarman

2016-05-12

Leishmaniasis is a vector-borne disease caused by different species of protozoan parasites of the genus Leishmania. It is a major health problem yet neglected tropical diseases, with approximately 350 million people worldwide at risk and more than 1.5 million infections occurring each year. Leishmaniasis has different clinical manifestations, including visceral (VL or kala-azar), cutaneous (CL), mucocutaneous (MCL), diffuse cutaneous (DCL) and post kala-azar dermal leishmaniasis (PKDL). Currently, the only mean to treat and control leishmaniasis is by rational medications and vector control. However, the number of available drugs is limited and even these are either exorbitantly priced, have toxic side effects or prove ineffective due to the emergence of resistant strains. On the other hand, the vector control methods are not so efficient. Therefore, there is an urgent need for developing a safe, effective, and affordable vaccine for the prevention of leishmaniasis. Although in recent years a large body of researchers has concentrated their efforts on this issue, yet only three vaccine candidates have gone for clinical trial, until date. These are: (i) killed vaccine in Brazil for human immunotherapy; (ii) live attenuated vaccine for humans in Uzbekistan; and (iii) second-generation vaccine for dog prophylaxis in Brazil. Nevertheless, there are at least half a dozen vaccine candidates in the pipeline. One can expect that, in the near future, the understanding of the whole genome of Leishmania spp. will expand the vaccine discovery and strategies that may provide novel vaccines. The present review focuses on the development and the status of various vaccines and potential vaccine candidates against leishmaniasis.

Synthon preference in the cocrystal of 3,4,5-trifluorophenylboronic acid with urea.

PubMed

Kopczyńska, Karolina; Marek, Paulina H; Banaś, Bartłomiej; Madura, Izabela D

2017-11-01

The comprehensive description of the crystal structure of a novel 1:1 cocrystal of 3,4,5-trifluorophenylboronic acid with urea, C 6 H 4 BF 3 O 2 ·CH 4 N 2 O, is presented. Both components are good candidates for crystal engineering as they can create a variety of supramolecular synthons. The preference for the formation of different hetrosynthons is verified based on theoretical calculations. The syn-anti conformation of boronic acid has been found to be the most favourable in the formation of intermolecular interactions with urea. Moreover, the distortions present in the boron coordination sphere have been described quantitatively based on experimental data according to bond-valence vector model calculations. The results revealed that the deformation of the sphere is typical for a syn-anti conformation of boronic acids. The supramolecular structure of the cocrystal is composed of large synthons in the form of layers made up of O-H...O and N-H...O hydrogen bonds. The layers are joined via N-H...F hydrogen bonds which are unusual for urea cocrystal structures.

A noncompact Weyl-Einstein-Yang-Mills model: A semiclassical quantum gravity

NASA Astrophysics Data System (ADS)

Dengiz, Suat

2017-08-01

We construct and study perturbative unitarity (i.e., ghost and tachyon analysis) of a 3 + 1-dimensional noncompact Weyl-Einstein-Yang-Mills model. The model describes a local noncompact Weyl's scale plus SU(N) phase invariant Higgs-like field,conformally coupled to a generic Weyl-invariant dynamical background. Here, the Higgs-like sector generates the Weyl's conformal invariance of system. The action does not admit any dimensionful parameter and genuine presence of de Sitter vacuum spontaneously breaks the noncompact gauge symmetry in an analogous manner to the Standard Model Higgs mechanism. As to flat spacetime, the dimensionful parameter is generated within the dimensional transmutation in quantum field theories, and thus the symmetry is radiatively broken through the one-loop Effective Coleman-Weinberg potential. We show that the mere expectation of reducing to Einstein's gravity in the broken phases forbids anti-de Sitter space to be its stable vacua. The model is unitary in de Sitter and flat vacua around which a massless graviton, N2 - 1 massless scalar bosons, N massless Dirac fermions, N2 - 1 Proca-type massive Abelian and non-Abelian vector bosons are generically propagated.

PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells.

PubMed

Ghorai, Atanu; Sarma, Asitikantha; Chowdhury, Priyanka; Ghosh, Utpal

2016-09-22

Hadron therapy is an innovative technique where cancer cells are precisely killed leaving surrounding healthy cells least affected by high linear energy transfer (LET) radiation like carbon ion beam. Anti-metastatic effect of carbon ion exposure attracts investigators into the field of hadron biology, although details remain poor. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are well-known radiosensitizer and several PARP-1 inhibitors are in clinical trial. Our previous studies showed that PARP-1 depletion makes the cells more radiosensitive towards carbon ion than gamma. The purpose of the present study was to investigate combining effects of PARP-1 inhibition with carbon ion exposure to control metastatic properties in HeLa cells. Activities of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) were measured using the gelatin zymography after 85 MeV carbon ion exposure or gamma irradiation (0- 4 Gy) to compare metastatic potential between PARP-1 knock down (HsiI) and control cells (H-vector - HeLa transfected with vector without shRNA construct). Expression of MMP-2, MMP-9, tissue inhibitor of MMPs such as TIMP-1, TIMP-2 and TIMP-3 were checked by immunofluorescence and western blot. Cell death by trypan blue, apoptosis and autophagy induction were studied after carbon ion exposure in each cell-type. The data was analyzed using one way ANOVA and 2-tailed paired-samples T-test. PARP-1 silencing significantly reduced MMP-2 and MMP-9 activities and carbon ion exposure further diminished their activities to less than 3 % of control H-vector. On the contrary, gamma radiation enhanced both MMP-2 and MMP-9 activities in H-vector but not in HsiI cells. The expression of MMP-2 and MMP-9 in H-vector and HsiI showed different pattern after carbon ion exposure. All three TIMPs were increased in HsiI, whereas only TIMP-1 was up-regulated in H-vector after irradiation. Notably, the expressions of all TIMPs were significantly higher in HsiI than H-vector at 4 Gy. Apoptosis was the predominant mode of cell death and no autophagic death was observed. Our study demonstrates for the first time that PARP-1 inhibition in combination with carbon ion synergistically decreases MMPs activity along with overall increase of TIMPs. These data open up the possibilities of improvement of carbon ion therapy with PARP-1 inhibition to control highly metastatic cancers.

Evidence for Personal Protective Measures to Reduce Human Contact With Blacklegged Ticks and for Environmentally Based Control Methods to Suppress Host-Seeking Blacklegged Ticks and Reduce Infection with Lyme Disease Spirochetes in Tick Vectors and Rodent Reservoirs

PubMed Central

Eisen, Lars; Dolan, Marc C.

2018-01-01

In the 1980s, the blacklegged tick, Ixodes scapularis Say, and rodents were recognized as the principal vector and reservoir hosts of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, and deer were incriminated as principal hosts for I. scapularis adults. These realizations led to pioneering studies aiming to reduce the risk for transmission of B. burgdorferi to humans by attacking host-seeking ticks with acaricides, interrupting the enzootic transmission cycle by killing immatures infesting rodent reservoirs by means of acaricide-treated nesting material, or reducing deer abundance to suppress tick numbers. We review the progress over the past three decades in the fields of: 1) prevention of human–tick contact with repellents and permethrin-treated clothing, and 2) suppression of I. scapularis and disruption of enzootic B. burgdorferi transmission with environmentally based control methods. Personal protective measures include synthetic and natural product-based repellents that can be applied to skin and clothing, permethrin sprays for clothing and gear, and permethrin-treated clothing. A wide variety of approaches and products to suppress I. scapularis or disrupt enzootic B. burgdorferi transmission have emerged and been evaluated in field trials. Application of synthetic chemical acaricides is a robust method to suppress host-seeking I. scapularis ticks within a treated area for at least 6–8 wk. Natural product-based acaricides or entomopathogenic fungi have emerged as alternatives to kill host-seeking ticks for homeowners who are unwilling to use synthetic chemical acaricides. However, as compared with synthetic chemical acaricides, these approaches appear less robust in terms of both their killing efficacy and persistence. Use of rodent-targeted topical acaricides represents an alternative for homeowners opposed to open distribution of acaricides to the ground and vegetation on their properties. This host-targeted approach also provides the benefit of the intervention impacting the entire rodent home range. Rodent-targeted oral vaccines against B. burgdorferi and a rodent-targeted antibiotic bait have been evaluated in laboratory and field trials but are not yet commercially available. Targeting of deer—via deer reduction or treatment of deer with topical acaricides—can provide area-wide suppression of host-seeking I. scapularis. These two deer-targeted approaches combine great potential for protection that impacts the entire landscape with severe problems relating to public acceptance or implementation logistics. Integrated use of two or more methods has unfortunately been evaluated in very few published studies, but additional field evaluations of integrated tick and pathogen strategies are underway. PMID:27439616

Gravitational form factors and decoupling in 2D

NASA Astrophysics Data System (ADS)

Ribeiro, Tiago G.; Shapiro, Ilya L.; Zanusso, Omar

2018-07-01

We calculate and analyse non-local gravitational form factors induced by quantum matter fields in curved two-dimensional space. The calculations are performed for scalars, spinors and massive vectors by means of the covariant heat kernel method up to the second order in the curvature and confirmed using Feynman diagrams. The analysis of the ultraviolet (UV) limit reveals a generalized "running" form of the Polyakov action for a nonminimal scalar field and the usual Polyakov action in the conformally invariant cases. In the infrared (IR) we establish the gravitational decoupling theorem, which can be seen directly from the form factors or from the physical beta function for fields of any spin.

Pyrethroid Treatment of Cattle for Tsetse Control: Reducing Its Impact on Dung Fauna

PubMed Central

Vale, Glyn A.; Hargrove, John W.; Chamisa, Andrew; Grant, Ian F.; Torr, Stephen J.

2015-01-01

Background African trypansomiases of humans and animals can be controlled by attacking the vectors, various species of tsetse fly. Treatment of cattle with pyrethroids to kill tsetse as they feed is the most cost-effective method. However, such treatments can contaminate cattle dung, thereby killing the fauna which disperse the dung and so play an important role in soil fertility. Hence there is a need to identify cost-effective methods of treating cattle with minimal impact on dung fauna. Methodology/Principal Findings We used dung beetles to field bioassay the levels of dung contamination following the use of spray and pour-on formulations of deltamethrin, applied to various parts of the body of cattle in Zimbabwe. Results suggested that dung was contaminated by contact with insecticide on the body surface as the cattle defecated, and by ingestion of insecticide as the cattle licked themselves. Death of dung beetles was reduced to negligible levels by using only the spray and applying it to the legs and belly or legs alone, i.e., places where most tsetse feed. Conclusion/Significance The restricted applications suitable for minimising the impact on dung fauna have the collateral benefits of improving the economy and convenience of cattle treatments for tsetse control. The demonstration of collateral benefits is one of the surest ways of promoting environmentally friendly procedures. PMID:25738836

Temephos Resistance in Aedes aegypti in Colombia Compromises Dengue Vector Control

PubMed Central

Grisales, Nelson; Poupardin, Rodolphe; Gomez, Santiago; Fonseca-Gonzalez, Idalyd; Ranson, Hilary; Lenhart, Audrey

2013-01-01

Background Control and prevention of dengue relies heavily on the application of insecticides to control dengue vector mosquitoes. In Colombia, application of the larvicide temephos to the aquatic breeding sites of Aedes aegypti is a key part of the dengue control strategy. Resistance to temephos was recently detected in the dengue-endemic city of Cucuta, leading to questions about its efficacy as a control tool. Here, we characterize the underlying mechanisms and estimate the operational impact of this resistance. Methodology/Principal Findings Larval bioassays of Ae. aegypti larvae from Cucuta determined the temephos LC50 to be 0.066 ppm (95% CI 0.06–0.074), approximately 15× higher than the value obtained from a susceptible laboratory colony. The efficacy of the field dose of temephos at killing this resistant Cucuta population was greatly reduced, with mortality rates <80% two weeks after application and <50% after 4 weeks. Neither biochemical assays nor partial sequencing of the ace-1 gene implicated target site resistance as the primary resistance mechanism. Synergism assays and microarray analysis suggested that metabolic mechanisms were most likely responsible for the temephos resistance. Interestingly, although the greatest synergism was observed with the carboxylesterase inhibitor, DEF, the primary candidate genes from the microarray analysis, and confirmed by quantitative PCR, were cytochrome P450 oxidases, notably CYP6N12, CYP6F3 and CYP6M11. Conclusions/Significance In Colombia, resistance to temephos in Ae. aegypti compromises the duration of its effect as a vector control tool. Several candidate genes potentially responsible for metabolic resistance to temephos were identified. Given the limited number of insecticides that are approved for vector control, future chemical-based control strategies should take into account the mechanisms underlying the resistance to discern which insecticides would likely lead to the greatest control efficacy while minimizing further selection of resistant phenotypes. PMID:24069492

Carbon ion beam triggers both caspase-dependent and caspase-independent pathway of apoptosis in HeLa and status of PARP-1 controls intensity of apoptosis.

PubMed

Ghorai, Atanu; Sarma, Asitikantha; Bhattacharyya, Nitai P; Ghosh, Utpal

2015-04-01

High linear energy transfer (LET) carbon ion beam (CIB) is becoming very promising tool for various cancer treatments and is more efficient than conventional low LET gamma or X-rays to kill malignant or radio-resistant cells, although detailed mechanism of cell death is still unknown. Poly (ADP-ribose) polymerase-1 (PARP-1) is a key player in DNA repair and its inhibitors are well-known as radio-sensitizer for low LET radiation. The objective of our study was to find mechanism(s) of induction of apoptosis by CIB and role of PARP-1 in CIB-induced apoptosis. We observed overall higher apoptosis in PARP-1 knocked down HeLa cells (HsiI) compared with negative control H-vector cells after irradiation with CIB (0-4 Gy). CIB activated both intrinsic and extrinsic pathways of apoptosis via caspase-9 and caspase-8 activation respectively, followed by caspase-3 activation, apoptotic body, nucleosomal ladder formation and sub-G1 accumulation. Apoptosis inducing factor translocation into nucleus in H-vector but not in HsiI cells after CIB irradiation contributed caspase-independent apoptosis. Higher p53 expression was observed in HsiI cells compared with H-vector after exposure with CIB. Notably, we observed about 37 % fall of mitochondrial membrane potential, activation of caspase-9 and caspase-3 and mild activation of caspase-8 without any detectable apoptotic body formation in un-irradiated HsiI cells. We conclude that reduction of PARP-1 expression activates apoptotic signals via intrinsic and extrinsic pathways in un-irradiated cells. CIB irradiation further intensified both intrinsic and extrinsic pathways of apoptosis synergistically along with up-regulation of p53 in HsiI cells resulting overall higher apoptosis in HsiI than H-vector.

Dyonic AdS black holes in maximal gauged supergravity

NASA Astrophysics Data System (ADS)

Chow, David D. K.; Compère, Geoffrey

2014-03-01

We present two new classes of dyonic anti-de Sitter black hole solutions of four-dimensional maximal N =8, SO(8) gauged supergravity. They are (1) static black holes of N=2, U(1)4 gauged supergravity with four electric and four magnetic charges, with spherical, planar or hyperbolic horizons; and (2) rotating black holes of N =2, U(1)2 gauged supergravity with two electric and two magnetic charges. We study their thermodynamics, and point out that the formulation of a consistent thermodynamics for dyonic anti-de Sitter black holes is dependent on the existence of boundary conditions for the gauge fields. We identify several distinct classes of boundary conditions for gauge fields in U(1)4 supergravity. We study a general family of metrics containing the rotating solutions, and find Killing-Yano tensors with torsion in two conformal frames, which underlie separability.

A deformation of Sasakian structure in the presence of torsion and supergravity solutions

NASA Astrophysics Data System (ADS)

Houri, Tsuyoshi; Takeuchi, Hiroshi; Yasui, Yukinori

2013-07-01

A deformation of Sasakian structure in the presence of totally skew-symmetric torsion is discussed on odd-dimensional manifolds whose metric cones are Kähler with torsion. It is shown that such a geometry inherits similar properties to those of Sasakian geometry. As their example, we present an explicit expression of local metrics. It is also demonstrated that our example of the metrics admits the existence of hidden symmetry described by non-trivial odd-rank generalized closed conformal Killing-Yano tensors. Furthermore, using these metrics as an ansatz, we construct exact solutions in five-dimensional minimal gauged/ungauged supergravity and 11-dimensional supergravity. Finally, the global structures of the solutions are discussed. We obtain regular metrics on compact manifolds in five dimensions, which give natural generalizations of Sasaki-Einstein manifolds Yp, q and La, b, c. We also briefly discuss regular metrics on non-compact manifolds in 11 dimensions.

Dirac equation in Kerr-NUT-(A)dS spacetimes: Intrinsic characterization of separability in all dimensions

NASA Astrophysics Data System (ADS)

Cariglia, Marco; Krtouš, Pavel; Kubizňák, David

2011-07-01

We intrinsically characterize separability of the Dirac equation in Kerr-NUT-(A)dS spacetimes in all dimensions. Namely, we explicitly demonstrate that, in such spacetimes, there exists a complete set of first-order mutually commuting operators, one of which is the Dirac operator, that allows for common eigenfunctions which can be found in a separated form and correspond precisely to the general solution of the Dirac equation found by Oota and Yasui [Phys. Lett. BPYLBAJ0370-2693 659, 688 (2008)10.1016/j.physletb.2007.11.057]. Since all the operators in the set can be generated from the principal conformal Killing-Yano tensor, this establishes the (up-to-now) missing link among the existence of hidden symmetry, presence of a complete set of commuting operators, and separability of the Dirac equation in these spacetimes.

Whole cell biocatalysts: essential workers from Nature to the industry.

PubMed

de Carvalho, Carla C C R

2017-03-01

Microorganisms have been exposed to a myriad of substrates and environmental conditions throughout evolution resulting in countless metabolites and enzymatic activities. Although mankind have been using these properties for centuries, we have only recently learned to control their production, to develop new biocatalysts with high stability and productivity and to improve their yields under new operational conditions. However, microbial cells still provide the best known environment for enzymes, preventing conformational changes in the protein structure in non-conventional medium and under harsh reaction conditions, while being able to efficiently regenerate necessary cofactors and to carry out cascades of reactions. Besides, a still unknown microbe is probably already producing a compound that will cure cancer, Alzeihmer's disease or kill the most resistant pathogen. In this review, the latest developments in screening desirable activities and improving production yields are discussed. © 2016 The Author. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Synthetic sex pheromone attracts the leishmaniasis vector Lutzomyia longipalpis to experimental chicken sheds treated with insecticide

PubMed Central

2010-01-01

Background Current strategies for controlling American visceral leishmaniasis (AVL) have been unable to prevent the spread of the disease across Brazil. With no effective vaccine and culling of infected dogs an unpopular and unsuccessful alternative, new tools are urgently needed to manage populations of the sand fly vector, Lutzomyia longipalpis Lutz and Neiva (Diptera: Psychodidae). Here, we test two potential strategies for improving L. longipalpis control using the synthetic sand fly pheromone (±)-9-methylgermacrene-B: the first in conjunction with spraying of animal houses with insecticide, the second using coloured sticky traps. Results Addition of synthetic pheromone resulted in greater numbers of male and female sand flies being caught and killed at experimental chicken sheds sprayed with insecticide, compared to pheromone-less controls. Furthermore, a ten-fold increase in the amount of sex pheromone released from test sheds increased the number of females attracted and subsequently killed. Treating sheds with insecticide alone resulted in a significant decrease in numbers of males attracted to sheds (compared to pre-spraying levels), and a near significant decrease in numbers of females. However, this effect was reversed through addition of synthetic pheromone at the time of insecticide spraying, leading to an increase in number of flies attracted post-treatment. In field trials of commercially available different coloured sticky traps, yellow traps caught more males than blue traps when placed in chicken sheds. In addition, yellow traps fitted with 10 pheromone lures caught significantly more males than pheromone-less controls. However, while female sand flies showed a preference for both blue and yellow pheromone traps sticky traps over white traps in the laboratory, neither colour caught significant numbers of females in chicken sheds, either with or without pheromone. Conclusions We conclude that synthetic pheromone could currently be most effectively deployed for sand fly control through combination with existing insecticide spraying regimes. Development of a standalone pheromone trap remains a possibility, but such devices may require an additional attractive host odour component to be fully effective. PMID:20222954

Symmetry operators of Killing spinors and superalgebras in AdS5

NASA Astrophysics Data System (ADS)

Ertem, Ümit

2016-04-01

We construct the first-order symmetry operators of Killing spinor equation in terms of odd Killing-Yano forms. By modifying the Schouten-Nijenhuis bracket of Killing-Yano forms, we show that the symmetry operators of Killing spinors close into an algebra in AdS5 spacetime. Since the symmetry operator algebra of Killing spinors corresponds to a Jacobi identity in extended Killing superalgebras, we investigate the possible extensions of Killing superalgebras to include higher-degree Killing-Yano forms. We found that there is a superalgebra extension but no Lie superalgebra extension of the Killing superalgebra constructed out of Killing spinors and odd Killing-Yano forms in AdS5 background.

Viral Vector-Based Innovative Approaches to Directly Abolishing Tumorigenic Pluripotent Stem Cells for Safer Regenerative Medicine.

PubMed

Mitsui, Kaoru; Ide, Kanako; Takahashi, Tomoyuki; Kosai, Ken-Ichiro

2017-06-16

Human pluripotent stem cells (hPSCs) are a promising source of regenerative material for clinical applications. However, hPSC transplant therapies pose the risk of teratoma formation and malignant transformation of undifferentiated remnants. These problems underscore the importance of developing technologies that completely prevent tumorigenesis to ensure safe clinical application. Research to date has contributed to establishing safe hPSC lines, improving the efficiency of differentiation induction, and indirectly ensuring the safety of products. Despite such efforts, guaranteeing the clinical safety of regenerative medicine products remains a key challenge. Given the intrinsic genome instability of hPSCs, selective growth advantage of cancer cells, and lessons learned through failures in previous attempts at hematopoietic stem cell gene therapy, conventional strategies are unlikely to completely overcome issues related to hPSC tumorigenesis. Researchers have recently embarked on studies aimed at locating and directly treating hPSC-derived tumorigenic cells. In particular, novel approaches to directly killing tumorigenic cells by transduction of suicide genes and oncolytic viruses are expected to improve the safety of hPSC-based therapy. This article discusses the current status and future perspectives of methods aimed at directly eradicating undifferentiated tumorigenic hPSCs, with a focus on viral vector transduction.

An age-structured model to evaluate the potential of novel malaria-control interventions: a case study of fungal biopesticide sprays

PubMed Central

Hancock, P.A; Thomas, M.B; Godfray, H.C.J

2008-01-01

It has recently been proposed that mosquito vectors of human diseases, particularly malaria, may be controlled by spraying with fungal biopesticides that increase the rate of adult mortality. Though fungal pathogens do not cause instantaneous mortality, they can kill mosquitoes before they are old enough to transmit disease. A model is developed (i) to explore the potential for fungal entomopathogens to reduce significantly infectious mosquito populations, (ii) to assess the relative value of the many different fungal strains that might be used, and (iii) to help guide the tactical design of vector-control programmes. The model follows the dynamics of different classes of adult mosquitoes with the risk of mortality due to the fungus being assumed to be a function of time since infection (modelled using the Weibull distribution). It is shown that substantial reductions in mosquito numbers are feasible for realistic assumptions about mosquito, fungus and malaria biology and moderate to low daily fungal infection probability. The choice of optimal fungal strain and spraying regime is shown to depend on local mosquito and malaria biology. Fungal pathogens may also influence the ability of mosquitoes to transmit malaria and such effects are shown to further reduce vectorial capacity. PMID:18765347

Liquid-phase study of ozone inactivation of Venezuelan equine encephalomyelitis virus.

PubMed Central

Akey, D H; Walton, T E

1985-01-01

Ozone, in a liquid-phase application, was evaluated as a residue-free viral inactivant that may be suitable for use in an arboviral research laboratory. Commonly used sterilizing agents may leave trace residues, be flammable or explosive, and require lengthy periods for gases or residues to dissipate after decontamination of equipment such as biological safety cabinets. Complete liquid-phase inactivation of Venezuelan equine encephalomyelitis virus was attained at 0.025 mg of ozone per liter within 45 min of exposure. The inactivation of 10(6.5) median cell culture infective doses (CCID50 of Venezuelan equine encephalomyelitis virus per milliliter represented a reduction of 99.99997% of the viral particles from the control levels of 10(7.25-7.5) CCID50/ml. A dose-response relationship was demonstrated. Analysis by polynomial regression of the logarithmic values for both ozone concentrations and percent reduction of viral titers had a highly significant r2 of 0.8 (F = 63.6; df = 1, 16). These results, together with those of Akey (J. Econ. Entomol. 75:387-392, 1982) on the use of ozone to kill a winged arboviral vector, indicate that ozone is a promising candidate as a sterilizing agent in some applications for biological safety cabinets and other equipment used in vector studies with arboviruses. PMID:4083884

Liquid-phase study of ozone inactivation of Venezuelan equine encephalomyelitis virus.

PubMed

Akey, D H; Walton, T E

1985-10-01

Ozone, in a liquid-phase application, was evaluated as a residue-free viral inactivant that may be suitable for use in an arboviral research laboratory. Commonly used sterilizing agents may leave trace residues, be flammable or explosive, and require lengthy periods for gases or residues to dissipate after decontamination of equipment such as biological safety cabinets. Complete liquid-phase inactivation of Venezuelan equine encephalomyelitis virus was attained at 0.025 mg of ozone per liter within 45 min of exposure. The inactivation of 10(6.5) median cell culture infective doses (CCID50 of Venezuelan equine encephalomyelitis virus per milliliter represented a reduction of 99.99997% of the viral particles from the control levels of 10(7.25-7.5) CCID50/ml. A dose-response relationship was demonstrated. Analysis by polynomial regression of the logarithmic values for both ozone concentrations and percent reduction of viral titers had a highly significant r2 of 0.8 (F = 63.6; df = 1, 16). These results, together with those of Akey (J. Econ. Entomol. 75:387-392, 1982) on the use of ozone to kill a winged arboviral vector, indicate that ozone is a promising candidate as a sterilizing agent in some applications for biological safety cabinets and other equipment used in vector studies with arboviruses.

Infrared modified gravity with propagating torsion: Instability of torsionfull de Sitter-like solutions

NASA Astrophysics Data System (ADS)

Nikiforova, Vasilisa; Damour, Thibault

2018-06-01

We continue the exploration of the consistency of a modified-gravity theory that generalizes general relativity by including a dynamical torsion in addition to the dynamical metric. The six-parameter theory we consider was found to be consistent around arbitrary torsionless Einstein backgrounds, in spite of its containing a (notoriously delicate) massive spin-2 excitation. At zero bare cosmological constant, this theory was found to admit a self-accelerating solution whose exponential expansion is sustained by a nonzero torsion background. The scalar-type perturbations of the latter torsionfull self-accelerating solution were recently studied and were found to preserve the number of propagating scalar degrees of freedom, but to exhibit, for some values of the torsion background, some exponential instabilities (of a rather mild type). Here, we study the tensor-type and vector-type perturbations of the torsionfull self-accelerating solution, and of its deformation by a nonzero bare cosmological constant. We find strong, "gradient" instabilities in the vector sector. No tuning of the parameters of the theory can kill these instabilities without creating instabilities in the other sectors. Further work is needed to see whether generic torsionfull backgrounds are prone to containing gradient instabilities, or if the instabilities we found are mainly due to the (generalized) self-accelerating nature of the special de Sitter backgrounds we considered.

LAMP-1-chimeric DNA vaccines enhance the antibody response in Japanese flounder, Paralichthys olivaceus.

PubMed

Rondón-Barragán, Iang; Nozaki, Reiko; Hirono, Ikuo; Kondo, Hidehiro

2017-08-01

DNA vaccination is one method to protect farmed fish from viral and bacterial diseases. Chimeric antigens encoded by DNA vaccines have been shown to increase the resistance to viral diseases. Here, we sequenced the gene encoding lysosome-associated membrane protein-1 from Japanese flounder, Paralichthys olivaceus, (JfLAMP-1) and assessed its use in a chimeric DNA vaccine fused with the major capsule protein (MCP) from red seabream iridovirus (RSIV). JfLAMP-1 cDNA has a length of 1248 bp encoding 415 aa, which contains transmembrane and cytoplasmic domains. JfLAMP-1 is constitutively expressed in several tissues and its expression in spleen was upregulated following injection of formalin-killed cells (FKC) of Edwardsiella tarda. Immunofluorescence analysis showed that JfLAMP-1 is distributed in the small and large granules in the cytoplasm and groups close to the nucleus. The DNA encoding the luminal domain of JfLAMP-1 was replaced with the gene for the RSIV MCP, and the construct was cloned in an expression vector (pCIneo). Fish vaccinated with pCLAMP-MCP had significantly higher antibody levels than fish vaccinated with pCIneo vector harboring the MCP gene (p < 0.05) at day 30 post-vaccination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and analysis of a STOL supersonic cruise fighter concept

NASA Technical Reports Server (NTRS)

Dollyhigh, S. M.; Foss, W. E., Jr.; Morris, S. J., Jr.; Walkley, K. B.; Swanson, E. E.; Robins, A. W.

1984-01-01

The application of advanced and emerging technologies to a fighter aircraft concept is described. The twin-boom fighter (TBF-1) relies on a two dimensional vectoring/reversing nozzle to provide STOL performance while also achieving efficient long range supersonic cruise. A key feature is that the propulsion package is placed so that the nozzle hinge line is near the aircraft center-of-gravity to allow large vector angles and, thus, provide large values of direct lift while minimizing the moments to be trimmed. The configurations name is derived from the long twin booms extending aft of the engine to the twin vertical tails which have a single horizontal tail mounted atop and between them. Technologies utilized were an advanced engine (1985 state-of-the-art), superplastic formed/diffusion bonded titanium structure, advanced controls/avionics/displays, supersonic wing design, and conformal weapons carriage. The integration of advanced technologies into this concept indicate that large gains in takeoff and landing performance, maneuver, acceleration, supersonic cruise speed, and range can be acieved relative to current fighter concepts.

SVAS3: Strain Vector Aided Sensorization of Soft Structures.

PubMed

Culha, Utku; Nurzaman, Surya G; Clemens, Frank; Iida, Fumiya

2014-07-17

Soft material structures exhibit high deformability and conformability which can be useful for many engineering applications such as robots adapting to unstructured and dynamic environments. However, the fact that they have almost infinite degrees of freedom challenges conventional sensory systems and sensorization approaches due to the difficulties in adapting to soft structure deformations. In this paper, we address this challenge by proposing a novel method which designs flexible sensor morphologies to sense soft material deformations by using a functional material called conductive thermoplastic elastomer (CTPE). This model-based design method, called Strain Vector Aided Sensorization of Soft Structures (SVAS3), provides a simulation platform which analyzes soft body deformations and automatically finds suitable locations for CTPE-based strain gauge sensors to gather strain information which best characterizes the deformation. Our chosen sensor material CTPE exhibits a set of unique behaviors in terms of strain length electrical conductivity, elasticity, and shape adaptability, allowing us to flexibly design sensor morphology that can best capture strain distributions in a given soft structure. We evaluate the performance of our approach by both simulated and real-world experiments and discuss the potential and limitations.

Dual stimuli polysaccharide nanovesicles for conjugated and physically loaded doxorubicin delivery in breast cancer cells.

PubMed

Pramod, P S; Shah, Ruchira; Jayakannan, Manickam

2015-04-21

The present work reports the development of pH and enzyme dual responsive polysaccharide vesicular nano-scaffolds for the administration of doxorubicin via physical loading and polymer-drug conjugation to breast cancer cells. Dextran was suitably modified with a renewable resource 3-pentadecyl phenol unit through imine and aliphatic ester chemical linkages that acted as pH and esterase enzyme stimuli, respectively. These dual responsive polysaccharide derivatives self-organized into 200 ± 10 nm diameter nano-vesicles in water. The water soluble anticancer drug doxorubicin (DOX·HCl) was encapsulated in the hydrophilic pocket to produce core-loaded polysaccharide vesicles whereas chemical conjugation produced DOX anchored at the hydrophobic layer of the dextran nano-vesicles. In vitro studies revealed that about 70-80% of the drug was retained under circulatory conditions at pH = 7.4 and 37 °C. At a low pH of 6.0 to 5.0 and in the presence of esterase; both imine and ester linkages were cleaved instantaneously to release 100% of the loaded drugs. Cytotoxicity assays on Wild Type Mouse Embryonic Fibroblasts (WTMEFs) confirmed the non-toxicity of the newly developed dextran derivatives at up to 500 μg mL(-1) in PBS. MTT assays on fibroblast cells revealed that DOX·HCl loaded nano-vesicles exhibited better killing abilities than DOX conjugated polymer nano-vesicles. Both DOX loaded and DOX conjugated nano-vesicles were found to show significant killing in breast cancer cells (MCF 7). Confocal microscopy images confirmed the uptake of DOX loaded (or conjugated) nano-vesicles by cells compared to free DOX. Thus, the newly developed pH and enzyme dual responsive polysaccharide vesicular assemblies are potential drug vectors for the administration of DOX in both loaded and chemically conjugated forms for the efficient killing of breast cancer cells.

Constructing TC-1-GLUC-LMP2 Model Tumor Cells to Evaluate the Anti-Tumor Effects of LMP2-Related Vaccines

PubMed Central

Sun, Liying; Hao, Yanzhe; Wang, Zhan; Zeng, Yi

2018-01-01

Epstein-Barr virus (EBV) is related to a variety of malignant tumors, and its encoded protein, latent membrane protein 2 (LMP2), is an effective target antigen that is widely used to construct vector vaccines. However, the model cells carrying LMP2 have still not been established to assess the oncolytic effect of LMP2-related vaccines at present. In this study, TC-1-GLUC-LMP2 tumor cells were constructed as target cells to evaluate the anti-tumor effects of LMP2-assosiated vaccines. The results showed that both LMP2 and Gaussia luciferase (GLuc) genes could be detected by polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR) in TC-1-GLUC-LMP2 cells. Western blot results showed that the LMP2 and Gaussia luciferase proteins were stably expressed in tumor cells for at least 30 generations. We mixed 5 × 104 LMP2-specific mouse splenic lymphocytes with 5 × 103 TC-1-GLUC-LMP2 target cells and found that the target cells were killed as the specific killing effect was obviously enhanced by the increased quantities of LMP2-peptide stimulated spleens. Furthermore, the tumor cells could not be observed in the mice inoculated TC-1-GLUC-LMP2 cells after being immunized with vaccine-LMP2, while the vaccine-NULL immunized mice showed that tumor volume gradually grew with increased inoculation time. These results indicated that the TC-1-GLUC-LMP2 cells stably expressing LMP2 and GLuc produced tumors in mice, and that the LMP2-specific cytotoxic T lymphocyte (CTL) effectively killed the cells in vitro and in vivo, suggesting that TC-1-GLUC-LMP2 cells can be used as model cells to assess the immune and antitumor effects of LMP2-related vaccines. PMID:29570629

Imprudent fishing harvests and consequent trophic cascades on the West Florida shelf over the last half century: A harbinger of increased human deaths from paralytic shellfish poisoning along the southeastern United States, in response to oligotrophication?

NASA Astrophysics Data System (ADS)

Walsh, J. J.; Tomas, C. R.; Steidinger, K. A.; Lenes, J. M.; Chen, F. R.; Weisberg, R. H.; Zheng, L.; Landsberg, J. H.; Vargo, G. A.; Heil, C. A.

2011-06-01

Within the context of ubiquitous overfishing of piscivores, recent consequent increments of jellyfish and clupeids have occurred at the zooplanktivore trophic level in the eastern Gulf of Mexico (GOM), after overfishing of one of their predators, i.e. red snapper. Initiation of a local trophic cascade thence led to declines of herbivore stocks, documented here on the West Florida shelf. These exacerbating world-wide trophic cascades have resulted in larger harmful algal blooms (HABs), already present at the base of most coastal food webs. Impacts on human health have thus far been minimal within nutrient-rich coastal regions. To provide a setting for past morbidities, consideration is given to chronologies of other trophic cascades within eutrophic, cold water marine ecosystems of the Scotian Sea, in the Gulf of Alaska, off Southwest Africa, within the Barents, White, and Black Seas, in the Gulf of Maine, and finally in the North Sea. Next, comparison is now made here of recent ten-fold increments within Florida waters of both relatively benign and saxitoxic HABs, some of which are fatal to humans. These events are placed in a perspective of other warm shelf systems of the South China and Caribbean Seas to assess prior and possible future poison toxicities of oligotrophic coastal habitats. Past wide-spread kills of fishes and sea urchins over the Caribbean Sea and the downstream GOM are examined in relation to the potential transmission of dinoflagellate saxitoxin and other epizootic poison vectors by western boundary currents over larger "commons" than local embayments. Furthermore, since some HABs produce more potent saxitoxins upon nutrient depletion, recent decisions to ban seasonal fertilizer applications to Florida lawns may have unintended consequences. In the future, human-killing phytoplankton, rather than relatively benign fish-killing HABs of the past, may be dispersed along the southeastern United States seaboard.

An efficient strategy for cell-based antibody library selection using an integrated vector system.

PubMed

Yoon, Hyerim; Song, Jin Myung; Ryu, Chun Jeih; Kim, Yeon-Gu; Lee, Eun Kyo; Kang, Sunghyun; Kim, Sang Jick

2012-09-18

Cell panning of phage-displayed antibody library is a powerful tool for the development of therapeutic and imaging agents since disease-related cell surface proteins in native complex conformation can be directly targeted. Here, we employed a strategy taking advantage of an integrated vector system which allows rapid conversion of scFv-displaying phage into scFv-Fc format for efficient cell-based scFv library selection on a tetraspanin protein, CD9. A mouse scFv library constructed by using a phagemid vector, pDR-D1 was subjected to cell panning against stable CD9 transfectant, and the scFv repertoire from the enriched phage pool was directly transferred to a mammalian cassette vector, pDR-OriP-Fc1. The resulting constructs enabled transient expression of enough amounts of scFv-Fcs in HEK293E cells, and flow cytometric screening of binders for CD9 transfectant could be performed simply by using the culture supernatants. All three clones selected from the screening showed correct CD9-specificity. They could immunoprecipitate CD9 molecules out of the transfectant cell lysate and correctly stain endogenous CD9 expression on cancer cell membrane. Furthermore, competition assay with a known anti-CD9 monoclonal antibody (mAb) suggested that the binding epitopes of some of them overlap with that of the mAb which resides within the large extracellular loop of CD9. This study demonstrates that scFv-Fc from mammalian transient expression can be chosen as a reliable format for rapid screening and validation in cell-based scFv library selection, and the strategy described here will be applicable to efficient discovery of antibodies to diverse cell-surface targets.

33 CFR 117.801 - Newtown Creek, Dutch Kills, English Kills and their tributaries.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., English Kills and their tributaries. 117.801 Section 117.801 Navigation and Navigable Waters COAST GUARD....801 Newtown Creek, Dutch Kills, English Kills and their tributaries. (a) The following requirements apply to all bridges across Newtown Creek, Dutch Kills, English Kills, and their tributaries: (1) The...

Plants traditionally used as mosquito repellents and the implication for their use in vector control.

PubMed

Tisgratog, Rungarun; Sanguanpong, Unchalee; Grieco, John P; Ngoen-Kluan, Ratchadawan; Chareonviriyaphap, Theeraphap

2016-05-01

Numerous plants with insect repelling properties are native to the tropics where they are produced for a wide range of medicinal purposes. In Thailand, these native plant species have a history of use for personal protection against biting insects. From our investigation we identified 37 plant species within 14 plant families that showed some mosquito repellent properties. Of these, 9 plant species were characterized using an excito-repellency test system against several Thai mosquito species. Results from these studies revealed that five essential oils extracted from plants demonstrated promising insect repellent activity. These active ingredients show promise for further development into formulations that may serve as alternatives to DEET or possibly be used as natural bio-pesticides to kill mosquitoes. Copyright © 2016 Elsevier B.V. All rights reserved.

Isolation of Brucella pinnipedialis from Grey Seals (Halichoerus grypus) in the Baltic Sea.

PubMed

Hirvelä-Koski, Varpu; Nylund, Minna; Skrzypczak, Teresa; Heikkinen, Petra; Kauhala, Kaarina; Jay, Maryne; Isomursu, Marja

2017-10-01

Brucella infection in seals was reported for the first time in 1994 around the coast of Scotland. Since then, marine mammal Brucella infections were found to be widely distributed in the northern hemisphere. Two Brucella species affect marine mammals: Brucella pinnipedialis in pinnipeds and Brucella ceti in cetaceans. We examined the livers of Baltic grey seals (Halichoerus grypus) from the Finnish coast (n=122) hunted, found dead, or killed as by-catch in fishing gear in 2013-15 as part of population health monitoring. We detected B. pinnipedialis in the livers of three grey seals. The bacterium was isolated from livers displaying parasitic cholangitis. We also detected Brucella DNA in liver flukes (Pseudamphistomum truncatum) obtained from a Brucella-infected grey seal, suggesting that flukes might be possible vectors of this pathogen in the marine environment.

Characterization of (asymptotically) Kerr-de Sitter-like spacetimes at null infinity

NASA Astrophysics Data System (ADS)

Mars, Marc; Paetz, Tim-Torben; Senovilla, José M. M.; Simon, Walter

2016-08-01

We investigate solutions ({M},g) to Einstein's vacuum field equations with positive cosmological constant Λ which admit a smooth past null infinity {{I}}- à la Penrose and a Killing vector field whose associated Mars-Simon tensor (MST) vanishes. The main purpose of this work is to provide a characterization of these spacetimes in terms of their Cauchy data on {{I}}-. Along the way, we also study spacetimes for which the MST does not vanish. In that case there is an ambiguity in its definition which is captured by a scalar function Q. We analyze properties of the MST for different choices of Q. In doing so, we are led to a definition of ‘asymptotically Kerr-de Sitter-like spacetimes’, which we also characterize in terms of their asymptotic data on {{I}}-. Preprint UWThPh-2016-5.

Optimizing HIV-1-specific CD8+ T-cell induction by recombinant BCG in prime-boost regimens with heterologous viral vectors.

PubMed

Hopkins, Richard; Bridgeman, Anne; Bourne, Charles; Mbewe-Mvula, Alice; Sadoff, Jerald C; Both, Gerald W; Joseph, Joan; Fulkerson, John; Hanke, Tomáš

2011-12-01

The desire to induce HIV-1-specific responses soon after birth to prevent breast milk transmission of HIV-1 led us to propose a vaccine regimen which primes HIV-1-specific T cells using a recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) vaccine. Because attenuated live bacterial vaccines are typically not sufficiently immunogenic as stand-alone vaccines, rBCG-primed T cells will likely require boost immunization(s). Here, we compared modified Danish (AERAS-401) and Pasteur lysine auxotroph (222) strains of BCG expressing the immunogen HIVA for their potency to prime HIV-1-specific responses in adult BALB/c mice and examined four heterologous boosting HIVA vaccines for their immunogenic synergy. We found that both BCG.HIVA(401) and BCG.HIVA(222) primed HIV-1-specific CD8(+) T-cell-mediated responses. The strongest boosts were delivered by human adenovirus-vectored HAdV5.HIVA and sheep atadenovirus-vectored OAdV7.HIVA vaccines, followed by poxvirus MVA.HIVA; the weakest was plasmid pTH.HIVA DNA. The prime-boost regimens induced T cells capable of efficient in vivo killing of sensitized target cells. We also observed that the BCG.HIVA(401) and BCG.HIVA(222) vaccines have broadly similar immunologic properties, but display a number of differences mainly detected through distinct profiles of soluble intercellular signaling molecules produced by immune splenocytes in response to both HIV-1- and BCG-specific stimuli. These results encourage further development of the rBCG prime-boost regimen. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel approach to abuse the hyperactive K-Ras pathway for adenoviral gene therapy of colorectal cancer

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

Naumov, Inna; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv; Kazanov, Dina

2012-01-15

Background: Functional activation of oncogenic K-Ras signaling pathway plays an important role in the early events of colorectal carcinogenesis (CRC). K-Ras proto-oncogene is involved in 35-40% of CRC cases. Mutations in the Ras gene trigger the transduction of proliferative and anti-apoptotic signals, even in the absence of extra cellular stimuli. The objective of the current study was to use a gene-targeting approach to kill human CRC cells selectively harboring mutated K-Ras. Results: A recombinant adenovirus that carries a lethal gene, PUMA, under the control of a Ras responsive promoter (Ad-Py4-SV40-PUMA) was used selectively to target CRC cells (HCT116, SW480, DLD1more » and RIE-Ras) that possess a hyperactive Ras pathway while using HT29 and RIE cells as a control that harbors wild type Ras and exhibit very low Ras activity. Control vector, without the Ras responsive promoter elements was used to assess the specificity of our 'gene therapy' approach. Both adenoviral vectors were assed in vitro and in xenograft model in vivo. Ad-Py4-SV40-PUMA showed high potency to induce {approx} 50% apoptosis in vitro, to abolish completely tumor formation by infecting cells with the Ad-Py4-SV40-PUMA prior xenografting them in nude mice and high ability to suppress by {approx} 35% tumor progression in vivo in already established tumors. Conclusions: Selective targeting of CRC cells with the activated Ras pathway may be a novel and effective therapy in CRC. The high potency of this adenoviral vector may help to overcome an undetectable micro metastasis that is the major hurdle in challenging with CRC.« less

Chimaera and its modern virus-like descendants.

PubMed

Ulrich, R; Gerlich, W H; Krüger, D H

1996-01-01

Chimaera was a monster in ancient Greek mythology combining elements from different animal species in its body. Modern molecular biology enabled the generation of harmless but useful chimaeras consisting of elements from different nonrelated viruses. The objective is that the resulting chimaeras form highly immunogenic virus-like particles (VLPs). Such chimaeric VLPs can be used as highly efficient carriers for sequential and conformational B cell epitopes and T cell epitopes. Most VLPs are readily produced in heterologous hosts and are easy to purify. This article deals with various systems of VLPs described in this topical issue of Intervirology and makes comparisons with chimaeric replication-competent viruses, recombinant virus vectors expressing foreign proteins, and DNA vaccines.

Bootstrapping the O(N) archipelago

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

Kos, Filip; Poland, David; Simmons-Duffin, David

2015-11-17

We study 3d CFTs with an O(N) global symmetry using the conformal bootstrap for a system of mixed correlators. Specifically, we consider all nonvanishing scalar four-point functions containing the lowest dimension O(N) vector Φ i and the lowest dimension O(N) singlet s, assumed to be the only relevant operators in their symmetry representations. The constraints of crossing symmetry and unitarity for these four-point functions force the scaling dimensions (Δ Φ , Δ s ) to lie inside small islands. Here, we also make rigorous determinations of current two-point functions in the O(2) and O(3) models, with applications to transport inmore » condensed matter systems.« less

Attenuated Human Parainfluenza Virus Type 1 Expressing the Respiratory Syncytial Virus (RSV) Fusion (F) Glycoprotein from an Added Gene: Effects of Prefusion Stabilization and Packaging of RSV F

PubMed Central

Liu, Xiang; Liang, Bo; Ngwuta, Joan; Liu, Xueqiao; Surman, Sonja; Lingemann, Matthias; Kwong, Peter D.; Graham, Barney S.; Collins, Peter L.

2017-01-01

ABSTRACT Human respiratory syncytial virus (RSV) is the most prevalent worldwide cause of severe respiratory tract infection in infants and young children. Human parainfluenza virus type 1 (HPIV1) also causes severe pediatric respiratory illness, especially croup. Both viruses lack vaccines. Here, we describe the preclinical development of a bivalent RSV/HPIV1 vaccine based on a recombinant HPIV1 vector, attenuated by a stabilized mutation, that expresses RSV F protein modified for increased stability in the prefusion (pre-F) conformation by previously described disulfide bond (DS) and hydrophobic cavity-filling (Cav1) mutations. RSV F was expressed from the first or second gene position as the full-length protein or as a chimeric protein with its transmembrane and cytoplasmic tail (TMCT) domains substituted with those of HPIV1 F in an effort to direct packaging in the vector particles. All constructs were recovered by reverse genetics. The TMCT versions of RSV F were packaged in the rHPIV1 particles much more efficiently than their full-length counterparts. In hamsters, the presence of the RSV F gene, and in particular the TMCT versions, was attenuating and resulted in reduced immunogenicity. However, the vector expressing full-length RSV F from the pre-N position was immunogenic for RSV and HPIV1. It conferred complement-independent high-quality RSV-neutralizing antibodies at titers similar to those of wild-type RSV and provided protection against RSV challenge. The vectors exhibited stable RSV F expression in vitro and in vivo. In conclusion, an attenuated rHPIV1 vector expressing a pre-F-stabilized form of RSV F demonstrated promising immunogenicity and should be further developed as an intranasal pediatric vaccine. IMPORTANCE RSV and HPIV1 are major viral causes of acute pediatric respiratory illness for which no vaccines or suitable antiviral drugs are available. The RSV F glycoprotein is the major RSV neutralization antigen. We used a rHPIV1 vector, bearing a stabilized attenuating mutation, to express the RSV F glycoprotein bearing amino acid substitutions that increase its stability in the pre-F form, the most immunogenic form that elicits highly functional virus-neutralizing antibodies. RSV F was expressed from the pre-N or N-P gene position of the rHPIV1 vector as a full-length protein or as a chimeric form with its TMCT domain derived from HPIV1 F. TMCT modification greatly increased packaging of RSV F into the vector particles but also increased vector attenuation in vivo, resulting in reduced immunogenicity. In contrast, full-length RSV F expressed from the pre-N position was immunogenic, eliciting complement-independent RSV-neutralizing antibodies and providing protection against RSV challenge. PMID:28835504

Restoration of visual response in aged dystrophic RCS rats using AAV-mediated channelopsin-2 gene transfer.

PubMed

Tomita, Hiroshi; Sugano, Eriko; Yawo, Hiromu; Ishizuka, Toru; Isago, Hitomi; Narikawa, Satoko; Kügler, Sebastian; Tamai, Makoto

2007-08-01

To investigate whether the channelopsin-2 (Chop2) gene would restore visual responses in 10-month-old dystrophic Royal College of Surgeons (aged RCS; rdy/rdy) rats, the authors transferred the Chop2 gene into the retinal cells of aged RCS rats using the adenoassociated virus (AAV) vector. The N-terminal fragment (residues 1-315) of Chop2 was fused to a fluorescent protein, Venus, in frame at the end of the Chop2 coding fragment. The viral vector construct (AAV-Chop2V) for the expression of the Chop2V in the retina was made by subcloning into an adenoassociated virus vector, including the CAG promoter. To evaluate the expression profile of Chop2V in the retina, the rats were killed and the eyes were removed and fixed with 4% paraformaldehyde in 0.1 M phosphate-buffered saline. Retinal wholemount specimens and cryosections were made. Under anesthetized conditions, electrodes for the recording of visually evoked potentials (VEPs) were implanted onto the visual cortex in aged-RCS (rdy/rdy) rats. AAV-Chop2V vectors were then injected into the vitreous cavity of the left eyes. As a control, AAV-Venus vectors were applied to the right eyes. VEPs were evoked by the flash of a blue, white, or red light-emitting diode (LED) and were recorded from the visual cortex of the rats at various time points after the AAV vector injection. Chop2V fluorescence was predominantly observed in retinal ganglion cells (RGCs). Some fluorescence was observed in the inner nuclear layer and the inner plexiform layer neurites. A tendency of recovery was observed in the VEPs of aged RCS (rdy/rdy) rats after the AAV-Chop2V injection but not after the AAV-Venus injection. The visual response of AAV-Chop2V-injected aged RCS (rdy/rdy) rats was less sensitive to the blue LED flash than that of nondystrophic RCS (+/+) rats. The AAV-Chop2V-injected aged RCS (rdy/rdy) rats were insensitive to the red LED flash, which evoked a robust VEP in the RCS (+/+) rats. The visual response of aged RCS (rdy/rdy) rats was partially restored by transduction of the Chop2 gene through AAV into the inner retinal neurons, mainly RGCs. These results suggest that the transduction of Chop2 would provide a new strategy to treat some retinitis pigmentosa (RP) symptoms independent of their etiology.

Bone generation in the reconstruction of a critical size calvarial defect in an experimental model.

PubMed

Por, Yong-Chen; Barceló, C Raul; Salyer, Kenneth E; Genecov, David G; Troxel, Karen; Gendler, El; Elsalanty, Mohammed E; Opperman, Lynne A

2008-03-01

This study was designed to investigate the optimal combination of known osteogenic biomaterials with shape conforming struts to achieve calvarial vault reconstruction, using a canine model. Eighteen adolescent beagles were divided equally into 6 groups. A critical-size defect of 6 x 2 cm traversed the sagittal suture. The biomaterials used for calvarial reconstruction were demineralized perforated bone matrix (DBM), recombinant human bone morphogenetic protein 2 (rhBMP2), and autogenous platelet-rich plasma (PRP). The struts used were cobalt chrome (metal) or resorbable plate. The groupings were as follows: 1) DBM + metal, 2) DBM + PRP + metal, 3) DBM + PRP + resorbable plate, 4) DBM + rhBMP2 + metal, 5) DBM + rhBMP2 + PRP + metal, and 6) DBM + rhBMP2 + resorbable plate. Animals were killed at 3 months after surgery. There was no mortality or major complications. Analysis was performed macroscopically and histologically and with computed tomography. There was complete bony regeneration in the rhBMP2 groups only. Non-rhBMP2 groups had minimal bony ingrowth from the defect edges and on the dural surface, a finding confirmed by computed tomographic scan and histology. Platelet-rich plasma did not enhance bone regeneration. Shape conformation was good with both metal and resorbable plate. rhBMP2, but not PRP, accelerated calvarial regeneration in 3 months. The DBMs in the rhBMP2 groups were substituted by new trabecular bone. Shape molding was good with both metal and resorbable plate.

β-Boomerang Antimicrobial and Antiendotoxic Peptides: Lipidation and Disulfide Bond Effects on Activity and Structure.

PubMed

Mohanram, Harini; Bhattacharjya, Surajit

2014-04-21

Drug-resistant Gram-negative bacterial pathogens and endotoxin- or lipopolysaccharide (LPS)-mediated inflammations are among some of the most  prominent health issues globally. Antimicrobial peptides (AMPs) are eminent molecules that can kill drug-resistant strains and neutralize LPS toxicity. LPS, the outer layer of the outer membrane of Gram-negative bacteria safeguards cell integrity against hydrophobic compounds, including antibiotics and AMPs. Apart from maintaining structural integrity, LPS, when released into the blood stream, also induces inflammatory pathways leading to septic shock. In previous works, we have reported the de novo design of a set of 12-amino acid long cationic/hydrophobic peptides for LPS binding and activity. These peptides adopt β-boomerang like conformations in complex with LPS. Structure-activity studies demonstrated some critical features of the β-boomerang scaffold that may be utilized for the further development of potent analogs. In this work, β-boomerang lipopeptides were designed and structure-activity correlation studies were carried out. These lipopeptides were homo-dimerized through a disulfide bridge to stabilize conformations and for improved activity. The designed peptides exhibited potent antibacterial activity and efficiently neutralized LPS toxicity under in vitro assays. NMR structure of C4YI13C in aqueous solution demonstrated the conserved folding of the lipopeptide with a boomerang aromatic lock stabilized with disulfide bond at the C-terminus and acylation at the N-terminus. These lipo-peptides displaying bacterial sterilization and low hemolytic activity may be useful for future applications as antimicrobial and antiendotoxin molecules.

Management of Listeria monocytogenes in fermented sausages using the Food Safety Objective concept underpinned by stochastic modeling and meta-analysis.

PubMed

Mataragas, M; Alessandria, V; Rantsiou, K; Cocolin, L

2015-08-01

In the present work, a demonstration is made on how the risk from the presence of Listeria monocytogenes in fermented sausages can be managed using the concept of Food Safety Objective (FSO) aided by stochastic modeling (Bayesian analysis and Monte Carlo simulation) and meta-analysis. For this purpose, the ICMSF equation was used, which combines the initial level (H0) of the hazard and its subsequent reduction (ΣR) and/or increase (ΣI) along the production chain. Each element of the equation was described by a distribution to investigate the effect not only of the level of the hazard, but also the effect of the accompanying variability. The distribution of each element was determined by Bayesian modeling (H0) and meta-analysis (ΣR and ΣI). The output was a normal distribution N(-5.36, 2.56) (log cfu/g) from which the percentage of the non-conforming products, i.e. the fraction above the FSO of 2 log cfu/g, was estimated at 0.202%. Different control measures were examined such as lowering initial L. monocytogenes level and inclusion of an additional killing step along the process resulting in reduction of the non-conforming products from 0.195% to 0.003% based on the mean and/or square-root change of the normal distribution, and 0.001%, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Conformational flexibility determines selectivity and antibacterial, antiplasmodial, and anticancer potency of cationic α-helical peptides.

PubMed

Vermeer, Louic S; Lan, Yun; Abbate, Vincenzo; Ruh, Emrah; Bui, Tam T; Wilkinson, Louise J; Kanno, Tokuwa; Jumagulova, Elmira; Kozlowska, Justyna; Patel, Jayneil; McIntyre, Caitlin A; Yam, W C; Siu, Gilman; Atkinson, R Andrew; Lam, Jenny K W; Bansal, Sukhvinder S; Drake, Alex F; Mitchell, Graham H; Mason, A James

2012-10-05

We used a combination of fluorescence, circular dichroism (CD), and NMR spectroscopies in conjunction with size exclusion chromatography to help rationalize the relative antibacterial, antiplasmodial, and cytotoxic activities of a series of proline-free and proline-containing model antimicrobial peptides (AMPs) in terms of their structural properties. When compared with proline-free analogs, proline-containing peptides had greater activity against Gram-negative bacteria, two mammalian cancer cell lines, and intraerythrocytic Plasmodium falciparum, which they were capable of killing without causing hemolysis. In contrast, incorporation of proline did not have a consistent effect on peptide activity against Mycobacterium tuberculosis. In membrane-mimicking environments, structures with high α-helix content were adopted by both proline-free and proline-containing peptides. In solution, AMPs generally adopted disordered structures unless their sequences comprised more hydrophobic amino acids or until coordinating phosphate ions were added. Proline-containing peptides resisted ordering induced by either method. The roles of the angle subtended by positively charged amino acids and the positioning of the proline residues were also investigated. Careful positioning of proline residues in AMP sequences is required to enable the peptide to resist ordering and maintain optimal antibacterial activity, whereas varying the angle subtended by positively charged amino acids can attenuate hemolytic potential albeit with a modest reduction in potency. Maintaining conformational flexibility improves AMP potency and selectivity toward bacterial, plasmodial, and cancerous cells while enabling the targeting of intracellular pathogens.

Cryo-EM structures of two bovine adenovirus type 3 intermediates

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

Cheng, Lingpeng; Huang, Xiaoxing; Li, Xiaomin

2014-02-15

Adenoviruses (Ads) infect hosts from all vertebrate species and have been investigated as vaccine vectors. We report here near-atomic structures of two bovine Ad type 3 (BAd3) intermediates obtained by cryo-electron microscopy. A comparison between the two intermediate structures reveals that the differences are localized in the fivefold vertex region, while their facet structures are identical. The overall facet structure of BAd3 exhibits a similar structure to human Ads; however, BAd3 protein IX has a unique conformation. Mass spectrometry and cryo-electron tomography analyses indicate that one intermediate structure represents the stage during DNA encapsidation, whilst the other intermediate structure representsmore » a later stage. These results also suggest that cleavage of precursor protein VI occurs during, rather than after, the DNA encapsidation process. Overall, our results provide insights into the mechanism of Ad assembly, and allow the first structural comparison between human and nonhuman Ads at backbone level. - Highlights: • First structure of bovine adenovirus type 3. • Some channels are located at the vertex of intermediate during DNA encapsidation. • Protein IX exhibits a unique conformation of trimeric coiled–coiled structure. • Cleavage of precursor protein VI occurs during the DNA encapsidation process.« less

The conformation of Pluronic block copolymers adsorbed on carbon nanotubes and their interaction with water studied by small-angle neutron scattering

NASA Astrophysics Data System (ADS)

Cohen, Yachin; Granite, Meirav; Pyckhout-Hintzen, Wim; Radulescu, Aurel

2010-03-01

Amphiphilic block copolymers are particularly useful in dispersing single-walled carbon nanotubes (SWCNT) in water. Small-angle neutron scattering measurements conducted at different D2O/H2O content of the dispersing medium provide quantitative information on the adsorption density and conformation of the polymer interacting with the nanotube surface. Data is presented on Pluronic F108 - (EO)132(PO)50(EO)132 and F127 (EO)100(PO)65(EO)100, where EO-ethylene oxide and PO-propylene oxide, well below the critical micellization temperature of the polymer. A dense coating of the PPO blocks on the nanotube surface is determined with the PEO chains extended from the cylindrical core-shell structure. The data from the two Pluronic systems show minimal scattering at about 70% D2O in the dispersing water, which exhibit a q -1 power law of the scattering vector (q ). This indicates near matching of the polymer chains at a surprisingly high scattering length density. The model fit required considerations of tight association of water molecules around PEO chains and slight isotopic selectivity.

Machine learning classification with confidence: application of transductive conformal predictors to MRI-based diagnostic and prognostic markers in depression.

PubMed

Nouretdinov, Ilia; Costafreda, Sergi G; Gammerman, Alexander; Chervonenkis, Alexey; Vovk, Vladimir; Vapnik, Vladimir; Fu, Cynthia H Y

2011-05-15

There is rapidly accumulating evidence that the application of machine learning classification to neuroimaging measurements may be valuable for the development of diagnostic and prognostic prediction tools in psychiatry. However, current methods do not produce a measure of the reliability of the predictions. Knowing the risk of the error associated with a given prediction is essential for the development of neuroimaging-based clinical tools. We propose a general probabilistic classification method to produce measures of confidence for magnetic resonance imaging (MRI) data. We describe the application of transductive conformal predictor (TCP) to MRI images. TCP generates the most likely prediction and a valid measure of confidence, as well as the set of all possible predictions for a given confidence level. We present the theoretical motivation for TCP, and we have applied TCP to structural and functional MRI data in patients and healthy controls to investigate diagnostic and prognostic prediction in depression. We verify that TCP predictions are as accurate as those obtained with more standard machine learning methods, such as support vector machine, while providing the additional benefit of a valid measure of confidence for each prediction. Copyright © 2010 Elsevier Inc. All rights reserved.

Elliptic surface grid generation on minimal and parmetrized surfaces

NASA Technical Reports Server (NTRS)

Spekreijse, S. P.; Nijhuis, G. H.; Boerstoel, J. W.

1995-01-01

An elliptic grid generation method is presented which generates excellent boundary conforming grids in domains in 2D physical space. The method is based on the composition of an algebraic and elliptic transformation. The composite mapping obeys the familiar Poisson grid generation system with control functions specified by the algebraic transformation. New expressions are given for the control functions. Grid orthogonality at the boundary is achieved by modification of the algebraic transformation. It is shown that grid generation on a minimal surface in 3D physical space is in fact equivalent to grid generation in a domain in 2D physical space. A second elliptic grid generation method is presented which generates excellent boundary conforming grids on smooth surfaces. It is assumed that the surfaces are parametrized and that the grid only depends on the shape of the surface and is independent of the parametrization. Concerning surface modeling, it is shown that bicubic Hermite interpolation is an excellent method to generate a smooth surface which is passing through a given discrete set of control points. In contrast to bicubic spline interpolation, there is extra freedom to model the tangent and twist vectors such that spurious oscillations are prevented.

An engineering closure for heavily under-resolved coarse-grid CFD in large applications

NASA Astrophysics Data System (ADS)

Class, Andreas G.; Yu, Fujiang; Jordan, Thomas

2016-11-01

Even though high performance computation allows very detailed description of a wide range of scales in scientific computations, engineering simulations used for design studies commonly merely resolve the large scales thus speeding up simulation time. The coarse-grid CFD (CGCFD) methodology is developed for flows with repeated flow patterns as often observed in heat exchangers or porous structures. It is proposed to use inviscid Euler equations on a very coarse numerical mesh. This coarse mesh needs not to conform to the geometry in all details. To reinstall physics on all smaller scales cheap subgrid models are employed. Subgrid models are systematically constructed by analyzing well-resolved generic representative simulations. By varying the flow conditions in these simulations correlations are obtained. These comprehend for each individual coarse mesh cell a volume force vector and volume porosity. Moreover, for all vertices, surface porosities are derived. CGCFD is related to the immersed boundary method as both exploit volume forces and non-body conformal meshes. Yet, CGCFD differs with respect to the coarser mesh and the use of Euler equations. We will describe the methodology based on a simple test case and the application of the method to a 127 pin wire-wrap fuel bundle.

Normal mode-guided transition pathway generation in proteins

PubMed Central

Lee, Byung Ho; Seo, Sangjae; Kim, Min Hyeok; Kim, Youngjin; Jo, Soojin; Choi, Moon-ki; Lee, Hoomin; Choi, Jae Boong

2017-01-01

The biological function of proteins is closely related to its structural motion. For instance, structurally misfolded proteins do not function properly. Although we are able to experimentally obtain structural information on proteins, it is still challenging to capture their dynamics, such as transition processes. Therefore, we need a simulation method to predict the transition pathways of a protein in order to understand and study large functional deformations. Here, we present a new simulation method called normal mode-guided elastic network interpolation (NGENI) that performs normal modes analysis iteratively to predict transition pathways of proteins. To be more specific, NGENI obtains displacement vectors that determine intermediate structures by interpolating the distance between two end-point conformations, similar to a morphing method called elastic network interpolation. However, the displacement vector is regarded as a linear combination of the normal mode vectors of each intermediate structure, in order to enhance the physical sense of the proposed pathways. As a result, we can generate more reasonable transition pathways geometrically and thermodynamically. By using not only all normal modes, but also in part using only the lowest normal modes, NGENI can still generate reasonable pathways for large deformations in proteins. This study shows that global protein transitions are dominated by collective motion, which means that a few lowest normal modes play an important role in this process. NGENI has considerable merit in terms of computational cost because it is possible to generate transition pathways by partial degrees of freedom, while conventional methods are not capable of this. PMID:29020017

The influence of novel gemini surfactants containing cycloalkyl side-chains on the structural phases of DNA in solution.

PubMed

Pietralik, Zuzanna; Kumita, Janet R; Dobson, Christopher M; Kozak, Maciej

2015-07-01

Very important to gene therapy is the delivery system of the nucleic acids (called a vector), which will enhance the efficiency of the transport of new DNA into cells whilst protecting against damage. A promising alternative to the currently used viral vectors are the systems based on amphiphilic compounds - lipoplexes. Among them, gemini surfactants, which consist of two hydrophobic chains and two cationic heads connected by a linker - spacer group, appear to be promising candidates. The subject of this study involves two gemini surfactants, alkoxy derivatives of bis-imidazolium quaternary salts, differing in the length of their spacer groups and how they interact with two types of salmon sperm DNA (low and high molecular weight (MW)) or plasmid DNA (pDNA). The mixtures of gemini surfactants with nucleic acids of differing p/n ratios (positive-to-negative charge ratio) were characterised by small angle X-ray scattering (SAXS) of synchrotron radiation, dynamic light scattering (DLS), circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM) and gel electrophoresis techniques. This analysis allows for the selection of the most suitable and promising candidates for non-viral vectors in gene therapy, determination of the conditions needed to form stable complexes, identification of conformational changes in the DNA molecules upon interactions with gemini surfactants and in some cases, determination of the structures formed in these lipoplexes. Copyright © 2015 Elsevier B.V. All rights reserved.

The measurement of an aspherical mirror by three-dimensional nanoprofiler

NASA Astrophysics Data System (ADS)

Tokuta, Yusuke; Okita, Kenya; Okuda, Kohei; Kitayama, Takao; Nakano, Motohiro; Nakatani, Shun; Kudo, Ryota; Yamamura, Kazuya; Endo, Katsuyoshi

2015-09-01

Aspherical optical elements with high accuracy are important in several fields such as third-generation synchrotron radiation and extreme-ultraviolet lithography. Then the demand of measurement method for aspherical or free-form surface with nanometer resolution is rising. Our purpose is to develop a non-contact profiler to measure free-form surfaces directly with repeatability of figure error of less than 1 nm PV. To achieve this purpose we have developed three-dimensional Nanoprofiler which traces normal vectors of sample surface. The measurement principle is based on the straightness of LASER light and the accuracy of a rotational goniometer. This machine consists of four rotational stages, one translational stage and optical head which has the quadrant photodiode (QPD) and LASER head at optically equal position. In this measurement method, we conform the incident light beam to reflect the beam by controlling five stages and determine the normal vectors and the coordinates of the surface from signal of goniometers, translational stage and QPD. We can obtain three-dimensional figure from the normal vectors and the coordinates by a reconstruction algorithm. To evaluate performance of this machine we measure a concave aspherical mirror ten times. From ten results we calculate measurement repeatability, and we evaluate measurement uncertainty to compare the result with that measured by an interferometer. In consequence, the repeatability of measurement was 2.90 nm (σ) and the difference between the two profiles was +/-20 nm. We conclude that the two profiles was correspondent considering systematic errors of each machine.

An experimental hut evaluation of Olyset Plus, a long-lasting insecticidal net treated with a mixture of permethrin and piperonyl butoxide, against Anopheles fluviatilis in Odisha State, India.

PubMed

Gunasekaran, Kasinathan; Sahu, Sudhansu Sekhar; Vijayakumar, Tharmalingam; Subramanian, Swaminathan; Yadav, Rajpal Singh; Pigeon, Olivier; Jambulingam, Purushothaman

2016-07-21

Fast development of pyrethroid resistance in malaria vectors prompted the development of new vector control tools including combination of insecticides with different modes of action as part of resistance management strategies. Olyset Plus® is a new long-lasting insecticidal net, in which, permethrin and a synergist, piperonyl butoxide (PBO), are incorporated into filaments. Mixture nets such as this may have application against resistant mosquitoes, particularly those whose resistance is based on oxidative metabolism. There may also be enhanced activity against susceptible mosquitoes since mixed function oxidases are involved in a many metabolic activities including activation to form bioactive compounds. Bio-efficacy of Olyset Plus was evaluated against susceptible malaria vector, Anopheles fluviatilis in experimental huts. Deterrence, blood feeding inhibition, induced exophily and killing effect were measured to assess the bio-efficacy. The results were compared with Olyset Net®, a polyethylene permethrin-incorporated LLIN and a conventionally treated polyester net (with permethrin) washed to just before exhaustion. Results showed significant reduction in entry (treatment: 0.4-0.8; control: 4.2 per trap-night) and increase in exit (56.3-82.9 % and 44.2 %) rates of Anopheles fluviatilis in the treatment arms compared to control (P < 0.05). While blood feeding rates declined in treatment arms (18.8-30.6 %), it increased in control (77.6 %) (P < 0.05). This was further evident from the blood-feeding inhibition rates in treatment arms (60.6-90.6 %). Total mortality was significantly higher in all treatment arms (96.3-100 %) compared to control arm (2 %) (P < 0.05). Chemical analysis for active ingredient (AI) showed retention of 75 and 88 % in Olyset plus and Olyset net respectively after 20 washes. Performance of Olyset Plus washed 20 times was equal to the CTN and Olyset Net against the susceptible malaria vector An. fluviatilis, fulfilling the WHO efficacy criteria of Phase II evaluation for LLIN. However, the benefit of incorporating PBO and permethrin together in a long-lasting treatment could not be demonstrated in the current study as the target vector species was fully susceptible to pyrethroids. Olyset Plus, with its intrinsic bio-efficacy could be an effective vector control tool to prevent transmission of malaria by susceptible vectors like An. fluviatilis. However, the results of the current study need to be further supported by testing the net at village level (Phase III) for community acceptability. Before taking the net to village level, it needs to be verified whether the net is better than pyrethroid nets in terms of bio-efficacy against resistant An. culicifacies, another malaria vector that has developed resistance to synthetic pyrethroids in India.

Spiroplasma infection causes either early or late male killing in Drosophila, depending on maternal host age

NASA Astrophysics Data System (ADS)

Kageyama, Daisuke; Anbutsu, Hisashi; Shimada, Masakazu; Fukatsu, Takema

2007-04-01

Symbiont-induced male-killing phenotypes have been found in a variety of insects. Conventionally, these phenotypes have been divided into two categories according to the timing of action: early male killing at embryonic stages and late male killing at late larval stages. In Drosophila species, endosymbiotic bacteria of the genus Spiroplasma have been known to cause early male killing. Here, we report that a spiroplasma strain normally causing early male killing also induces late male killing depending on the maternal host age: male-specific mortality of larvae and pupae was more frequently observed in the offspring of young females. As the lowest spiroplasma density and occasional male production were also associated with newly emerged females, we proposed the density-dependent hypothesis for the expression of early and late male-killing phenotypes. Our finding suggested that (1) early and late male-killing phenotypes can be caused by the same symbiont and probably by the same mechanism; (2) late male killing may occur as an attenuated expression of early male killing; (3) expression of early and late male-killing phenotypes may be dependent on the symbiont density, and thus, could potentially be affected by the host immunity and regulation; and (4) early male killing and late male killing could be alternative strategies adopted by microbial reproductive manipulators.

Colonization of Rhodnius prolixus gut by Trypanosoma cruzi involves an extensive parasite killing.

PubMed

Ferreira, Roberta Carvalho; Kessler, Rafael Luis; Lorenzo, Marcelo Gustavo; Paim, Rafaela Magalhães Macedo; Ferreira, Luciana De Lima; Probst, Christian Macagnan; Alves-Silva, Juliana; Guarneri, Alessandra Aparecida

2016-04-01

Trypanosoma cruzi, the etiological agent of Chagas disease, is ingested by triatomines during their bloodmeal on an infected mammal. Aiming to investigate the development and differentiation of T. cruzi inside the intestinal tract of Rhodnius prolixus at the beginning of infection we fed insects with cultured epimastigotes and blood trypomastigotes from infected mice to determine the amount of recovered parasites after ingestion. Approximately 20% of the ingested parasites was found in the insect anterior midgut (AM) 3 h after feeding. Interestingly, a significant reduction (80%) in the numbers of trypomastigotes was observed after 24 h of infection suggesting that parasites were killed in the AM. Moreover, few parasites were found in that intestinal portion after 96 h of infection. The evaluation of the numbers of parasites in the posterior midgut (PM) at the same periods showed a reduced parasite load, indicating that parasites were not moving from the AM. Additionally, incubation of blood trypomastigotes with extracts from R. prolixus AMs revealed that components of this tissue could induce significant death of T. cruzi. Finally, we observed that differentiation from trypomastigotes to epimastigotes is not completed in the AM; instead we suggest that trypomastigotes change to intermediary forms before their migration to the PM, where differentiation to epimastigotes takes place. The present work clarifies controversial points concerning T. cruzi development in insect vector, showing that parasite suffers a drastic decrease in population size before epimastigonesis accomplishment in PM.

Enhanced EJ Cell Killing of (125)I Radiation by Combining with Cytosine Deaminase Gene Therapy Regulated by Synthetic Radio-Responsive Promoter.

PubMed

Li, Ling; Zhang, Chun-li; Kang, Lei; Wang, Rong-Fu; Yan, Ping; Zhao, Qian; Yin, Lei; Guo, Feng-qin

2015-10-01

To investigate the enhancing effect of radionuclide therapy by the therapeutic gene placed under the control of radio-responsive promoter. The recombinant lentivirus E8-codA-GFP, including a synthetic radiation-sensitive promoter E8, cytosine deaminase (CD) gene, and green fluorescent protein gene, was constructed. The gene expression activated by (125)I radiation was assessed by observation of green fluorescence. The ability of converting 5-fluorocytosine (5-FC) to 5-fluorourial (5-FU) by CD enzyme was assessed by high-performance liquid chromatography. The viability of the infected cells exposed to (125)I in the presence of 5-FC was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the infected cells exposed to (125)I alone served as negative control and 5-FU as positive control. The recombinant lentiviral vector was constructed successfully. On exposure of infected cells to (125)I, green fluorescence can be observed and 5-FU can be detected. MTT assay showed that the survival rate for infected cells treated with (125)I was lower compared with the (125)I control group, but higher than the positive control group. The synthetic promoter E8 can induce the expression of downstream CD gene under (125)I radiation, and the tumor killing effect of (125)I can be enhanced by combining CD gene therapy with radiosensitive promoter.

33 CFR 117.801 - Newtown Creek, Dutch Kills, English Kills and their tributaries.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Newtown Creek, Dutch Kills, English Kills and their tributaries. 117.801 Section 117.801 Navigation and Navigable Waters COAST GUARD....801 Newtown Creek, Dutch Kills, English Kills and their tributaries. (a) The following requirements...

33 CFR 117.801 - Newtown Creek, Dutch Kills, English Kills and their tributaries.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Newtown Creek, Dutch Kills, English Kills and their tributaries. 117.801 Section 117.801 Navigation and Navigable Waters COAST GUARD....801 Newtown Creek, Dutch Kills, English Kills and their tributaries. (a) The following requirements...

33 CFR 117.801 - Newtown Creek, Dutch Kills, English Kills and their tributaries.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Newtown Creek, Dutch Kills, English Kills and their tributaries. 117.801 Section 117.801 Navigation and Navigable Waters COAST GUARD....801 Newtown Creek, Dutch Kills, English Kills and their tributaries. (a) The following requirements...

33 CFR 117.801 - Newtown Creek, Dutch Kills, English Kills and their tributaries.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Newtown Creek, Dutch Kills, English Kills and their tributaries. 117.801 Section 117.801 Navigation and Navigable Waters COAST GUARD....801 Newtown Creek, Dutch Kills, English Kills and their tributaries. (a) The following requirements...

Evidence for Personal Protective Measures to Reduce Human Contact With Blacklegged Ticks and for Environmentally Based Control Methods to Suppress Host-Seeking Blacklegged Ticks and Reduce Infection with Lyme Disease Spirochetes in Tick Vectors and Rodent Reservoirs.

PubMed

Eisen, Lars; Dolan, Marc C

2016-07-20

In the 1980s, the blacklegged tick, Ixodes scapularis Say, and rodents were recognized as the principal vector and reservoir hosts of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, and deer were incriminated as principal hosts for I. scapularis adults. These realizations led to pioneering studies aiming to reduce the risk for transmission of B. burgdorferi to humans by attacking host-seeking ticks with acaricides, interrupting the enzootic transmission cycle by killing immatures infesting rodent reservoirs by means of acaricide-treated nesting material, or reducing deer abundance to suppress tick numbers. We review the progress over the past three decades in the fields of: 1) prevention of human-tick contact with repellents and permethrin-treated clothing, and 2) suppression of I. scapularis and disruption of enzootic B. burgdorferi transmission with environmentally based control methods. Personal protective measures include synthetic and natural product-based repellents that can be applied to skin and clothing, permethrin sprays for clothing and gear, and permethrin-treated clothing. A wide variety of approaches and products to suppress I. scapularis or disrupt enzootic B. burgdorferi transmission have emerged and been evaluated in field trials. Application of synthetic chemical acaricides is a robust method to suppress host-seeking I. scapularis ticks within a treated area for at least 6-8 wk. Natural product-based acaricides or entomopathogenic fungi have emerged as alternatives to kill host-seeking ticks for homeowners who are unwilling to use synthetic chemical acaricides. However, as compared with synthetic chemical acaricides, these approaches appear less robust in terms of both their killing efficacy and persistence. Use of rodent-targeted topical acaricides represents an alternative for homeowners opposed to open distribution of acaricides to the ground and vegetation on their properties. This host-targeted approach also provides the benefit of the intervention impacting the entire rodent home range. Rodent-targeted oral vaccines against B. burgdorferi and a rodent-targeted antibiotic bait have been evaluated in laboratory and field trials but are not yet commercially available. Targeting of deer-via deer reduction or treatment of deer with topical acaricides-can provide area-wide suppression of host-seeking I. scapularis These two deer-targeted approaches combine great potential for protection that impacts the entire landscape with severe problems relating to public acceptance or implementation logistics. Integrated use of two or more methods has unfortunately been evaluated in very few published studies, but additional field evaluations of integrated tick and pathogen strategies are underway. Published by Oxford University Press on behalf of Journal of Medical Entomology 2016. This work is written by US Government employees and is in the public domain in the US.

A 750 GeV messenger of dark conformal symmetry breaking

DOE PAGES

Davoudiasl, Hooman; Zhang, Cen

2016-03-03

The tentative hints for a diphoton resonance at a mass of ~750 GeV from the ATLAS and CMS experiments at the LHC may be interpreted as first contact with a “dark” sector with a spontaneously broken conformal symmetry. The implied TeV scale of the dark sector may be motivated by the interaction strength required to accommodate a viable thermal relic dark matter (DM) candidate. We model the conformal dynamics using a Randall-Sundrum-type five-dimensional geometry whose IR boundary is identified with the dynamics of the composite dark sector, while the Standard Model (SM) matter content resides on the UV boundary, correspondingmore » to “elementary” fields. We allow the gauge fields to reside in the five-dimensional bulk, which can be minimally chosen to be SU(3)c×U(1)Y. The “dark” radion is identified as the putative 750 GeV resonance. Heavy vectorlike fermions, often invoked to explain the diphoton excess, are not explicitly present in our model and are not predicted to appear in the spectrum of TeV scale states. Our minimal setup favors scalar DM of O(TeV) mass. A generic expectation in this scenario, suggested by DM considerations, is the appearance of vector bosons at ~ few TeV, corresponding to the gluon and hypercharge Kaluza-Klein (KK) modes that couple to UV boundary states with strengths that are suppressed uniformly compared to their SM values. Furthermore, our analysis suggests that these KK modes could be within the reach of the LHC in the coming years.« less

A 750 GeV messenger of dark conformal symmetry breaking

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

Davoudiasl, Hooman; Zhang, Cen

The tentative hints for a diphoton resonance at a mass of ~750 GeV from the ATLAS and CMS experiments at the LHC may be interpreted as first contact with a “dark” sector with a spontaneously broken conformal symmetry. The implied TeV scale of the dark sector may be motivated by the interaction strength required to accommodate a viable thermal relic dark matter (DM) candidate. We model the conformal dynamics using a Randall-Sundrum-type five-dimensional geometry whose IR boundary is identified with the dynamics of the composite dark sector, while the Standard Model (SM) matter content resides on the UV boundary, correspondingmore » to “elementary” fields. We allow the gauge fields to reside in the five-dimensional bulk, which can be minimally chosen to be SU(3)c×U(1)Y. The “dark” radion is identified as the putative 750 GeV resonance. Heavy vectorlike fermions, often invoked to explain the diphoton excess, are not explicitly present in our model and are not predicted to appear in the spectrum of TeV scale states. Our minimal setup favors scalar DM of O(TeV) mass. A generic expectation in this scenario, suggested by DM considerations, is the appearance of vector bosons at ~ few TeV, corresponding to the gluon and hypercharge Kaluza-Klein (KK) modes that couple to UV boundary states with strengths that are suppressed uniformly compared to their SM values. Furthermore, our analysis suggests that these KK modes could be within the reach of the LHC in the coming years.« less

Risk of false decision on conformity of a multicomponent material when test results of the components' content are correlated.

PubMed

Kuselman, Ilya; Pennecchi, Francesca R; da Silva, Ricardo J N B; Hibbert, D Brynn

2017-11-01

The probability of a false decision on conformity of a multicomponent material due to measurement uncertainty is discussed when test results are correlated. Specification limits of the components' content of such a material generate a multivariate specification interval/domain. When true values of components' content and corresponding test results are modelled by multivariate distributions (e.g. by multivariate normal distributions), a total global risk of a false decision on the material conformity can be evaluated based on calculation of integrals of their joint probability density function. No transformation of the raw data is required for that. A total specific risk can be evaluated as the joint posterior cumulative function of true values of a specific batch or lot lying outside the multivariate specification domain, when the vector of test results, obtained for the lot, is inside this domain. It was shown, using a case study of four components under control in a drug, that the correlation influence on the risk value is not easily predictable. To assess this influence, the evaluated total risk values were compared with those calculated for independent test results and also with those assuming much stronger correlation than that observed. While the observed statistically significant correlation did not lead to a visible difference in the total risk values in comparison to the independent test results, the stronger correlation among the variables caused either the total risk decreasing or its increasing, depending on the actual values of the test results. Copyright © 2017 Elsevier B.V. All rights reserved.

Horizon fluffs: In the context of generalized minimal massive gravity

NASA Astrophysics Data System (ADS)

Setare, Mohammad Reza; Adami, Hamed

2018-02-01

We consider a metric which describes Bañados geometries and show that the considered metric is a solution of the generalized minimal massive gravity (GMMG) model. We consider the Killing vector field which preserves the form of the considered metric. Using the off-shell quasi-local approach we obtain the asymptotic conserved charges of the given solution. Similar to the Einstein gravity in the presence of negative cosmological constant, for the GMMG model, we also show that the algebra among the asymptotic conserved charges is isomorphic to two copies of the Virasoro algebra. Eventually, we find a relation between the algebra of the near-horizon and the asymptotic conserved charges. This relation shows that the main part of the horizon fluffs proposed by Afshar et al., Sheikh-Jabbari and Yavartanoo appear for generic black holes in the class of Bañados geometries in the context of the GMMG model.