bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperelliptic Curves with Extra Involutions
Authors: Gutierrez J. , Shaska T.
Published: August 2013

The purpose of this paper is to study hyperelliptic curves with extra involutions. The locusLgof such genus-ghyperelliptic curves is ag-dimensional subvariety of the moduli space of hyperelliptic curvesHg. The authors present a birational parameterization ofLgvia dihedral invariants, and show how these invariants can be used to determine the field of moduli of points p ∈ Lg. They conjecture that for p ∈Hgwith |Aut(p)| > 2, the field of moduli is a field of definition, and they prove this conjecture for any point p ∈Lgsuch that the Klein 4-group is embedded in the reduced automorphism group ofp. Further, forg= 3, they show that for every moduli point p ∈H3such that |Aut(p)| > 4, the field of moduli is a field of definition. A rational model of the curve over its field of moduli is provided.
Generalised Sifting in Black-Box Groups
Authors: Ambrose Sophie , Neunhöffer Max , Praeger Cheryl E. , Schneider Csaba
Published: August 2013

This paper presents a generalisation of the sifting procedure introduced originally by Sims for computation with finite permutation groups, and now used for many computational procedures for groups, such as membership testing and finding group orders. The new procedure is a Monte Carlo algorithm, and it is presented and analysed in the context of black-box groups. It is based on a chain of subsets instead of a subgroup chain. Two general versions of the procedure are worked out in detail, and applications are given for membership tests for several of the sporadic simple groups. The authors' major objective was that the procedures could be proved to be Monte Carlo algorithms, and the costs computed. In addition, they explicitly determined suitable subset chains for six of the sporadic groups, and then implemented the algorithms involving these chains in the GAP computational algebra system. It turns out that sample imple-mentations perform well in practice. The implementations will be made available publicly in the form of a GAP package.
A New Geometric Algorithm to Generate Smooth Interpolating Curves on Riemannian Manifolds
Authors: Rodrigues Rui C. , Silva Leite F. , Jakubiak Janusz
Published: August 2013

This paper presents a new geometric algorithm to construct a Ck-smooth spline curve that interpolates a given set of data (points and velocities) on a complete Riemannian manifold. Although based on a modification of the De Casteljau procedure, this new algorithm is implemented in only three steps, independently of the required degree of smoothness, and therefore introduces a significant reduction in complexity. The key role is played by the choice of an appropriate smoothing function, which is defined as soon as the degree of smoothness is fixed.
The Equivalence between the DHP and DLP for Elliptic Curves Used in Practical Applications
Authors: Muzereau A. , Smart N. P. , Vercauteren F.
Published: August 2013

In this paper, the authors re-examine the reduction of Maurer and Wolf of the discrete logarithm problem to the Diffie-Hellman problem. They give a precise estimate for the number of operations required in the reduction, and then use this to estimate the exact security of the elliptic curve variant of the Diffie-Hellman protocol for various elliptic curves defined in standards.
The Alperin Weight Conjecture and Uno's Conjecture for the Baby Monster B, p Odd
Authors: An Jianbei , Wilson R. A.
Published: August 2013

Suppose that p is 3, 5 or 7. In this paper, faithful permutation representations of maximal p-local subgroups are constructed, and the radical p-chains of the Baby Monster B are classified. Hence, the Alperin weight conjecture and the Uno reductive conjecture can be verified for B, the latter being a refinement of Dade's reductive conjecture and the Isaacs-Navarro conjecture.
Generalising the GHS Attack on the Elliptic Curve Discrete Logarithm Problem
Authors: Hess F.
Published: August 2013

The Weil descent construction of the GHS attack on the elliptic curve discrete logarithm problem (ECDLP) is generalised in this paper, to arbitrary Artin-Schreier extensions. A formula is given for the characteristic polynomial of Frobenius for the curves thus obtained, as well as a proof that the large cyclic factor of the input elliptic curve is not contained in the kernel of the composition of the conorm and norm maps. As an application, the number of elliptic curves that succumb to the basic GHS attack is considerably increased, thereby further weakening curves over GF2155.

Other possible extensions or variations of the GHS attack are discussed, leading to the conclusion that they are unlikely to yield further improvements.
Estimation of Riemannian Barycentres
Authors: Le Huiling
Published: August 2013

Using Jacobi field arguments, this paper describes an iterative procedure for finding the Riemannian barycentres of a class of probability measures on complete, simply connected Riemannian manifolds with a finite upper bound on their sectional curvatures. This, in particular, generalises an earlier result of the author's (‘Locating Fréchet means with application to shape spaces’, Adv. Appl. Probab. 33 (2001) 324-338).
Extending the Promise of the Deutsch–Jozsa–Høyer Algorithm for Finite Groups
Authors: Batty Michael , Duncan Andrew J. , Braunstein Samuel L.
Published: August 2013

Høyer has given a generalisation of the Deutsch–Jozsa algorithm which uses the Fourier transform on a group G which is (in general) non-Abelian. His algorithm distinguishes between functions which are either perfectly balanced (m-to-one) or constant, with certainty, and using a single quantum query. Here, we show that this algorithm (which we call the Deutsch–Jozsa–Høyer algorithm) can in fact deal with a broader range of promises, which we define in terms of the irreducible representations of G.
Riemannian Means as Solutions of Variational Problems
Authors: Machado Luís , Leite F. Silva , Hüper Knut
Published: August 2013

We formulate a variational problem on a Riemannian manifoldMwhose solutions are piecewise smooth geodesies that best fit a given data set of time labelled points inM. By a limiting process, these solutions converge to a single point inM. which we prove to be the Riemannian mean of the given points for some particular Riemannian manifolds such as Euclidean spaces, connected and compact Lie groups, and spheres.
Computing in Nilpotent Matrix Groups
Authors: Detinko A.S. , Flannery D.L.
Published: August 2013

We present algorithms for testing nilpotency of matrix groups over finite fields, and for deciding irreducibility and primitivity of nilpotent matrix groups. The algorithms also construct modules and imprimitivity systems for nilpotent groups. In order to justify our algorithms, we prove several structural results for nilpotent linear groups, and computational and theoretical results for abstract nil-potent groups, which are of independent interest.
A Reduction Algorithm for Large-Base Primitive Permutation Groups
Authors: Law Maska , Niemeyer Alice C. , Praeger Cheryl E. , Seress Ákos
Published: August 2013

The authors present a nearly linear-time Las Vegas algorithm that, given a large-base primitive permutation group, constructs its natural imprimitive representation. A large-base primitive permutation group is a subgroup of a wreath product of symmetric groups Sn and Sr in product action on r-tuples of k-element subsets of {1, …, n}, containing Anr. The algorithm is a randomised speed-up of a deterministic algorithm of Babai, Luks, and Seress.
A Recursive Method for Computing Zeta Functions of Varieties
Authors: Lauder Alan G. B.
Published: August 2013

We present an algorithm that reduces the problem of calculating a numerical approximation to the action of absolute Frobenius on the middle-dimensional rigid cohomology of a smooth projective variety over a finite held, to that of performing the same calculation for a smooth hyperplane section. When combined with standard geometric techniques, this yields a method for computing zeta functions which proceeds ‘by induction on the dimension’. The ‘inductive step’ combines previous work of the author on the deformation of Frobenius with a higher rank generalisation of Kedlaya's algorithm. The analysis of the loss of precision during the algorithm uses a deep theorem of Christol and Dwork on p-adic solutions to differential systems at regular singular points. We apply our algorithm to compute the zeta functions of compactifications of certain surfaces which are double covers of the affine plane.
The Sharpiro–Lopatinskij Condition for Elliptic Boundary Value Problems
Authors: Krupchyk Katsiaryna , Tuomela Jukka
Published: August 2013

Elliptic boundary value problems are well posed in suitable Sobolev spaces, if the boundary conditions satisfy the Shapiro–Lopatinskij condition. We propose here a criterion (which also covers over-determined elliptic systems) for checking this condition. We present a constructive method for computing the compatibility operator for the given boundary value problem operator, which is also necessary when checking the criterion. In the case of two independent variables we give a formulation of the criterion for the Shapiro–Lopatinskij condition which can be checked in a finite number of steps. Our approach is based on formal theory of PDEs, and we use constructive module theory and polynomial factorisation in our test. Actual computations were carried out with computer algebra systems Singular and MuPad.
Non-Hurwitz Classical Groups
Authors: Vincent R. , Zalesski A.E.
Published: August 2013

In previous work by Di Martino, Tamburini and Zalesski [Comm. Algebra28 (2000) 5383–5404] it is shown that certain low-dimensional classical groups over finite fields are not Hurwitz. In this paper the list is extended by adding the special linear and special unitary groups in dimensions 8.9,11.13. We also show that all groups Sp(n, q) are not Hurwitz forqeven andn= 6,8,12,16. In the range 11 <n< 32 many of these groups are shown to be non-Hurwitz. In addition, we observe that PSp(6, 3),PΩ±(8, 3k),PΩ±10k), Ω(11,3k), Ω±(14,3k), Ω±(16,7k), Ω(n, 7k) forn= 9,11,13, PSp(8, 7k) are not Hurwitz.
A Domain-Theoretic Account of Picard's Theorem
Authors: Edalat Abbas , Pattinson Dirk
Published: August 2013

We present a domain-theoretic version of Picard's theorem for solving classical initial value problems in ℝn. For the case of vector fields that satisfy a Lipschitz condition, we construct an iterative algorithm that gives two sequences of piecewise linear maps with rational coefficients, which converge, from below and above respectively, exponentially fast, to the unique solution of the initial value problem. We provide a detailed analysis of the speed of convergence and the complexity of computing the iterates. The algorithm uses proper data types based on rational arithmetic, where no rounding of real numbers is required. Thus we obtain a sound implementation framework to solve initial value problems. In particular, the use of rational arithmetic guarantees that implementations of our technique will adhere to the bounds on convergence speed and algebraic complexity.
The Pathwise Convergence of Approximation Schemes for Stochastic Differential Equations
Authors: Kloeden P.E. , Neuenkirch A.
Published: August 2013

The authors of this paper study approximation methods for stochastic differential equations, and point out a simple relation between the order of convergence in the pth mean and the order of convergence in the pathwise sense: Convergence in the pth mean of order α for all p ≥ 1 implies pathwise convergence of order α – ε for arbitrary ε > 0. The authors then apply this result to several one-step and multi-step approximation schemes for stochastic differential equations and stochastic delay differential equations. In addition, they give some numerical examples.
Construction of Some Irreducible Subgroups of E8 and E6
Authors: Ryba A.J.E
Published: August 2013

We construct two embeddings of finite groups into groups of Lie type. These embeddings have the interesting property that the finite subgroup acts irreducibly on a minimal module for the group of Lie type. We present our constructions as examples of a general method that obtains embeddings into groups of Lie type.
The Brauer-Manin Obstruction and III[2]
Authors: Bright M.J. , Bruin N. , Flynn E.V , Logan A.
Published: August 2013

We discuss the Brauer-Manin obstruction on del Pezzo surfaces of degree 4. We outline a detailed algorithm for computing the obstruction and provide associated programs in MAGMA. This is illustrated with the computation of an example with an irreducible cubic factor in the singular locus of the defining pencil of quadrics (in contrast to previous examples, which had at worst quadratic irreducible factors). We exploit the relationship with the Tate-Shafarevich group to give new types of examples of III [2], for families of curves of genus 2 of the form y2 = f(x), where f(x) is a quintic containing an irreducible cubic factor.
Global Duality, Signature Calculus and the Discrete Logarithm Problem
Authors: Huang Ming-Deh , Raskind Wayne
Published: August 2013

We develop a formalism for studying the discrete logarithm problem for the multiplicative group and for elliptic curves over finite fields by lifting the respective group to an algebraic number field and using global duality. One of our main tools is thesignatureof a Dirichlet character (in the multiplicative group case) or principal homogeneous space (in the elliptic curve case), which is a measure of its ramification at certain places. We then developsignature calculus, which generalizes and refines the index calculus method. Finally, using some heuristics, we show the random polynomial time equivalence for these two cases between the problem of computing signatures and the discrete logarithm problem. This relates the discrete logarithm problem to some very well-known problems in algebraic number theory and arithmetic geometry.
Long‐ and short‐term intravital imaging reveals differential spatiotemporal recruitment and function of myelomonocytic cells after spinal cord injury
Authors: Fenrich Keith K. , Weber Pascal , Rougon Geneviève , Debarbieux Franck
Published: August 2013

Key points

Inflammatory cells such as myelomonocytic cells are key players in the progression and recovery from spinal cord injury (SCI).

However, the precise spatiotemporal distributions and roles of different subpopulations of myelomonocytic cells remain unclear in part because their dynamics have not been examined in vivo.

Using chronic in vivo two‐photon microscopy techniques in adult transgenic mice with SCI, we show that infiltrating and resident myelomonocytic cells have differential spatiotemporal distribution patterns to injury sites.

We also show that infiltrating myelomonocytic cells are associated with the collapse of certain cut axon terminals thus potentially impeding recovery, whereas resident myelomonocytic cells clear axon debris, which may be important for axon regrowth and recovery.

These results set a framework to understand the roles of different subpopulations of myelomonocytic cells in SCI, and may be important for the development of therapies that target specific immune cell populations at precise times post‐injury.

Abstract  After spinal cord injury (SCI), resident and peripheral myelomonocytic cells are recruited to the injury site and play a role in injury progression. These cells are important for clearing cellular debris, and can modulate the retraction and growth of axons in vitro. However, their precise spatiotemporal recruitment dynamics is unknown, and their respective roles after SCI remain heavily debated. Using chronic, quantitative intravital two‐photon microscopy of adult mice with SCI, here we show that infiltrating lysozyme M (LysM(+)) and resident CD11c(+) myelomonocytic cells have distinct spatiotemporal recruitment profiles, and exhibit changes in morphology, motility, phagocytic activity and axon interaction patterns over time. This study provides the first in vivo description of the influx of inflammatory and resident myelomonocytic cells into the injured spinal cord and their interactions with cut axons, and underscores the importance of precise timing and targeting of specific cell populations in developing therapies for SCI.
Calibrated Coarse Grid-Finite Volume Method for the Fast Calculation of the Underhood Flow of a Vehicle
Authors: Langmayr D. , Almbauer R. A. , Peller N. , Puntigam W. , Lichtenberger A.
Published: August 2013

In this paper we introduce a novel method for calculating 3D flow through the underhood compartement of a vehicle. The method is based on the system of Euler equations, which are numerically solved by a finite volume approach. The total number of finite volumes is very low (<1000 cells). The applied numerics are calibrated to recapture a preceding detailed computational fluid dynamics {CFD) simulation. This calibration is established by two sets of factors. The main advantage of the present approach is that the calibration factors can be inter- and extrapolated between different CFD simulations.
Nonlinear Parametric Resonance of a Fractional Damped Axially Moving String
Authors: Yang Tian-Zhi , Yang Xiaodong , Chen Fei , Fang Bo
Published: August 2013

Nonlinear parametric vibration of an axially accelerating viscoelastic string is investigated. The string is constituted by the fractional Kelvin model. The principal parametric resonance is analyzed by using an asymptotic approach. The modulation equation is derived from the solvability condition. Closed-form expressions of the amplitudes and the existence conditions of steady-state responses are obtained from the modulation equation. Numerical examples are presented to highlight the effects of fractional order and other system parameters on the responses.
Vehicles Drag Reduction With Control of Critical Reynolds Number
Authors: Amromin E. L.
Published: August 2013

Various vehicles have been designed as short blunt bodies. Drag coefficients of these bodies are high because adverse pressure gradients cause boundary layer separation from their surfaces, but a reduction of the size of separation zone allows for a substantial reduction of the body drag. It can be done via displacement of their boundary layer separation far downstream. In this study, such displacement was achieved with a combination of passive and active flow control. First, the whole body side surface includes two constant pressure surfaces of selected lengths and the surface of a high adverse pressure gradient in the middle of them. Second, the boundary layer suction maintained on this middle surface prevents separation there. The concept feasibility is manifested for very short axisymmetric bodies (of length to width ratios from 1.02 till 1.25). For moderate Reynolds numbers (from 3,000,000 to 10,000,000) and at the optimum suction intensity, the total drag coefficient of the designed bodies is about tenfold lower than the drag of spheroids of the same slenderness. The 3D design problem is also considered.
On the Robustness of Instabilities in Friction–Induced Vibration
Authors: Kruse Sebastian , Hoffmann Norbert P.
Published: August 2013

Friction-induced vibration and the noise or wear it causes are everlasting problems in the design of dynamical mechanical systems. The most common way to analyze friction-induced vibration is to determine the borders of linear stability. In that framework, the present study focuses on robustness concepts of systems prone to friction-induced vibration. Here, robustness is defined on two different levels. First, robustness will be considered in a global design perspective, giving an answer to the question of how many realizations within an overall ensemble of possible designs will show instability and if a given stability characteristic remains robust under parameter variations. Second, robustness will be understood with respect to the sensitivity of the system’s eigenvalues against parameter variations in general, focusing on the questions of how single eigenvalues react to parameter variation and if the real parts of the system’s eigenvalues give a measure for changes of stability characteristics under parameter variation. To answer the posed questions, dynamical model systems subject to friction-induced vibration are generated on the basis of specified random processes and evaluated in statistical terms. It shows that the size of the real parts of the eigenvalues, i.e., the growth or decay rates of the linear modes, which are in practice often used as decisive values in the interpretation of stability calculations, cannot be used as a well defined indicator for any kind of the considered robustness concepts. We, thus, suggest a novel measure taking into account variance properties to rate the robustness of systems subject to friction-induced vibration.
Numerical Calculation of Unsteady Flow Fields: Feasibility of Applying the Weis-Fogh Mechanism to Water Turbines
Authors: Ro Kideok , Zhu Baoshan
Published: August 2013

In this study, a reciprocating-type water turbine model that applies the principle of the Weis-Fogh mechanism was proposed, and the model's unsteady flow field was calculated by an advanced vortex method. The primary conditions were as follows: wing chord C=1, wing shaft stroke length hs=2.5C, and the maximum opening angle of the wing α=36 deg. The dynamic characteristics and unsteady flow fields of a Weis-Fogh type water turbine were investigated with velocity ratios U/V = 1.0 ∼ 3.0. Force coefficients Cu and Cv acting on the wing in the U and V directions, respectively, were found to have a strong correlation each other. The size of a separated region on the back face of the wing increased as the velocity ratio increased and as the wing approached the opposite wall. The rapid drop in Cv during a stroke increased as the velocity ratio increased, and the average Cu and Cv increased as the velocity ratio increased. The maximum efficiency of this water turbine was 14.1% at U/V = 2.0 for one wing.
Dispersion in Electro-Osmotic Flow Through a Slit Channel With Axial Step Changes of Zeta Potential
Authors: Ng Chiu-On , Chen Bo
Published: August 2013

An analytical study is presented in this paper on hydrodynamic dispersion due to steady electro-osmotic flow (EOF) in a slit microchannel with longitudinal step changes of ζ potential. The channel wall is periodically patterned with alternating stripes of distinct ζ potentials. Existing studies in the literature have considered dispersion in EOF with axial nonuniformity of ζ potential only in the limiting case where the length scale for longitudinal variation is much longer than the cross-sectional dimension of the channel. Hence, the existing theories on EOF dispersion subject to nonuniform charge distributions are all based on the lubrication approximation, by which cross-sectional mixing is ignored. In the present study, the general case where the length of one periodic unit of wall pattern (which involves a step change of ζ potential) is comparable with the channel height, as well as the long-wave limiting case, are investigated. The problem for the hydrodynamic dispersion coefficient is solved numerically in the general case, and analytically in the long-wave lubrication limit. The dispersion coefficient and the plate height are found to have strong, or even nonmonotonic, dependence on the controlling parameters, including the period length of the wall pattern, the area fraction of the EOF-suppressing region, the Debye parameter, the Péclet number, and the ratio of the two ζ potentials.
Measurements on the Temperature, Dynamic Strain Amplitude and Magnetic Field Strength Dependence of the Dynamic Shear Modulus of Magnetosensitive Elastomers in a Wide Frequency Range
Authors: Lejon Jonas , Kari Leif
Published: August 2013

A measurement study is conducted to investigate how changes in temperature, dynamic strain amplitude, and magnetic field strength influence the behavior of a magnetosensitive material. During the measurements seven temperatures, four magnetic fields, and three dynamic strain amplitudes are used over a 200 to 800 Hz frequency range. The results indicate a decrease in shear modulus magnitude as the dynamic strain amplitude is increased. As the frequency and magnetic field strength increases the magnitude increases. However, the measurements indicate that the temperature is the most influential of the parameters as the material stiffens significantly when the temperature reaches the transition phase. Understanding the temperature dependence increases the knowledge of magnetosensitive materials.
Toward a new world of molecular devices: Making metallic contacts to molecules
Authors: Walker Amy V.
Published: August 2013

The incorporation of molecular layers into electronic devices has many applications from sensing to energy harvesting. While many devices have been demonstrated and some are close to market, there are many challenges that must be overcome before molecular assemblies are incorporated in every device. Perhaps the most important is the development of reliable, reproducible metallic contacts to connect molecular layers with other device components. In order for this to happen, the following must be developed: an understanding of the interaction between the electrode and the different parts of the molecular layer, methods for the large-scale integration of molecules into devices, and eliminate variability in the contact. In this paper, the progress and remaining challenges in making metallic contacts to molecules will be discussed. Methods employed range from those that measure single molecules to ensembles of molecules, as well as those that could be employed in manufacturing processes.
A comparative study of automatic thresholding approaches for 3D x‐ray microtomography of trabecular bone
Authors: Gómez W. , Sales E. , Lopes R. T. , Pereira W. C. A.
Published: August 2013

Purpose:

This paper presents a comparative study of automatic thresholding algorithms for segmenting trabecular bone volume in x‐ray microtomography (μ CT).

Methods:

First, a preprocessing stage was established, which considered noise reduction by applying anisotropic diffusion filtering and contrast enhancement by using morphological top‐hats. Next, four automatic thresholding algorithms were implemented: clustering, maximum entropy, moment preservation, and concavity‐based. These approaches analyze the preprocessed 3Dμ CT image histogram to optimize some parameters to find the best gray‐level threshold. Thirty‐eight vertebra bone samples were acquired from 19 normal Wistar rats, specifically the L3 and L4 vertebrae. The μ CT images were acquired with a microfocus x‐ray device at 100 slices/sample. Next, three human operators segmented the entire 3D μ CT images manually to establish ground‐truth segmentations so as to associate the segmentation problem with perceptual grouping. The normalized probabilistic Rand index (NPRI) was used to quantify the agreement between each computerized segmentation and the corresponding set of three ground‐truth segmentations. Hence, the NPRI value should tend toward unity for an acceptable performance. Finally, a statistical analysis was done to determine which thresholding approach achieved the best performance. Besides, 3D morphometric indices were also measured.

Results:

The Games‐Howell test (α = 0.05) was used to compare the equality of means from the NPRI results considering the four thresholding algorithms (multiple comparisons). This statistical analysis indicated that the clustering and moment preservation techniques performed similarly, with NPRI values of 0.594 ± 0.126 and 0.607 ± 0.127, respectively.

Conclusions:

The main advantage of computerized segmentation is that it is fully automatic; that is, no interaction with the user is required. Thus, the method could be considered objective. Besides, the proposed preprocessing stage plays an important role in enhancing theμ CT image quality to achieve better separation between the background volume and the trabecular bone volume.
Interference with Akt Signaling Protects Against Myocardial Infarction and Death by Limiting the Consequences of Oxidative Stress
Authors: Kerr Bethany A. , Ma Lining , West Xiaoxia Z. , Ding Liang , Malinin Nikolay L. , Weber Malory E. , Tischenko Mira , Goc Anna , Somanath Payaningal R. , Penn Marc S. , Podrez Eugene A. , Byzova Tatiana V.
Published: August 2013

Reducing Akt activity might alleviate cardiovascular complications and mortality associated with atherosclerosis.
As the Worm Squirms
Authors: Ray L. Bryan
Published: August 2013

A worm model of ischemia-reperfusion injury reveals protective mechanisms potentially relevant to stroke and heart attack.
Simple Signals?
Authors: Ray L. Bryan
Published: August 2013

Information theory analysis of cell signaling reveals mechanisms for reliable cellular responses despite signal variability.
Mechanism of Action of T-705 Ribosyl Triphosphate against Influenza Virus RNA Polymerase
Authors: Sangawa Hidehiro , Komeno Takashi , Nishikawa Hiroshi , Yoshida Atsushi , Takahashi Kazumi , Nomura Nobuhiko , Furuta Yousuke
Published: August 2013

T-705 (favipiravir; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) selectively and strongly inhibits replication of the influenza virus
in vitro
and
in vivo
. T-705 has been shown to be converted to T-705-4-ribofuranosyl-5-triphosphate (T-705RTP) by intracellular enzymes and then functions as a nucleotide analog to selectively inhibit RNA-dependent RNA polymerase (RdRp) of the influenza virus. To elucidate these inhibitory mechanisms, we analyzed the enzyme kinetics of inhibition using Lineweaver-Burk plots of four natural nucleoside triphosphates and conducted polyacrylamide gel electrophoresis of the primer extension products initiated from
32
P-radiolabeled 5′Cap1 RNA. Enzyme kinetic analysis demonstrated that T-705RTP inhibited the incorporation of ATP and GTP in a competitive manner, which suggests that T-705RTP is recognized as a purine nucleotide by influenza virus RdRp and inhibited the incorporation of UTP and CTP in noncompetitive and mixed-type manners, respectively. Primer extension analysis demonstrated that a single molecule of T-705RTP was incorporated into the nascent RNA strand of the influenza virus and inhibited the subsequent incorporation of nucleotides. These results suggest that a single molecule of T-705RTP is incorporated into the nascent RNA strand as a purine nucleotide analog and inhibits strand extension, even though the natural ribose of T-705RTP has a 3′-OH group, which is essential for forming a covalent bond with the phosphate group.
Pharmacokinetic Properties of Artemether, Dihydroartemisinin, Lumefantrine, and Quinine in Pregnant Women with Uncomplicated Plasmodium falciparum Malaria in Uganda
Authors: Tarning Joel , Kloprogge Frank , Dhorda Mehul , Jullien Vincent , Nosten Francois , White Nicholas J. , Guerin Philippe J. , Piola Patrice
Published: August 2013

Pregnancy alters the pharmacokinetic properties of many drugs used in the treatment of malaria, usually resulting in lower drug exposures. This increases the risks of treatment failure, adverse outcomes for the fetus, and the development of resistance. The pharmacokinetic properties of artemether and its principal metabolite dihydroartemisinin (
n
= 21), quinine (
n
= 21), and lumefantrine (
n
= 26) in pregnant Ugandan women were studied. Lumefantrine pharmacokinetics in a nonpregnant control group (
n
= 17) were also studied. Frequently sampled patient data were evaluated with noncompartmental analysis. No significant correlation was observed between estimated gestational age and artemether, dihydroartemisinin, lumefantrine, or quinine exposures. Artemether/dihydroartemisinin and quinine exposures were generally low in these pregnant women compared to values reported previously for nonpregnant patients. Median day 7 lumefantrine concentrations were 488 (range, 30.7 to 3,550) ng/ml in pregnant women compared to 720 (339 to 2,150) ng/ml in nonpregnant women (
P
= 0.128). There was no statistical difference in total lumefantrine exposure or maximum concentration. More studies with appropriate control groups in larger series are needed to characterize the degree to which pregnant women are underdosed with current antimalarial dosing regimens.
Characterization of Fecal Extended-Spectrum-β-Lactamase-Producing Escherichia coli in a Remote Community during a Long Time Period
Authors: Woerther Paul-Louis , Angebault Cécile , Jacquier Hervé , Clermont Olivier , El Mniai Assyia , Moreau Brigitte , Djossou Félix , Peroz Gilles , Catzeflis François , Denamur Erick , Andremont Antoine
Published: August 2013

Carriage of extended-spectrum beta-lactamase-producing enterobacteria (ESBL-E) has increased in community settings. Little is known about their long-term evolution. French Guiana Amerindians living in a very remote village, already sampled in 2001 and 2006 for ESBL-E fecal carriage, were screened again in October 2010. Sociodemographic data and antibiotic intake data were collected during the previous year. ESBL-E strains collected in 2010 and their plasmid contents were typed. The results were compared to those of the previous campaigns. The prevalence of ESBL-E carriage in 2010 was 5.3%, whereas it was 8.0% and 3.2% in 2006 and 2001, respectively. As previously determined, no individual factor was associated with carriage, including personal antibiotic exposure. However, overall antibiotic use had decreased to a 0.67 treatments/subject/year in 2010 versus 1.09 in 2006 (
P
< 0.001), which supports the idea that population exposure to antibiotics impacts on ESBL-E community carriage rates. A wide diversity of ESBL
Escherichia coli
strains belonging to the A
0
, A
1
, B1, and D
2
phylogroups and producing the CTX-M-1, CTX-M-2, and CTX-M-8 enzymes were isolated. Despite the overall genetic diversity of the strains evaluated by repetitive extragenic palindromic PCR (rep-PCR) and multilocus sequence typing, two CTX-M-1-producing clones were found to have spread. In contrast, similar ESBL-bearing I1/Iγ plasmids were present in various strains both within and between carriers, suggesting high rates of plasmid transfer. Our results suggest that overall antibiotic exposure affects ESBL-E fecal carriage in the community. ESBL-E spread may be the result of both strain dissemination and the transfer of plasmids in intestinal microbiota.
Human Biotransformation of the Nonnucleoside Reverse Transcriptase Inhibitor Rilpivirine and a Cross-Species Metabolism Comparison
Authors: Lade Julie M. , Avery Lindsay B. , Bumpus Namandjé N.
Published: August 2013

Rilpivirine is a nonnucleoside reverse transcriptase inhibitor used to treat HIV-1. In the present study, the pathways responsible for the biotransformation of rilpivirine were defined. Using human liver microsomes, the formation of two mono- and two dioxygenated metabolites were detected via ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Mass spectral analysis of the products suggested that these metabolites resulted from oxygenation of the 2,6-dimethylphenyl ring and methyl groups of rilpivirine. Chemical inhibition studies and cDNA-expressed cytochrome P450 (CYP) assays indicated that oxygenations were catalyzed primarily by CYP3A4 and CYP3A5. Glucuronide conjugates of rilpivirine and a monomethylhydroxylated metabolite of rilpivirine were also detected and were found to be formed by UDP-glucuronosyltransferases (UGTs) UGT1A4 and UGT1A1, respectively. All metabolites that were identifiedin vitrowere detectablein vivo. Further, targeted UHPLC-MS/MS-basedin vivometabolomics screening revealed that rilpivirine treatment versus efavirenz treatment may result in differential levels of endogenous metabolites, including tyrosine, homocysteine, and adenosine. Rilpivirine biotransformation was also assessed across species using liver microsomes isolated from a range of mammals, and the metabolite profile identified using human liver microsomes was largely conserved for both oxidative and glucuronide metabolite formation. These studies provide novel insight into the metabolism of rilpivirine and the potential differential effects of rilpivirine- and efavirenz-containing antiretroviral regimens on the endogenous metabolome.
Characterization of Botulinum Neurotoxin A Subtypes 1 Through 5 by Investigation of Activities in Mice, in Neuronal Cell Cultures, and
In Vitro
Authors: Whitemarsh Regina C. M. , Tepp William H. , Bradshaw Marite , Lin Guangyun , Pier Christina L. , Scherf Jacob M. , Johnson Eric A. , Pellett Sabine
Published: August 2013

Botulinum neurotoxins (BoNTs) are synthesized by
Clostridium botulinum
and exist as seven immunologically distinct serotypes designated A through G. For most serotypes, several subtypes have now been described based on nominal differences in the amino acid sequences. BoNT/A1 is the most well-characterized subtype of the BoNT/A serotype, and many of its properties, including its potency, its prevalence as a food poison, and its utility as a pharmaceutical, have been thoroughly studied. In contrast, much remains unknown of the other BoNT/A subtypes. In this study, BoNT/A subtype 1 (BoNT/A1) to BoNT/A5 were characterized utilizing a mouse bioassay, an
in vitro
cleavage assay, and several neuronal cell-based assays. The data indicate that BoNT/A1 to -5 have distinct
in vitro
and
in vivo
toxicological properties and that, unlike those for BoNT/A1, the neuronal and mouse results for BoNT/A2 to -5 do not correlate with their enzymatic activity. These results indicate that BoNT/A1 to -5 have distinct characteristics, which are of importance for a greater understanding of botulism and for pharmaceutical applications.
Deletion of
arcD
in Streptococcus pneumoniae D39 Impairs Its Capsule and Attenuates Virulence
Authors: Gupta Radha , Yang Jun , Dong Yimin , Swiatlo Edwin , Zhang Jing-Ren , Metzger Dennis W. , Bai Guangchun
Published: August 2013

The arginine deiminase system (ADS) is associated with arginine catabolism and plays a role in virulence of several pathogenic bacteria. In
Streptococcus pneumoniae
, the ADS genes exist as a locus consisting of
arcABCDT
. A recent genome-wide mutagenesis approach revealed that both
arcD
and
arcT
are potentially essential in a chinchilla otitis media (OM) model. In the present study, we generated Δ
arcD
, Δ
arcT
, and Δ
arcDT
mutants by homologous recombination and evaluated their infectivity. Our results showed that only
arcD
, and not
arcT
, of an OM isolate is required during chinchilla middle ear infection. Additionally, D39 Δ
arcD
exhibited enhanced nasopharyngeal colonization and was attenuated in both mouse pneumonia and bacteremia models.
In vitro
, D39 Δ
arcD
displayed enhanced adherence to A549 epithelial cells and increased phagocytosis by J774A.1 macrophages compared to those with the parental strain. This mutant also exhibited an impaired capsule, as detected using electron microscopy, immunofluorescence, and a capsule assay. We demonstrated that the capsule defect in the D39 Δ
arcD
mutant may not be associated with a deficiency in arginine but rather is likely caused by a loss of interaction between the capsule and the transmembrane protein ArcD.
Leptospiral LruA Is Required for Virulence and Modulates an Interaction with Mammalian Apolipoprotein AI
Authors: Zhang Kunkun , Murray Gerald L. , Seemann Torsten , Srikram Amporn , Bartpho Thanatchaporn , Sermswan Rasana W. , Adler Ben , Hoke David E.
Published: August 2013

Leptospirosis is a worldwide zoonosis caused by spirochetes of the genus
Leptospira
. While understanding of pathogenesis remains limited, the development of mutagenesis in
Leptospira
has provided a powerful tool for identifying novel virulence factors. LruA is a lipoprotein that has been implicated in leptospiral uveitis as a target of the immune response. In this study, two
lruA
mutants, M754 and M765, generated by transposon mutagenesis from
Leptospira interrogans
serovar Manilae, were characterized. In M754, the transposon inserted in the middle of
lruA
, resulting in no detectable expression of LruA. In M765, the transposon inserted toward the 3′ end of the gene, resulting in expression of a truncated protein. LruA was demonstrated to be on the cell surface in M765 and the wild type (WT). M754, but not M765, was attenuated in a hamster model of acute infection. A search for differential binding to human serum proteins identified a serum protein of around 30 kDa bound to the wild type and the LruA deletion mutant (M754), but not to the LruA truncation mutant (M765). Two-dimensional separation of proteins from leptospiral cells incubated with guinea pig serum identified the 28-kDa apolipoprotein A-I (ApoA-I) as a major mammalian serum protein that binds
Leptospira
in vitro
. Interestingly, M754 (with no detectable LruA) bound more ApoA-I than did the LruA-expressing strains Manilae wild type and M765. Our data thus identify LruA as a surface-exposed leptospiral virulence factor that contributes to leptospiral pathogenesis, possibly by modulating cellular interactions with serum protein ApoA-I.
Appendico-cutaneous fistula 20 years after groin hernia repair with a polypropylene plug
Authors: Wijers Olivier , Conijn Anne , Wiese Hans , Sjer Mike
Published: August 2013

The formation of an appendico-cutaneous fistula is rare. Few case reports have been published; most describe the formation of a fistula after appendicitis. Here we describe the case of a 79-year-old woman presenting with an appendico-cutaneous fistula after groin hernia repair. She was referred to our outpatient department with a painful mass in the right groin. An ultrasound showed a fluid containing mass. Incision and drainage was performed. After 9 weeks she was referred again with a persisting open wound. Fistulogram and CT scan showed a fistuleous tract involving the appendix. Wound culture showedEscherichia coli. Diagnostic laparoscopy showed an appendix stuck to the ventral wall of the abdomen without any sign of previous infection. After an appendectomy, pathological investigation revealed an appendix sana. After operation, the fistula persisted due to a polypropylene plug from the previous groin hernia correction. The (infected) plug was removed and the fistula healed.
Non-Hodgkin lymphoma mimics retroperitoneal fibrosis
Authors: Wan Ningxin , Jiao Yang
Published: August 2013

A 33-year-old man presented with lymphoedema and obstructive nephropathy and was first diagnosed as retroperitoneal fibrosis (RF) with consistent clinical picture and radiographic findings. Further CT-guided biopsy was performed and non-Hodgkin lymphoma was diagnosed based on pathological results. RF is usually diagnosed through clinical presentation and imaging studies. However, our case proved that biopsy should be considered to exclude malignancy, even with typical presentations of RF. Follow-up after six courses of R-CHOP (rituximab, cyclophosphamide, vindesine, epirubicin and prednisone) regimen revealed complete resolution of symptoms.
Behavioural interventions to reduce sexual risk for HIV in heterosexual couples: a meta-analysis
Authors: LaCroix Jessica M , Pellowski Jennifer A , Lennon Carter A , Johnson Blair T
Published: August 2013

Objectives

The current study was conducted to synthesise evaluations of couple-based HIV prevention interventions, assess the efficacy of these interventions in reducing sexual risk, and identify moderators of intervention efficacy.

Methods

A comprehensive literature search identified 29 interventions (22 reports; N=5168 couples) that met the inclusion criteria, including enrolment of both members of a heterosexual couple, measurement of condom use at baseline and follow-up, and sufficient statistical information to calculate effect sizes. Effect sizes were analysed using fixed-effects and random-effects assumptions; factors related to intervention efficacy were identified using metaregression.

Results

Overall, there were significant increases in condom use from baseline to follow-up (d+=0.78, 95% CI 0.48 to 1.09) and significant decreases in partner concurrency (d+=0.37, 95% CI 0.13 to 0.60). Condom use increased to a greater extent when studies were conducted toward the beginning of the epidemic, were located in countries scoring lower on the Human Development Index, enrolled serodiscordant couples, and delivered intervention content in multiple contexts. Couples who had been together longer, reported higher incidence of sexually transmitted infection, were provided voluntary counselling and testing, and provided outcome measures during face-to-face interviews also reported larger increases in condom use.

Conclusions

Couple-based interventions are efficacious in reducing unprotected sex within the context of romantic relationships. Future research should continue to improve risk reduction for couples.
Implantation serine proteinase 2 is a monomeric enzyme with mixed serine proteolytic activity and can silence signalling via proteinase activated receptors
Authors: Sharma Navneet , Fahr Jochen , Renaux Bernard , Saifeddine Mahmoud , Kumar Rajeev , Nishikawa Sandra , Mihara Koichiro , Ramachandran Rithwik , Hollenberg Morley D. , Rancourt Derrick E.
Published: August 2013

Implantation serine proteinase 2 (ISP2), a S1 family serine proteinase, is known for its role in the critical processes of embryo hatching and implantation in the mouse uterus. Native implantation serine proteinases (ISPs) are co-expressed and co-exist as heterodimers in uterine and blastocyst tissues. The ISP1–ISP2 enzyme complex shows trypsin-like substrate specificity. In contrast, we found that ISP2, isolated as a 34 kDa monomer from a Pichia pastoris expression system, exhibited a mixed serine proteolytic substrate specificity, as determined by a phage display peptide cleavage approach and verified by the in vitro cleavage of synthetic peptides. Based upon the peptide sequence substrate selectivity, a database search identified many potential ISP2 targets of physiological relevance, including the proteinase activated receptor 2 (PAR2). The in vitro cleavage studies with PAR2-derived peptides confirmed the mixed substrate specificity of ISP2. Treatment of cell lines expressing proteinase-activated receptors (PARs) 1, 2, and 4 with ISP2 prevented receptor activation by either thrombin (PARs 1 and 4) or trypsin (PAR2). The disarming and silencing of PARs by ISP2 may play a role in successful embryo implantation.
Phylogenetic inference and trait evolution of the psychedelic mushroom genusPsilocybesensu lato (Agaricales)
Authors: Ramírez-Cruz Virginia , Guzmán Gastón , Villalobos-Arámbula Alma Rosa , Rodríguez Aarón , Matheny P. Brandon , Sánchez-García Marisol , Guzmán-Dávalos Laura
Published: August 2013

The genus Psilocybe contains iconic species of fungi renowned for their hallucinogenic properties. Recently, Psilocybe also included non-hallucinogenic species that have since been shifted to the genus Deconica. Here, we reconstruct a multigene phylogeny for Psilocybe, Deconica, and other exemplars of the families Hymenogastraceae and Strophariaceae sensu stricto (s. str.), using three nuclear markers (nLSU-rRNA, 5.8S rRNA, and rpb1). Our results confirm the monophyly of Deconica within Strophariaceae s. str., as well as numerous robust infrageneric relationships. Psilocybe is also recovered as a monophyletic group in the Hymenogastraceae, in which two principal lineages are recognized, including several nested subgroups. Most sections of Psilocybe following classifications based on morphological features are not supported in these analyses. Ancestral character state reconstruction analyses suggest that basidiospore shape in frontal view and spore wall thickness, commonly used to characterize sections in Deconica and Psilocybe, are homoplastic. Chrysocystidia, sterile cells located in the hymenium, evolved on at least two occasions in the Strophariaceae s. str., including in a novel lineage of Deconica.