bluuebunny/crossref_metadata_2025 huggingface dataset:
The onset of three-dimensionality and time-dependence in Görtler vortices: neutrally stable wavy modes
Authors: Bassom Andrew P. , Seddougui Sharon O.
Published: April 2006

Recently Hall & Seddougui (1989) considered the secondary instability of large-amplitude Görtler vortices in a growing boundary layer into a three-dimensional flow with wavy vortex boundaries. They obtained a pair of coupled, linear ordinary differential equations for this instability which constituted an eigenproblem for the wavelength and frequency of this wavy mode. In the course of investigating the nonlinear version of this problem (Seddougui & Bassom 1990), we have found that the numerical work of Hall & Seddougui (1989) is incomplete; this deficiency is rectified here. In particular, we find that many neutrally stable modes are possible; we derive the properties of such modes in a high-wavenumber limit and show that the combination of the results of Hall & Seddougui and our modifications lead to conclusions which are consistent with the available experimental observations.
Interaction of a viscous vortex pair with a free surface
Authors: Ohring Samuel , Lugt Hans J.
Published: April 2006

A vortex pair in a viscous, incompressible fluid rises vertically toward a deformable free surface. The mathematical, description of this flow situation is a time-dependent nonlinear free-surface problem that has been solved numerically for a two-dimensional laminar flow with the aid of the Navier-Stokes equations by using boundary-fitted coordinates. For a number of selected flow parameters, results are presented on the decay of the primary vortices and their paths, the generation of surface vorticity and secondary vortices, the development and final stage of the disturbed free surface, and the influence of surface tension. High and low Froude numbers represent the two extremes of free-surface yielding and stiffness, respectively. For an intermediate Froude number, a special rebounding due to the presence of secondary vortices has been observed: the path of the primary vortex centre portrays a complete loop.
On strongly nonlinear vortex/wave interactions in boundary-layer transition
Authors: Hall P. , Smith F. T.
Published: April 2006

The interactions between longitudinal vortices and accompanying waves considered here are strongly nonlinear, in the sense that the mean-flow profile throughout the boundary layer is completely altered from its original undisturbed state. Nonlinear interactions between vortex flow and Tollmien-Schlichting waves are addressed first, and some analytical and computational properties are described. These include the possibility in the spatial-development case of a finite-distance break-up, inducing a singularity in the displacement thickness. Second, vortex/Rayleigh-wave nonlinear interactions are considered for the compressible boundary layer, along with certain special cases of interest and some possible solution properties. Both types, vortex/Tollmien-Schlichting and vortex/Rayleigh, are short-scale/long-scale interactions and they have potential applications to many flows at high Reynolds numbers. Their strongly nonlinear nature is believed to make them very relevant to fully fledged transition to turbulence.
Nonlinear wave reflection from a submerged circular cylinder
Authors: Palm Enok
Published: April 2006

The paper discusses analytically the nonlinear wave reflection caused by a circular cylinder, submerged under a free surface in water of infinite depth. For monochromatic incident waves it is shown that there is no reflection of order m and frequency mω (m integer). This means that the dominant part of the mode of frequency mω is not reflected. For bichromatic incident waves it is found that the second-order wave with ‘sum frequency’ has no reflection. It is shown that the x- and y-components of the oscillatory force of order m and frequency mω have identical amplitudes and a phase-difference ½π. A corresponding result is also true for bichromatic waves.
Laboratory measurements of modulation of short-wave slopes by long surface waves
Authors: Miller Sarah J. , Shemdin Omar H. , Longuet-Higgins Michael S.
Published: April 2006

Hydrodynamic modulation of wind waves by long surface waves in a wave tank is investigated, at wind speeds ranging from 1.5 to 10 m s−1. The results are compared with the linear, non-dissipative, theory of Longuet-Higgins & Stewart (1960), which describes the modulation of a group of short gravity waves due to straining of the surface by currents produced by the orbital motions of the long wave, and work done against the radiation stresses of the short waves. In most cases the theory is in good agreement with the experimental results when the short waves are not too steep, and the rate of growth due to the wind is relatively small. At the higher wind speeds, the effects of wind-wave growth, dissipation and wave-wave interactions are dominant.
Comparison principles for free-surface flows with gravity
Authors: Craig Walter , Sternberg Peter
Published: April 2006

This article considers certain two-dimensional, irrotational, steady flows in fluid regions of finite depth and infinite horizontal extent. Geometrical information about these flows and their singularities is obtained, using a variant of a classical comparison principle. The results are applied to three types of problems: (i) supercritical solitary waves carrying planing surfaces or surfboards, (ii) supercritical flows past ship hulls and (iii) supercritical interfacial solitary waves in systems consisting of two immiscible fluids.
Nonlinear oscillations of liquid shells in zero gravity
Authors: Pelekasis N. A. , Tsamopoulos J. A. , Manolis G. D.
Published: April 2006

It has been shown experimentally (Lee et al. 1982) that water drops with injected air bubbles inside them may be forced dynamically to assume the spherosymmetric shape. Linear analysis is unable to predict a centring mechanism, but provides two distinct modes of oscillation. Weakly nonlinear theory (Tsamopoulos & Brown 1987) indicates that centring of the bubble inside the drop occurs when the two interfaces move out of phase. A hybrid boundary element-finite element schemes is used here to study the complete effect of nonlinearity on the dynamics of the motion. The gas inside the liquid shell may be considered either incompressible or compressible by using a polytropic relation. In both cases, the present calculations show that besides the fast oscillation of the shell due to an initial disturbance, a slow oscillatory motion of the centres of the bubble and the drop is induced around the concentric configuration. This occurs in both modes of oscillation and is a direct result of Bernoulli's law. Furthermore, when this slow oscillation is damped by viscous forces, it is anticipated that it will lead to a spherosymmetric shape.
On the viscous modes of instability of a trailing line vortex
Authors: Khorrami Mehdi R.
Published: April 2006

A viscous linear stability analysis of a trailing line (Batchelor) vortex is presented. Employing a staggered Chebyshev spectral collocation technique, very accurate results were obtained. The destabilising role of viscous forces has been shown to produce two types of viscous instability modes. These viscous disturbances consist of an axisymmetric mode and an asymmetric mode. Both disturbances are long-wave instabilities with maximum growth rates which are orders of magnitude smaller than the inviscid modes which have been found by others. Comparison with experimental results and condensation trail observations are found to be in good qualitative agreement with the present study.
An investigation of transition to turbulence in bounded oscillatory Stokes flows Part 2. Numerical simulations
Authors: Akhavan R. , Kamm R. D. , Shapiro A. H.
Published: April 2006

The stability of oscillatory channel flow to different classes of infinitesimal and finite-amplitude two- and three-dimensional disturbances has been investigated by direct numerical simulations of the Navier–Stokes equations using spectral techniques. All infinitesimal disturbances were found to decay monotonically to a periodic steady state, in agreement with earlier Floquet theory calculations. However, before reaching this periodic steady state an infinitesimal disturbance introduced in the boundary layer was seen to experience transient growth in accordance with the predictions of quasi-steady theories for the least stable eigenmodes of the Orr–Sommerfeld equation for instantaneous ‘frozen’ profiles. The reason why this growth is not sustained in the periodic steady state is explained. Two-dimensional infinitesimal disturbances reaching finite amplitudes were found to saturate in an ordered state of two-dimensional quasi-equilibrium waves that decayed on viscous timescales. No finite-amplitude equilibrium waves were found in our cursory study. The secondary instability of these two-dimensional finite-amplitude quasi-equilibrium states to infinitesimal three-dimensional perturbations predicts transitional Reynolds numbers and turbulent flow structures in agreement with experiments.
Similarity and asymptotic analysis for gun-firing aerodynamics
Authors: Merlen A. , Dyment A.
Published: April 2006

An experimental observation of the flow following the discharge of firearms has been carried out by means of ultra-high-speed visualization. The theory of similarity has been applied in order to define the rules governing the tests on models, chiefly for gun firing-air intake interference problems. When the blast effect predominates, no geometric similarity is required between the simulation gun and the simulated one, so the model and the simulation gun can have different scales. It is shown that the main parameter characterizing the blast effect is the energy rate at the muzzle which can be considered as a point source of energy caused by a very hot gas. So, the muzzle wave tends asymptotically toward the blast wave of a non-instantaneous intense point explosion. Specific experiments confirm this assertion. All previous results allow a theoretical modelling of gun-firing aerodynamic phenomena which will be presented in a separate paper.
Spanwise pairing of finite-amplitude longitudinal vortex rolls in inclined free-convection boundary layers
Authors: Chen C. C. , Labhabi A. , Chang H.-C , Kelly R. E.
Published: April 2006

Buoyancy-driven flow on a heated inclined plate can become unstable to static longitudinal roil instability at a critical distance, measured by $\tilde{R}_{\rm c}$, from the leading edge. Experiments in water by Sparrow & Husar (1969) indicate that these rolls undergo a second transition further downstream such that adjacent rolls merge and their spanwise wavelength is doubled. We study this secondary bifurcation phenomenon here with a set of model equations by first constructing the full eigenspectrum and eigenfunctions with a Chebyshev–Tau spectral method and then deriving the pertinent amplitude equations. By stipulating that the dimensional cross-stream wavelength of the rolls remains constant beyond $\tilde{R}_{\rm c}$, which is consistent with experimental observation, we show that the finite-amplitude primary rolls are destabilized by the ½ subharmonic mode at another critical distance $\tilde{R}_{\frac{1}{2}}$ from the edge. This ½ mode is shown to have an asymmetric spatial phase shift of ½π relative to the original 1 mode of the primary rolls, thus explaining the unique dislocation of tracer streaks after the rolls coalesce in the experiments. Also consistent with experimental observation is the theoretical result that the merged rolls are annihilated downstream by a saddle-node bifurcation before further wavclength doubling can occur. Simple amplitude criteria and critical distances from the leading edge for the various transitions are derived and compared to experimental values.
Response of the shear layers separating from a circular cylinder to small-amplitude rotational oscillations
Authors: Filler J. R. , Marston P. L. , Mih W. C.
Published: April 2006

The frequency response of the shear layers separating from a circular cylinder subject to small-amplitude rotational oscillations has been investigated experimentally in water for the Reynolds number (Re) range 250 to 1200. A hot-film anemometer was placed in the separated shear layers from 1 to 1.5 diameters downstream of the cylinder, and connected to a lock-in analyser. by referencing the lock-in analyser to the cylinder oscillations, the amplitude and phase of the response to different frequency oscillations were measured directly. It is shown that rotational oscillations corresponding to cylinder peripheral speeds between 0.5 and 3% of the free stream can be used to influence the primary (Kármán) mode of vortex generation. For Re greater than ≈ 500, such oscillations can also force the shear-layer vortices associated with the instability of the separating shear layers. Corresponding to the primary and shear-layer modes are two distinct peaks in response amplitude versus frequency curves, and two very different phase versus frequency curves. The response of the shear layers (and near wake) in the range of Kármán frequency suggests qualitative similarities with the response of an oscillator near resonance. Forced oscillations in the higher-frequency shear-layer mode range are simply convected by the shear layers. Close to the cylinder, the shear-layer response is shown to be comparable to that of generic free shear layers studied by others.
New Labour and Reconciling Work and Family Life: Making It Fathers' Business?
Authors: Kilkey Majella
Published: April 2006

Under New Labour, policies designed to help families reconcile paid work and family life have increasingly become part of the UK's family-policy terrain. These policies are usually analysed from the perspective of mothers. In this paper, however, we examine how fathers have been situated within these developments. We argue that, while there is evidence of increased optimism on the part of New Labour about fathers' capacity as care-givers, the policies to have emerged since 1998 are only minimally facilitative of opportunities for fathers to reconfigure their paid work and care patterns. We suggest that the reason for this has much to do with the economistic rationale under which the reconciling work and family-life agenda has emerged.
Gender Equality in Agriculture: Examining State Intervention in Australia and Northern Ireland
Authors: Pini Barbara , Shortall Sally
Published: April 2006

This paper is concerned with the extent to which the state offers potential for furthering farm women's status and rights. Using case studies of Australia and Northern Ireland, it examines the extent to which the state has intervened to address gender inequality in the agricultural sector. These two locations provide a particularly rich scope for analysis because while Australia has a long history of state feminism and an extensive legislative framework for pursing gender equity, this is not the case with Northern Ireland. At the same time, the restructuring of the state in Northern Ireland, following on from the Belfast Agreement of 1998 and the Northern Ireland Act of 1998, has generated new opportunities for state intervention regarding gender equality. Moreover, while gender is now for the first time being placed on the state agenda in Northern Ireland, gender reform is being wound back in Australia, as equity discourses are subsumed by the hegemonic discourses of neo-liberalism.
Introducing Role and Service Changes in Health and Social Care: The Impact and Influence of User Involvement in England and Wales
Authors: Young Ruth
Published: April 2006

A key characteristic of the English and Welsh system of care provision is that the supply function is divided between two types of organisation: the National Health Service (NHS) and local authorities. These inter-organisational and the related inter-professional divides have long been recognised as problematic from a user and carer viewpoint; and various policy changes have attempted to address them. This paper draws on three different research projects to describe practical experiences of user and carer involvement in this context (a) the Evaluation of the 1999 Health Act Section 31 flexibilities encouraging more effective service delivery partnerships between the NHS and local authorities in England; (b) a Baseline Study of Partnership Working and Flexibilities Use in Wales; and (c) the Evaluation of the NHS Changing Workforce Programme, which implemented new ways of working to improve patient care across health and social care in England. In synthesising the studies' findings, the paper also begins to explore relationships between involvement effectiveness and different types of NHS–local authority partnership as they seek to introduce change and deliver more effective services.
Partnerships and Collaborative Governance in Welfare: The Citizenship Challenge
Authors: Rummery Kirstein
Published: April 2006

Whilst there is ample literature on the governance and management of partnerships in welfare, particularly within mixed-economy states, much of it has focused on the governance and organisational capacity issues. This paper draws on that body of literature and evidence from health and social care partnerships, and attempts to develop the theoretical and empirical work in the area to address the issue of citizens' social rights, asking whether collaborative governance and partnerships between agencies are the solution to promoting citizens' social participation, or another state-driven method of indirectly enhancing social exclusion.
Structural and functional analysis of the putative pH sensor in the Kir1.1 (ROMK) potassium channel
Authors: Rapedius Markus , Haider Shozeb , Browne Katharine F , Shang Lijun , Sansom Mark S P , Baukrowitz Thomas , Tucker Stephen J
Published: April 2006

The pH‐sensitive renal potassium channel Kir1.1 is important for K+ homeostasis. Disruption of the pH‐sensing mechanism causes type II Bartter syndrome. The pH sensor is thought to be an anomalously titrated lysine residue (K80) that interacts with two arginine residues as part of an ‘RKR triad’. We show that a Kir1.1 orthologue from Fugu rubripes lacks this lysine and yet is still highly pH sensitive, indicating that K80 is not the H+ sensor. Instead, K80 functionally interacts with A177 on transmembrane domain 2 at the ‘helix‐bundle crossing’ and controls the ability of pH‐dependent conformational changes to induce pore closure. Although not required for pH inhibition, K80 is indispensable for the coupling of pH gating to the extracellular K+ concentration, explaining its conservation in most Kir1.1 orthologues. Furthermore, we demonstrate that instead of interacting with K80, the RKR arginine residues form highly conserved inter‐ and intra‐subunit interactions that are important for Kir channel gating and influence pH sensitivity indirectly.
Beating patterns in the oscillatory magnetoresistance originatedfrom zero-field spin splitting in AlxGa1−xN∕GaN heterostructures
Authors: Tang N. , Shen B. , Wang M. J. , Han K. , Yang Z. J. , Xu K. , Zhang G. Y. , Lin T. , Zhu B. , Zhou W. Z. , Chu J. H.
Published: April 2006

Beating patterns in the oscillatory magnetoresistance in Al0.11Ga0.89N∕GaN heterostructures with one subband occupation have been investigated by means of temperature dependent Shubnikov–de Haas measurements at low temperatures and high magnetic fields. The zero-field spin splitting effect is observed by excluding the magnetointersubband scattering effect. The obtained zero-field spin splitting energy is 2.5meV, and the obtained spin-orbit coupling parameter is 2.2×10−12eVm. Despite the strong polarization-induced electric field in the heterostructures, the spin-orbit coupling parameter in AlxGa1−xN∕GaN heterostructures is smaller than that in other heterostructures, such as InxGa1−xAs∕InyAl1−yAs ones. This is due to the large effective mass of the two-dimensional electron gas and the large GaN energy band gap in AlxGa1−xN∕GaN heterostructures. With an increase in magnetic field, the spin splitting energy becomes smaller. The zero-field effect is still the dominant mechanism in AlxGa1−xN∕GaN heterostructures at a magnetic field as high as 4.4T.
Influence of doping density on the normal incident absorption of quantum-dot infrared photodetectors
Authors: Chou Shu-Ting , Wu Meng-Chyi , Lin Shih-Yen , Chi Jim-Yong
Published: April 2006

The influences of doping densities at the quantum-dot (QD) region for 30-period InAs∕GaAs quantum-dot infrared photodetectors (QDIPs) are investigated. The InAs∕GaAs QDIPs with a lower doping density can operate at high responsivity and high background-limited-performance temperature. Also observed is the decreasing photocurrent ratio of s∕p-polarized lights for the QDIPs with increasing QD doping density. Compared to the similar photocurrent ratio of s∕p-polarized lights for the GaAs∕AlGaAs quantum-well infrared photodetectors at different applied voltages, the observed voltage-dependent response ratio for QDIPs is attributed to the strong scattering characteristics of QDs occupied with photoexcited electrons for electron transport through the QD region.
Systematics of the Australasian spider family Pararchaeidae (Arachnida:Araneae)
Authors: Rix Michael G.
Published: April 2006

The Pararchaeidae, a family of cryptic spiders known only from Australia and New Zealand, is revised. Six new genera: Anarchaea, gen. nov., Flavarchaea, gen. nov., Forstrarchaea, gen. nov., Nanarchaea, gen. nov., Ozarchaea, gen. nov., Westrarchaea, gen. nov., and 24 new species are described, 23 from mainland Australia and one from New Zealand. Anarchaea, gen. nov. from eastern Australia contains four species: A. corticola (Hickman, 1969), comb. nov. (type species), A. falcata, sp. nov., A. raveni, sp. nov. and A. robusta (Rix, 2005), comb. nov. Flavarchaea from eastern, southern and south-western Australia contains seven species: F. anzac, sp. nov., F. badja, sp. nov., F. barmah, sp. nov., F. hickmani (Rix, 2005), comb. nov., F. lofty, sp. nov., F. lulu (Rix, 2005), comb. nov. (type species) and F. stirlingensis, sp. nov. Forstrarchaea is represented only by the type species F. rubra (Forster, 1949), comb. nov. from New Zealand. Nanarchaea from eastern Australia contains two species: N. bryophila (Hickman, 1969), comb. nov. and N. binnaburra (Forster, 1955), comb. nov. (type species). Ozarchaea from Australia and New Zealand contains 16 species: O. bodalla, sp. nov., O. bondi, sp. nov., O. daviesae, sp. nov., O. forsteri, sp. nov., O. harveyi, sp. nov., O. janineae, sp. nov., O. ornata (Hickman, 1969), comb. nov. (type species), O. platnicki, sp. nov., O. saxicola (Hickman, 1969), comb. nov., O. spurgeon, sp. nov., O. stradbroke, sp. nov., O. valida, sp. nov., O. waldockae, sp. nov., O. werrikimbe, sp. nov., O. westraliensis, sp. nov. and O. wiangarie, sp. nov. Pararchaea Forster, 1955 is represented only by the type species P. alba Forster, 1955 from New Zealand. Westrarchaea, endemic to south-western Western Australia, contains three species: W. pusilla, sp. nov., W. sinuosa, sp. nov. (type species) and W. spinosa, sp. nov. A morphological cladistic analysis of the Pararchaeidae supported monophyly of the genera. Natural history information is summarised for each species where known, and the moulting behaviour, mating behaviour and egg sac of a pararchaeid species are described for the first time.
In situsuperexchange electron transfer through a single molecule: A rectifying effect
Authors: Kornyshev Alexei A. , Kuznetsov Alexander M. , Ulstrup Jens
Published: April 2006

An increasingly comprehensive body of literature is being devoted to single-molecule bridge-mediated electronic nanojunctions, prompted by their prospective applications in molecular electronics and single-molecule analysis. These junctions may operate in gas phase or electrolyte solution (in situ). For biomolecules, the latter is much closer to their native environment. Convenient target molecules are aromatic molecules, peptides, oligonucleotides, transition metal complexes, and, broadly, molecules with repetitive units, for which the conducting orbitals are energetically well below electronic levels of the solvent. A key feature for these junctions is rectification in the current–voltage relation. A common view is that asymmetric molecules or asymmetric links to the electrodes are needed to acquire rectification. However, as we show here, this requirement could be differentin situ, where a structurally symmetric system can provide rectification because of the Debye screening of the electric field in the nanogap if the screening length is smaller than the bridge length. The Galvani potentials of each electrode can be varied independently and lead to a transistor effect. We explore this behavior for the superexchange mechanism of electron transport, appropriate for a wide class of molecules. We also include the effect of conformational fluctuations on the lowest unoccupied molecular orbital (LUMO) energy levels; that gives rise to non-Arrhenius temperature dependence of the conductance, affected by the molecule length. Our study offers an analytical formula for the current–voltage characteristics that demonstrates all these features. A detailed physical interpretation of the results is given with a discussion of reported experimental data.
A contribution of core polarization to the hyperfine structure parameters
Authors: A V Loginov
Published: April 2006

A method earlier suggested by the author for calculating the contribution of a particular interaction to a particular semiempirical parameter is adopted to calculate the contribution of core polarization to semiempirical values of the hyperfine structure parameters. Core polarization is envisaged as mixing with configurations originated by excitation of electrons from inner s2shells. A contribution of configuration mixing

3s23p63d4s + 3s3p63d4s2+ 3s3p63d4sns(n= 5-7),3s23p63d2+ 3s3p63d2ns(n= 4-7),3s23p63d4p + 3s3p63d4pns(n= 4-7)

to the hyperfine structure parameters of the configurations 3d4s, 3d2, 3d4p in Sc II spectrum is calculated.
Multicenter, Randomized, Double‐Blind Study Comparing 10, 20 and 40 mg Pantoprazole in Children (5‐11 Years) With Symptomatic Gastroesophageal Reflux Disease
Authors: Tolia Vasundhara , Bishop Phyllis R. , Tsou V. Marc , Gremse David , Soffer Elaine F. , Comer Gail M. ,   Member of the 322 Study Group
Published: April 2006

Objective:

To evaluate symptom improvement in 53 children (aged 5‐11 years) with endoscopically proven gastroesophageal reflux disease (GERD) treated with pantoprazole (10, 20 and 40 mg) using the GERD Assessment of Symptoms in Pediatrics Questionnaire.

Methods:

The GERD Assessment of Symptoms in Pediatrics Questionnaire was used to measure the frequency and severity over the previous 7 days of abdominal/belly pain, chest pain/heartburn, difficulty swallowing, nausea, vomiting/regurgitation, burping/belching, choking when eating and pain after eating. Individual symptom scores were based on the product of the frequency and usual severity of each symptom. The sum of the individual symptom score values made up the composite symptom score (CSS). The primary end point was the change in the mean CSS from baseline to week 8.

Results:

Mean frequency and severity of each symptom significantly decreased (from P < 0.006 to P < 0.001) over time. Similar significant decreases in CSS at week 8 versus baseline (P < 0.001) were seen in all groups. Significant decreases from baseline in CSS were noted from weeks 1 to 8 in the 20‐mg (P < 0.003) and 40‐mg (P < 0.001) groups. The 20‐ and 40‐mg doses were significantly (P < 0.05) more effective than the 10‐mg dose in improving GERD symptoms at week 1. Adverse events were similar among the treatment groups.

Conclusions:

Pantoprazole (20 and 40 mg) is effective in reducing endoscopically proven GERD symptoms in children. Both 20 and 40 mg pantoprazole significantly reduced symptoms as early as 1 week.
An algorithm for predicting protein–protein interaction sites: Abnormally exposed amino acid residues and secondary structure elements
Authors: Hoskins Jemima , Lovell Simon , Blundell Tom L.
Published: April 2006

Multiprotein systems mediate most regulatory processes in living organisms. Although the structures of the individual proteins are often defined, less is known of the structures of multiprotein systems. Computational methods for predicting interfaces, using evolutionary conservation and/or physicochemical data, have been developed. Here we consider the use of solvent accessibility, residue propensity, and hydrophobicity, in conjunction with secondary structure data, as prediction parameters. We analyze the influence of residue type and secondary structure on solvent accessibility and define a measure of “relative exposedness.” Clustering abnormally high scoring residues provides a basis for predicting interaction sites. The analysis is extended to investigate abnormally exposed secondary structure elements, particularly β‐sheet strands. We show that surface‐exposed β‐strands lacking protective features are more likely to be found at protein–protein interfaces, allowing us to create an algorithm with ∼68% and ∼75% accuracy in differentiating between interacting and edge strands in isolated β‐strands and β‐sheet strands, respectively. These methods of identifying abnormally exposed surface regions are combined in an algorithm, which, on a data set of 77 unbound and disjoint (single chain extracted from complex) structures, predicts 79% of the protein–protein interfaces correctly. If enzyme–inhibitor complexes, where the inhibitor mimics a nonprotein substrate, are excluded, the accuracy increases to 85%.
3‐Nitrotyrosine as a spectroscopic probe for investigating protein–protein interactions
Authors: De Filippis Vincenzo , Frasson Roberta , Fontana Angelo
Published: April 2006

3‐Nitrotyrosine (NT) is ∼103‐fold more acidic than Tyr, and its absorption properties are strongly pH‐dependent. NT absorbs radiation in the wavelength range where Tyr and Trp emit fluorescence (300 450 nm), and it is essentially nonfluorescent. Therefore, NT may function as an energy acceptor in resonance energy transfer (FRET) studies for investigating ligand protein interactions. Here, the potentialities of NT were tested on the hirudin thrombin system, a well‐characterized protease inhibitor pair of key pharmacological importance. We synthesized two analogs of the N‐terminal domain (residues 1 47) of hirudin: Y3NT, in which Tyr3 was replaced by NT, and S2R/Y3NT, containing the substitutions Ser2 → Arg and Tyr3 → NT. The binding of these analogs to thrombin was investigated at pH 8 by FRET and UV/Vis‐absorption spectroscopy. Upon hirudin binding, the fluorescence of thrombin was reduced by ∼50%, due to the energy transfer occurring between the Trp residues of the enzyme (i.e., the donors) and the single NT of the inhibitor (i.e., the acceptor). The changes in the absorption spectra of the enzyme inhibitor complex indicate that the phenate moiety of NT in the free state becomes protonated to phenol in the thrombin‐bound form. Our results indicate that the incorporation of NT can be effectively used to detect protein protein interactions with sensitivity in the low nanomolar range, to uncover subtle structural features at the ligand protein interface, and to obtain reliable Kd values for structure activity relationship studies. Furthermore, advances in chemical and genetic methods, useful for incorporating noncoded amino acids into proteins, highlight the broad applicability of NT in biotechnology and pharmacological screening.
Characterization of single nucleotide polymorphisms in sheep and their variation as evidence of selection
Authors: Pariset L. , Cappuccio I. , Joost S. , D'Andrea M. , Marletta D. , Ajmone Marsan P. , Valentini A. ,   The ECONOGENE Consortium
Published: April 2006

The discovery of SNPs was performed using animals from eight European sheep breeds. Eleven SNPs were further characterized using about 1700 sheep belonging to 57 breeds. A method for the identification of loci that were likely subject to selection was applied; three of the 11 SNPs lying outside the 95% confidence region of the conditional joint distribution of FST and mean heterozygosity were identified as outliers.
Does premature aging of the mtDNA mutator mouse prove that mtDNA mutations are involved in natural aging?
Authors: Khrapko Konstantin , Kraytsberg Yevgenya , De Grey Aubrey DNJ , Vijg Jan , Schon Eric A.
Published: April 2006

Recent studies have demonstrated that transgenic mice with an increased rate of somatic point mutations in mitochondrial DNA (mtDNA mutator mice) display a premature aging phenotype reminiscent of human aging. These results are widely interpreted as implying that mtDNA mutations may be a central mechanism in mammalian aging. However, the levels of mutations in the mutator mice typically are more than an order of magnitude higher than typical levels in aged humans. Furthermore, most of the aging‐like features are not specific to the mtDNA mutator mice, but are shared with several other premature aging mouse models, where no mtDNA mutations are involved. We conclude that, although mtDNA mutator mouse is a very useful model for studies of phenotypes associated with mtDNA mutations, the aging‐like phenotypes of the mouse do not imply that mtDNA mutations are necessarily involved in natural mammalian aging. On the other hand, the fact that point mutations in aged human tissues are much less abundant than those causing premature aging in mutator mice does not mean that mtDNA mutations are not involved in human aging. Thus, mtDNA mutations may indeed be relevant to human aging, but they probably differ by origin, type, distribution, and spectra of affected tissues from those observed in mutator mice.
Call My Bluff
Authors: Woodward Phil
Published: April 2006

Poker used to be the card game of choice for hard men late at night in smoke-filled rooms. Now online poker is bidding for respectability and a site on the home computer. Phil Woodward gives us the straight dope.
Progress, spread and natural transmission of Bahia bark scaling of citrus in Brazil
Authors: Laranjeira F.F. , Barbosa C.J. , Santos‐Filho H.P. , Gonçalves T.F. , Nickel O.
Published: April 2006

Progress, spread and natural transmission of Bahia bark scaling of citrus were evaluated in a trial where 240 screenhouse‐nursed nucellar grapefruit plants –‘Clason’, ‘Little River Seedless’, ‘Red Blush’, ‘Reed’ and ‘Howell Seedless’ cvs – were planted alongside and 5 m apart from a 10‐year‐old symptomatic ‘Marsh Seedless’ grapefruit orchard. Plants were distributed in 16 rows of 15 trees, with three plants of each cultivar per row. Eight trial plants were kept in screen cages. Incidence of symptomatic plants was assessed at 3‐months intervals, for 5 years, and for further 2 years at irregular intervals. Cumulative maps of disease incidence were produced for each assessment date and used in all analyses. Temporal progress was analysed by nonlinear fitting of three disease progress models. Spread was characterised in three levels of spatial hierarchy by the following analyses: ordinary runs, binomial dispersion index, binary power law fitting, isopath mapping and nonlinear fitting of disease gradient models. The first symptomatic plant was detected 2 years after planting. In the last disease assessment, 5 years after the first, 98% of the unprotected plants were symptomatic. None of the screen‐caged trees showed any symptoms. Bahia bark scaling progress was polyetic and best described by the logistic model. Ordinary runs analysis showed little if any evidence of transmission between adjacent trees. Diseased plants showed a very aggregated pattern inside quadrats (D > 5 and b > 1.53). Isopath mapping showed that main spread was only because of the primary inoculum source. Secondary foci were also observed, but they were never dissociated from main initial disease focus. Disease gradient followed wind direction, starting near the original inoculum source and was best described by exponential model. These results support a hypothesis of Bahia bark scaling transmission by air‐borne vectors with limited dispersion ability.
Proteomic Study of Peptide Deformylase Inhibition inStreptococcus pneumoniaeandStaphylococcus aureus
Authors: Wang Wen , White Richard , Yuan Zhengyu
Published: April 2006

Peptide deformylase (PDF) is an essential enzyme in both gram-negative and gram-positive bacteria. It hydrolyzes formylated N-terminal peptides to generate free N-terminal peptides during the process of protein maturation. Inhibition of this enzyme results in cessation of bacterial growth. We have examined the effect of a potent PDF inhibitor, LBM-415 (also known as VIC-104959), on the proteomes ofStaphylococcus aureusandStreptococcus pneumoniaeusing two-dimensional electrophoresis. BothS. aureusandS. pneumoniaeshowed accumulation of many N-terminal formylated peptides/proteins upon PDF inhibition. InS. pneumoniae, formylated peptide/protein accumulation was time dependent. Following inhibition, subsequent removal of the inhibitor resulted in deformylation of formylated peptides/proteins; this recovery process was also time dependent. If instead the inhibited cells were maintained in the presence of sub-MIC levels of the PDF inhibitor, the formylated peptides/proteins remained for a much longer time, which correlated with a prolonged postantibiotic effect in vitro. These observations may have broader implications for the application of this class of antibiotics in vivo.
Clinical and Bacteriological Efficacy in Treatment of Acute Exacerbations of Chronic Bronchitis with Cefditoren-Pivoxil versus Cefuroxime-Axetil
Authors: Alvarez-Sala Jose-Luis , Kardos Peter , Martínez-Beltrán Jesús , Coronel Pilar , Aguilar Lorenzo ,   the Cefditoren AECB Working Group
Published: April 2006

A randomized, double-blind, double-dummy trial was performed comparing 200 mg of cefditoren-pivoxil twice daily for 5 days versus standard cefuroxime-axetil treatment (250 mg twice daily for 10 days) of Anthonisen type I or II acute exacerbations of chronic bronchitis. The modified intention-to-treat population included 541 patients. Patients were assessed during therapy, at the end of therapy (visit 3; primary evaluation time point), and at follow-up. Clinical success was obtained in 79.9% of the 264 patients included in the cefditoren-pivoxil group and in 82.7% of the 277 patients in the cefuroxime-axetil group (treatment difference, 95% confidence interval [CI]: −2.8, −9.7 to 3.6%). Treatment clinical effects were more clearly seen in sputum signs (decreasing volume and purulence from approximately 80% to approximately 10% of the patients). At the end of treatment, exploratory analysis of the per-pathogen bacteriological response showed 72.8% (of 103 isolates) in the cefditoren-pivoxil arm versus 67.0% (of 94 isolates) in the cefuroxime-axetil group (treatment difference; 95% CI: 5.8, −7.0 to 18.6%). Globally, the per-pathogen bacteriological response correlated well with clinical success: 83.5% of 164 baseline isolates from patients with a clinical success were eradicated or presumably eradicated, in contrast to only 3% of 33 isolates from patients with a clinical failure. Clinical success in patients infected with
Haemophilus influenzae
, the most frequent isolate, was 84% (of 50) and 82.5% (of 40) (treatment difference; 95% CI: 1.5, −14 to 17%) in the cefditoren-pivoxil versus the cefuroxime-axetil group. Although this study does not prove that either drug is better than a placebo, cefditoren-pivoxil and the standard 10-day cefuroxime-axetil course had similar point estimates of success in acute exacerbations of chronic bronchitis.
Intrapulmonary Penetration of Voriconazole in Patients Receiving an Oral Prophylactic Regimen
Authors: Capitano Blair , Potoski Brian A. , Husain Shahid , Zhang Shimin , Paterson David L. , Studer Sean M. , McCurry Kenneth R. , Venkataramanan Raman
Published: April 2006

Voriconazole penetrated well into the pulmonary epithelial lining fluid (ELF) in lung transplant patients receiving oral prophylaxis. The ELF concentrations exceeded those of the plasma, with an average ELF-to-plasma ratio of 11 (±8). A strong association between plasma and ELF concentrations (
r
2
= 0.95) was noted.
Selection of
Plasmodium falciparum pfmdr1
Alleles following Therapy with Artemether-Lumefantrine in an Area of Uganda where Malaria Is Highly Endemic
Authors: Dokomajilar Christian , Nsobya Samuel L. , Greenhouse Bryan , Rosenthal Philip J. , Dorsey Grant
Published: April 2006

Polymorphisms in the
Plasmodium falciparum pfmdr1
gene were assayed in pretreatment samples and in samples from patients reinfected following therapy with artemether-lumefantrine. The
pfmdr1
alleles 86N, 184F, and 1246D significantly increased in prevalence after treatment. All samples had a single
pfmdr1
copy. Treatment with artemether-lumefantrine selects for polymorphisms that may alter antimalarial drug response.
Significance of Mutations in
embB
Codon 306 for Prediction of Ethambutol Resistance in Clinical
Mycobacterium tuberculosis
Isolates
Authors: Plinke Claudia , Rüsch-Gerdes Sabine , Niemann Stefan
Published: April 2006

We analyzed 159
Mycobacterium tuberculosis
isolates (101 ethambutol [EMB]-resistant strains, 33 multidrug-resistant but not EMB-resistant strains, and 25 fully susceptible strains) for the presence of mutations in
embB
codon 306 (
embB
306). Mutations were detected only in EMB-resistant strains (
n
= 69; 68%), thus confirming the significance of
embB
306 mutations for the prediction of resistance to EMB.
DC-SIGN Facilitates Fusion of Dendritic Cells with Human T-Cell Leukemia Virus Type 1-Infected Cells
Authors: Ceccaldi Pierre-Emmanuel , Delebecque Frédéric , Prevost Marie-Christine , Moris Arnaud , Abastado Jean-Pierre , Gessain Antoine , Schwartz Olivier , Ozden Simona
Published: April 2006

Interactions between the oncogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) and dendritic cells (DCs) are poorly characterized. We show here that monocyte-derived DCs form syncytia and are infected upon coculture with HTLV-1-infected lymphocytes. We examined the role of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a C-type lectin expressed in DCs, in HTLV-1-induced syncytium formation. DC-SIGN is known to bind with high affinity to various viral envelope glycoproteins, including human immunodeficiency virus (HIV) and hepatitis C virus, as well as to the cellular receptors ICAM-2 and ICAM-3. After cocultivating DCs and HTLV-1-infected cells, we found that anti-DC-SIGN monoclonal antibodies (MAbs) were able to decrease the number and size of HTLV-1-induced syncytia. Moreover, expression of the lectin in epithelial-cell lines dramatically enhanced the ability to fuse with HTLV-1-positive cells. Interestingly, in contrast to the envelope (Env) glycoproteins of HIV and other viruses, that of HTLV-1 does not bind directly to DC-SIGN. The facilitating role of the lectin in HTLV-1 syncytium formation is mediated by its interaction with ICAM-2 and ICAM-3, as demonstrated by use of MAbs directed against these adhesion molecules. Altogether, our results indicate that DC-SIGN facilitates HTLV-1 infection and fusion of DCs through an ICAM-dependent mechanism.
Lymphoma Cell Apoptosis in the Liver Induced by Distant Murine Cytomegalovirus Infection
Authors: Erlach Katja C. , Böhm Verena , Seckert Christof K. , Reddehase Matthias J. , Podlech Jürgen
Published: April 2006

Cytomegalovirus (CMV) poses a threat to the therapy of hematopoietic malignancies by hematopoietic stem cell transplantation, but efficient reconstitution of antiviral immunity prevents CMV organ disease. Tumor relapse originating from a minimal residual leukemia poses another threat. Although a combination of risk factors was supposed to enhance the incidence and severity of transplantation-associated disease, a murine model of a liver-adapted B-cell lymphoma has previously shown a survival benefit and tumor growth inhibition by nonlethal subcutaneous infection with murine CMV. Here we have investigated the underlying antitumoral mechanism. Virus replication proved to be required, since inactivated virions or the highly attenuated enhancerless mutant mCMV-ΔMIEenh did not impact the lymphoma in the liver. Surprisingly, the dissemination-deficient mutant mCMV-ΔM36 inhibited tumor growth, even though this virus fails to infect the liver. On the other hand, various strains of herpes simplex viruses consistently failed to control the lymphoma, even though they infect the liver. A quantitative analysis of the tumor growth kinetics identified a transient tumor remission by apoptosis as the antitumoral effector mechanism. Tumor cell colonies with cells surviving the CMV-induced “apoptotic crisis” lead to tumor relapse even in the presence of full-blown tissue infection. Serial transfer of surviving tumor cells did not indicate a selection of apoptosis-resistant genetic variants. NK cell activity of CD49b-expressing cells failed to control the lymphoma upon adoptive transfer. We propose the existence of an innate antitumoral mechanism that is triggered by CMV infection and involves an apoptotic signal effective at a distant site of tumor growth.
Simian Immunodeficiency Virus SIVagm.sab Infection of Caribbean African Green Monkeys: a New Model for the Study of SIV Pathogenesis in Natural Hosts
Authors: Pandrea Ivona , Apetrei Cristian , Dufour Jason , Dillon Nora , Barbercheck Joseph , Metzger Michael , Jacquelin Béatrice , Bohm Rudolf , Marx Preston A. , Barre-Sinoussi Françoise , Hirsch Vanessa M. , Müller-Trutwin Michaela C. , Lackner Andrew A. , Veazey Ronald S.
Published: April 2006

Caribbean-born African green monkeys (AGMs) were classified as
Chlorocebus sabaeus
by cytochrome
b
sequencing. Guided by these phylogenetic analyses, we developed a new model for the study of simian immunodeficiency virus (SIV) infection in natural hosts by inoculating Caribbean AGMs with their species-specific SIVagm.sab. SIVagm.sab replicated efficiently in Caribbean AGM peripheral blood mononuclear cells in vitro. During SIVagm.sab primary infection of six Caribbean AGMs, the virus replicated at high levels, with peak viral loads (VLs) of 10
7
to 10
8
copies/ml occurring by day 8 to 10 postinfection (p.i.). Set-point values of up to 2 × 10
5
copies/ml were reached by day 42 p.i. and maintained throughout follow-up (through day 450 p.i.). CD4
+
T-cell counts in the blood showed a transient depletion at the peak of VL, and then returned to near preinfection values by day 28 p.i. and remained relatively stable during the chronic infection. Preservation of CD4 T cells was also found in lymph nodes (LNs) of chronic SIVagm.sab-infected Caribbean AGMs. No activation of CD4
+
T cells was detected in the periphery in SIV-infected Caribbean AGMs. These virological and immunological profiles from peripheral blood and LNs were identical to those previously reported in African-born AGMs infected with the same viral strain (SIVagm.sab92018). Due to these similarities, we conclude that Caribbean AGMs are a useful alternative to AGMs of African origin as a model for the study of SIV infection in natural African hosts.
${\mathcal{PT}}$-SYMMETRIC SUPERSYMMETRY IN A SOLVABLE SHORT-RANGE MODEL
Authors: BAGCHI B. , MALLIK S. , BÍLA H. , JAKUBSKÝ V. , ZNOJIL M. , QUESNE C.
Published: April 2006

The simplest purely imaginary and piecewise constant [Formula: see text]-symmetric potential located inside a larger box is studied. Unless its strength exceeds a certain critical value, all the spectrum of its bound states remains real and discrete. We interpret such a model as an initial element of the generalized non-Hermitian Witten's hierarchy of solvable Hamiltonians and construct its first supersymmetric partner in closed form.