bluuebunny/crossref_metadata_2025 huggingface dataset:
Geometrically Nonlinear Behavior of Composite Plates: A Review
Authors: Chia Chuen-Yuan
Published: June 2009

Advances in the understanding of static large deflection, postbuckling, and nonlinear dynamic response by using the analytical method are summarized for laminated elastic plates. In the case of symmetric laminates, bending-stretching coupling vanishes. The classical nonlinear theory of orthotropic or anisotropic plates applies, and references are also presented for these plates. A nonlinear shear-deformable theory of generally laminated plates and a general method of solution are briefly reviewed for a wide class of boundary conditions. Several effects, which complicate the geometric nonlinear behavior of composite plates, discussed in this survey paper are: transverse shear and normal stresses, rotatory and in-plane inertia, initial in-plane edge forces, geometric imperfections, cutouts, and nonclassical boundary conditions.
Nondestructive Evaluation of Offshore Structures Using Fracture Mechanics
Authors: Dharmavasan S. , Dover W. D.
Published: June 2009

Developments in fast modelling of processes, materials response and methodology in combination with appropriate knowledge based systems opens up the possibility of linking CAD/CAM with Computer Aided Serviceability (CAS) for use in a few industries. This paper reviews the tools and techniques which are available and being developed to implement this philosophy in non-destructive evaluation of offshore structures using fracture mechanics.
Fracture Mechanics Made Easy
Authors: Milne I.
Published: June 2009

The R6 method of evaluating the integrity of cracked structures was devised to provide a standardised procedure with the following objectives: to provide a method of analysis for failure avoidance; to be user insensitive; to be relatively simple in application; to be well validated. This required the standardisation of treatment material properties, both tensile and toughness data, as well as developing a standard format of analysis. Some of the background to the procedure is described, paying particular attention to these issues, and how the procedure is applied in practice.
Conventional and Unconventional Plastic Response and Representation
Authors: Drucker Daniel C.
Published: June 2009

The development and the present state of a few key aspects of the theory of plasticity are sketched as a guide to the literature for those new to or not centrally involved in the subject. Only a small fraction of this extensive literature is cited. Special attention is paid to the frequently inspirational but more often misleading influence of the theory of elasticity and the role of initial isotropy. The required simplicity of stress-strain relations to be usable with the most powerful of computers, for the analysis or design of metalworking processes or of ductile engineering structures and devices, is contrasted with the enormous complexity needed to model real behavior in quite crude detail. An attempt is made to place in perspective a variety of older and current representations, both conventional and unconventional. Applicable regimes of transference of results between the atomic, dislocation, or single crystal level and the macroscopic or continuum level also are explored.
Approaches to the Automatic Generation and Control of Finite Element Meshes
Authors: Shephard Mark S.
Published: June 2009

This review paper discusses the algorithmic approaches being taken to the development of finite element mesh generators capable of automatically discretizing general domains without the need for user intervention. The paper demonstrates that because of the modeling demands placed on an automatic mesh generator, all the approaches taken to date produce unstructured meshes. Consideration is also given to both a priori and a posteriori mesh control devices for automatic mesh generators as well as their integration with geometric modeling and adaptive analysis procedures.
Sixty-Five Years of Extended Surface Technology (1922–1987)
Authors: Kraus Allan D.
Published: June 2009

The extended surface literature from 1922 to 1987 is reviewed. The review begins with the classic NACA report of Harper and Brown published in 1922 and concludes with the works of Marto, Wanniarachchi, Rose, Mitrou, and Razelos published in 1986. A section entitled “The Beginnings” traces the accomplishments of the pioneers and it covers the period from 1922 to 1945 which coincides with the publication of Gardner’s landmark paper. At this point, a chronological approach is abandoned in favor of a categorization into topical areas. These are the elimination of the Murray–Gardner assumptions, boiling and condensation, experimental endeavors, compact heat exchangers, internally finned configurations, numerical analyses, optimizations, analyses of finned arrays, and additional topics including the use of extended surface to augment heat transfer, heat transfer in electrical and electronic equipment, purely mathematical techniques, and heat and mass transfer.
Flow Control
Authors: Gad-el-Hak Mohamad
Published: June 2009

The ability to actively or passively manipulate a flow field to effect a desired change is of immense technological importance. In this article, methods of control to achieve transition delay, separation postponement, lift enhancement, drag reduction, turbulence augmentation, or noise suppression are considered. The treatment is tutorial at times, making the material accessible to the advanced graduate student in the field of fluid mechanics. Emphasis is placed on external boundary-layer flows although applicability of some of the methods reviewed for internal flows will be mentioned. An attempt is made to present a unified view of the means by which different methods of control achieve a variety of end results. Performance penalties associated with a particular method such as cost, complexity, or trade-off will be elaborated.
On the Generalization of Displacement-Based Laminate Theories
Authors: Reddy J. N.
Published: June 2009

A review and generalization of the displacement-based two-dimensional plate theories is presented. The classical and shear deformation single–layer theories up to the third-order are presented in a single theory through tracers. The layer–wise laminate theory developed by the author is reviewed. Numerical results are presented to illustrate the accuracy of the layer–wise theory by comparison with the analytical solution of the 3–D elasticity theory.
A Mindlin–Reissner Variational Principle to Analyze the Behavior of Moderately Thick Plates
Authors: Carnicer Roberto S. , Alliney Stefano
Published: June 2009

In the present work a method to solve the plate behavior under the assumption of the Mindlin plate theory is analyzed by means of finite element techniques, avoiding the tendency of the thin element to lock when the thickness of the plates becomes very small. A different formulation is developed from the Mindlin–Reissner principle for general boundary conditions. Numerical examples to evaluate the noninfluence of locking on clamped and simple support plates are calculated.
A Hybrid Perturbation-Galerkin Method for Differential Equations Containing a Parameter
Authors: Geer James F. , Andersen Carl M.
Published: June 2009

A two-step hybrid perturbation-Galerkin method to solve a variety of differential equations which involve a parameter is presented and discussed. The method consists of: (1) the use of a perturbation method to determine the asymptotic expansion of the solution about one or more values of the parameter; and (2) the use of some of the perturbation coefficient functions as trial functions in the classical Bubnov-Galerkin method. This hybrid method has the potential of overcoming some of the drawbacks of the perturbation method and the Bubnov-Galerkin method when they are applied by themselves, while combining some of the good features of both. The proposed method is illustrated first with a simple linear two-point boundary value problem and is then applied to a nonlinear two-point boundary value problem in lubrication theory. The results obtained from the hybrid method are compared with approximate solutions obtained by purely numerical methods. Some general features of the method, as well as some special tips for its implementation, are discussed. A survey of some current research application areas is presented and its degree of applicability to broader problem areas is discussed.
Unified Constitutive Modelling of Nonlinear Time-Dependent Materials
Authors: Glockner P. G. , Szyszkowski W.
Published: June 2009

A semi-empirical engineering constitutive law modelling in a unified and continuous manner the main characteristic features of time-dependent materials, including creep, strain softening, relaxation and recovery and tensile brittleness, is briefly reviewed. The model, which contains 13 parameters, is a hereditary single Volterra-type integral representation of material response with stress/strain nonlinearity assumed in the form of a power law, the strain tensor dependent on the entire stress history and the stress-anisotropy/brittleness feature handled by means of a tensile-stress dependent damage function. The capability/versatility of the model is illustrated by examples for several materials.
Ceramics for Transportation Engines—Siren or Solution
Authors: Myers Phillip S.
Published: June 2009

The major challenges facing transportation engines—shrinking resources, preserving the environment, and competition—are reviewed and the promise of new materials, specifically ceramics, in helping to meet these challenges is discussed. As a background for understanding the properties of materials, the structure of materials (first at the subatomic level, then the molecular level, and finally at the mircostructure level) is reviewed. The relationship of this structure to properties of ceramics judged to be of importance to engines is then presented. The effect of these properties on engine performance such as volumetric efficiency, fuel economy, heat rejection, inertia, friction, wear, fuel tolerance, and packaging are discussed. It is concluded that ceramics have special properties that, for selected applications, are already justifying their use in transportation engines. It is further concluded that these special application uses will continue to grow and precede general use of ceramics for in-cylinder insulation aimed at improving fuel economy.
Acoustic characteristics of clearly spoken English fricatives
Authors: Maniwa Kazumi , Jongman Allard , Wade Travis
Published: June 2009

Speakers can adopt a speaking style that allows them to be understood more easily in difficult communication situations, but few studies have examined the acoustic properties of clearly produced consonants in detail. This study attempts to characterize the adaptations in the clear production of American English fricatives in a carefully controlled range of communication situations. Ten female and ten male talkers produced fricatives in vowel-fricative-vowel contexts in both a conversational and a clear style that was elicited by means of simulated recognition errors in feedback received from an interactive computer program. Acoustic measurements were taken for spectral, amplitudinal, and temporal properties known to influence fricative recognition. Results illustrate that (1) there were consistent overall style effects, several of which (consonant duration, spectral peak frequency, and spectral moments) were consistent with previous findings and a few (notably consonant-to-vowel intensity ratio) of which were not; (2) specific acoustic modifications in clear productions of fricatives were influenced by the nature of the recognition errors that prompted the productions and were consistent with efforts to emphasize potentially misperceived contrasts both within the English fricative inventory and based on feedback from the simulated listener; and (3) talkers differed widely in the types and magnitude of all modifications.
Synchronized time-reversal focusing with application to remote imaging from a distant virtual source array
Authors: Walker S. C. , Roux Philippe , Kuperman W. A.
Published: June 2009

Time-reversing the transfer function between a time-reversal mirror (TRM) and a distant probe source location generates an acoustic spatio-temporal focus at the location. It is shown that a TR focus behaves as a “virtual” source (in the far-field limit) in the outbound direction with respect to the TRM. By extension, a collection of TRM-to-probe source transfer functions constitutes a virtual source array (VSA) that can serve as a remote platform for active imaging methods such as beam-steering and other coherent wavefront techniques. As a demonstration, a set of a-priori sampled TRM-to-VSA transfer functions are steered to coherently focus at a selected location beyond the VSA for which the transfer function is not known a-priori. In this case the VSA acts as a lens that refocuses the TRM field to the target location. Under proper conditions, the resolution is comparable to that of standard TR. While the specific application of active focusing is presented as a validation of the concept, the relationship between coherent focusing and the transfer function implies that the virtual array concept may find use in a range of imaging methods, both active and passive. Possible applications are discussed, and simulation and experimental results are presented.
Excitation and scattering of guided waves: Relationships between solutions for plates and pipes
Authors: Velichko Alexander , Wilcox Paul D.
Published: June 2009

The detection of localized defects such as cracks and corrosion in pipes using guided elastic waves is now an established non-destructive testing procedure. However, the prediction of guided wave excitation and scattering in pipes is a complex three-dimensional (3D) problem with many parameters that can generally only be solved using numerical methods. In many important industrial applications, the diameter of a pipe is much larger than wall thickness. In this case an approximate theory is applicable, when a pipe is considered as an unwrapped isotropic plate. In this paper, a technique for obtaining pipe mode amplitudes in terms of the solution to the forced 3D problem on a plate is presented. The same principle is extended to relate guided wave scattering from defects in plates to scattered circumferential modal amplitudes from defects in pipe. This is of practical benefit as the scattering of guided waves by defects in a plate is a much simpler problem than that in a pipe, and one that, in some cases, can be solved using analytical methods. Results are shown that illustrate the application of the method to reflection from through-thickness circumferential cracks in pipes.
Bistable and dynamic states of parametrically excited ultrasound in a fluid-filled interferometer
Authors: Pérez-Arjona Isabel , Sánchez-Morcillo Víctor J. , Espinosa Víctor
Published: June 2009

In this paper the problem of parametric sound generation in an acoustic resonator filled with a fluid is considered, taking explicitly into account the influence of the nonlinearly generated second harmonic. A simple model is presented, and its stationary solutions were obtained. The main feature of these solutions is the appearance of bistable states of the fundamental field resulting from the coupling to the second harmonic. An experimental setup was designed to check the predictions of the theory. The results are consistent with the predicted values for the mode amplitudes and parametric thresholds. At higher driving values a self-modulation of the amplitudes is observed. This phenomenon is identified with a secondary instability previously reported in the frame of the theoretical model.
Rhythmic structure in humpback whale (Megaptera novaeangliae) songs: Preliminary implications for song production and perception
Authors: Handel Stephen , Todd Sean K. , Zoidis Ann M.
Published: June 2009

The hierarchical organization of the male humpback whale song has been well documented. However, it is unknown how singers keep these intricate songs intact over multiple repetitions or how they learn variations that occur sequentially during each mating season. Rather than focus on the sequence of sounds within a song, results presented here demonstrate that the individual sounds are organized into rhythmic groups that make the production and perception of the lengthy songs tractable by yielding a set of simple groups that, although arranged in rigid order, can be repeated multiple times to generate the entire song.
Stirring and mixing of liquids using acoustic radiation force
Authors: Sarvazyan Armen , Ostrovsky Lev
Published: June 2009

The possibility of using acoustic radiation force in standing waves for stirring and mixing small volumes of liquids is theoretically analyzed. The principle of stirring considered in this paper is based on moving the microparticles suspended in a standing acoustic wave by changing the frequency so that one standing wave mode is replaced by the other, with differently positioned minima of potential energy. The period-average transient dynamics of solid microparticles and gas microbubbles is considered, and simple analytical solutions are obtained for the case of standing waves of variable amplitude. It is shown that bubbles can be moved from one equilibrium position to another two to three orders of magnitude faster than solid particles. For example, radiation force in a standing acoustic wave field may induce movement of microbubbles with a speed of the order of a few m/s at a frequency of 1MHz and ultrasound pressure amplitude of 100kPa, whereas the speed of rigid particles does not exceed 1cm∕s under the same conditions. The stirring effect can be additionally enhanced due to the fact that the bubbles that are larger and smaller than the resonant bubbles move in opposite directions. Possible applications of the analyzed stirring mechanism, such as in microarrays, are discussed.
Self-masking: Listening during vocalization. Normal hearing
Authors: Borg Erik , Bergkvist Christina , Gustafsson Dan
Published: June 2009

What underlying mechanisms are involved in the ability to talk and listen simultaneously and what role does self-masking play under conditions of hearing impairment? The purpose of the present series of studies is to describe a technique for assessment of masked thresholds during vocalization, to describe normative data for males and females, and to focus on hearing impairment. The masking effect of vocalized [a:] on narrow-band noise pulses (250–8000 Hz) was studied using the maximum vocalization method. An amplitude-modulated series of sound pulses, which sounded like a steam engine, was masked until the criterion of halving the perceived pulse rate was reached. For masking of continuous reading, a just-follow-conversation criterion was applied. Intra-session test-retest reproducibility and inter-session variability were calculated. The results showed that female voices were more efficient in masking high frequency noise bursts than male voices and more efficient in masking both a male and a female test reading. The male had to vocalize 4 dBA louder than the female to produce the same masking effect on the test reading. It is concluded that the method is relatively simple to apply and has small intra-session and fair inter-session variability. Interesting gender differences were observed.
Graph theory applied to noise and vibration control in statistical energy analysis models
Authors: Guasch Oriol , Cortés Lluís
Published: June 2009

A fundamental aspect of noise and vibration control in statistical energy analysis (SEA) models consists in first identifying and then reducing the energy flow paths between subsystems. In this work, it is proposed to make use of some results from graph theory to address both issues. On the one hand, linear and path algebras applied to adjacency matrices of SEA graphs are used to determine the existence of any order paths between subsystems, counting and labeling them, finding extremal paths, or determining the power flow contributions from groups of paths. On the other hand, a strategy is presented that makes use of graph cut algorithms to reduce the energy flow from a source subsystem to a receiver one, modifying as few internal and coupling loss factors as possible.
The personal papers of Wallace C. Sabine
Authors: Beranek Leo L.
Published: June 2009

The notebooks of Wallace Clement Sabine were discovered in 1975, and his consulting files were discovered in 1979. Both findings were reported [J. Acoust. Soc. Am. 61, 629–639 (1977); J. Acoust. Soc. Am. 69, 1–7 (1981)]. By chance, his personal papers were discovered recently and highlights from them are presented here with emphasis on his European activities from 1906 to 1917.
Anomalous signed passive fathometer impulse response when using adaptive beam forming
Authors: Harrison Chris H.
Published: June 2009

The impulse response of the seabed can be extracted from sea surface ambient noise by cross-correlating the time series from an upward and a downward steered beam. When the steering for each beam is standard minimum variance adaptive beam forming it has been found that the impulse response for significant echoes appears to have the same amplitude but opposite sign. A mathematical explanation is offered for this strange phenomenon. Crucial contributing factors are that the cross-spectral density matrix for the vertical array typically consists of the sum of a Toeplitz matrix and a much weaker Hankel matrix and that it is ill-conditioned.
Non-linear, adaptive array processing for acoustic interference suppression
Authors: Hoppe Elizabeth , Roan Michael
Published: June 2009

A method is introduced where blind source separation of acoustical sources is combined with spatial processing to remove non-Gaussian, broadband interferers from space-time displays such as bearing track recorder displays. This differs from most standard techniques such as generalized sidelobe cancellers in that the separation of signals is not done spatially. The algorithm performance is compared to adaptive beamforming techniques such as minimum variance distortionless response beamforming. Simulations and experiments using two acoustic sources were used to verify the performance of the algorithm. Simulations were also used to determine the effectiveness of the algorithm under various signal to interference, signal to noise, and array geometry conditions. A voice activity detection algorithm was used to benchmark the performance of the source isolation.
Resolving the shape of a sonoluminescence pulse in sulfuric acid by the use of streak camera
Authors: Huang Wei , Chen Weizhong , Cui Weicheng
Published: June 2009

A streak camera is used to measure the shape of sonoluminescence pulses from a cavitation bubble levitated stably in a sulfuric acid solution. The shape and response to an acoustic pressure field of the sonoluminescence pulse in 85% by weight sulfuric acid are qualitatively similar to those in water. However, the pulse width in sulfuric acid is wider than that in water by over one order of magnitude. The width of the sonoluminescence pulse is strongly dependent on the concentration of the sulfuric acid solution, while the skewed distribution of the shape remains unchanged.
Anthropogenic Impacts on Nitrogen Isotopes of Ice-Core Nitrate
Authors: Hastings M. G. , Jarvis J. C. , Steig E. J.
Published: June 2009

The isotopic composition of nitrogen in nitrate deposited in Greenland has changed markedly over the past 150 years.
Natural Quasicrystals
Authors: Bindi Luca , Steinhardt Paul J. , Yao Nan , Lu Peter J.
Published: June 2009

Forbidden Crystals

In crystalline materials, a unit cell is replicated in space through a series of rotations, inversions, and reflections. In order to fully fill space, only certain rotational symmetries are allowed. Quasicrystals contain aperiodic tilings of two or more basic shapes that allow these forbidden rotation symmetries. A number of quasicrystalline materials have been synthesized in the lab, including a number of aluminum alloys.

Bindi
et al.

(p.
1306
) examined samples of the mineral khatyrkite, with a nominal composition of (Cu,Zn)Al
2
. A number of quasicrystalline grains with composition similar to synthetically formed materials were observed. Thus, quasicrystals can form in nature under geological conditions.
Numbers to Remember By

The Housekeeper and the Professor
by Yoko Ogawa

Translated from the Japanese () by Stephen Snyder. Picador, New York, 2009. 190 pp. Paper, $14, $C18. ISBN 9780312427801.
Authors: Ott Katharine
Published: June 2009

In Ogawa's quiet novel, numbers allow a mathematician who can't form memories to connect with his housekeeper and her son.
Amino Acid Addiction
Authors: Blander J. Magarian , Amsen Derk
Published: June 2009

Signaling pathways that control cellular responses to stress may also specify T cell differentiation.
Report Finds No Gender Bias in Faculty Hiring, Resources
Authors: Mervis Jeffrey
Published: June 2009

A new report by the U.S. National Academies says that women are getting a fair shake from major research universities in being hired, promoted, and given access to resources—once they can grab onto the academic ladder and start climbing the rungs.
Eugenie Scott Toils in Defense of Evolution
Authors: Bhattacharjee Yudhijit
Published: June 2009

As executive director of the National Center for Science Education, Eugenie Scott has spent the past 2 decades on the frontlines of the contentious battle over teaching evolution in U.S. public schools. Scott spoke to
Science
last week about where things now stand.
On the Origin of Sexual Reproduction
Authors: Zimmer Carl
Published: June 2009

Why sex? In the sixth essay in
Science
's series in honor of the Year of Darwin, Carl Zimmer explores why so many species take such a labyrinthine path to reproduction, when straightforward routes are available.
Hydrogen Cars: Fad or the Future?
Authors: Service Robert F.
Published: June 2009

The Obama Administration wants to end the hydrogen fuel cell vehicles program, which proponents see as the ultimate clean-car technology.
Hemagglutination Test for Rapid Serodiagnosis of Human Pythiosis
Authors: Jindayok Thanyasiri , Piromsontikorn Savittree , Srimuang Somboon , Khupulsup Kalayanee , Krajaejun Theerapong
Published: June 2009

Human pythiosis is an emerging, life-threatening infectious disease, caused by the oomycetePythium insidiosum. Thailand is an area where human pythiosis is endemic and the genetic blood disorder thalassemia is a predisposing factor. Patients with pythiosis present with arterial occlusions of the lower extremities, corneal ulcers, or chronic cutaneous infections. Diagnosis relies on time-consuming, relatively insensitive tests such as culture identification and immunodiffusion assay. Most patients undergo surgical removal of infected organs, and many die from the infection. Delayed diagnosis results in a poor prognosis. Here, we describe a hemagglutination (HA) test for rapid diagnosis of human pythiosis. Sheep red blood cells were coated withP. insidiosumprotein extract and used in duplicated detection assays using serum samples from 33 patients with vascular (n= 27), cutaneous (n= 2), or ocular (n= 4) pythiosis and serum samples from 289 control patients with other infectious diseases (n= 77), with highly positive antinuclear antibody (n= 5), with thalassemia (n= 21), or with no known disorder (i.e., healthy blood donors) (n= 186). Based on receiver-operating characteristic analysis, a serum titer of 1:160 was selected as the cutoff point for the HA test. Serum samples that generated HA at the cutoff titer were read as positive, while samples that did not were read as negative. Positive results were obtained with the serum samples of all patients with vascular and cutaneous pythiosis and with two serum samples from the control group. Negative results were obtained with serum samples from all ocular pythiosis patients and the 287 remaining serum samples from the control group. Sensitivity and specificity of the HA were 88% and 99%, respectively. In conclusion, the HA test for detection of anti-Pythiumantibodies is a simple, rapid, and reliable test for serodiagnosis of vascular and cutaneous pythiosis.
Recovery of Anti-
Toxoplasma gondii
Immunoglobulin M in Stored Guthrie Card Blood Spots
Authors: Tan Hooi-Kuan , Petersen Eskild , Møller Lone N. , Phillips Pamela , Neto Eurico Camargo , Gilbert Ruth E.
Published: June 2009

Retrospective testing of neonatal Guthrie card blood spots for specific immunoglobulin M (IgM) can distinguish congenital toxoplasmosis from acquired toxoplasmosis. We determined whether storage temperature reduced IgM detection, using filter paper blood samples “spiked” with anti-
Toxoplasma
IgM. After 300 days, IgM detection deteriorated with storage at room temperature but not at temperatures of 4°C or lower.
Polyomavirus Shedding in the Stool of Healthy Adults
Authors: Vanchiere John A. , Abudayyeh Suhaib , Copeland Christina M. , Lu Lee B. , Graham David Y. , Butel Janet S.
Published: June 2009

We recently reported the frequent detection of polyomaviruses (BK virus [BKV] or simian virus 40 [SV40]) in 46% of stool samples from hospitalized children. In order to determine if adults exhibit fecal shedding of polyomavirus, single stool specimens from healthy adults were evaluated by PCR. Overall, 20 (18.2%) of 110 specimens were positive for human polyomaviruses: 9 with BKV, 9 with JC virus (JCV), 1 with SV40, and 1 with both JCV and SV40. Among the 94 subjects without immune compromise, 17 (18.1%) were excreting polyomaviruses. This shedding frequency in adults was significantly lower than that observed in children (
P
< 0.001). These findings support the hypothesis that the gastrointestinal tract may be a site of polyomavirus persistence, and they suggest a fecal-oral route of viral transmission.
The CXCR4-Tropic Human Immunodeficiency Virus Envelope Promotes More-Efficient Gene Delivery to Resting CD4+T Cells than the Vesicular Stomatitis Virus Glycoprotein G Envelope
Authors: Agosto Luis M. , Yu Jianqing J. , Liszewski Megan K. , Baytop Clifford , Korokhov Nikolay , Humeau Laurent M. , O'Doherty Una
Published: June 2009

Current gene transfer protocols for resting CD4+T cells include an activation step to enhance transduction efficiency. This step is performed because it is thought that resting cells are resistant to transduction by lentiviral-based gene therapy vectors. However, activating resting cells prior to transduction alters their physiology, with foreseeable and unforeseeable negative consequences. Thus, it would be desirable to transduce resting CD4+T cells without activation. We recently demonstrated, contrary to the prevailing belief, that wild-type human immunodeficiency virus (HIV) integrates into resting CD4+T cells. Based on that finding, we investigated whether a commonly used, vesicular stomatitis virus glycoprotein G (VSV-G)-pseudotyped lentiviral gene therapy vector could also integrate into resting CD4+T cells. To investigate this, we inoculated resting CD4+T cells with lentiviral particles that were pseudotyped with VSV-G or CXCR4-tropic HIV Env and assayed binding, fusion, reverse transcription, and integration. We found that the VSV-G-pseudotyped lentiviral vector failed to fuse to resting CD4+T cells while HIV Env-pseudotyped lentiviral vectors fused, reverse transcribed, and integrated in resting cells. Our findings suggest that HIV Env could be used effectively for the delivery of therapeutic genes to resting CD4+T cells and suggest that fusion may be the critical step restricting transduction of resting CD4+T cells by lentiviral gene therapy vectors.
Simian Immunodeficiency Virus SIVrcm, a Unique CCR2-Tropic Virus, Selectively Depletes Memory CD4
+
T Cells in Pigtailed Macaques through Expanded Coreceptor Usage In Vivo
Authors: Gautam Rajeev , Gaufin Thaidra , Butler Isolde , Gautam Aarti , Barnes Mary , Mandell Daniel , Pattison Melissa , Tatum Coty , Macfarland Jeanne , Monjure Christopher , Marx Preston A. , Pandrea Ivona , Apetrei Cristian
Published: June 2009

Simian immunodeficiency virus SIVrcm, which naturally infects red-capped mangabeys (RCMs), is the only SIV that uses CCR2 as its main coreceptor due to the high frequency of a CCR5 deletion in RCMs. We investigated the dynamics of SIVrcm infection to identify specific pathogenic mechanisms associated with this major difference in SIV biology. Four pigtailed macaques (PTMs) were infected with SIVrcm, and infection was monitored for over 2 years. The dynamics of in vivo SIVrcm replication in PTMs was similar to that of other pathogenic and nonpathogenic lymphotropic SIVs. Plasma viral loads (VLs) peaked at 10
7
to 10
9
SIVrcm RNA copies/ml by day 10 postinoculation (p.i.). A viral set point was established by day 42 p.i. at 10
3
to 10
5
SIVrcm RNA copies/ml and lasted up to day 180 p.i., when plasma VLs decreased below the threshold of detection, with blips of viral replication during the follow-up. Intestinal SIVrcm replication paralleled that of plasma VLs. Up to 80% of the CD4
+
T cells were depleted by day 28 p.i. in the gut. The most significant depletion (>90%) involved memory CD4
+
T cells. Partial CD4
+
T-cell restoration was observed in the intestine at later time points. Effector memory CD4
+
T cells were the least restored. SIVrcm strains isolated from acutely infected PTMs used CCR2 coreceptor, as reported, but expansion of coreceptor usage to CCR4 was also observed. Selective depletion of effector memory CD4
+
T cells is in contrast with predicted in vitro tropism of SIVrcm for macrophages and is probably due to expansion of coreceptor usage. Taken together, these findings emphasize the importance of understanding the selective forces driving viral adaptation to a new host.
Determinants of Hepatitis C Virus p7 Ion Channel Function and Drug Sensitivity Identified In Vitro
Authors: StGelais Corine , Foster Toshana L. , Verow Mark , Atkins Elizabeth , Fishwick Colin W. G. , Rowlands David , Harris Mark , Griffin Stephen
Published: June 2009

Hepatitis C virus (HCV) chronically infects 170 million individuals, causing severe liver disease. Although antiviral chemotherapy exists, the current regimen is ineffective in 50% of cases due to high levels of innate virus resistance. New, virus-specific therapies are forthcoming although their development has been slow and they are few in number, driving the search for new drug targets. The HCV p7 protein forms an ion channel in vitro and is critical for the secretion of infectious virus. p7 displays sensitivity to several classes of compounds, making it an attractive drug target. We recently demonstrated that p7 compound sensitivity varies according to viral genotype, yet little is known of the residues within p7 responsible for channel activity or drug interactions. Here, we have employed a liposome-based assay for p7 channel function to investigate the genetic basis for compound sensitivity. We demonstrate using chimeric p7 proteins that neither the two
trans
-membrane helices nor the p7 basic loop individually determines compound sensitivity. Using point mutation analysis, we identify amino acids important for channel function and demonstrate that null mutants exert a dominant negative effect over wild-type protein. We show that, of the three hydrophilic regions within the amino-terminal
trans
-membrane helix, only the conserved histidine at position 17 is important for genotype 1b p7 channel activity. Mutations predicted to play a structural role affect both channel function and oligomerization kinetics. Lastly, we identify a region at the p7 carboxy terminus which may act as a specific sensitivity determinant for the drug amantadine.
Functional Characterization of Negri Bodies (NBs) in Rabies Virus-Infected Cells: Evidence that NBs Are Sites of Viral Transcription and Replication
Authors: Lahaye Xavier , Vidy Aurore , Pomier Carole , Obiang Linda , Harper Francis , Gaudin Yves , Blondel Danielle
Published: June 2009

Rabies virus infection induces the formation of cytoplasmic inclusion bodies that resemble Negri bodies found in the cytoplasm of some infected nerve cells. We have studied the morphogenesis and the role of these Negri body-like structures (NBLs) during viral infection. The results indicate that these spherical structures (one or two per cell in the initial stage of infection), composed of the viral N and P proteins, grow during the virus cycle before appearing as smaller structures at late stages of infection. We have shown that the microtubule network is not necessary for the formation of these inclusion bodies but is involved in their dynamics. In contrast, the actin network does not play any detectable role in these processes. These inclusion bodies contain Hsp70 and ubiquitinylated proteins, but they are not misfolded protein aggregates. NBLs, in fact, appear to be functional structures involved in the viral life cycle. Specifically, using in situ fluorescent hybridization techniques, we show that all viral RNAs (genome, antigenome, and every mRNA) are located inside the inclusion bodies. Significantly, short-term RNA labeling in the presence of BrUTP strongly suggests that the NBLs are the sites where viral transcription and replication take place.
Introduction of Exogenous Epitopes in the Variable Regions of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein: Effect on Viral Infectivity and the Neutralization Phenotype
Authors: Wallace Aaron , Stamatatos Leonidas
Published: June 2009

In this study we examined whether human immunodeficiency virus type 1 (HIV-1) is equally susceptible to neutralization by a given antibody when the epitope of this antibody is introduced at different positions within the viral envelope glycoprotein (Env). To this end, we introduced two exogenous “epitope tags” at different locations within three major Env regions in two distinct HIV-1 isolates. We examined how the introduction of the exogenous epitopes affects Env expression, Env incorporation into virions, Env fusogenic potential, and viral susceptibility to neutralization. Our data indicate that even within the same Env region, the exact positioning of the epitope impacts the susceptibility of the virus to neutralization by the antibody that binds to that epitope. Our data also indicate that even if the same epitope is introduced in the exact same position on two different Envs, its exposure and, as a result, the neutralization susceptibility of the virus, can be very different. In contrast to the findings of previous studies conducted with HIV-1 isolates other than those used here, but in agreement with results obtained with simian immunodeficiency virus, we observed that tagging of the fourth variable region of Env (V4) did not result in neutralization by the anti-tag antibodies. Our data indicate that epitopes in V4 are not properly exposed within the functional HIV-1 trimeric Env spike, suggesting that V4 may not be a good target for vaccine-elicited neutralizing antibodies.
Truncation of TRIM5 in the
Feliformia
Explains the Absence of Retroviral Restriction in Cells of the Domestic Cat
Authors: McEwan William A. , Schaller Torsten , Ylinen Laura M. , Hosie Margaret J. , Towers Greg J. , Willett Brian J.
Published: June 2009

TRIM5α mediates a potent retroviral restriction phenotype in diverse mammalian species. Here, we identify a TRIM5 transcript in cat cells with a truncated B30.2 capsid binding domain and ablated restrictive function which, remarkably, is conserved across the
Feliformia
. Cat TRIM5 displayed no restriction activity, but ectopic expression conferred a dominant negative effect against human TRIM5α. Our findings explain the absence of retroviral restriction in cat cells and suggest that disruption of the TRIM5 locus has arisen independently at least twice in the
Carnivora
, with implications concerning the evolution of the host and pathogen in this taxon.
Population-based estimates of injuries in Sri Lanka
Authors: Navaratne K V , Fonseka P , Rajapakshe L , Somatunga L , Ameratunga S , Ivers R , Dandona R
Published: June 2009

Background:

Injuries are the leading cause of public hospital admission in Sri Lanka. Data on injury epidemiology to plan prevention programmes to reduce injury burden are not readily available.

Objectives:

To assess the incidence of various types of injuries in the Galle district, Sri Lanka.

Methods:

9568 individuals of all ages were selected from 2000 households in a population-based cross-sectional survey using a stratified cluster sampling technique. Data on non-fatal injuries in the last 30 days irrespective of severity, fatal injuries and those that resulted in disability in the last 12 months were documented. Proxy data were used for half of the injury cases.

Results:

195 (2%) individuals reported non-fatal injuries during the last 30 days, giving an age-sex-urban-rural adjusted annual incidence of 24.6 per 100 population. The leading causes of non-fatal injuries were falls (adjusted annual incidence 6.7 per 100 population, 95% CI 6.0 to 7.3) and mechanical injuries (6.3; 95% CI 5.7 to 6.8), followed by road traffic injuries (4.9; 95% CI 4.4 to 5.5). 114 (58.5%) individuals needed outpatient care and 50 (25.6%) needed inpatient care for their injuries. The annual injury mortality rate and disability rate were 177 (95% CI 72 to 283) and 290 (95% CI 250 to 330) per 100 000 population, respectively.

Conclusions:

Nearly one in four people reported non-fatal injury; the majority sought medical attention in this population. It is important to utilise injury epidemiology to develop and implement interventions to reduce the burden of injuries in the population and on the hospitals in Sri Lanka.
Neighbourhood income gradients in hospitalisations due to motor vehicle traffic incidents among Canadian children
Authors: Oliver L , Kohen D
Published: June 2009

Objective:

To investigate income gradients in motor vehicle traffic injury hospitalisation for vehicle occupants and pedestrians/cyclists among children in urban and rural Canada.

Design:

Four years (2001/02–2004/05) of acute-care hospitalisation discharge records for children aged 0–19 years were analysed. International Classification of Disease codes were used to determine hospitalisations due to motor vehicle traffic incidents for occupants and pedestrians/cyclists. Rates of injury (per 10 000 person years) were calculated by neighbourhood income quintiles for urban and rural areas.

Results:

Among children (0–19 years), rates of vehicle occupant hospitalisation were higher in rural (5.07, 95% CI 4.90 to 5.25) than urban areas (2.08, 95% CI 2.03 to 2.14). In rural areas, children from lower income neighbourhoods had higher vehicle occupant hospitalisation rates than those from the richest neighbourhoods (5.52, 95% CI 5.13 to 5.93 vs 4.30, 95% CI 3.97 to 4.66). In urban areas vehicle occupant hospitalisation rates were similar among children from the poorest and richest neighbourhoods—but higher among children from middle income neighbourhoods. In urban areas, but not rural areas, the hospitalisation rate for pedestrians/cyclists systematically increased with decreasing neighbourhood income. In urban areas the pedestrian/cyclist hospitalisation rate was four times higher for children from the poorest (1.40, 95% CI 1.25 to 1.57) than from the richest (0.34, 95% CI 0.28 to 0.43) neighbourhoods.

Conclusions:

While vehicle occupant and pedestrian/cyclist motor vehicle traffic injuries are more frequent among children from lower income neighbourhoods, gradients are most pronounced for pedestrians/cyclists in urban areas.
Causes of injuries resulting in hospitalisation in Australia: assessing coder agreement on external causes
Authors: McKenzie K , Enraght-Moony E L , Waller G , Walker S M , Harrison J E , McClure R J
Published: June 2009

Objective:

To assess extent of coder agreement for external causes of injury using ICD-10-AM for injury-related hospitalisations in Australian public hospitals.

Methods:

A random sample of 4850 discharges from 2002 to 2004 was obtained from a stratified random sample of 50 hospitals across four states in Australia. On-site medical record reviews were conducted and external cause codes were assigned blinded to the original coded data. Code agreement levels were grouped into the following agreement categories: block level, 3-character level, 4-character level, 5th-character level, and complete code level.

Results:

At a broad block level, code agreement was found in over 90% of cases for most mechanisms (eg, transport, fall). Percentage disagreement was 26.0% at the 3-character level; agreement for the complete external cause code was 67.6%. For activity codes, the percentage of disagreement at the 3-character level was 7.3% and agreement for the complete activity code was 68.0%. For place of occurrence codes, the percentage of disagreement at the 4-character level was 22.0%; agreement for the complete place code was 75.4%.

Conclusions:

With 68% agreement for complete codes and 74% agreement for 3-character codes, as well as variability in agreement levels across different code blocks, place and activity codes, researchers need to be aware of the reliability of their specific data of interest when they wish to undertake trend analyses or case selection for specific causes of interest.
Inter-Annual Distributions of Larval and Pelagic Juvenile Cod (Gadus morhua) in Southwestern Nova Scotia determined with two Different Gear Types
Authors: Suthers Iain M. , Frank Kenneth T.
Published: June 2009

Ichthyoplankton surveys conducted during 1979 on the Scotian Shelf have shown coincident egg and larval distributions for cod (Gadus morhua) and other related groundfish species. These data have been used by other investigators to support the larval retention hypothesis, in spite of three limitations: the exclusive use of a single type of small sampling gear, limited sampling landward of the 50-m isobath, and analysis of data collected in a single year. During May of 1985, 1986, and 1987 two gear types were used, from the shelf to coastal waters in southwestern Nova Scotia to assess the horizontal distributions of larval and pelagic juvenile cod. Tucker trawl collections made in each year revealed a cohort of cod [Formula: see text] that was not evident in the smaller gear, which effectively sampled cod larvae < 10 mm. During 1985 and 1986, when both larvae and juveniles were abundant, their distributions coincided. The mixture of sizes of cod from 3–45 mm reduced the importance of using multiple gear types. The interannual location of young cod shifted markedly between the nearshore and offshore demonstrating that a single year of sampling effort is inadequate to assess their distribution. Nearshore sampling revealed high densities of young cod as much as three-fold greater than offshore. The inshore waters may serve as a nursery area for young cod originating from offshore spawning sites. Our results confirm the existence of two important sampling limitations of previous cod ichthyoplankton surveys that reduce their utility as empirical support for the retention hypothesis.
Migration Timing, Size, and Salinity Tolerance of Sea-Type Sockeye Salmon (Oncorhynchus nerka) in an Alaska Estuary
Authors: Heifetz Jonathan , Johnson Scott W. , Koski K V. , Murphy Michael L.
Published: June 2009

Migration timing, size, and salinity tolerance were determined for sea-type sockeye salmon (Oncorhynchus nerka), which migrate to sea as underyearlings (age-0), in the Situk River estuary, Southeast Alaska. Ten sites in three habitat types were seined monthly from Sate April through August, 1987, and age-0 sockeye from the estuary were tested for salinity tolerance. Age-0 sockeye were most abundant (up to 13∙m−2) from late April through June, and by late July, most sockeye had left the estuary. Mean fork length (FL) was 31 mm in April and increased 0.4 mm∙d−1 to 70 mm in late July when most (72%) remaining sockeye had grown to about the same size as age-1 smolts (69–95 mm) emigrating in May and June. Mean FL of age-0 sockeye in the estuary in July was 23 mm greater than in freshwater areas of the river. Salinity tolerance was directly related to fish size, and a size of at least 50 mm was required for 100% survival in seawater. Because salinity in the estuary ranged 0–30‰, sockeye of all sizes could survive in the estuary. Thus, in 3–4 mo, sea-type sockeye attained a size large enough to adapt to seawater and migrate to sea.