bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive beamforming for multipath environments
Authors: Cox Henry
Published: October 2013

Coherent multipaths present a significant challenge to most adaptive beamformers because they violate the common assumption of a rank-one plane wave or geometrically focused signal. When the multipath arrivals that characterize shallow water propagation are resolvable by the array’s aperture, the mismatch between the assumed and the true signal spatial structure causes signal suppression. If the amplitude and phase relationships among the various multipaths were known, they could, in principle, be included in a matched field beamforming approach. This is usually impractical due to inadequate knowledge of propagation parameters, especially bottom characteristics, and source/receiver motion. A generalization of the standard MVDR approach, called multirank MVDR, assumes only that the signal lies in a subspace of multiple rank rather than the usual rank-one assumption. An example of a subspace is a small fan of beams that cover the potential multipath directions. The signal may be rank one corresponding to fully coherent multipath or higher rank corresponding to incoherent or partially coherent multipath. The multirank approach is applied to the shallow water multipath problem and compared with the related technique of employing multiple linear constraints. Realistic simulations of alternative beamforming approaches for a large horizontal array are presented. [Work supported by ONR.]
Robust adaptive algorithm based on nonlinear error cost function for acoustic echo cancellation
Authors: Shimauchi Suehiro , Haneda Yoichi , Kataoka Akitoshi
Published: October 2013

Motivated by recent progress in the blind source separation (BSS) technique, a robust echo cancellation algorithm is investigated, which would inherently identify the echo path even during double-talk by separating the acoustic echo from the local speech. An adaptive filter has been introduced into acoustic echo cancellers to identify the acoustic echo path impulse response and generate the echo replica. However, most adaptive algorithms suffer from instability during double-talk. Although step-size control cooperating with a double-talk detector (DTD) is a promising approach to stop the adaptation temporarily during double-talk, it cannot handle the echo path change during double-talk. To overcome this problem, novel robust algorithms are derived by applying nonlinearity to the cost function of a conventional echo cancellation algorithm such as the normalized least mean squares algorithm (NLMS) or the affine projection algorithm (APA). Using the simulation results, there is a discussion about how the robustness of the derived algorithms depends on the choice of the nonlinear function and the original algorithm.
Realistic modeling of adaptive beamformer performance in nonstationary noise
Authors: Newhall Bruce K.
Published: October 2013

Most adaptive beamformers (ABFs) operate under the assumption that the noise field is quasistationary. They estimate the present noise field by averaging, assuming stationarity over the estimation time. The adaptive beamformer responds to slow changes in the noise field across multiple estimation intervals. Unfortunately, in many low-frequency underwater sound applications, the shipping noise may change rapidly, due to nearby ship motion. This motion can be significant during the estimation interval and degrade ABF performance. A realistic model has been developed, including two effects of source motion on horizontal towed arrays. Bearing rate produces a differential Doppler shift across the array. Range rate produces an amplitude modulation as the multipath interference pattern shifts along the array. The ABF model begins with a realization of ship locations and motion based on historical shipping density. Each ship generates realistic random noise composed of tonals in a broadband background. The noise is propagated from each ship to each hydrophone by a normal mode model. For each time sample the position of each ship is updated and propagation recalculated. The ability of a variety of ABF algorithms to reduce shipping noise clutter is simulated and compared.
Vector sensor array sensitivity and mismatch: Generalization of the Gilbert-Morgan formula
Authors: Poulsen Andrew J. , Baggeroer Arthur B.
Published: October 2013

The practical implementation of any sensing platform is susceptible to imperfections in system components. This mismatch or difference between the assumed and actual sensor configuration can significantly impact system performance. This paper addresses the sensitivity of an acoustic vector sensor array to system mismatch by generalizing the approach used by Gilbert and Morgan for an array with scalar, omnidirectional elements [E.N. Gilbert and S.P. Morgan, Bell Syst. Tech. J. 34, (1955)]. As such, the sensor orientation is not an issue because it does not affect performance for an array of omnidirectional sensors. Since vector sensors measure both the scalar acoustic pressure and acoustic particle velocity or acceleration, the sensor orientation must also be measured to place the vector measurement in a global reference frame. Here, theoretical expressions for the mean and variance of the vector sensor array spatial response are derived using a Gaussian perturbation model. Such analysis leads to insight into theoretical limits of both conventional and adaptive processing in the presence of system imperfections. Comparisons of theoretical results and simulations are excellent. One noteworthy result is the variance is now a function of the steering angle. [Work supported by the PLUSNeT program of the Office of Naval Research.]
A study on combining acoustic echo cancelers with impulse response shortening
Authors: Goetze Stefan , Kammeyer Karl-Dirk , Kallinger Markus , Mertins Alfred
Published: October 2013

In hands-free video conferencing systems acoustic echo cancelers (AECs) have to face the problem of very high-order impulse responses (IRs), which have to be compensated. Time-domain algorithms for adaptation often suffer from slow convergence (as the NLMS algorithm, e.g.) or high computational complexity (e.g., the RLS). On the other hand frequency-domain algorithms introduce undesired delays [S. Haykin, Filter Theory, 2002]. For high-quality hands-free systems IR shortening concepts and IR shaping concepts developed for listening room compensation (LRC) [M.Kallinger and A. Mertins, in Proc. Asilomar, 2005] can be applied to increase speech intelligibility for the near-end speaker. The aim of this study is the synergetic combination of LRC concepts with acoustic echo cancellation. For this scenario two different forms of concatenating the subsystems are possible. Either the AEC filter follows the LRC or vice versa. In the first case the equalization filter reduces the length of the effective IR seen by the AEC filter. Thus, shorter AEC filters can be used which results in faster convergence. However, an estimation algorithm for the room IR is necessary for the LRC subsystem. In the second case the AEC delivers an estimate of the room IR which can be used as an input for the LRC filter. Experimental results confirm the superiority of the new combined approach.
Krylov and predictive sequential least-squares methods for dimensionality reduction in adaptive signal processing and system identification
Authors: Preisig James , Li Weichang
Published: October 2013

Rapid time variation of the environment, a large number of parameters which need to be adjusted, and the presence of a reduced subset of the parameters that are relevant at any point in time create significant challenges for adaptive signal-processing algorithms in underwater acoustic applications. In applications such as underwater acoustic communications, the environment is represented by the ‘‘taps’’ of the time-varying impulse response. The instability of estimation algorithms or inability to track rapid channel fluctuations are among the problems that are encountered. An approach to addressing these challenges is to dynamically select a subspace in which the adjustment of taps takes place. Here, two algorithms for doing this are presented. The first is based upon using subspace basis vectors, which form a Krylov subspace with respect to the channel input correlation matrix and the channel input/output correlation vector. This method does not use a prediction residual error to select the basis vectors. A second algorithm is a new variant of the matching pursuit algorithm. In this case, ‘‘important’’ taps of the channel impulse response are selected to minimize a forward prediction residual error. The properties and performance of these two algorithms are presented and compared using simulation and field data.
A comprehensive unbiased third party evaluation of a signal processor for detecting submerged sources among clutter signals and noise
Authors: Wagstaff Ronald
Published: October 2013

The Wagstaff’s integration silencing processor, WISPR’, was developed to detect and identify signals in the ocean from sources that are submerged well below the sea surface. WISPR is the type of signal processor that exploits the reciprocal of the spectral power amplitude, rather than the amplitude as the average power processor does. Processing the reciprocal of the power represented a significant departure in the prevailing signal processing philosophy that governed most conventional signal processing algorithms that were in use when WISPR first appeared on the scene several years ago. Furthermore, WISPR’s claimed submerged-source detection capability made it an attractive candidate for some high interest signal processing applications. Accordingly, one influential national organization considered its potential use in their mission and decided to commission a credible third party laboratory to conduct an unbiased evaluation of the WISPR processor. The emphasis was to be on its performance for automatic unalerted detection of signals from submerged sources. The techniques and evaluation methods used to test the WISPR processor will be described. The results of the evaluation will be presented, and the influence of those results on the development of other, more advanced, fluctuation-based processors will be discussed.
Motion compensation of multiple sources
Authors: Park Joung-Soo , Kim Jae-Soo , Kim Young-Gyu
Published: October 2013

Matched field processing has a advantage of detection of multiple targets. But, if a strong interferer is moving fast near a quiet target, detection of the target is difficult due to the motion effect of the interferer. The motion of the interferer introduces energy spreading and results in poorer detection. A waveguide-invariant-based motion compensation algorithm was proposed to mitigate the motion effect of a dominant signal component, which is estimated by eigenvalue method. The eigenvalue method is good for a strong interferer, but not good for multiple targets. In this presentation, we will propose a steered beam processing method to mitigate the motion effect of multiple targets. We will verify the proposed method with numerical simulations and SwellEx96 data processing.
Predicting sonar performance using observations of mesoscale eddies
Authors: DeFerrari Harry
Published: October 2013

A predictive relationship has been observed between the location of offshore mesoscale eddies and the performance of active and passive sonar on the shallow water shelf area inside of the eddy. The passage of an eddy produces a prograde front that modifies acoustic propagation by two mechanisms. First, the density gradient serves as a conduit for offshore internal waves to propagate onto the shelf. A long-lived front can result in order of magnitude increases in potential energy of the internal wave field and corresponding increases in sound speed variability. Second, the circulation of the eddy produces a unique sound speed profile that is strongly downward refracting but has a nearly iso-velocity layer near the bottom owing to turbulent mixing. The shape of the profile closely approximates a hyperbolic cosine. Such a profile has mode group velocities that are equal for all refracted modes, thus producing strong focusing and a caustic at the depth of the source at all ranges. The experimental observations are confirmed with oceanographic and acoustic propagation models and, in turn, the models predict FOM fluctuations of as much as 15 dB for passive sonar and 24 dB for active sonar, depending on location of the eddy.
L. M. Brekhovskikh’s studies on nonlinear wave interaction and atmospheric sound
Authors: Naugolnykh Konstantin
Published: October 2013

Nonlinear interaction of waves in a compressible fluid is an underlying factor in many geophysical effects, and L. M. Brekhovskikh made essential contributions to investigation of these phenomena. In particular, he suggested the mechanism of the infrasound generation by stormy areas in the ocean based on the nonlinear interaction of the counter-propagating sea-surface gravity waves. The estimates of the order of magnitude of sound intensities were made indicating that the main part of the infrasound generated by the surface waves is absorbed in the upper layers of the atmosphere, resulting in the heating of these layers. The other part of the sound energy can be trapped by the atmospheric acoustic waveguide and then returned to earth at distances of hundreds of kilometers, producing the voice of the sea.
Tangent-plane approximation by L. M. Brekhovskikh and connected methods in the theory of wave scattering from rough surfaces
Authors: Voronovich Alexander G.
Published: October 2013

Starting from pioneering work by Rayleigh in 1907, scattering of waves from rough surfaces was restricted by the case of small Rayleigh parameter. In this case perturbation analysis describing the process of Bragg scattering applies. Apparently, smallness of the roughness is too restrictive for many applications. In 1952 L. M. Brekhovskikh suggested a tangent-plane approximation (TPA). For ideal boundary conditions it represents the first iteration of the appropriate boundary integral equation. However, for more complex situations (e.g., dielectric or solid-fluid interfaces) appropriate boundary integral equations are rather complicated and, even worse, they cannot be readily iterated. The TPA allows bypassing this step providing the answer in closed form for arbitrary boundary conditions and for scalar or vector waves in terms of the local reflection coefficient. Unfortunately, the TPA does not correctly describe the Bragg scattering. However, later it was realized that the TPA allows simple generalization, which treats both low- and high-frequency limits within single theoretical scheme. This is achieved by considering the local reflection coefficient as an operator rather than a factor. New methods going beyond the two classical ones with much wider regions of validity were developed based on this idea. Some of them will be reviewed in this talk.
Under-balcony acoustics in concert halls: Single source versus an array of multiple sources
Authors: Kwon Youngmin , Siebein Gary W.
Published: October 2013

The conventional measurement protocol using a single omnidirectional sound source may have limits or uncertainty in objective acoustical analysis of a performance hall. This study conducted monaural and binaural impulse response measurements with an array of 16 directional loudspeakers for quantitative acoustical assessment of specifically under-balcony area in a concert hall. The measurements were executed in a real performance hall. The measured time- and frequency-domain responses as well as the results of room acoustical parameters including binaural parameters were compared to the ones measured with a single omnidirectional source. The results were also compared to the ones taken at the main orchestra seating area. The time-domain responses showed a clear distinction particularly in early responses between single source and multiple sources. On the other hand, the magnitude of frequency response showed significantly lower at frequencies above 1 kHz than the one measured at the main area. The results of a binaural parameter, IACC, were found to be marginal between single source and multiple sources but critically different between under-balcony area and main area. Variations were also observed in the results of other room acoustical parameters when compared either between single source and multiple sources or between under-balcony area and main area.
Alternative metrics for the directivity of acoustic sources
Authors: Leishman Timothy W.
Published: October 2013

While the directivity of an acoustic source at a given frequency is thoroughly characterized by a directivity function over the angular coordinates, it may also be characterized to a lesser degree by a single-number directivity factor. The directivity index (i.e., the logarithmic version of the directivity factor) is a related figure of merit. Recent efforts to quantify the directivity of sources for architectural acoustics measurements have led to several alternatives to these values. One example is the area-weighted spatial standard deviation of radiated levels over a free-field measurement sphere. This paper presents and compares this and other directivity metrics for several types of sources, and discusses their benefits.
In situ measurements for evaluating the scattering surfaces in a concert hall
Authors: Jeon Jin Yong , Sato Shin-ichi
Published: October 2013

Sound diffusion by a wall structure is one of the main concerns with respect to the sound quality of concert halls. There is a need to develop measurement and evaluation methods for determining the performance of scattering wall surfaces not only in a laboratory but also in actual halls. In this study, the acoustical measurements were conducted in a concert hall which has diffusers with ceramic cubic tiles on the side walls of the stage and the audience area. Binaural impulse responses were measured at all of the seats under two conditions, that is, with and without diffusers. The area which was affected by the diffusive wall was determined and quantified. The condition without diffusers was produced by covering them with the movable reflectors. From the binaural impulse responses, the temporal diffusion [H. Kuttruff, Room Acoustics, (Elsevier Science, London, 1991)], which is calculated from the autocorrelation of the impulse response, and other acoustical parameters were analyzed. From the relationship between the scattering coefficient and the acoustical parameters, sound scattering index for real halls, which represents the degree of the diffusion of a hall, was proposed.
Parameter Space Compression Underlies Emergent Theories and Predictive Models
Authors: Machta Benjamin B. , Chachra Ricky , Transtrum Mark K. , Sethna James P.
Published: October 2013

Information Physics

Multiparameter models, which can emerge in biology and other disciplines, are often sensitive to only a small number of parameters and robust to changes in the rest; approaches from information theory can be used to distinguish between the two parameter groups. In physics, on the other hand, one does not need to know the details at smaller length and time scales in order to understand the behavior on large scales. This hierarchy has been recognized for a long time and formalized within the renormalization group (RG) approach.

Machta
et al.

(p.
604
) explored the connection between two scales by using an information-theoretical approach based on the Fisher Information Matrix to analyze two commonly used physics models—diffusion in one dimension and the Ising model of magnetism—as the time and length scales, respectively, were progressively coarsened. The expected “stiff” parameters emerged, in agreement with RG intuition.
New Experiment Torpedoes Lightweight Dark Matter
Authors: Cho Adrian
Published: October 2013

This week, researchers working with the Large Underground Xenon (LUX) detector at the Sanford Underground Research Facility in Lead, South Dakota, announced that they see no signs of the lightweight dark matter particles hinted at by other experiments.
RNA Helps Resurrect Ancient DNA
Authors: Kaiser Jocelyn
Published: October 2013

A relatively inexpensive way of reading contaminated DNA samples promises to help researchers learn more about the genetics of ancient humans and animals.
Antibody Response to Achromobacter xylosoxidans during HIV Infection Is Associated with Lower CD4 Levels and Increased Lymphocyte Activation
Authors: Tatro Erick T. , Purnajo Intan , Richman Douglas D. , Smith Davey M. , Gianella Sara
Published: October 2013

Inflammation during HIV infection is associated with worse disease outcomes and progression. Many mechanisms have been indicted, including HIV itself, coinfections, and gut microbial translocation. Concerning microbial translocation, we hypothesized that adaptive immune responses to a specific bacterial species known to be present in gut-associated lymphoid tissue are higher among HIV-infected individuals than among HIV-uninfected controls and are associated with T cell activation and lower CD4 T cell counts. By characterizing the IgG response toAchromobacter xylosoxidans, we found that HIV-infected participants who were immunoresponsive (n= 48) had significantly lower CD4 percentages (P= 0.01), greater CD4 activation (percentages of RA−CD38+) (P= 0.03), and higher soluble CD14 (P= 0.01). HIV-positive individuals had higher anti-A. xylosoxidansIgG titers than HIV-uninfected individuals (P= 0.04). The results suggest an abnormal adaptive immune activation to gut microflora during HIV infection.
Safety and Immunogenicity of Single-Dose Live Oral Cholera Vaccine Strain CVD 103-HgR, Prepared from New Master and Working Cell Banks
Authors: Chen Wilbur H. , Greenberg Richard N. , Pasetti Marcela F. , Livio Sofie , Lock Michael , Gurwith Marc , Levine Myron M.
Published: October 2013

Currently, no cholera vaccine is available for persons traveling from the United States to areas of high cholera transmission and who for reasons of occupation or host factors are at increased risk for development of the disease. A single-dose oral cholera vaccine with a rapid onset of protection would be particularly useful for such travelers and might also be an adjunct control measure for cholera outbreaks. The attenuatedVibrio choleraeO1 vaccine strain CVD 103-HgR harbors a 94% deletion of the cholera toxin A subunit gene (ctxA) and has a mercury resistance gene inserted in the gene encoding hemolysin A. We undertook a phase I randomized placebo-controlled two-site trial to assess the safety and immunogenicity of a preliminary formulation of CVD 103-HgR prepared from new master and working cell banks. Healthy young adults were randomized (5:1 vaccinees to placebo recipients) to receive a single oral dose of ∼4.4 × 108CFU of vaccine or a placebo. Blood serum vibriocidal and cholera toxin-specific IgG antibodies were measured before and 10, 14, and 28 days following vaccination or placebo. Excretion of the vaccine strain in the stool was assessed during the first week postvaccination. A total of 66 subjects were enrolled, comprising 55 vaccinees and 11 placebo recipients. The vaccine was well tolerated. The overall vibriocidal and anti-cholera toxin seroconversion rates were 89% and 57%, respectively. CVD 103-HgR is undergoing renewed manufacture for licensure in the United States under the auspices of PaxVax. Our data mimic those from previous commercial formulations that elicited vibriocidal antibody seroconversion (a correlate of protection) in ∼90% of vaccinees. (This study has been registered at ClinicalTrials.gov under registration no. NCT01585181.)
Blood Collection Tubes Influence Serum Ficolin-1 and Ficolin-2 Levels
Authors: Brady Allison M. , Spencer Brady L. , Falsey Ann R. , Nahm Moon H.
Published: October 2013

The ficolins are members of a recently discovered family of host innate opsonins that can activate the lectin pathway of complement. The ficolins bind many ligands, although they are typically described as binding acetylated sugars. Ficolin-1 (M-ficolin) and ficolin-2 (L-ficolin) are known to bindStreptococcus pneumoniaeserotypes 19C and 11A, respectively. While studying the binding of ficolins to pneumococci, we found variations in ficolin-2 binding among serum samples collected in different types of blood collection tubes. Plastic tubes, which contain a silica clot activator, yielded sera with reduced ficolin-2 binding and apparent ficolin-2 levels. We found that the silica clot activator eluted from plastic red-top tubes inhibited ficolin-2 ligand binding, while other related proteins, like mannose-binding lectin (MBL) and ficolin-1, were not affected. These tube types did not affect the concentrations of other related opsonins (C1q, MBL, or ficolin-3 [H-ficolin]). Interestingly, we also found that ficolin-1 levels were increased 2- to 3-fold in plastic serum separator tubes compared to the increases in other tube types. These findings have implications for future ficolin-1 and ficolin-2 studies, as proper sample collection and handling are essential.
Proposal of a Consensus Set of Hypervariable Mycobacterial Interspersed Repetitive-Unit–Variable-Number Tandem-Repeat Loci for Subtyping of Mycobacterium tuberculosis Beijing Isolates
Authors: Allix-Béguec Caroline , Wahl Céline , Hanekom Madeleine , Nikolayevskyy Vladyslav , Drobniewski Francis , Maeda Shinji , Campos-Herrero Isolina , Mokrousov Igor , Niemann Stefan , Kontsevaya Irina , Rastogi Nalin , Samper Sofia , Sng Li-Hwei , Warren Robin M. , Supply Philip
Published: October 2013

Mycobacterium tuberculosis
Beijing strains represent targets of special importance for molecular surveillance of tuberculosis (TB), especially because they are associated with spread of multidrug resistance in some world regions. Standard 24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) typing lacks resolution power for accurately discriminating closely related clones that often compose Beijing strain populations. Therefore, we evaluated a set of 7 additional, hypervariable MIRU-VNTR loci for better resolution and tracing of such strains, using a collection of 535 Beijing isolates from six world regions where these strains are known to be prevalent. The typeability and interlaboratory reproducibility of these hypervariable loci were lower than those of the 24 standard loci. Three loci (2163a, 3155, and 3336) were excluded because of their redundant variability and/or more frequent noninterpretable results compared to the 4 other markers. The use of the remaining 4-locus set (1982, 3232, 3820, and 4120) increased the number of types by 52% (from 223 to 340) and reduced the clustering rate from 58.3 to 36.6%, when combined with the use of the standard 24-locus set. Known major clonal complexes/24-locus-based clusters were all subdivided, although the degree of subdivision varied depending on the complex. Only five single-locus variations were detected among the hypervariable loci of an additional panel of 92 isolates, representing 15 years of clonal spread of a single Beijing strain in a geographically restricted setting. On this calibrated basis, we propose this 4-locus set as a consensus for subtyping Beijing clonal complexes and clusters, after standard typing.
The Bacteriostatic Protein Lipocalin 2 Is Induced in the Central Nervous System of Mice with West Nile Virus Encephalitis
Authors: Noçon Aline L. , Ip Jacque P. K. , Terry Rachael , Lim Sue Ling , Getts Daniel R. , Müller Marcus , Hofer Markus J. , King Nicholas J. C. , Campbell Iain L.
Published: October 2013

Lipocalin 2 (Lcn2) is a bacteriostatic factor produced during the innate immune response to bacterial infection. Whether Lcn2 has a function in viral infection is unknown. We investigated the regulation and function of Lcn2 in the central nervous system (CNS) of mice during West Nile virus (WNV) encephalitis. Lcn2 mRNA and protein were induced in the brain by day 5, and this induction increased further by day 7 postinfection but was delayed compared with the induction of the toll-like receptor 3 (TLR3) gene, retinoic acid-inducible gene 1 (RIG-I), and melanoma differentiation-associated protein 5 (MDA5) gene. The Lcn2 mRNA and protein were both found at high levels in the choroid plexus, vascular endothelium, macrophage/microglia, and astrocytes. However, some neuronal subsets contained Lcn2 protein but no detectable mRNA. In Lcn2 knockout (KO) mice, with the exception of CXC motif chemokine 5 (CXCL5), which was significantly more downregulated than in wild-type (WT) mice, expression levels of a number of other host response genes were similar in the two genotypes. The brain from Lcn2 and WT mice with WNV encephalitis contained similar numbers of infiltrating macrophages, granulocytes, and T cells. Lcn2 KO and WT mice had no significant difference in tissue viral loads or survival after infection with different doses of WNV. We conclude that Lcn2 gene expression is induced to high levels in a time-dependent fashion in a variety of cells and regions of the CNS of mice with WNV encephalitis. The function of Lcn2 in the host response to WNV infection remains largely unknown, but our data indicate that it is dispensable as an antiviral or immunoregulatory factor in WNV encephalitis.
Delayed Sequelae of Neonatal Respiratory Syncytial Virus Infection Are Dependent on Cells of the Innate Immune System
Authors: Harker James A. , Yamaguchi Yuko , Culley Fiona J. , Tregoning John S. , Openshaw Peter J. M.
Published: October 2013

Infection with respiratory syncytial virus (RSV) in neonatal mice leads to exacerbated disease if mice are reinfected with the same virus as adults. Both T cells and the host major histocompatibility complex genotype contribute to this phenomenon, but the part played by innate immunity has not been defined. Since macrophages and natural killer (NK) cells play key roles in regulating inflammation during RSV infection of adult mice, we studied the role of these cells in exacerbated inflammation following neonatal RSV sensitization/adult reinfection. Compared to mice undergoing primary infection as adults, neonatally sensitized mice showed enhanced airway fluid levels of interleukin-6 (IL-6), alpha interferon (IFN-α), CXCL1 (keratinocyte chemoattractant/KC), and tumor necrosis factor alpha (TNF-α) at 12 to 24 h after reinfection and IL-4, IL-5, IFN-γ, and CCL11 (eotaxin) at day 4 after reinfection. Weight loss during reinfection was accompanied by an initial influx of NK cells and granulocytes into the airways and lungs, followed by T cells. NK cell depletion during reinfection attenuated weight loss but did not alter T cell responses. Depletion of alveolar macrophages with inhaled clodronate liposomes reduced both NK and T cell numbers and attenuated weight loss. These findings indicate a hitherto unappreciated role for the innate immune response in governing the pathogenic recall responses to RSV infection.
Hemagglutinin Receptor Specificity and Structural Analyses of Respiratory Droplet-Transmissible H5N1 Viruses
Authors: de Vries Robert P. , Zhu Xueyong , McBride Ryan , Rigter Alan , Hanson Anthony , Zhong Gongxun , Hatta Masato , Xu Rui , Yu Wenli , Kawaoka Yoshihiro , de Haan Cornelis A. M. , Wilson Ian A. , Paulson James C.
Published: October 2013

Two ferret-adapted H5N1 viruses capable of respiratory droplet transmission have been reported with mutations in the hemagglutinin receptor-binding site and stalk domains. Glycan microarray analysis reveals that both viruses exhibit a strong shift toward binding to “human-type” α2-6 sialosides but with notable differences in fine specificity. Crystal structure analysis further shows that the stalk mutation causes no obvious perturbation of the receptor-binding pocket, consistent with its impact on hemagglutinin stability without affecting receptor specificity.
Rodent Herpesvirus Peru Encodes a Secreted Chemokine Decoy Receptor
Authors: Lubman Olga Y. , Cella Marina , Wang Xinxin , Monte Kristen , Lenschow Deborah J. , Huang Yina H. , Fremont Daved H.
Published: October 2013

Viruses have long been studied not only for their pathology and associated disease but also as model systems for understanding cellular and immunological processes. Rodent herpesvirus Peru (RHVP) is a recently characterized rhadinovirus related to murine gammaherpesvirus 68 (MHV68) and Kaposi's sarcoma-associated herpesvirus (KSHV) that establishes acute and latent infection in laboratory mice. RHVP encodes numerous unique proteins that we hypothesize might facilitate host immune evasion during infection. We report here that open reading frame (ORF) R17 encodes a high-affinity chemokine binding protein that broadly recognizes human and murine CC and C chemokines. The interaction of R17 with chemokines is generally characterized by rapid association kinetics, and in the case of CCL3, CCL4, CCL5, CCL24, and XCL1, extremely stable complexes are formed. Functionally, R17 potently inhibited CCL2-driven chemotaxis of the human monocytic cell line THP-1, CCL3-driven chemotaxis of peripheral blood mononuclear cells, and CCL2-mediated calcium flux. Our studies also reveal that R17 binds to glycosaminoglycans (GAGs) in a process dependent upon two BBXB motifs and that chemokine and GAG binding can occur simultaneously at distinct sites. Collectively, these studies suggest that R17 may play a role in RHVP immune evasion through the targeted sabotage of chemokine-mediated immune surveillance.
Sendai Virus C Proteins Regulate Viral Genome and Antigenome Synthesis To Dictate the Negative Genome Polarity
Authors: Irie Takashi , Okamoto Isao , Yoshida Asuka , Nagai Yoshiyuki , Sakaguchi Takemasa
Published: October 2013

The order
Mononegavirales
comprises a large number of nonsegmented negative-strand RNA viruses (NNSVs). How the genome polarity is determined is a central issue in RNA virus biology. Using a prototypic species, vesicular stomatitis virus (VSV), it has been established that the negative polarity of the viral genome is defined solely by different strengths of the
cis
-acting replication promoters located at the 3′ ends of the genome and antigenome, resulting in the predominance of the genome over the antigenome. This VSV paradigm has long been applied for the
Mononegavirales
in general without concrete proof. We now found that another prototypic species, Sendai virus (SeV), undergoes a marked shift from the early antigenome-dominant to the late genome-dominant phase during the course of infection. This shift appeared to be governed primarily by the expression of the accessory C protein, because no such shift occurred in a recombinant SeV with the C gene deleted, and antigenomes were dominant throughout infection, generating antigenome-dominant and noninfectious progeny virions. Therefore, we proposed for the first time a
trans
-regulatory mechanism, the SeV paradigm, to dictate the genome polarity of an NNSV. A series of promoter-swapped SeV recombinants suggested the importance of the primary as well as secondary structures of the promoters in this
trans
-regulation.
The Cellular Peptidyl-Prolyl
cis
/
trans
Isomerase Pin1 Regulates Reactivation of Kaposi's Sarcoma-Associated Herpesvirus from Latency
Authors: Guito Jonathan , Gavina Aileen , Palmeri Diana , Lukac David M.
Published: October 2013

Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma and primary effusion lymphoma. KSHV-infected cells are predominantly latent, with a subset undergoing lytic reactivation. Rta is the essential lytic switch protein that reactivates virus by forming transactivation-competent complexes with the Notch effector protein RBP-Jk and promoter DNA. Strikingly, Rta homolog analysis reveals that prolines constitute 17% of conserved residues. Rta is also highly phosphorylated
in vivo
. We previously demonstrated that proline content determines Rta homotetramerization and function. We hypothesize that proline-directed modifications regulate Rta function by controlling binding to peptidyl-prolyl
cis
/
trans
isomerases (PPIases). Cellular PPIase Pin1 binds specifically to phosphoserine- or phosphothreonine-proline (pS/T-P) motifs in target proteins. Pin1 dysregulation is implicated in myriad human cancers and can be subverted by viruses. Our data show that KSHV Rta protein contains potential pS/T-P motifs and binds directly to Pin1. Rta transactivation is enhanced by Pin1 at two delayed early viral promoters in uninfected cells. Pin1's effect, however, suggests a rheostat-like influence on Rta function. We show that in infected cells, endogenous Pin1 is active during reactivation and enhances Rta-dependent early protein expression induced by multiple signals, as well as DNA replication. Surprisingly, ablation of Pin1 activity by the chemical juglone or dominant-negative Pin1 enhanced late gene expression and production of infectious virus, while ectopic Pin1 showed inhibitory effects. Our data thus suggest that Pin1 is a unique, dose-dependent molecular timer that enhances Rta protein function, but inhibits late gene synthesis and virion production, during KSHV lytic reactivation.
Septic shock during platelet transfusion in a patient with acute myeloid leukaemia
Authors: Haesebaert Julie , Bénet Thomas , Michallet Mauricette , Vanhems Philippe
Published: October 2013

Although rare, transfusion-associated bacterial contamination (TABC) is nowadays the main risk associated with platelet concentrate (PC) transfusion. Consequences vary from spontaneously resolving symptoms to severe sepsis and death. In this report we have summarised a case of bacterial contamination and sepsis during PC transfusion in a patient with acute myeloid leukaemia. Fifteen minutes after the PC transfusion began, she developed chills and rapidly worsened to septic shock. The episode was managed appropriately. The patient's blood cultures and PC unit cultures grewEscherichia coli. The microbiological susceptibilities of isolates from the patient and platelet bag were identical. No other source ofE coliwas found. Donor and blood products issued from the same donation investigations were negative. The causality between sepsis and PC transfusion might be difficult to confirm. As no method is available in daily practice to eliminate TABC risk, physicians should always consider TABC by immediately stopping the transfusion and conducting appropriate investigations.
C reactive protein may not be reliable as a marker of severe bacterial infection in patients receiving tocilizumab
Authors: Bari Syed Farhan , Khan Afsha , Lawson Tom
Published: October 2013

This is a case of a 65-year-old man with seropositive erosive rheumatoid arthritis (RA), well controlled on methotrexate, sulfasalazine, low-dose prednisolone and monthly infusions of tocilizumab. He presented with a 3-week history of pain and swelling in his left knee, gradually increasing in severity with an inability to bear weight . He was systemically well with normal vital signs. Examination confirmed an effusion and aspiration was turbid in appearance. C reactive protein (CRP) was normal. He was treated empirically with antibiotics. Synovial fluid and blood cultures confirmedStaphylococcus aureusinfection. He completed a 6 weeks course of antibiotics with complete resolution of symptoms. Throughout the treatment his CRP remained normal which is likely to have been the result of prior treatment with tocilizumab.
Enterobius vermicularisinfection of the ovary
Authors: Powell George , Sarmah Piyush , Sethi Bhawana , Ganesan Raji
Published: October 2013

Enterobius vermicularisis an intestinal parasite, which may occasionally involve extraintestinal sites including the female genital tract. We report a rare case of ovarian involvement, which presented with chronic right iliac fossa pain in a 31-year-old woman. A transvaginal ultrasound scan was suggestive of a right adnexal dermoid cyst; however, histological examination of the subsequent salpingo-oophorectomy specimen showed an abscess containing viableE. vermicularisova.E. vermicularisis the most prevalent human nematode worldwide. Its ova are ingested, larvae hatch and mature female worms journey to the perianal region where they lay eggs. Female worms may also migrate from the anus along the female genital tract. Although of low pathogenicity, complications such as infertility or peritonitis may arise.
Evisceration for the management of ocular trauma
Authors: McAlinden Colm , Saldanha Mario , Laws David
Published: October 2013

Despite the eye being surrounded by orbital bones and protective mechanisms such as the blink reflex, it is vulnerable to trauma. The two key issues to consider when presented with a case of ocular trauma are the visual potential of the eye and the risk of sympathetic ophthalmia. The Ocular Trauma Score can be used to assess the visual potential of the injured eye. Surgical management may be either repair or removal of the eye (evisceration or enucleation). Herein we describe a case of ocular trauma and the decision-making process in the management of the injury.
Recurrent atraumatic metatarsal, rib and sacral insufficiency fractures in a woman with the antiphospholipid syndrome
Authors: Villiers Joseph , Khamashta Munther , Hepburn Alastair
Published: October 2013

Antiphospholipid syndrome (APS) is characterised by recurrent arterial and/or venous thromboses and recurrent late miscarriages in the presence of antiphospholipid antibodies, and can be a hugely debilitating disorder. While the commonest thrombotic manifestations of this condition such as deep vein thrombosis and stroke are well documented, there has been increasing recognition of numerous less common complications in most organ systems. We present a female patient with APS and a lupus-like illness who had atraumatic sacral fractures as well as multiple spontaneous fractures affecting her ribs and the metatarsals in both her feet.
Intermittent swelling in the chest; a case of spontaneous intermittent lung herniation
Authors: Bangalore Lakshminarayana Umesh , Cowen Michael , Kastelik Jack A , Morjaria Jaymin B
Published: October 2013

Herniation of the lung is uncommon and occurs due to protrusion of the lung beyond the confines of the thoracic cavity through an abnormal opening in the chest wall. Any condition associated with raised intrathoracic pressure or that which weakens the thoracic wall may result in lung herniation. We present a case of spontaneous lung herniation which was managed successfully by minimally invasive thoracic surgery.
Treating lateral epicondylitis with corticosteroid injections or non-electrotherapeutical physiotherapy: a systematic review
Authors: Olaussen Morten , Holmedal Oeystein , Lindbaek Morten , Brage Soeren , Solvang Hiroko
Published: October 2013

Objectives

To evaluate the current evidence for the efficacy of corticosteroid injection and non-electrotherapeutic physiotherapy compared with control for treating lateral epicondylitis.

Design

Systematic review.

Participants

We searched five databases in September 2012 for randomised controlled studies with a minimum quality rating. Of the 640 studies retrieved, 11 were included, representing 1161 patients of both sexes and all ages.

Interventions

Corticosteroid injection and non-electrotherapeutic physiotherapy.

Outcome measures

Relative risk (RR) or standardised mean difference (SMD) for overall improvement, pain and grip strength at 4–12, 26 and 52 weeks of follow-up.

Results

Corticosteroid injection gave a short-term reduction in pain versus no intervention or non-steroidal anti-inflammatory drugs (SMD −1.43, 95% CI −1.64 to −1.23). At intermediate follow-up, we found an increase in pain (SMD 0.32, 95% CI 0.13 to 0.51), reduction in grip strength (SMD −0.48, 95% CI −0.73 to −0.24) and negative effect on the overall improvement effect (RR 0.66 (0.53 to 0.81)). For corticosteroid injection versus lidocaine injection, the evidence was conflicting. At long-term follow-up, there was no difference on overall improvement and grip strength, with conflicting evidence for pain. Manipulation and exercise versus no intervention showed beneficial effect at short-term follow-up (overall improvement RR 2.75, 95% CI 1.30 to 5.82), but no significant difference at intermediate or long-term follow-up. We found moderate evidence for short-term and long-term effects of eccentric exercise and stretching versus no intervention. For exercise versus no intervention and eccentric or concentric exercise and stretching versus stretching alone, we found moderate evidence of no short-term effect.

Conclusions

Corticosteroid injections have a short-term beneficial effect on lateral epicondylitis, but a negative effect in the intermediate term. Evidence on the long-term effect is conflicting. Manipulation and exercise and exercise and stretching have a short-term effect, with the latter also having a long-term effect.
Timing of access to secondary healthcare services for diabetes management and lower extremity amputation in people with diabetes: a protocol of a case–control study
Authors: Buckley Claire M , Ali Fauzi , Roberts Graham , Kearney Patricia M , Perry Ivan J , Bradley Colin P
Published: October 2013

Background

Lower extremity amputation (LEA) is a complication of diabetes and a marker of the quality of diabetes care. Clinical and sociodemographic determinants of LEA in people with diabetes are well known. However, the role of service-related factors has been less well explored. Early referral to secondary healthcare is assumed to prevent the occurrence of LEA. The objective of this study is to investigate a possible association between the timing of patient access to secondary healthcare services for diabetes management, as a key marker of service-related factors, and LEA in patients with diabetes.

Methods/design

This is a case–control study. The source population is people with diabetes. Cases will be people with diabetes who have undergone a first major LEA, identified from the hospital discharge data at each of three regional centres for diabetes care. Controls will be patients with diabetes without LEA admitted to the same centre either electively or as an emergency. Frequency-matching will be applied for gender, type of diabetes, year and centre of LEA. Three controls per case will be selected from the same population as the cases. With a power of 90% to detect OR of 0.4 for an association between ‘good quality care’ and LEA in people with diabetes, 107 cases and 321 controls are required. Services involved in diabetes management are endocrinology, ophthalmology, renal, cardiology, vascular surgery and podiatry; timing of first contact with any of these services is the main exploratory variable. Using unconditional logistic regression, an association between this exposure and the outcome of major LEA in people with diabetes will be explored, while adjusting for confounders.

Ethics and dissemination

Ethical approval was granted by the Clinical Research Ethics Committee of the Cork Teaching Hospitals, Ireland. Results will be presented at conferences and published in peer-reviewed journals.