bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustic contrast, planarity and robustness of sound zone methods using a circular loudspeaker array
Authors: Coleman Philip , Jackson Philip J. B. , Olik Marek , Møller Martin , Olsen Martin , Abildgaard Pedersen Jan
Published: April 2014

Since the mid 1990s, acoustics research has been undertaken relating to the sound zone problem—using loudspeakers to deliver a region of high sound pressure while simultaneously creating an area where the sound is suppressed—in order to facilitate independent listening within the same acoustic enclosure. The published solutions to the sound zone problem are derived from areas such as wave field synthesis and beamforming. However, the properties of such methods differ and performance tends to be compared against similar approaches. In this study, the suitability of energy focusing, energy cancelation, and synthesis approaches for sound zone reproduction is investigated. Anechoic simulations based on two zones surrounded by a circular array show each of the methods to have a characteristic performance, quantified in terms of acoustic contrast, array control effort and target sound field planarity. Regularization is shown to have a significant effect on the array effort and achieved acoustic contrast, particularly when mismatched conditions are considered between calculation of the source weights and their application to the system.
Minimizing the transient vibroacoustic response of a window to sonic booms by using stiffeners
Authors: Ou Dayi , Ming Mak Cheuk
Published: April 2014

A stiffened-window strategy is proposed for reducing the window's transient responses to sonic booms. Additional movable and controllable stiffeners are used, which can improve the window's transient vibration and noise isolation performance without significantly reducing transparency. A simple prediction model is proposed as a design tool for implementing the stiffened-window structure, which allows for the computation of a plate with arbitrary elastic boundary conditions and arbitrarily located stiffeners. The predicted results agree well with experimental data. Also, the feasibility and validity of the stiffened-window strategy for improving the window's performance in response to sonic booms is demonstrated by parametric studies.
Smoothing individual head-related transfer functions in the frequency and spatial domains
Authors: Rasumow Eugen , Blau Matthias , Hansen Martin , van de Par Steven , Doclo Simon , Mellert Volker , Püschel Dirk
Published: April 2014

When re-synthesizing individual head related transfer functions (HRTFs) with a microphone array, smoothing HRTFs spectrally and/or spatially prior to the computation of appropriate microphone filters may improve the synthesis accuracy. In this study, the limits of the associated HRTF modifications, until which no perceptual degradations occur, are explored. First, complex spectral smoothing of HRTFs into constant relative bandwidths was considered. As a prerequisite to complex smoothing, the HRTF phase spectra were substituted by linear phases, either for the whole frequency range or above a certain cut-off frequency only. The results indicate that a broadband phase linearization of HRTFs can be perceived for certain directions/subjects and that the thresholds can be predicted by a simple model. HRTF phase spectra can be linearized above 1 kHz without being detectable. After substituting the original phase by a linear phase above 5 kHz, HRTFs may be smoothed complexly into constant relative bandwidths of 1/5 octave, without introducing noticeable artifacts. Second, spatially smoother HRTF directivity patterns were obtained by levelling out spatial notches. It turned out that spatial notches do not have to be retained if they are less than 29 dB below the maximum level in the directivity pattern.
Inverting for a deterministic surface gravity wave using the sensitivity-kernel approach
Authors: Roux Philippe , Nicolas Barbara
Published: April 2014

The dynamic imaging of a deterministic gravity wave propagating at an air–water interface requires continuous sampling of every point at this interface. This sampling can be done acoustically using waves that propagate in the water column but have specular reflection points that fully scan the air–water interface. This study aims to perform this complex task experimentally, with identical ultrasonic source and receiver arrays that face each other in a 1-m-long, 5-cm-deep fluid waveguide, and with frequencies in the MHz range. The waveguide transfer matrix is recorded 100 times per second between the source–receiver arrays, while a gravity wave is generated at the air–water interface. Through the beamforming process, a large set of acoustic multi-reverberated beams are isolated and identified that interact with the air–water interface. The travel-time and amplitude modulations of each eigenbeam are measured when the surface gravity wave travels through the source–receiver plane. Linear inversion of the travel-time and amplitude perturbations is performed from a few thousand eigenbeams using diffraction-based sensitivity kernels. Inversion results using travel-times, amplitudes, or these two observables together, lead to accurate spatial–temporal patterns of the surface deformation. The advantages and limitations of the method are discussed.
Target localization through a data-based sensitivity kernel: A perturbation approach applied to a multistatic configuration
Authors: Yildiz Selda , Roux Philippe , Rakotonarivo Sandrine T. , Marandet Christian , Kuperman W. A.
Published: April 2014

A method to isolate the forward scattered field from the incident field on an object in a complex environment is developed for the purpose of localization. The method is based on a finite-frequency perturbation approach, through the measurement of a data-based sensitivity kernel. Experimental confirmation of the method is obtained using a cylindrical tank and an aggregate of ping-pong balls as targets surrounded by acoustic sources and receivers in a multistatic configuration. The spatial structure of the sensitivity kernel is constructed from field data for the target at a sparse set of positions, and compared with the expected theoretical structure. The localization of one or a few targets is demonstrated using the direct-path only. The experimental observations also show that the method benefits from including later arrivals from the tank wall and the bottom/surface reverberation, which indeed enhance the localization.
Analysis of the soundscape in an intensive care unit based on the annotation of an audio recording
Authors: Park Munhum , Kohlrausch Armin , de Bruijn Werner , de Jager Peter , Simons Koen
Published: April 2014

The acoustic environments in hospitals, particularly in intensive care units (ICUs), are characterized by frequent high-level sound events which may negatively affect patient outcome. Many studies performed acoustic surveys, but the measurement protocol was not always reported in detail, and the scope of analysis was limited by the selected mode of sound level meters. Fewer studies systematically investigated the noise sources in ICUs by employing an observer in the patient room, which may potentially bias the measurement. In the current study, the soundscape of an ICU was evaluated where acoustic parameters were extracted from a ∼67-h audio recording, and a selected 24-h recording was annotated off-line for a source-specific analysis. The results showed that the patient-involved noise accounted for 31% of the acoustic energy and 11% of the predicted loudness peaks (PLPs). Excluding the patient-involved noise, the remaining acoustic energy was attributed to staff members (57%), alarms (30%), and the operational noise of life-supporting devices (13%). Furthermore, the contribution of each noise category to the PLPs was found to be more uneven: Staff (92%), alarms (6%), and device noise (2%). The current study suggests that most of the noise sources in ICUs may be associated with modifiable human factors.
Auditory detection of ultrasonic coded transmitters by seals and sea lions
Authors: Cunningham Kane A. , Hayes Sean A. , Michelle Wargo Rub A. , Reichmuth Colleen
Published: April 2014

Ultrasonic coded transmitters (UCTs) are high-frequency acoustic tags that are often used to conduct survivorship studies of vulnerable fish species. Recent observations of differential mortality in tag control studies suggest that fish instrumented with UCTs may be selectively targeted by marine mammal predators, thereby skewing valuable survivorship data. In order to better understand the ability of pinnipeds to detect UCT outputs, behavioral high-frequency hearing thresholds were obtained from a trained harbor seal (Phoca vitulina) and a trained California sea lion (Zalophus californianus). Thresholds were measured for extended (500 ms) and brief (10 ms) 69 kHz narrowband stimuli, as well as for a stimulus recorded directly from a Vemco V16-3H UCT, which consisted of eight 10 ms, 69 kHz pure-tone pulses. Detection thresholds for the harbor seal were as expected based on existing audiometric data for this species, while the California sea lion was much more sensitive than predicted. Given measured detection thresholds of 113 dB re 1 μPa and 124 dB re 1 μPa, respectively, both species are likely able to detect acoustic outputs of the Vemco V16-3H under water from distances exceeding 200 m in typical natural conditions, suggesting that these species are capable of using UCTs to detect free-ranging fish.
Automated aural classification used for inter-species discrimination of cetaceans
Authors: Binder Carolyn M. , Hines Paul C.
Published: April 2014

Passive acoustic methods are in widespread use to detect and classify cetacean species; however, passive acoustic systems often suffer from large false detection rates resulting from numerous transient sources. To reduce the acoustic analyst workload, automatic recognition methods may be implemented in a two-stage process. First, a general automatic detector is implemented that produces many detections to ensure cetacean presence is noted. Then an automatic classifier is used to significantly reduce the number of false detections and classify the cetacean species. This process requires development of a robust classifier capable of performing inter-species classification. Because human analysts can aurally discriminate species, an automated aural classifier that uses perceptual signal features was tested on a cetacean data set. The classifier successfully discriminated between four species of cetaceans—bowhead, humpback, North Atlantic right, and sperm whales—with 85% accuracy. It also performed well (100% accuracy) for discriminating sperm whale clicks from right whale gunshots. An accuracy of 92% and area under the receiver operating characteristic curve of 0.97 were obtained for the relatively challenging bowhead and humpback recognition case. These results demonstrated that the perceptual features employed by the aural classifier provided powerful discrimination cues for inter-species classification of cetaceans.
On the near non-existence of “pure” energetic masking release for speech
Authors: Stone Michael A. , Moore Brian C. J.
Published: April 2014

Stone et al. [(2012). J. Acoust. Soc. Am. 132, 317–326] showed that a masker constructed to produce a near-constant envelope at the output of each auditory filter reduced speech intelligibility less than maskers of the same mean level with fluctuating envelopes, produced by 100% sinusoidal amplitude modulation (SAM) at 8 Hz. Here, this effect was explored for a range of SAM rates from 1 to 81 Hz. Speech was filtered into 28 channels. A sinusoidal masker centered on each channel was added to the channel signal. The maskers were either unmodulated or had 100% SAM. In most conditions, even-numbered channels were presented to one ear and odd-numbered channels to the other. The signal-to-masker ratio was adapted to measure the Speech Reception Threshold (SRT) corresponding to 50% correct. The fluctuating masker benefit (FMB), the difference in SRT between the SAM and unmodulated masker, was negative for all SAM frequencies except 1 Hz. Due to the different slopes of the psychometric functions, when SRTs were inferred for more realistic performance levels, 74% or more, FMB was zero or negative for all SAM rates. It is concluded that a positive FMB, when it occurs, is a release from modulation and not energetic masking.
Parametric uncertainty quantification of sound insulation values
Authors: Reynders Edwin
Published: April 2014

A probabilistic framework is developed for quantifying the combined effect of uncertain parameters in sound insulation measurements, such as test sample dimensions, room properties, and loudspeaker positions, on the sound insulation values. The joint probability distribution of the uncertain parameters is constructed from the available information by means of a maximum entropy approach. The resulting sound insulation predictions are fully compatible with the available information but otherwise maximally conservative, so that the robustness of the predictions is guaranteed. Fundamental insight in the inherent uncertainty of the measurement procedure for airborne sound insulation is obtained by combining the method with detailed numerical simulations of the measurement procedure for single and double walls. The resulting uncertainty levels are very large, especially in the lowest frequency bands, and agree with experimental results. Furthermore, the probability distribution of the band-averaged sound reduction index of modally sparse walls can be of bimodal form.
Phase-based dispersion analysis for acoustic array borehole logging data
Authors: Assous Said , Elkington Peter , Linnett Laurie
Published: April 2014

A phase-based dispersion analysis method for velocity (slowness) extraction from guided waves recorded by an acoustic borehole logging tool in a geological formation is presented. The technique consists of acquiring waveforms from an array of receivers distributed along the tool and constructing the dispersion characteristic by processing in the frequency domain and exploiting phase information to measure the travel time for each frequency component. The approach is nonparametric and completely data-driven and provides high resolution estimates that do not rely on velocity guesses or assumptions regarding the type of modes. Results are free of the aliases and spurious modes which are characteristic of some prior approaches. Examples of dispersion estimation curves are presented using synthesized flexural waves and field data from wireline dipole sonic tools; results are compared with those from the weighted spectral semblance (WSS) and amplitude and phase slowness estimation (APES) methods to demonstrate the effectiveness and utility of the proposed method.
Quasi-scaling of the extinction efficiency of spheres in high frequency Bessel beams
Authors: Marston Philip L.
Published: April 2014

The extinction efficiency Qext of a sphere is defined to be the ratio of its extinction cross section to the area of its profile. For non-dissipative situations Qext reduces to the scattering efficiency. For a sphere centered on the axis of a Bessel beam Qext has a complicated dependence on dimensionless frequency ka and on the conic angle β of the beam, even in the simple case of a rigid sphere. With appropriate scaling using Babinet's principle, however, the dependence reduces approximately to a function of ka sin(β) when ka is large. An example is also shown for a metal shell in water.
Numerical and experimental study of the nonlinear interaction between a shear wave and a frictional interface
Authors: Blanloeuil Philippe , Croxford Anthony J. , Meziane Anissa
Published: April 2014

The nonlinear interaction of shear waves with a frictional interface are presented and modeled using simple Coulomb friction. Analytical and finite difference implementations are proposed with both in agreement and showing a unique trend in terms of the generated nonlinearity. A dimensionless parameter ξ is proposed to uniquely quantify the nonlinearity produced. The trends produced in the numerical study are then validated with good agreement experimentally. This is carried out loading an interface between two steel blocks and exciting this interface with different amplitude normal incidence shear waves. The experimental results are in good agreement with the numerical results, suggesting the simple friction model does a reasonable job of capturing the fundamental physics. The resulting approach offers a potential way to characterize a contacting interface; however, the difficulty in activating that interface may ultimately limit its applicability.
Fluorescence-Based Quasicontinuous and
In Situ
Monitoring of Biofilm Formation Dynamics in Natural Marine Environments
Authors: Fischer M. , Friedrichs G. , Lachnit T.
Published: April 2014

Analyzing the dynamics of biofilm formation helps to deepen our understanding of surface colonization in natural environments. While methods for screening biofilm formation in the laboratory are well established, studies in marine environments have so far been based upon destructive analysis of individual samples and provide only discontinuous snapshots of biofilm establishment. In order to explore the development of biofilm over time and under various biotic and abiotic conditions, we applied a recently developed optical biofilm sensor to quasicontinuously analyze marine biofilm dynamics
in situ
. Using this technique in combination with microscope-assisted imaging, we investigated biofilm formation from its beginning to mature multispecies biofilms. In contrast to laboratory studies on biofilm formation, a smooth transition from initial attachment to colony formation and exponential growth could not be observed in the marine environment. Instead, initial attachment was followed by an adaptation phase of low growth and homogeneously distributed solitary bacterial cells. Moreover, we observed a diurnal variation of biofilm signal intensity, suggesting a transient state of biofilm formation of bacteria. Overall, the biofilm formation dynamics could be modeled by three consecutive development stages attributed to initial bacterial attachment, bacterial growth, and attachment and growth of unicellular eukaryotic microorganisms. Additional experiments showed that the presence of seaweed considerably shortened the adaptation phase in comparison with that on control surfaces but yielded similar growth rates. The outlined examples highlight the advantages of a quasicontinuous
in situ
detection that enabled, for the first time, the exploration of the initial attachment phase and the diurnal variation during biofilm formation in natural ecosystems.
Bacterial Symbionts of a Devastating Coffee Plant Pest, the Stinkbug Antestiopsis thunbergii (Hemiptera: Pentatomidae)
Authors: Matsuura Yu , Hosokawa Takahiro , Serracin Mario , Tulgetske Genet M. , Miller Thomas A. , Fukatsu Takema
Published: April 2014

Stinkbugs of the genus
Antestiopsis
, so-called antestia bugs or variegated coffee bugs, are notorious pests of coffee plants in Africa. We investigated the symbiotic bacteria associated with
Antestiopsis thunbergii
, a major coffee plant pest in Rwanda. PCR, cloning, sequencing, and phylogenetic analysis of bacterial genes identified four distinct bacterial lineages associated with
A. thunbergii
: a gammaproteobacterial gut symbiont and symbionts representing the genera
Sodalis
,
Spiroplasma
, and
Rickettsia
.
In situ
hybridization showed that the gut symbiont densely occupied the lumen of midgut crypts, whereas the
Sodalis
symbiont, the
Spiroplasma
symbiont, and the
Rickettsia
symbiont sparsely and sporadically infected various cells and tissues. Diagnostic PCR survey of 154
A. thunbergii
individuals collected at 8 localities in Rwanda revealed high infection frequencies (100% for the gut symbiont, 51.3% for the
Sodalis
symbiont, 52.6% for the
Spiroplasma
symbiont, and 24.0% for the
Rickettsia
symbiont). These results suggest that the gut symbiont is the primary symbiotic associate of obligate nature for
A. thunbergii
, whereas the
Sodalis
symbiont, the
Spiroplasma
symbiont, and the
Rickettsia
symbiont are the secondary symbiotic associates of facultative nature. We observed high coinfection frequencies, i.e., 7.8% of individuals with quadruple infection with all the symbionts, 32.5% with triple infections with the gut symbiont and two of the secondary symbionts, and 39.6% with double infections with the gut symbiont and any of the three secondary symbionts, which were statistically not different from the expected coinfection frequencies and probably reflected random associations. The knowledge of symbiotic microbiota in
A. thunbergii
will provide useful background information for controlling this devastating coffee plant pest.
Phosphate Starvation in Fungi Induces the Replacement of Phosphatidylcholine with the Phosphorus-Free Betaine Lipid Diacylglyceryl-
N
,
N
,
N
-Trimethylhomoserine
Authors: Riekhof Wayne R. , Naik Surabhi , Bertrand Helmut , Benning Christoph , Voelker Dennis R.
Published: April 2014

Diacylglyceryl-
N
,
N
,
N
-trimethylhomoserine (DGTS) is a phosphorus-free betaine-lipid analog of phosphatidylcholine (PtdCho) synthesized by many soil bacteria, algae, and nonvascular plants. Synthesis of DGTS and other phosphorus-free lipids in bacteria occurs in response to phosphorus (P) deprivation and results in the replacement of phospholipids by nonphosphorous lipids. The genes encoding DGTS biosynthetic enzymes have previously been identified and characterized in bacteria and the alga
Chlamydomonas reinhardtii
. We now report that many fungal genomes, including those of plant and animal pathogens, encode the enzymatic machinery for DGTS biosynthesis, and that fungi synthesize DGTS during P limitation. This finding demonstrates that replacement of phospholipids by nonphosphorous lipids is a strategy used in divergent eukaryotic lineages for the conservation of P under P-limiting conditions. Mutants of
Neurospora crassa
were used to show that DGTS synthase encoded by the
BTA1
gene is solely responsible for DGTS biosynthesis and is under the control of the fungal phosphorus deprivation regulon, mediated by the NUC-1/Pho4p transcription factor. Furthermore, we describe the rational reengineering of lipid metabolism in the yeast
Saccharomyces cerevisiae
, such that PtdCho is completely replaced by DGTS, and demonstrate that essential processes of membrane biogenesis and organelle assembly are functional and support growth in the engineered strain.
A New Strategy of RNA Interference That Targets Heterologous Sequences Reveals CITFA1 as an Essential Component of Class I Transcription Factor A in Trypanosoma brucei
Authors: Park Sung Hee , Nguyen Bao N. , Kirkham Justin K. , Nguyen Tu N. , Günzl Arthur
Published: April 2014

Conditional gene silencing by RNA interference in
Trypanosoma brucei
can be inconclusive if knockdowns are inefficient or have off-target effects. To enable efficient, specific silencing of single-copy genes in mammalian-infective, bloodstream form trypanosomes, we developed a system that targets the heterologous and functional
Trypanosoma cruzi
U2AF35
3′ untranslated region (UTR) (Tc3) or, alternatively, the sequence of the PTP tag, which can be fused to any mRNA of interest. Two cell lines were created, single-marker Tc3 (smTc3) and smPTP, which conditionally express Tc3 and PTP double-stranded RNA (dsRNA), respectively. The system depends on manipulating both alleles of the gene of interest so that cells exclusively express the target mRNA as a fusion to one of these heterologous sequences. We generated allele integration vectors in which the C-terminal part of a gene's coding sequence can be fused to either heterologous sequence in a single cloning step. We first tested this system with
CITFA7
, which encodes a well-characterized subunit of the class I transcription factor A (CITFA), an essential factor for transcription initiation by RNA polymerase I. Targeting either Tc3 or PTP fused to the
CITFA7
mRNA resulted in gene knockdowns that were as efficient and specific as targeting the endogenous
CITFA7
mRNA. Moreover, application of this system to
CITFA1
, which could not be silenced by established methods, demonstrated that the gene encodes an essential CITFA subunit that mediates binding of the transcription factor complex to RNA polymerase I promoters.
Distinct and Redundant Roles of Protein Tyrosine Phosphatases Ptp1 and Ptp2 in Governing the Differentiation and Pathogenicity of Cryptococcus neoformans
Authors: Lee Kyung-Tae , Byun Hyo-Jeong , Jung Kwang-Woo , Hong Joohyeon , Cheong Eunji , Bahn Yong-Sun
Published: April 2014

Protein tyrosine phosphatases (PTPs) serve as key negative-feedback regulators of mitogen-activated protein kinase (MAPK) signaling cascades. However, their roles and regulatory mechanisms in human fungal pathogens remain elusive. In this study, we characterized the functions of two PTPs, Ptp1 and Ptp2, in
Cryptococcus neoformans
, which causes fatal meningoencephalitis.
PTP1
and
PTP2
were found to be stress-inducible genes, which were controlled by the MAPK Hog1 and the transcription factor Atf1. Ptp2 suppressed the hyperphosphorylation of Hog1 and was involved in mediating vegetative growth, sexual differentiation, stress responses, antifungal drug resistance, and virulence factor regulation through the negative-feedback loop of the HOG pathway. In contrast, Ptp1 was not essential for Hog1 regulation, despite its Hog1-dependent induction. However, in the absence of Ptp2, Ptp1 served as a complementary PTP to control some stress responses. In differentiation, Ptp1 acted as a negative regulator, but in a Hog1- and Cpk1-independent manner. Additionally, Ptp1 and Ptp2 localized to the cytosol but were enriched in the nucleus during the stress response, affecting the transient nuclear localization of Hog1. Finally, Ptp1 and Ptp2 played minor and major roles, respectively, in the virulence of
C. neoformans
. Taken together, our data suggested that PTPs could be exploited as novel antifungal targets.
Histidine Degradation via an Aminotransferase Increases the Nutritional Flexibility of Candida glabrata
Authors: Brunke Sascha , Seider Katja , Richter Martin Ernst , Bremer-Streck Sibylle , Ramachandra Shruthi , Kiehntopf Michael , Brock Matthias , Hube Bernhard
Published: April 2014

The ability to acquire nutrients during infections is an important attribute in microbial pathogenesis. Amino acids are a valuable source of nitrogen if they can be degraded by the infecting organism. In this work, we analyzed histidine utilization in the fungal pathogen of humansCandida glabrata. Hemiascomycete fungi, likeC. glabrataorSaccharomyces cerevisiae, possess no gene coding for a histidine ammonia-lyase, which catalyzes the first step of a major histidine degradation pathway in most other organisms. We show thatC. glabratainstead initializes histidine degradation via the aromatic amino acid aminotransferase Aro8. AlthoughARO8is also present inS. cerevisiaeand is induced by extracellular histidine, the yeast cannot use histidine as its sole nitrogen source, possibly due to growth inhibition by a downstream degradation product. Furthermore,C. glabratarelies only on Aro8 for phenylalanine and tryptophan utilization, sinceARO8, but not its homologueARO9, was transcriptionally activated in the presence of these amino acids. Accordingly, anARO9deletion had no effect on growth with aromatic amino acids. In contrast, inS. cerevisiae,ARO9is strongly induced by tryptophan and is known to support growth on aromatic amino acids. Differences in the genomic structure of theARO9gene betweenC. glabrataandS. cerevisiaeindicate a possible disruption in the regulatory upstream region. Thus, we show that, in contrast toS. cerevisiae,C. glabratahas adapted to use histidine as a sole source of nitrogen and that the aromatic amino acid aminotransferase Aro8, but not Aro9, is the enzyme required for this process.
Arginine Deiminase in Staphylococcus epidermidis Functions To Augment Biofilm Maturation through pH Homeostasis
Authors: Lindgren J. K. , Thomas V. C. , Olson M. E. , Chaudhari S. S. , Nuxoll A. S. , Schaeffer C. R. , Lindgren K. E. , Jones J. , Zimmerman M. C. , Dunman P. M. , Bayles K. W. , Fey P. D.
Published: April 2014

Allelic replacement mutants were constructed within arginine deiminase (
arcA1
and
arcA2
) to assess the function of the arginine deiminase (ADI) pathway in organic acid resistance and biofilm formation of
Staphylococcus epidermidis
1457. A growth-dependent acidification assay (pH ∼5.0 to ∼5.2) determined that strain 1457 devoid of arginine deiminase activity (1457 ΔADI) was significantly less viable than the wild type following depletion of glucose and in the presence of arginine. However, no difference in viability was noted for individual 1457 Δ
arcA1
(native) or Δ
arcA2
(arginine catabolic mobile element [ACME]-derived) mutants, suggesting that the native and ACME-derived ADIs are compensatory in
S. epidermidis
. Furthermore, flow cytometry and electron paramagnetic resonance spectroscopy results suggested that organic acid stress resulted in oxidative stress that could be partially rescued by the iron chelator dipyridyl. Collectively, these results suggest that formation of hydroxyl radicals is partially responsible for cell death via organic acid stress and that ADI-derived ammonia functions to counteract this acid stress. Finally, static biofilm assays determined that viability, ammonia synthesis, and pH were reduced in strain 1457 ΔADI following 120 h of growth in comparison to strain 1457 and the
arcA1
and
arcA2
single mutants. It is hypothesized that ammonia synthesis via the ADI pathway is important to reduce pH stress in specific microniches that contain high concentrations of organic acids.
Involvement of
rppH
in Thermoregulation in Pseudomonas syringae
Authors: Hockett Kevin L. , Ionescu Michael , Lindow Steven E.
Published: April 2014

Temperature, among other environmental factors, influences the incidence and severity of many plant diseases. Likewise, numerous traits, including the expression of virulence factors, are regulated by temperature. Little is known about the underlying genetic determinants of thermoregulation in plant-pathogenic bacteria. Previously, we showed that the expression of both
fliC
(encoding flagellin) and
syfA
(encoding a nonribosomal polypeptide synthetase) was suppressed at high temperatures in
Pseudomonas syringae
. In this work, we used a high-throughput screen to identify mutations that conferred overexpression of
syfA
at elevated temperatures (28°C compared to 20°C). Two genes, Psyr_2474, encoding an acyl-coenzyme A (CoA) dehydrogenase, and Psyr_4843, encoding an ortholog of RppH, which in
Escherichia coli
mediates RNA turnover, contribute to thermoregulation of
syfA
. To assess the global role of
rppH
in thermoregulation in
P. syringae
, RNA sequencing was used to compare the transcriptomes of an
rppH
deletion mutant and the wild-type strain incubated at 20°C and 30°C. The disruption of
rppH
had a large effect on the temperature-dependent transcriptome of
P. syringae
, affecting the expression of 569 genes at either 20°C or 30°C but not at both temperatures. Intriguingly, RppH is involved in the thermoregulation of ribosome-associated proteins, as well as of RNase E, suggesting a prominent role of
rppH
on the proteome in addition to its effect on the transcriptome.
The SdiA-Regulated Gene
srgE
Encodes a Type III Secreted Effector
Authors: Habyarimana Fabien , Sabag-Daigle Anice , Ahmer Brian M. M.
Published: April 2014

Salmonella enterica
serovar Typhimurium is a food-borne pathogen that causes severe gastroenteritis. The ability of
Salmonella
to cause disease depends on two type III secretion systems (T3SSs) encoded in two distinct
Salmonella
pathogenicity islands, 1 and 2 (SPI1 and SPI2, respectively).
S
. Typhimurium encodes a solo LuxR homolog, SdiA, which can detect the acyl-homoserine lactones (AHLs) produced by other bacteria and upregulate the
rck
operon and the
srgE
gene. SrgE is predicted to encode a protein of 488 residues with a coiled-coil domain between residues 345 and 382.
In silico
studies have provided conflicting predictions as to whether SrgE is a T3SS substrate. Therefore, in this work, we tested the hypothesis that SrgE is a T3SS effector by two methods, a β-lactamase activity assay and a split green fluorescent protein (GFP) complementation assay. SrgE with β-lactamase fused to residue 40, 100, 150, or 300 was indeed expressed and translocated into host cells, but SrgE with β-lactamase fused to residue 400 or 488 was not expressed, suggesting interference by the coiled-coil domain. Similarly, SrgE with GFP S11 fused to residue 300, but not to residue 488, was expressed and translocated into host cells. With both systems, translocation into host cells was dependent upon SPI2. A phylogenetic analysis indicated that
srgE
is found only within
Salmonella enterica
subspecies. It is found sporadically within both typhoidal and nontyphoidal serovars, although the SrgE protein sequences found within typhoidal serovars tend to cluster separately from those found in nontyphoidal serovars, suggesting functional diversification.
An erupted compound odontoma
Authors: Gupta Anil , Vij Hitesh , Vij Ruchieka , Malhotra Ritika
Published: April 2014

Odontomas are familiar entities but their eruption into the oral cavity is an extraordinary occurrence, which may be associated with pain, infection, malocclusion, etc. Not many cases of erupted odontomas have been reported in the literature. This paper puts forth a case of erupting odontoma in an attempt to add to the list of reported cases of this unique pathology.
Osseous haemophilic pseudotumour and concurrent primary hyperparathyroidism: a diagnostic conundrum
Authors: Low Soo Fin , Sridharan Radhika , Ngiu Chai Soon , Mohamed Haflah Nor Hazla
Published: April 2014

Pseudotumours are rare, occurring in 1–2% of severe haemophiliacs. Osseous locations are far less frequent than soft tissue location. We report a case of a 43-year-old man with haemophilia A, who presented with a gradually enlarging left thigh mass for 8 months. There were no constitutional symptoms. Plain radiograph showed an expansile lytic lesion with ‘soap-bubble’ appearance arising from the left femur diaphysis. On MRI, it appeared as a non-enhancing, multilobulated lesion expanding the medullary and subperiosteal spaces. The mass exhibited concentric ring sign with heterogeneous intermediate signal intensity in the core lesion, reflective of chronic haematoma with blood degradation products of different stages. A diagnosis of haemophilic pseudotumour was made. Hypercalcaemia, however, raised a diagnostic dilemma as bone malignancy needed to be considered. An open excisional biopsy and subsequent amputation confirmed the diagnosis of osseous haemophilic pseudotumour. Nuclear medicine study later revealed a concurrent parathyroid adenoma.
Pituitary metastasis from breast cancer presenting as diabetes insipidus
Authors: Gormally Joseph F , Izard Michael A , Robinson Bruce G , Boyle Frances M
Published: April 2014

An 83-year-old woman developed pituitary metastasis while being treated for metastatic breast cancer. She presented with visual disturbance and headache followed by thirst, nocturia and polyuria. A visual field defect was present. MRI revealed a sellar mass consistent with metastasis to the pituitary gland. She was successfully treated with radiotherapy to the sella and had improvement of her visual symptoms and visual field defect. She then required ongoing treatment for diabetes insipidus. Her symptoms had not shown any sign of recurring up to 9 months after treatment. Pituitary metastases are rare but should be suspected in patients with metastatic cancer who present with features similar to those seen here. With improvements in survival in metastatic breast cancer, pituitary metastases may be seen more commonly and active local treatment is warranted given the possibility of resolution of symptoms related to the pituitary metastases.
Haematological complete remission by ponatinib and bortezomib in a patient with relapsed, Ph+pre-B acute lymphoblastic leukaemia
Authors: Robinson Sara , Levy Yair , Maisel Christopher , Tong Alex W
Published: April 2014

A 74-year-old man was previously diagnosed with BCR-ABL1-positive pre-B cell acute lymphoblastic leukaemia (pre-B ALL) based on bone marrow cytology, flow cytometry, cytogenetics and fluorescent in situ hybridisation findings. Following a highly complicated hospital course, the patient achieved cytogenetic remission by consolidated chemotherapy and the tyrosine kinase inhibitor dasatinib. He subsequently presented with relapsed pre-B ALL after 3 years in remission. In consideration of his challenging clinical history, he was started on concurrent ponatinib (45 mg daily) and bortezomib (1.3 mg/m2intravenous weekly). The major molecular response was achieved (<0.0893% BCR-ABL1 transcripts) after 3 months. Bone marrow now demonstrates a BCR-ABL1-negative, complete cytogenetic response. The patient continues to do well with mild thrombocytopenia and improved anaemia on bortezomib and 30 mg daily ponatinib. Our experience with a single patient suggests the feasibility of combined targeted therapy with ponatinib and bortezomib. This novel treatment approach achieved clinical remission with a manageable toxicity profile.
Effect of pore-water chemistry on undrained shear behaviour of saturated loess
Authors: Zhang Fanyu , Wang Gonghui , Kamai Toshitaka , Chen Wenwu
Published: April 2014

Pore-water chemistry can have a fundamental influence on the shear behaviour of soil. To study the effects of salt concentration and desalinization on undrained shear behaviour, a series of ring shear tests was conducted on Chinese loess saturated with various NaCl solutions of differing concentration, under the same initial void ratio and consolidating stress conditions. Results showed that the peak and steady-state shear strengths increase as the NaCl concentration increases only up to a certain level. When this level is exceeded, any further increase of NaCl concentration results in lower shear strengths. After desalinization the peak and steady-state shear strengths recover to those of the original sample, showing that the salinization of loess is reversible. A pore pressure ratio of 0.6 can be used as a criterion to assess whether liquefaction can be induced in saturated loess. These findings may provide a useful explanation for progressive or seasonal activity of some irrigation-induced loess landslides in the Chinese Loess Plateau.
A novel adipocytokine, omentin, inhibits platelet-derived growth factor-BB-induced vascular smooth muscle cell migration through antioxidative mechanism
Authors: Kazama Kyosuke , Okada Muneyoshi , Yamawaki Hideyuki
Published: April 2014

Omentin is a novel adipocytokine expressed in visceral adipose tissue. Secretion and blood concentration of omentin decrease in the obese subjects. We previously demonstrated that omentin is anti-inflammatory in vascular smooth muscle cells (SMCs). While vascular remodeling via migration of SMCs is also important for hypertension development, it remains to be clarified whether omentin affects this process. Here we examined whether omentin controls SMC migration. Omentin (300 ng/ml, 2 h) significantly inhibited platelet-derived growth factor (PDGF)-BB (10 ng/ml, 6 h)-induced migration of rat mesenteric arterial SMCs, as determined by Boyden chamber assay. Omentin (300 ng/ml, 2 h) significantly inhibited PDGF-BB (10 ng/ml, 30 min)-induced phosphorylation of p38 and heat shock protein (HSP) 27. Omentin (300 ng/ml, 2 h) significantly inhibited PDGF-BB (10 ng/ml, 30 min)-induced NADPH oxidase (NOX) activation as determined by lucigenin assay. Omentin (300 ng/ml, 24 h) significantly inhibited fetal bovine serum (5%, 4 days)-induced SMC outgrowth from rat isolated mesenteric artery. In vivo, omentin significantly inhibited carotid intimal hyperplasia in mouse ligation model. In summary, we for the first time demonstrate that omentin prevents PDGF-BB-induced SMC migration by preventing NOX/O2−/p38/HSP27 pathways, which might be at least partly responsible for the preventive effects on neointimal hyperplasia. Our data suggest that omentin may be protective against hypertension development by inhibiting vascular structural remodeling.
Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells
Authors: Chen Zhi-Hua , Cao Jiao-Fei , Zhou Jie-Sen , Liu Hui , Che Luan-Qing , Mizumura Kenji , Li Wen , Choi Augustine M. K. , Shen Hua-Hao
Published: April 2014

Autophagy plays a pivotal role in cellular homeostasis and adaptation to adverse environments, although the regulation of this process remains incompletely understood. We have recently observed that caveolin-1 (Cav-1), a major constituent of lipid rafts on plasma membrane, can regulate autophagy in cigarette smoking-induced injury of lung epithelium, although the underlying molecular mechanisms remain incompletely understood. In the present study we found that Cav-1 interacted with and regulated the expression of ATG12-ATG5, an ubiquitin-like conjugation system crucial for autophagosome formation, in lung epithelial Beas-2B cells. Deletion of Cav-1 increased basal and starvation-induced levels of ATG12-ATG5 and autophagy. Biochemical analyses revealed that Cav-1 interacted with ATG5, ATG12, and their active complex ATG12-ATG5. Overexpression of ATG5 or ATG12 increased their interactions with Cav-1, the formation of ATG12-ATG5 conjugate, and the subsequent basal levels of autophagy but resulted in decreased interactions between Cav-1 and another molecule. Knockdown of ATG12 enhanced the ATG5-Cav-1 interaction. Mutation of the Cav-1 binding motif on ATG12 disrupted their interaction and further augmented autophagy. Cav-1 also regulated the expression of ATG16L, another autophagy protein associating with the ATG12-ATG5 conjugate during autophagosome formation. Altogether these studies clearly demonstrate that Cav-1 competitively interacts with the ATG12-ATG5 system to suppress the formation and function of the latter in lung epithelial cells, thereby providing new insights into the molecular mechanisms by which Cav-1 regulates autophagy and suggesting the important function of Cav-1 in certain lung diseases via regulation of autophagy homeostasis.
Applying metabolomics to uncover novel biology in ARDS
Authors: Rogers Angela J. , Matthay Michael A.
Published: April 2014

A better understanding of the pathogenesis and the resolution of the acute respiratory distress syndrome (ARDS) is needed. Although some progress has been made with the use of protein biomarkers and candidate gene studies in understanding the pathobiology of ARDS, we propose that new studies that measure the chemical breakdown products of cellular metabolism (metabolomics) may provide new insights into ARDS, in part because metabolomics targets a later point in the genomics cascade than is possible with studies of DNA, RNA, and protein biomarkers. Technological advances have made large-scale metabolomic profiling increasingly feasible. Metabolomic approaches have already achieved novel insights in nonpulmonary diseases such as diabetes mellitus and malignancy, as well as in sepsis, a major risk factor for developing ARDS. Metabolomic profiling is a promising approach to identify novel pathways in both patients at risk for developing ARDS as well as in the early phase of established ARDS.
A Phase I Trial of LY2510924, a CXCR4 Peptide Antagonist, in Patients with Advanced Cancer
Authors: Galsky Matthew D. , Vogelzang Nicholas J. , Conkling Paul , Raddad Eyas , Polzer John , Roberson Stephanie , Stille John R. , Saleh Mansoor , Thornton Donald
Published: April 2014

Purpose: Overexpression of C-X-C motif receptor 4 (CXCR4) is implicated in tumor progression. LY2510924 is a peptide antagonist, which blocks stromal cell–derived factor-1 (SDF1) from CXCR4 binding.

Experimental Design: This phase I study included two parts: a 3+3 dose escalation (part A) and dose confirmation (part B). LY2510924 was administered as a daily subcutaneous injection on a 28-day cycle. The primary objective was to determine the recommended phase II dose. Secondary objectives included safety, pharmacokinetics, efficacy, and pharmacodynamic response, including mobilization of CD34+ hematopoietic stem cells into the peripheral blood.

Results: Forty-five patients were enrolled, 25 in part A and 20 in part B. Patients were administered increasing doses of LY2510924: 1.0, 2.5, 5.0, 10, 20, and 30 mg/day for part A and 2.5 or 20 mg/day for part B. Two patients (30-mg/day cohort) experienced dose-limiting toxicities of grade 3 increased neutrophil count. The maximum tolerated dose (MTD) was 20 mg/day. The most common drug-related treatment-emergent adverse events were fatigue (9%), injection-site reaction (9%), injection site pruritus (7%), and nausea (7%). The best response was stable disease for nine patients (20%). At the end of cycle 1, mean peak LY2510924 plasma concentration and the 24-hour area under the plasma concentration versus time curve increased slightly more than dose proportionally. LY2510924 dose dependently increased CD34+ cell counts in peripheral blood up to 18-fold.

Conclusions: LY2510924 demonstrated CD34+ cell mobilization at doses ≥2.5 mg/day with a tolerable safety profile up to an MTD of 20 mg/day. Clin Cancer Res; 20(13); 3581–8. ©2014 AACR.
Erlotinib, Erlotinib–Sulindac versus Placebo: A Randomized, Double-Blind, Placebo-Controlled Window Trial in Operable Head and Neck Cancer
Authors: Gross Neil D. , Bauman Julie E. , Gooding William E. , Denq William , Thomas Sufi M. , Wang Lin , Chiosea Simion , Hood Brian L. , Flint Melanie S. , Sun Mai , Conrads Thomas P. , Ferris Robert L. , Johnson Jonas T. , Kim Seungwon , Argiris Athanassios , Wirth Lori , Nikiforova Marina N. , Siegfried Jill M. , Grandis Jennifer R.
Published: April 2014

Purpose: The EGF receptor (EGFR) and COX2 pathways are upregulated in head and neck squamous cell carcinoma (HNSCC). Preclinical models indicate synergistic antitumor activity from dual blockade. We conducted a randomized, double-blind, placebo-controlled window trial of erlotinib, an EGFR inhibitor; erlotinib plus sulindac, a nonselective COX inhibitor; versus placebo.

Experimental Design: Patients with untreated, operable stage II-IVb HNSCC were randomized 5:5:3 to erlotinib, erlotinib–sulindac, or placebo. Tumor specimens were collected before and after seven to 14 days of treatment. The primary endpoint was change in Ki67 proliferation index. We hypothesized an ordering effect in Ki67 reduction: erlotinib–sulindac > erlotinib > placebo. We evaluated tissue microarrays by immunohistochemistry for pharmacodynamic modulation of EGFR and COX2 signaling intermediates.

Results: From 2005–2009, 47 patients were randomized for the target 39 evaluable patients. Thirty-four tumor pairs were of sufficient quality to assess biomarker modulation. Ki67 was significantly decreased by erlotinib or erlotinib–sulindac (omnibus comparison, two-sided Kruskal–Wallis, P = 0.04). Wilcoxon pairwise contrasts confirmed greater Ki67 effect in both erlotinib groups (erlotinib–sulindac vs. placebo, P = 0.043; erlotinib vs. placebo, P = 0.027). There was a significant trend in ordering of Ki67 reduction: erlotinib–sulindac > erlotinib > placebo (two-sided exact Jonckheere–Terpstra, P = 0.0185). Low baseline pSrc correlated with greater Ki67 reduction (R2 = 0.312, P = 0.024).

Conclusions: Brief treatment with erlotinib significantly decreased proliferation in HNSCC, with additive effect from sulindac. Efficacy studies of dual EGFR–COX inhibition are justified. pSrc is a potential resistance biomarker for anti-EGFR therapy, and warrants investigation as a molecular target. Clin Cancer Res; 20(12); 3289–98. ©2014 AACR.