bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Online Academic Publishing
Authors: Cooper Liam
Published: April 2013

Modern information technology allows academics many new ways to enhance their research activities. This article suggests that one of the most important changes in recent years has been the overwhelming proliferation of academic research. It proposes that many new developments in online publishing have been, and will continue to be, in response to this proliferation of research. It also offers some general principles based on six years' working for a series of innovative online journals, including examples of where new technologies have been used successfully to enrich a journal's content without adding substantively to the workloads of authors and editors.
Scientific Philosophy, Mathematical Philosophy, and All That
Authors: Leitgeb Hannes
Published: April 2013

This article suggests that scientific philosophy, especially mathematical philosophy, might be one important way of doing philosophy in the future. Along the way, the article distinguishes between different types of scientific philosophy; it mentions some of the scientific methods that can serve philosophers; it aims to undermine some worries about mathematical philosophy; and it tries to make clear why in certain cases the application of mathematical methods is necessary for philosophical progress.
The Future of Philosophy
Authors: Mulgan Tim
Published: April 2013

In this article the editor of the Philosophical Quarterly briefly outlines the editorial process at that journal; explains why it is foolhardy to attempt to predict the future of philosophy; and, finally, attempts such a prediction. Drawing on his recent book Ethics for a Broken World, he argues that climate change, or some other disaster, may lead to a broken world where the optimistic assumptions underlying contemporary philosophy no longer apply. He argues that the possibility of a broken world has deep and unexpected implications for philosophy.
Trends and Progress in Philosophy
Authors: Eklund Matti
Published: April 2013

This article is in three parts. The first discusses trends in philosophy. The second defends reliance on intuitions in philosophy from some doubts that have recently been raised. The third discusses Philip Kitcher's contention that contemporary analytic philosophy does not have its priorities straight. While the three parts are independent, there is a common theme. Each part defends what is regarded as orthodoxy from attacks. Of course there are other reasonable challenges to philosophical methodology. The article's aim is just to respond to some charges that have been made.
Christian Identity and Community – An Ethical Approach to Martin Luther
Authors: Seong ShinHyung
Published: April 2013

Christian identity is an important basis of Christian ethics since identity formulates the notion of how to live in and for the world. This research concentrates on Martin Luther's communitarian concept in his theology and ethics. Because the church is a liturgical community for the moral transformation, church needs to communicate with the world through her liturgical ceremonies. Based on this ethical concept in Luther, this research paper focuses on how Christian identity becomes the foundation of theological ethics, how Christian ethics is active in the relation with neighbors and how the church practises her ethics in community with the world.
Inter‐species protein trafficking endows dodder (Cuscuta pentagona) with a host‐specific herbicide‐tolerant trait
Authors: Jiang Linjian , Qu Feng , Li Zhaohu , Doohan Douglas
Published: April 2013

Besides photosynthates, dodder (Cuscuta spp.) acquires phloem‐mobile proteins from host; however, whether this could mediate inter‐species phenotype transfer was not demonstrated. Specifically, we test whether phosphinothricin acetyl transferase (PAT) that confers host plant glufosinate herbicide tolerance traffics and functions inter‐specifically.

Dodder tendrils excised from hosts can grow in vitro for weeks or resume in vivo by parasitizing new hosts. The level of PAT in in vivo and in vitro dodder tendrils was quantified by enzyme‐linked immunosorbent assay. The glufosinate sensitivity was examined by dipping the distal end of in vivo and in vitro tendrils, growing on or excised from LibertyLink® (LL; PAT‐transgenic and glufosinate tolerant) and conventional (CN; glufosinate sensitive) soybean hosts, into glufosinate solutions for 5 s. After in vitro tendrils excised from LL hosts reparasitized new CN and LL hosts, the PAT level and the glufosinate sensitivity were also examined.

When growing on LL host, dodder tolerated glufosinate and contained PAT at a level of 0.3% of that encountered in LL soybean leaf. After PAT was largely degraded in dodders, they became glufosinate sensitive. PAT mRNA was not detected by reverse transcription PCR in dodders.

In conclusion, the results indicated that PAT inter‐species trafficking confers dodder glufosinate tolerance.
Human Papillomavirus (HPV) Genotyping of Cutaneous Warts in Greek Children
Authors: Giannaki Maria , Kakourou Talia , Theodoridou Maria , Syriopoulou Vassiliki , Kabouris Marios , Louizou Eirini , Chrousos George
Published: April 2013

The human papillomavirus (HPV) infects the squamous epithelium of the skin and produces common warts, plantar warts, and flat warts, which occur commonly on the hands, face, and feet. The objective of this study was to determine the presence of HPV in warts in children in order to associate the virus with the disease. Sixty‐eight children with clinically diagnosed cutaneous warts were recruited. Skin biopsy samples were examined and DNA was extracted using a commercially available kit. To distinguish between the HPV types, we used a specific pair of primers to amplify the HPV DNA. Polymerase chain reaction amplification of the L1 region was followed by restriction fragment length polymorphism analysis and Luminex xMAP technology. HPV 57 was the predominant type in our study, although the detection of the high‐risk HPV type 16 in 33% of our positive samples indicates the presence of mucosal high‐risk HPV types in the skin of children. It seems that the newly introduced Luminex assay maximized the discrimination of genotypes even in the case of multiple HPV infections. Or findings also suggest the presence of high‐risk HPV types in cutaneous warts.
Wild rodents as a model to discover genes and pathways underlying natural variation in infectious disease susceptibility
Authors: Turner A. K. , Paterson S.
Published: April 2013

Individuals vary in their susceptibility to infectious disease, and it is now well established that host genetic factors form a major component of this variation. The discovery of genes underlying susceptibility has the potential to lead to improved disease control, through the identification and management of vulnerable individuals and the discovery of novel therapeutic targets. Laboratory rodents have proved invaluable for ascertaining the function of genes involved in immunity to infection. However, these captive animals experience conditions very different to the natural environment, lacking the genetic diversity and environmental pressures characteristic of natural populations, including those of humans. It has therefore often proved difficult to translate basic laboratory research to the real world. In order to further our understanding of the genetic basis of infectious disease resistance, and the evolutionary forces that drive variation in susceptibility, we propose that genetic research traditionally conducted on laboratory animals is expanded to the more ecologically valid arena of natural populations. In this article, we highlight the potential of using wild rodents as a new resource for biomedical research, to link the functional genetic knowledge gained from laboratory rodents with the variation in infectious disease susceptibility observed in humans and other natural populations.
Medical considerations relating to the oral health of older adults
Authors: Berkey Douglas B. , Scannapieco Frank A.
Published: April 2013

This review paper was written in conjunction with the 2010 National Coalition Consensus Conference: Oral Health of Vulnerable Older Adults and Persons with Disabilities. It provides an overview of specific medical considerations involved with dental diagnosis and treatment of this “at risk population.” The role of oral inflammation is referenced within the context of the oral/systemic paradigm (e.g., diabetes, cardiovascular disease/stroke, respiratory diseases, and cognition). Oral manifestations associated with multi‐organ diseases, tobacco/alcohol use, and medications are additionally discussed. Finally, the paper encourages development of interdisciplinary approaches to positively influence health outcomes.
Direct integration of subwavelength structure on a GaAs solar cell by using colloidal lithography and dry etching process
Authors: Kim Dae-Seon , Eo Sung-Hwa , Jang Jae-Hyung
Published: April 2013

An antireflective subwavelength structure (SWS) was realized on the InGaP layer of a GaAs solar cell by using colloidal lithography followed by dry etching process. The fabricated SWS with an aspect ratio of 1.33 and a period of 300 nm showed enhanced optical properties and device characteristics. The average reflectance of the SWS surface of the GaAs solar cell was 7.1% in the wavelength range between 300 and 1000 nm. More solar energy was absorbed by the GaAs solar cell due to the lowered surface reflection by the SWS. It is the dominant factor in the 28.2% improvement of the power-conversion efficiency (η) of the SWS-integrated GaAs solar cell as compared to that of the GaAs solar cells without SWS.
Analog receive signal processing for magnetic particle imaging
Authors: Graeser Matthias , Knopp Tobias , Grüttner Mandy , Sattel Timo F. , Buzug Thorsten M.
Published: April 2013

Purpose:

Magnetic particle imaging (MPI) applies oscillating magnetic fields to determine the distribution of magnetic nanoparticlesin vivo. Using a receive coil, the change of the particle magnetization can be detected. However, the signal induced by the nanoparticles is superimposed by the direct feedthrough interference of the sinusoidal excitation field, which couples into the receive coils. As the latter is several magnitudes higher, the extraction of the particle signal from the excitation signal is a challenging task.

Methods:

One way to remove the interfering signal is to suppress the excitation signal by means of a band‐stop filter. However, this technique removes parts of the desired particle signal, which are essential for direct reconstruction of the particle concentration. A way to recover the entire particle signal is to cancel out the excitation signal by coupling a matching cancellation signal into the receive chain. However, the suppression rates that can be achieved by signal cancellation are not as high as with the filtering method, which limits the sensitivity of this method. In order to unite the advantages of both methods, in this work the authors propose to combine the filtering and the cancellation technique. All methods were compared by measuring 10 μl Resovist, in the same field generator only switching the signal processing parts.

Results:

The reconstructed time signals of the three methods, show the advantage of the proposed combination of filtering and cancellation. The method preserves the fundamental frequency and is able to detect the tracer signal at its full bandwidth even for low concentrations.

Conclusions:

By recovering the full particle signal the SNR can be improved and errors in the x‐space reconstruction are prevented. The authors show that the combined method provides this full particle signal and makes it possible to improve image quality.
Evaluation of plastic materials for range shifting, range compensation, and solid‐phantom dosimetry in carbon‐ion radiotherapy
Authors: Kanematsu Nobuyuki , Koba Yusuke , Ogata Risa
Published: April 2013

Purpose:

Beam range control is the essence of radiotherapy with heavy charged particles. In conventional broad‐beam delivery, fine range adjustment is achieved by insertion of range shifting and compensating materials. In dosimetry, solid phantoms are often used for convenience. These materials should ideally be equivalent to water. In this study, the authors evaluated dosimetric water equivalence of four common plastics, high‐density polyethylene (HDPE), polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), and polyoxymethylene (POM).

Methods:

Using the Bethe formula for energy loss, the Gottschalk formula for multiple scattering, and the Sihver formula for nuclear interactions, the authors calculated the effective densities of the plastics for these interactions. The authors experimentally measured variation of the Bragg peak of carbon‐ion beams by insertion of HDPE, PMMA, and POM, which were compared with analytical model calculations.

Results:

The theoretical calculation resulted in slightly reduced multiple scattering and severely increased nuclear interactions for HDPE, compared to water and the other plastics. The increase in attenuation of carbon ions for 20‐cm range shift was experimentally measured to be 8.9% for HDPE, 2.5% for PMMA, and 0.0% for POM while PET was theoretically estimated to be in between PMMA and POM. The agreement between the measurements and the calculations was about 1% or better.

Conclusions:

For carbon‐ion beams, POM was dosimetrically indistinguishable from water and the best of the plastics examined in this study. The poorest was HDPE, which would reduce the Bragg peak by 0.45% per cm range shift, although with marginal superiority for reduced multiple scattering. Between the two clear plastics, PET would be superior to PMMA in dosimetric water equivalence.
ROC analysis in patient specific quality assurance
Authors: Carlone Marco , Cruje Charmainne , Rangel Alejandra , McCabe Ryan , Nielsen Michelle , MacPherson Miller
Published: April 2013

Purpose:

This work investigates the use of receiver operating characteristic (ROC) methods in patient specific IMRT quality assurance (QA) in order to determine unbiased methods to set threshold criteria forγ‐distance to agreement measurements.

Methods:

A group of 17 prostate plans was delivered as planned while a second group of 17 prostate plans was modified with the introduction of random multileaf collimator (MLC) position errors that are normally distributed withσ∼±0.5, ±1.0, ±2.0, and ±3.0 mm (a total of 68 modified plans were created). All plans were evaluated using five differentγ‐criteria. ROC methodology was applied by quantifying the fraction of modified plans reported as “fail” and unmodified plans reported as “pass.”

Results:

γ‐based criteria were able to attain nearly 100% sensitivity/specificity in the detection of large random errors (σ> 3 mm). Sensitivity and specificity decrease rapidly for allγ‐criteria as the size of error to be detected decreases below 2 mm. Predictive power is null with all criteria used in the detection of small MLC errors (σ< 0.5 mm). Optimal threshold values were established by determining which criteria maximized sensitivity and specificity. For 3%/3 mmγ‐criteria, optimal threshold values range from 92% to 99%, whereas for 2%/2 mm, the range was from 77% to 94%.

Conclusions:

The optimal threshold values that were determined represent a maximized test sensitivity and specificity and are not subject to any user bias. When applied to the datasets that we studied, our results suggest the use of patient specific QA as a safety tool that can effectively prevent large errors (e.g.,σ> 3 mm) as opposed to a tool to improve the quality of IMRT delivery.
Perceptual adaptation to gender and expressive properties in speech: The role of fundamental frequency
Authors: Hubbard Daniel J. , Assmann Peter F.
Published: April 2013

Recent studies have demonstrated perceptual adaptation to nonlinguistic properties of speech involving voice gender and emotional expression. The present study extends this work by examining the contribution of fundamental frequency (F0) to these effects. Voice recordings of vowel-consonant-vowel (VCV) syllables from six talkers were processed using the STRAIGHT vocoder and an auditory morphing technique to synthesize gender (experiment 1) and expressive (experiment 2) speech sound continua ranging from one category endpoint to the other (female to male; angry to happy). Continuum endpoints served as adaptors for F0 present and F0 removed conditions. F0 removed stimuli were created by replacing the periodic excitation source with broadband noise. Confirming previous findings, aftereffects were found in the F0 present condition, resulting in a decreased likelihood to identify test stimuli as belonging to the adaptor category. No aftereffects appeared when F0 was removed, highlighting the importance of F0 in adaptation. However, in an identification test listeners were still able to categorize F0 removed stimuli at better-than-chance levels, indicating that residual cues for gender and emotion were available even when F0 was not present.
Multipath correlations in underwater acoustic communication channels
Authors: Huang S. H. , Yang T. C. , Huang Chen-Fen
Published: April 2013

Uncorrelated scattering (US), which assumes that multipath arrivals undergo uncorrelated scattering and are thus uncorrelated, has been the standard model for digital communications including underwater acoustic communications. This paper examines the cross-correlation of multipath arrivals based on at-sea data with different temporal coherence time, assuming quasi-stationary statistics. It is found that multipath arrivals are highly cross-correlated when the channel is temporally coherent, and are uncorrelated when the channel is temporally incoherent. A theoretical model based on the path phase rates and relative-phase fluctuations is used to explain experimentally observed phenomena, assuming the path amplitudes vary slowly compared with the phases. The implications of correlated scattering for underwater acoustic communication channel tracking are discussed.
Localizing the sources of two independent noises: Role of time varying amplitude differences
Authors: Yost William A. , Brown Christopher A.
Published: April 2013

Listeners localized the free-field sources of either one or two simultaneous and independently generated noise bursts. Listeners' localization performance was better when localizing one rather than two sound sources. With two sound sources, localization performance was better when the listener was provided prior information about the location of one of them. Listeners also localized two simultaneous noise bursts that had sinusoidal amplitude modulation (AM) applied, in which the modulation envelope was in-phase across the two source locations or was 180° out-of-phase. The AM was employed to investigate a hypothesis as to what process listeners might use to localize multiple sound sources. The results supported the hypothesis that localization of two sound sources might be based on temporal-spectral regions of the combined waveform in which the sound from one source was more intense than that from the other source. The interaural information extracted from such temporal-spectral regions might provide reliable estimates of the sound source location that produced the more intense sound in that temporal-spectral region.
A model of harp plucking
Authors: Chadefaux Delphine , Le Carrou Jean-Loïc , Fabre Benoît
Published: April 2013

In this paper, a model of the harp plucking is developed. It is split into two successive time phases, the sticking and the slipping phases, and uses a mechanical description of the human finger's behavior. The parameters of the model are identified through measurements of the finger/string displacements during the interaction. The validity of the model is verified using a configurable and repeatable robotic finger, enhanced with a silicone layer. A parametric study is performed to investigate the influence of the model's parameters on the free oscillations of the string. As a result, a direct implementation of the model produces an accurate simulation of a string response to a given finger motion, as compared to experimental data. The set of parameters that govern the plucking action is divided into two groups: Parameters controlled by the harpist and parameters intrinsic to the plucking. The former group and to a lesser extent the latter highly influence the initial conditions of the string vibrations. The simulations of the string's free oscillations highlight the large impact the model parameters have on the sound produced and therefore allows the understanding of how different players on the same instrument can produce a specific/personal sound quality.
Combined effect of noise and vibration produced by high-speed trains on annoyance in buildings
Authors: Jik Lee Pyoung , Griffin Michael J.
Published: April 2013

The effects of noise and vibration on annoyance in buildings during the passage of a nearby high-speed train have been investigated in a laboratory experiment with recorded train noise and 20 Hz vibration. The noises included the effects of two types of façade: windows-open and windows-closed. Subjects were exposed to six levels of noise and six magnitudes of vibration, and asked to rate annoyance using an 11-point numerical scale. The experiment consisted of four sessions: (1) evaluation of noise annoyance in the absence of vibration, (2) evaluation of total annoyance from simultaneous noise and vibration, (3) evaluation of noise annoyance in the presence of vibration, and (4) evaluation of vibration annoyance in the absence of noise. The results show that vibration did not influence ratings of noise annoyance, but that total annoyance caused by combined noise and vibration was considerably greater than the annoyance caused by noise alone. The noise annoyance and the total annoyance caused by combined noise and vibration were associated with subject self-ratings of noise sensitivity. Two classical models of total annoyance due to combined noise sources (maximum of the single source annoyance or the integration of individual annoyance ratings) provided useful predictions of the total annoyance caused by simultaneous noise and vibration.
Transient axial solution for plane and axisymmetric waves focused by a paraboloidal reflector
Authors: Tsai Yi-Te , Zhu Jinying , Haberman Michael R.
Published: April 2013

A time domain analytical solution is presented to calculate the pressure response along the axis of a paraboloidal reflector for a normally incident plane wave. This work is inspired by Hamilton's axial solution for an ellipsoidal mirror and the same methodology is employed in this paper. Behavior of the reflected waves along reflector axis is studied, and special interest is placed on focusing gain obtained at the focal point. This analytical solution indicates that the focusing gain is affected by reflector geometry and the time derivative of the input signal. In addition, focused pressure response in the focal zone given by various reflector geometries and input frequencies are also investigated. This information is useful for selecting appropriate reflector geometry in a specific working environment to achieve the best signal enhancement. Numerical simulation employing the finite element method is used to validate the analytical solution, and visualize the wave field to provide a better understanding of the propagation of reflected waves. This analytical solution can be modified to apply to non-planar incident waves with axisymmetric wavefront and non-uniform pressure distribution. An example of incident waves with conical-shaped wavefront is presented.
Time and frequency constrained sonar signal design for optimal detection of elastic objects
Authors: Hamschin Brandon , Loughlin Patrick J.
Published: April 2013

In this paper, the task of model-based transmit signal design for optimizing detection is considered. Building on past work that designs the spectral magnitude for optimizing detection, two methods for synthesizing minimum duration signals with this spectral magnitude are developed. The methods are applied to the design of signals that are optimal for detecting elastic objects in the presence of additive noise and self-noise. Elastic objects are modeled as linear time-invariant systems with known impulse responses, while additive noise (e.g., ocean noise or receiver noise) and acoustic self-noise (e.g., reverberation or clutter) are modeled as stationary Gaussian random processes with known power spectral densities. The first approach finds the waveform that preserves the optimal spectral magnitude while achieving the minimum temporal duration. The second approach yields a finite-length time-domain sequence by maximizing temporal energy concentration, subject to the constraint that the spectral magnitude is close (in a least-squares sense) to the optimal spectral magnitude. The two approaches are then connected analytically, showing the former is a limiting case of the latter. Simulation examples that illustrate the theory are accompanied by discussions that address practical applicability and how one might satisfy the need for target and environmental models in the real-world.
Input/output functions of different-latency components of transient-evoked and stimulus-frequency otoacoustic emissions
Authors: Sisto Renata , Sanjust Filippo , Moleti Arturo
Published: April 2013

The input/output functions of the different-latency components of human transient-evoked and stimulus-frequency otoacoustic emissions are analyzed, with the goal of relating them to the underlying nonlinear dynamical properties of the basilar membrane response. Several cochlear models predict a cubic nonlinearity that would yield a correspondent compressive response. The otoacoustic response comes from different generation mechanisms, each characterized by a particular relation between local basilar membrane displacement and otoacoustic level. For the same mechanism (e.g., reflection from cochlear roughness), different generation places would imply differently compressive regimes of the local basilar membrane dynamics. Therefore, this kind of study requires disentangling these contributions, using suitable data acquisition and time-frequency analysis techniques. Fortunately, different generation mechanisms/places also imply different phase-gradient delays, knowledge of which can be used to perform this task. In this study, the different-latency otoacoustic components systematically show differently compressive response, consistent with two simple hypotheses: (1) all emissions come from the reflection mechanism and (2) the basilar membrane response is strongly compressive in the resonance region and closer to linear in more basal regions. It is not clear if such a compressive behavior also extends to arbitrarily low stimulus levels.
A beamformer post-filter for cochlear implant noise reduction
Authors: Hersbach Adam A. , Grayden David B. , Fallon James B. , McDermott Hugh J.
Published: April 2013

Cochlear implant users have limited ability to understand speech in noisy conditions. Signal processing methods to address this issue that use multiple microphones typically use beamforming to perform noise reduction. However, the effectiveness of the beamformer is diminished as the number of interfering noises increases and the acoustic environment becomes more diffuse. A multi-microphone noise reduction algorithm that aims to address this issue is presented in this study. The algorithm uses spatial filtering to estimate the signal-to-noise ratio (SNR) and attenuates time-frequency elements that have poor SNR. The algorithm was evaluated by measuring intelligibility of speech embedded in 4-talker babble where the interfering talkers were spatially separated and changed location during the test. Twelve cochlear implant users took part in the evaluation, which demonstrated a significant mean improvement of 4.6 dB (standard error 0.4, P < 0.001) in speech reception threshold compared to an adaptive beamformer. The results suggest that a substantial improvement in performance can be gained for cochlear implant users in noisy environments where the noise is spatially separated from the target speech.
Prosodic boundary tone classification with voice quality features
Authors: Han Ran , Choi Jeung-Yoon
Published: April 2013

Voice quality features such as harmonic structure and spectral tilt are investigated in classifying vocalic segments into one of five boundary tones in the tones and break indices system. Static and nonstatic features are examined, and performance is compared with features related to duration, pitch, and amplitude, along with adjacent segment characteristics. From statistical tests, voice quality features are found to be significant for classifying prosodic boundary tones, and especially for distinguishing low-tone boundaries. Classification results using features selected from Kruskal–Wallis tests, Akaike information criterion values, and from sequential forward search show that using voice quality features leads to lower balanced error rates.
A Tissue-Like Printed Material
Authors: Villar Gabriel , Graham Alexander D. , Bayley Hagan
Published: April 2013

Bio-Inspired Synthetic Network

Collective behavior comes through the ability of neighboring objects to communicate and interact with each other.

Villar
et al.

(p.
48
; see the cover) produced three-dimensionally patterned, interconnected networks of lipid-bounded structures functionalized with transmembrane proteins, which allowed electrical communication along specific pathways.
Decameric SelA•tRNA
Sec
Ring Structure Reveals Mechanism of Bacterial Selenocysteine Formation
Authors: Itoh Yuzuru , Bröcker Markus J. , Sekine Shun-ichi , Hammond Gifty , Suetsugu Shiro , Söll Dieter , Yokoyama Shigeyuki
Published: April 2013

Putting Selenium in Proteins

The 21st amino acid, selenocysteine (Sec), occurs in the active site of many redox enzymes. Its cognate transfer RNA (tRNA) is first loaded with Ser by seryl-tRNA synthetase and the Ser-tRNA
Sec
is then converted to Sec-tRNA
Sec
.

Itoh
et al.

(p.
75
) determined the crystal structures of the selenocysteine synthase, SelA, that is responsible for this conversion in bacteria, alone and in complex with tRNA. The decameric SelA complex binds to 10 tRNA
Sec
molecules. The structures, together with biochemistry, show how SelA discriminates tRNA
Sec
from tRNA
Ser
, give insight into the mechanism of catalysis, and show that decamerization is essential for function.
Broadband 2D Electronic Spectroscopy Reveals a Carotenoid Dark State in Purple Bacteria
Authors: Ostroumov Evgeny E. , Mulvaney Rachel M. , Cogdell Richard J. , Scholes Gregory D.
Published: April 2013

A Light in the Dark

Carotenoids enhance the efficiency of photosynthesis by absorbing light at wavelengths inaccessible to chlorophyll. However, the mechanism underlying transfer of the absorbed energy from these pigments to the site of chemical catalysis is unclear. Studies have debated the involvement of a “dark” state in the carotenoid electronic structure—a state inaccessible by direct absorption populated by partial relaxation of the initial excited state.

Ostroumov
et al.

(p.
52
) used two-dimensional electronic spectroscopy to provide evidence of this state.
Recovery of an Isolated Coral Reef System Following Severe Disturbance
Authors: Gilmour James P. , Smith Luke D. , Heyward Andrew J. , Baird Andrew H. , Pratchett Morgan S.
Published: April 2013

Reef Repair

Coral reefs suffer mass mortality because of coral bleaching, disease, and tropical storms, but we know much more about when, where, and how rapidly these ecosystems have collapsed than we do about their recovery.

Gilmour
et al.

(p.
69
; see the Perspective by

Polidoro and Carpenter

) studied a highly isolated coral reef before and after a climate-induced mass mortality event that killed 70 to 90% of the reef corals. The initial recovery of coral cover involved growth and survival of remnant colonies, which was followed by increases in larval recruitment. Thus, in the absence of chronic disturbance, even isolated reefs can recover from catastrophic disturbance.
Programmed Cell Death in Neuronal Development
Authors: Dekkers Martijn P. J. , Barde Yves-Alain
Published: April 2013

Life or death decisions in cortical interneurons during development are made independently of external cues, challenging current theory.
A Trace of Your Place
Authors: Poucet Bruno , Sargolini Francesca
Published: April 2013

Multiple signals of different cellular origin in the brain's cortex must be integrated in a single cell type in the hippocampus to assess spatial location.

[Also see Research Article by

Zhang
et al.

]
Real-Time PCR Assay for Detection and Quantification of Leishmania (Viannia) Organisms in Skin and Mucosal Lesions: Exploratory Study of Parasite Load and Clinical Parameters
Authors: Jara Marlene , Adaui Vanessa , Valencia Braulio M. , Martinez Dalila , Alba Milena , Castrillon Carlos , Cruz Maria , Cruz Israel , Van der Auwera Gert , Llanos-Cuentas Alejandro , Dujardin Jean-Claude , Arevalo Jorge
Published: April 2013

Earlier histopathology studies suggest that parasite loads may differ between cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) lesions and between acute and chronic CL. Formal demonstration requires highly sensitive detection and accurate quantification of
Leishmania
in human lesional tissue. In this study, we developed a quantitative real-time PCR (qPCR) assay targeting minicircle kinetoplast DNA (kDNA) to detect and quantify
Leishmania
(
Viannia
) parasites. We evaluated a total of 156 lesion biopsy specimens from CL or ML suspected cases and compared the quantitative performance of our kDNA qPCR assay with that of a previously validated qPCR assay based on the glucose-6-phosphate dehydrogenase (
G6PD
) gene. We also examined the relationship between parasite load and clinical parameters. The kDNA qPCR sensitivity for
Leishmania
detection was 97.9%, and its specificity was 87.5%. The parasite loads quantified by kDNA qPCR and
G6PD
qPCR assays were highly correlated (
r
= 0.87;
P
< 0.0001), but the former showed higher sensitivity (
P
= 0.000). CL lesions had 10-fold-higher parasite loads than ML lesions (
P
= 0.009). Among CL patients, the parasite load was inversely correlated with disease duration (
P
= 0.004), but there was no difference in parasite load according to the parasite species, the patient's age, and number or area of lesions. Our findings confirm that CL and recent onset of disease (<3 months) are associated with a high parasite load. Our kDNA qPCR assay proved highly sensitive and accurate for the detection and quantification of
Leishmania
(
Viannia
) spp. in lesion biopsy specimens. It has potential application as a diagnostic and follow-up tool in American tegumentary leishmaniasis.
Identification of Gram-Positive Cocci by Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry: Comparison of Different Preparation Methods and Implementation of a Practical Algorithm for Routine Diagnostics
Authors: Schulthess Bettina , Brodner Katharina , Bloemberg Guido V. , Zbinden Reinhard , Böttger Erik C. , Hombach Michael
Published: April 2013

This study compared three sample preparation methods (direct transfer, the direct transfer-formic acid method with on-target formic acid treatment, and ethanol-formic acid extraction) for the identification of Gram-positive cocci with matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). A total of 156 Gram-positive cocci representing the clinically most important genera,
Aerococcus
,
Enterococcus
,
Staphylococcus
, and
Streptococcus
, as well as more rare genera, such as
Gemella
and
Granulicatella
, were analyzed using a Bruker MALDI Biotyper. The rate of correct genus-level identifications was approximately 99% for all three sample preparation methods. The species identification rate was significantly higher for the direct transfer-formic acid method and ethanol-formic acid extraction (both 77.6%) than for direct transfer (64.1%). Using direct transfer-formic acid compared to direct transfer, the total time to result was increased by 22.6%, 16.4%, and 8.5% analyzing 12, 48, and 96 samples per run, respectively. In a subsequent prospective study, 1,619 clinical isolates of Gram-positive cocci were analyzed under routine conditions by MALDI-TOF MS, using the direct transfer-formic acid preparation, and by conventional biochemical methods. For 95.6% of the isolates, a congruence between conventional and MALDI-TOF MS identification was observed. Two major limitations were found using MALDI-TOF MS: the differentiation of members of the
Streptococcus mitis
group and the identification of
Streptococcus dysgalactiae
. The Bruker MALDI Biotyper system using the direct transfer-formic acid sample preparation method was shown to be a highly reliable tool for the identification of Gram-positive cocci. We here suggest a practical algorithm for the clinical laboratory combining MALDI-TOF MS with phenotypic and molecular methods.
A Variant Macaque-Tropic Human Immunodeficiency Virus Type 1 Is Resistant to Alpha Interferon-Induced Restriction in Pig-Tailed Macaque CD4+T Cells
Authors: Thippeshappa Rajesh , Ruan Hongmei , Wang Weiming , Zhou Paul , Kimata Jason T.
Published: April 2013

Human immunodeficiency virus type 1 (HIV-1) antagonizes innate restriction factors in order to infect and persistently replicate in a host. In a previous study, we demonstrated that HIV-1 NL4-3 with a simian immunodeficiency virus mne (SIVmne)vifgene substitution (HSIV-vif-NL4-3) could infect and replicate in pig-tailed macaques (PTM), indicating that APOBEC3 proteins are primary barriers to transmission. Because viral replication was persistent but low, we hypothesized that HSIV-vif-NL4-3 may be suppressed by type I interferons (IFN-I), which are known to upregulate the expression of innate restriction factors. Here, we demonstrate that IFN-α more potently suppresses HSIV-vif-NL4-3 in PTM CD4+T cells than it does pathogenic SIVmne027. Importantly, we identify a variant (HSIV-vif-Yu2) that is resistant to IFN-α, indicating that the IFN-α-induced barrier can be overcome by HSIV-vif chimeras in PTM CD4+T cells. Interestingly, HSIV-vif-Yu2 and HSIV-vif-NL4-3 are similarly restricted by PTM BST2/Tetherin, and neither virus downregulates it from the surface of infected PTM CD4+T cells. Resistance to IFN-α-induced restriction appears to be conferred by a determinant in HSIV-vif-Yu2 that includesenv su. Finally, we show that the Yu-2env suallele may overcome an IFN-α-induced barrier to entry. Together, our data demonstrate that the prototype macaque-tropic HIV-1 clones based on NL4-3 may not sufficiently antagonize innate restriction in PTM cells. However, variants with resistance to IFN-α-induced restriction factors in PTM CD4+T cells may enhance viral replication by overcoming a barrier early in the viral replication cycle.
Human La Protein Interaction with GCAC near the Initiator AUG Enhances Hepatitis C Virus RNA Replication by Promoting Linkage between 5′ and 3′ Untranslated Regions
Authors: Kumar Anuj , Ray Upasana , Das Saumitra
Published: April 2013

Human La protein has been implicated in facilitating the internal initiation of translation as well as replication of hepatitis C virus (HCV) RNA. Previously, we demonstrated that La interacts with the HCV internal ribosome entry site (IRES) around the GCAC motif near the initiator AUG within stem-loop IV by its RNA recognition motif (RRM) (residues 112 to 184) and influences HCV translation. In this study, we have deciphered the role of this interaction in HCV replication in a hepatocellular carcinoma cell culture system. We incorporated mutation of the GCAC motif in an HCV monocistronic subgenomic replicon and a pJFH1 construct which altered the binding of La and checked HCV RNA replication by reverse transcriptase PCR (RT-PCR). The mutation drastically affected HCV replication. Furthermore, to address whether the decrease in replication is a consequence of translation inhibition or not, we incorporated the same mutation into a bicistronic replicon and observed a substantial decrease in HCV RNA levels. Interestingly, La overexpression rescued this inhibition of replication. More importantly, we observed that the mutation reduced the association between La and NS5B. The effect of the GCAC mutation on the translation-to-replication switch, which is regulated by the interplay between NS3 and La, was further investigated. Additionally, our analyses of point mutations in the GCAC motif revealed distinct roles of each nucleotide in HCV replication and translation. Finally, we showed that a specific interaction of the GCAC motif with human La protein is crucial for linking 5′ and 3′ ends of the HCV genome. Taken together, our results demonstrate the mechanism of regulation of HCV replication by interaction of the
cis
-acting element GCAC within the HCV IRES with human La protein.
The Adenovirus L4-33K Protein Regulates both Late Gene Expression Patterns and Viral DNA Packaging
Authors: Wu Kai , Guimet Diana , Hearing Patrick
Published: April 2013

The adenovirus (Ad) L4-33K protein has been linked to disparate functions during infection. L4-33K is a virus-encoded alternative RNA splicing factor which activates splicing of viral late gene transcripts that contain weak 3′ splice sites. Additionally, L4-33K has been indicated to play a role in adenovirus assembly. We generated and characterized an Ad5 L4-33K mutant virus to further explore its function(s) during infection. Infectivity, viral genome replication, and most viral gene expression of the L4-33K mutant virus are comparable to those of the wild-type virus, except for a prominent decrease in the levels of the late proteins IIIa and pVI. The L4-33K mutant virus produces only empty capsids, indicating a defect in viral DNA packaging. We demonstrate that L4-33K does not preferentially bind to viral packaging sequences
in vivo
, and mutation of L4-33K does not interfere with the binding of the known viral packaging proteins IVa2, L4-22K, L1-52/55K, and IIIa to the packaging sequences
in vivo
. Collectively, these results demonstrate that the phenotype of an Ad5 L4-33K mutant virus is complex. The L4-33K protein regulates the accumulation of selective Ad late gene mRNAs and is involved in the proper transition of gene expression during the late phase of infection. The L4-33K protein also plays a role in adenovirus morphogenesis by promoting the packaging of the viral genome into the empty capsid. These results demonstrate the multifunctional nature of the L4-33K protein and its involvement in several different and critical aspects of viral infection.
Structure of a Classical Broadly Neutralizing Stem Antibody in Complex with a Pandemic H2 Influenza Virus Hemagglutinin
Authors: Dreyfus Cyrille , Ekiert Damian C. , Wilson Ian A.
Published: April 2013

We report the structural characterization of the first antibody identified to cross-neutralize multiple subtypes of influenza A viruses. The crystal structure of mouse antibody C179 bound to the pandemic 1957 H2N2 hemagglutinin (HA) reveals that it targets an epitope on the HA stem similar to those targeted by the recently identified human broadly neutralizing antibodies. C179 also inhibits the low-pH conformational change of the HA but uses a different angle of approach and both heavy and light chains.
Novel Recombinant Hepatitis B Virus Vectors Efficiently Deliver Protein and RNA Encoding Genes into Primary Hepatocytes
Authors: Hong Ran , Bai Weiya , Zhai Jianwei , Liu Wei , Li Xinyan , Zhang Jiming , Cui Xiaoxian , Zhao Xue , Ye Xiaoli , Deng Qiang , Tiollais Pierre , Wen Yumei , Liu Jing , Xie Youhua
Published: April 2013

Hepatitis B virus (HBV) has extremely restricted host and hepatocyte tropism. HBV-based vectors could form the basis of novel therapies for chronic hepatitis B and other liver diseases and would also be invaluable for the study of HBV infection. Previous attempts at developing HBV-based vectors encountered low yields of recombinant viruses and/or lack of sufficient infectivity/cargo gene expression in primary hepatocytes, which hampered follow-up applications. In this work, we constructed a novel vector based on a naturally occurring, highly replicative HBV mutant with a 207-bp deletion in the preS1/polymerase spacer region. By applying a novel insertion strategy that preserves the continuity of the polymerase open reading frame (ORF), recombinant HBV (rHBV) carrying protein or small interfering RNA (siRNA) genes were obtained that replicated and were packaged efficiently in cultured hepatocytes. We demonstrated that rHBV expressing a fluorescent reporter (DsRed) is highly infective in primary tree shrew hepatocytes, and rHBV expressing HBV-targeting siRNA successfully inhibited antigen expression from coinfected wild-type HBV. This novel HBV vector will be a powerful tool for hepatocyte-targeting gene delivery, as well as the study of HBV infection.
Chikungunya Virus Host Range E2 Transmembrane Deletion Mutants Induce Protective Immunity against Challenge in C57BL/6J Mice
Authors: Piper Amanda , Ribeiro Mariana , Smith Katherine M. , Briggs Caitlin M. , Huitt Emerson , Nanda Kavita , Spears Carla J. , Quiles Michelle , Cullen John , Thomas Malcolm E. , Brown Dennis T. , Hernandez Raquel
Published: April 2013

A vaccine against Chikungunya virus (ChikV), a reemerging pathogenic arbovirus, has been made by attenuating wild-type (WT) virus via truncation of the transmembrane domain (TMD) of E2 and selecting for host range (HR) mutants. Mice are a standard model system for ChikV disease and display the same symptoms of the disease seen in humans. Groups of mice were inoculated with one of three ChikV HR mutants to determine the ability of each mutant strain to elicit neutralizing antibody and protective immunity upon virus challenge. One mutant, ChikV TM17-2, fulfilled the criteria for a good vaccine candidate. It displayed no reactogenicity at the site of injection, no tissue disease in the foot/ankle and quadriceps, and no evidence of viral persistence in foot/ankle tissues 21 days after infection. Upon challenge with a highly pathogenic strain of ChikV, the mutant blocked viral replication in all tissues tested. This study identified a ChikV HR mutant that grows to high levels in insect cells but was restricted in the ability to assemble virus in mammalian cells
in vitro
. The study demonstrates that these HR strains are attenuated in the mammalian host and warrant further development as live-attenuated vaccine strains.
Deep lobe parotid pleomorphic adenoma presenting as obstructive sleep apnoea
Authors: Mulla Omar , Agada Frank , Dawson David , Sood Sanjai
Published: April 2013

We present a rare case of obstructive sleep apnoea (OSA) secondary to a deep lobe parotid pleomorphic adenoma and discuss its management, including the need for a thorough examination and multidisciplinary approach. Only a few cases of pleomorphic adenoma of the deep lobe of the parotid gland causing OSA have been reported. Our case is not only extremely rare but also highlights that key diagnoses maybe missed if a thorough assessment is not performed.
The isolated fourth ventricle
Authors: Ali Khalid , Nannapaneni Ravindra , Hamandi Khalid
Published: April 2013

Isolated enlargement of the fourth ventricle, or ‘encysted’ fourth ventricle is a rare late complication following shunt insertion of the lateral ventricles for hydrocephalus. Caudal and rostral obstruction of the fourth ventricle and its subsequent dilation results in compression of adjacent cerebellum and brain stem structures; treatment with further shunt insertion directly to the fourth ventricle is invariably successful. There is potential for diagnostic delay, when clinical symptoms and signs of cerebellar and brain stem compromise are unrecognised or attributed to other factors, and attention on the CT is focused on the lateral ventricular system and the already existing  ventriculoperitoneal shunt, which will appear unchanged from previous scans. We report two cases with isolated fourth ventricular obstruction and review the literature to highlight the importance of recognising this condition.