bluuebunny/crossref_metadata_2025 huggingface dataset:
Time‐resolved dosimetry using a pinpoint ionization chamber as quality assurance for IMRT and VMAT a)
Authors: Louwe Robert J. W. , Wendling Markus , Monshouwer René , Satherley Thomas , Day Rebecca A. , Greig Lynne
Published: March 2015

Purpose:

To develop a method to verify the dose delivery in relation to the individual control points of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) using an ionization chamber. In addition to more effective problem solving during patient‐specific quality assurance (QA), the aim is to eventually map out the limitations in the treatment chain and enable a targeted improvement of the treatment technique in an efficient way.

Methods:

Pretreatment verification was carried out for 255 treatment plans that included a broad range of treatment indications in two departments using the equipment of different vendors. In‐house developed software was used to enable calculation of the dose delivery for the individual beamlets in the treatment planning system (TPS), for data acquisition, and for analysis of the data. The observed deviations were related to various delivery and measurement parameters such as gantry angle, field size, and the position of the detector with respect to the field edge to distinguish between error sources.

Results:

The average deviation of the integral fraction dose during pretreatment verification of the planning target volume dose was −2.1% ± 2.2% (1 SD), −1.7% ± 1.7% (1 SD), and 0.0% ± 1.3% (1 SD) for IMRT at the Radboud University Medical Center (RUMC), VMAT (RUMC), and VMAT at the Wellington Blood and Cancer Centre, respectively. Verification of the dose to organs at risk gave very similar results but was generally subject to a larger measurement uncertainty due to the position of the detector at a high dose gradient. The observed deviations could be related to limitations of the TPS beam models, attenuation of the treatment couch, as well as measurement errors. The apparent systematic error of about −2% in the average deviation of the integral fraction dose in the RUMC results could be explained by the limitations of the TPS beam model in the calculation of the beam penumbra.

Conclusions:

This study showed that time‐resolved dosimetry using an ionization chamber is feasible and can be largely automated which limits the required additional time compared to integrated dose measurements. It provides a unique QA method which enables identification and quantification of the contribution of various error sources during IMRT and VMAT delivery.
Noninvasive estimation of the pressure profile in the male urethra using ultrasound imaging
Authors: Idzenga Tim , Arif Muhammad , van Mastrigt Ron , de Korte Chris L.
Published: March 2015

Purpose:

Decreased prostatic compliance as a result of benign prostatic enlargement can result in bladder outlet obstruction. This changes the urethral pressure profile during voiding. In this study, the authors propose noninvasive estimation of this pressure profile. In four soft tissue mimicking models of the urethra with increasing degree of obstruction, the authors measured deformation of the wall during flow, using ultrasound imaging. Combined with estimates of the model compliance, the authors were able to estimate the pressure profile.

Methods:

First, the compliances (Young's moduli) of the four models were derived by applying static luminal pressure and measuring the resulting strain of the tissue using an ultrasound imaging system. Next, continuous flow was applied to the models and the strain in the urethral wall was measured similarly. The luminal pressure profile was estimated from the strain (measured under continuous flow conditions) and the derived compliance (measured under static pressure conditions). The estimated pressures up‐ and downstream of the obstruction were compared with the corresponding measured pressures. In the obstructed region, the strain gradient was estimated using linear regression.

Results:

The luminal pressure values estimated from the ultrasound data up‐ and downstream of the obstruction were not significantly different from the corresponding measured pressures. The general pressure profile showed a decrease along the length of the obstruction followed by a small increase after the obstruction. The strain gradient in the obstructed region reflected the decrease in urethral pressure and increased with flow rate and degree of obstruction.

Conclusions:

The results from this model study illustrate the feasibility of noninvasive estimation of the urethral pressure profile using ultrasound. This offers the prospect of a noninvasive, ultrasound based diagnostic tool for assessment of bladder outlet obstruction in men with lower urinary tract symptoms.
The contribution of phonation type to the perception of vocal emotions in German: An articulatory synthesis study
Authors: Birkholz Peter , Martin Lucia , Willmes Klaus , Kröger Bernd J. , Neuschaefer-Rube Christiane
Published: March 2015

Vocal emotions are signaled by specific patterns of prosodic parameters, most notably pitch, phone duration, intensity, and phonation type. Phonation type was so far the least accessible parameter in emotion research, because it was difficult to extract from speech signals and difficult to manipulate in natural or synthetic speech. The present study built on recent advances in articulatory speech synthesis to exclusively control phonation type in re-synthesized German sentences spoken with seven different emotions. The goal was to find out to what extent the sole change of phonation type affects the perception of these emotions. Therefore, portrayed emotional utterances were re-synthesized with their original phonation type, as well as with each purely breathy, modal, and pressed phonation, and then rated by listeners with respect to the perceived emotions. Highly significant effects of phonation type on the recognition rates of the original emotions were found, except for disgust. While fear, anger, and the neutral emotion require specific phonation types for correct perception, sadness, happiness, boredom, and disgust primarily rely on other prosodic parameters. These results can help to improve the expression of emotions in synthesized speech and facilitate the robust automatic recognition of vocal emotions.
Rhythmic variability between speakers: Articulatory, prosodic, and linguistic factors
Authors: Dellwo Volker , Leemann Adrian , Kolly Marie-José
Published: March 2015

Between-speaker variability of acoustically measurable speech rhythm [%V, ΔV(ln), ΔC(ln), and Δpeak(ln)] was investigated when within-speaker variability of (a) articulation rate and (b) linguistic structural characteristics was introduced. To study (a), 12 speakers of Standard German read seven lexically identical sentences under five different intended tempo conditions (very slow, slow, normal, fast, very fast). To study (b), 16 speakers of Zurich Swiss German produced 16 spontaneous utterances each (256 in total) for which transcripts were made and then read by all speakers (4096 sentences; 16 speaker × 256 sentences). Between-speaker variability was tested using analysis of variance with repeated measures on within-speaker factors. Results revealed strong and consistent between-speaker variability while within-speaker variability as a function of articulation rate and linguistic characteristics was typically not significant. It was concluded that between-speaker variability of acoustically measurable speech rhythm is strong and robust against various sources of within-speaker variability. Idiosyncratic articulatory movements were found to be the most plausible factor explaining between-speaker differences.
Perceptual thresholds for the effects of room modes as a function of modal decay
Authors: Fazenda Bruno M. , Stephenson Matthew , Goldberg Andrew
Published: March 2015

Room modes cause audible artifacts in listening environments. Modal control approaches have emerged in scientific literature over the years and, often, their performance is measured by criteria that may be perceptually unfounded. Previous research has shown modal decay as a key perceptual factor in detecting modal effects. In this work, perceptual thresholds for the effects of modes as a function of modal decay have been measured in the region between 32 and 250 Hz. A test methodology has been developed to include modal interaction and temporal masking from musical events, which are important aspects in recreating an ecologically valid test regime. This method has been deployed in addition to artificial test stimuli traditionally used in psychometric studies, which provide unmasked, absolute thresholds. For artificial stimuli, thresholds decrease monotonically from 0.9 s at 32 Hz to 0.17 s at 200 Hz, with a knee at 63 Hz. For music stimuli, thresholds decrease monotonically from 0.51 s at 63 Hz to 0.12 s at 250 Hz. Perceptual thresholds are shown to be dependent on frequency and to a much lesser extent on level. The results presented here define absolute and practical thresholds, which are useful as perceptually relevant optimization targets for modal control methods.
Interaural envelope correlation change discrimination in bilateral cochlear implantees: Effects of mismatch, centering, and onset of deafness
Authors: Goupell Matthew J.
Published: March 2015

Bilateral cochlear implant (CI) listeners can perform binaural tasks, but they are typically worse than normal-hearing (NH) listeners. To understand why this difference occurs and the mechanisms involved in processing dynamic binaural differences, interaural envelope correlation change discrimination sensitivity was measured in real and simulated CI users. In experiment 1, 11 CI (eight late deafened, three early deafened) and eight NH listeners were tested in an envelope correlation change discrimination task. Just noticeable differences (JNDs) were best for a matched place-of-stimulation and increased for an increasing mismatch. In experiment 2, attempts at intracranially centering stimuli did not produce lower JNDs. In experiment 3, the percentage of correct identifications of antiphasic carrier pulse trains modulated by correlated envelopes was measured as a function of mismatch and pulse rate. Sensitivity decreased for increasing mismatch and increasing pulse rate. The experiments led to two conclusions. First, envelope correlation change discrimination necessitates place-of-stimulation matched inputs. However, it is unclear if previous experience with acoustic hearing is necessary for envelope correlation change discrimination. Second, NH listeners presented with CI simulations demonstrated better performance than real CI listeners. If the simulations are realistic representations of electrical stimuli, real CI listeners appear to have difficulty processing interaural information in modulated signals.
Effects of manipulating the signal-to-noise envelope power ratio on speech intelligibility
Authors: Jørgensen Søren , Decorsière Rémi , Dau Torsten
Published: March 2015

Jørgensen and Dau [(2011). J. Acoust. Soc. Am. 130, 1475–1487] suggested a metric for speech intelligibility prediction based on the signal-to-noise envelope power ratio (SNRenv), calculated at the output of a modulation-frequency selective process. In the framework of the speech-based envelope power spectrum model (sEPSM), the SNRenv was demonstrated to account for speech intelligibility data in various conditions with linearly and nonlinearly processed noisy speech, as well as for conditions with stationary and fluctuating interferers. Here, the relation between the SNRenv and speech intelligibility was investigated further by systematically varying the modulation power of either the speech or the noise before mixing the two components, while keeping the overall power ratio of the two components constant. A good correspondence between the data and the corresponding sEPSM predictions was obtained when the noise was manipulated and mixed with the unprocessed speech, consistent with the hypothesis that SNRenv is indicative of speech intelligibility. However, discrepancies between data and predictions occurred for conditions where the speech was manipulated and the noise left untouched. In these conditions, distortions introduced by the applied modulation processing were detrimental for speech intelligibility, but not reflected in the SNRenv metric, thus representing a limitation of the modeling framework.
Finite amplitude standing waves in resonators terminated by a general impedance
Authors: Bednarik Michal , Cervenka Milan
Published: March 2015

A general inhomogeneous Burgers equation describing finite-amplitude standing waves in resonators terminated by a general impedance is derived. This model equation can be used for modeling of nonlinear acoustic processes connected with some methods for enhancement of Q-factor of acoustic resonators. One of them is the method based on using a second-harmonics absorber. For better understanding of this method, it is convenient to know at least an approximate analytical solution of the model equation. This work presents some approximate solutions, which improve and extend the solutions that have been published previously. The solutions are compared with results obtained by numerical integration of the corresponding equations.
Wave propagation in a waveguide containing restrictions with circular arc shape
Authors: Félix Simon , Maurel Agnès , Mercier Jean-François
Published: March 2015

A multimodal method is used to analyze the wave propagation in waveguides containing restrictions (or corrugations) with circular arc shapes. This is done using a geometrical transformation which transforms the waveguide with complex geometry in the real space to a straight waveguide in the transformed space, or virtual space. In this virtual space, the Helmholtz equation has a modified structure which encapsulates the complexity of the geometry. It is solved using an improved modal method, which was proposed in a paper by A. Maurel, J.-F. Mercier, and S. Félix [Proc. R. Soc. A 470, 20130743 (2014)], that increases the accuracy and convergence of usual multimodal formulations. Results show the possibility to solve the wave propagation in a waveguide with a high density of circular arc shaped scatterers.
Divided attention disrupts perceptual encoding during speech recognition
Authors: Mattys Sven L. , Palmer Shekeila D.
Published: March 2015

Performing a secondary task while listening to speech has a detrimental effect on speech processing, but the locus of the disruption within the speech system is poorly understood. Recent research has shown that cognitive load imposed by a concurrent visual task increases dependency on lexical knowledge during speech processing, but it does not affect lexical activation per se. This suggests that “lexical drift” under cognitive load occurs either as a post-lexical bias at the decisional level or as a secondary consequence of reduced perceptual sensitivity. This study aimed to adjudicate between these alternatives using a forced-choice task that required listeners to identify noise-degraded spoken words with or without the addition of a concurrent visual task. Adding cognitive load increased the likelihood that listeners would select a word acoustically similar to the target even though its frequency was lower than that of the target. Thus, there was no evidence that cognitive load led to a high-frequency response bias. Rather, cognitive load seems to disrupt sublexical encoding, possibly by impairing perceptual acuity at the auditory periphery.
Complete Nucleotide Sequence of a Conjugative Plasmid Carrying
bla
PER-1
Authors: Li Ruichao , Wong Marcus Ho Yin , Zhou Yuanjie , Chan Edward Wai-chi , Chen Sheng
Published: March 2015

The nucleotide sequence of a self-transmissible plasmid pVPH1 harboring
bla
PER-1
from
Vibrio parahaemolyticus
was determined. pVPH1 was 183,730 bp in size and shared a backbone similar to pAQU1 and pAQU2, differing mainly in an ∼40-kb multidrug resistance (MDR) region. A complex class 1 integron was identified together with IS
CR1
and
bla
PER-1
(IS
CR1
-
bla
PER-1
-
gst
-
abct
-
qacE
Δ
1
-
sul1
), which was shown to form a circular intermediate playing an important role in the dissemination of
bla
PER-1
.
Evolution and Single-Nucleotide Polymorphisms in Methicillin-Resistant Staphylococcus aureus Strains with Reduced Susceptibility to Vancomycin and Daptomycin, Based on Determination of the Complete Genome
Authors: Yamaguchi Tetsuo , Suzuki Shingo , Okamura Sakiko , Miura Yuri , Tsukimori Ayaka , Nakamura Itaru , Ito Norihiko , Masuya Anri , Shiina Takashi , Matsumoto Tetsuya
Published: March 2015

We obtained a series of methicillin-resistant
Staphylococcus aureus
isolates, including both daptomycin-susceptible strain TD1 and daptomycin-resistant strain TD4, from a patient. We determined the complete genome sequences of TD1 and TD4 using next-generation sequencing, and only four single-nucleotide polymorphisms (SNPs) were identified, one each in
capB
(E58K),
rpoB
(H481Y),
lytN
(I16V), and
mprF
(V351E). We determined that these four SNPs were sufficient to cause the strains to develop daptomycin, vancomycin, and rifampin resistance.
High-Level Cellular and Humoral Immune Responses in Guinea Pigs Immunized Intradermally with a Heat-Inactivated Varicella-Zoster Virus Vaccine
Authors: Sarkadi Julia , Jankovics Mate , Fodor Kinga , Kis Zoltan , Takacs Maria , Visontai Ildiko , Jankovics Istvan , Gonczol Eva
Published: March 2015

The threat of varicella and herpes zoster in immunocompromised individuals necessitates the development of a safe and effective varicella-zoster virus (VZV) vaccine. The immune responses of guinea pigs to the intradermal (i.d.) or subcutaneous (s.c.) administration of a heat-inactivated or live VZV vaccine were investigated. Relative to nonimmunized animals, a single 399-PFU dose of vaccine induced nonsignificant increases in gamma interferon (IFN-γ), granzyme B, and perforin mRNA expression in the splenocytes of all groups, while two i.d. administrations of the inactivated vaccine increased IFN-γ mRNA expression significantly (P< 0.005). A single 1,995-PFU dose significantly increased the expression of IFN-γ mRNA in the groups receiving the vaccine either i.d. (P< 0.005) or s.c. (P< 0.05), that of granzyme B mRNA in the groups immunized i.d. with the inactivated (P< 0.005) or live (P< 0.005) vaccine, and that of perforin mRNA in the animals that received the inactivated vaccine i.d. (P< 0.005). Importantly, increases in the expression of IFN-γ (P= 0.025), granzyme B (P= 0.004), and perforin (P> 0.05) mRNAs were observed in the animals immunized i.d. with 1,995 PFU of inactivated vaccine relative to those immunized s.c. with the same dose. The proportion of animals expressing IFN-γ mRNA mirrored the proportion expressing IFN-γ protein (correlation coefficient of 0.88). VZV glycoprotein-specific and virus-neutralizing antibodies were produced with no significant intergroup differences. A booster i.d. administration of the 399-PFU dose of heat-inactivated vaccine enhanced the antibody responses. These results demonstrate that i.d. administration of an inactivated VZV vaccine can be an efficient mode of immunization against VZV.
Avoidance of Autophagy Mediated by PlcA or ActA Is Required for Listeria monocytogenes Growth in Macrophages
Authors: Mitchell Gabriel , Ge Liang , Huang Qiongying , Chen Chen , Kianian Sara , Roberts Mary F. , Schekman Randy , Portnoy Daniel A.
Published: March 2015

Listeria monocytogenesis a facultative intracellular pathogen that escapes from phagosomes and grows in the cytosol of infected host cells. Most of the determinants that govern its intracellular life cycle are controlled by the transcription factor PrfA, including the pore-forming cytolysin listeriolysin O (LLO), two phospholipases C (PlcA and PlcB), and ActA. We constructed a strain that lacked PrfA but expressed LLO from a PrfA-independent promoter, thereby allowing the bacteria to gain access to the host cytosol. This strain did not grow efficiently in wild-type macrophages but grew normally in macrophages that lacked ATG5, a component of the autophagy LC3 conjugation system. This strain colocalized more with the autophagy marker LC3 (42% ± 7%) at 2 h postinfection, which constituted a 5-fold increase over the colocalization exhibited by the wild-type strain (8% ± 6%). While mutants lacking the PrfA-dependent virulence factor PlcA, PlcB, or ActA grew normally, a double mutant lacking both PlcA and ActA failed to grow in wild-type macrophages and colocalized more with LC3 (38% ± 5%). Coexpression of LLO and PlcA in a PrfA-negative strain was sufficient to restore intracellular growth and decrease the colocalization of the bacteria with LC3. In a cell-free assay, purified PlcA protein blocked LC3 lipidation, a key step in early autophagosome biogenesis, presumably by preventing the formation of phosphatidylinositol 3-phosphate (PI3P). The results of this study showed that avoidance of autophagy byL. monocytogenesprimarily involves PlcA and ActA and that either one of these factors must be present forL. monocytogenesgrowth in macrophages.
Toll-Like Receptor 2-Dependent Extracellular Signal-Regulated Kinase Signaling in Mycobacterium tuberculosis-Infected Macrophages Drives Anti-Inflammatory Responses and Inhibits Th1 Polarization of Responding T Cells
Authors: Richardson Edward T. , Shukla Supriya , Sweet David R. , Wearsch Pamela A. , Tsichlis Philip N. , Boom W. Henry , Harding Clifford V.
Published: March 2015

Mycobacterium tuberculosissurvives within macrophages and employs immune evasion mechanisms to persist in the host. Protective T helper type 1 (Th1) responses are induced, and the immune response in most individuals is sufficient to restrictM. tuberculosisto latent infection, but most infections are not completely resolved. As T cells and macrophages respond, a balance is established between protective Th1-associated and other proinflammatory cytokines, such as interleukin-12 (IL-12), interferon gamma (IFN-γ), and tumor necrosis factor alpha, and anti-inflammatory cytokines, such as IL-10. The mechanisms by whichM. tuberculosismodulates host responses to promote its survival remain unclear. In these studies, we demonstrate thatM. tuberculosisinduction of IL-10, suppression of IL-12, and inhibition of class II major histocompatibility complex (MHC-II) molecules in infected macrophages are all driven by Toll-like receptor 2 (TLR2)-dependent activation of the extracellular signal-regulated kinases (ERK). Elimination of ERK signaling downstream of TLR2 by pharmacologic inhibition with U0126 or genetic deletion ofTpl2blocks IL-10 secretion and enhances IL-12 p70 secretion. We demonstrate thatM. tuberculosisregulation of these pathways in macrophages affects T cell responses to infected macrophages. Thus, genetic blockade of the ERK pathway inTpl2−/−macrophages enhances Th1 polarization and IFN-γ production by antigen-specific CD4+T cells responding toM. tuberculosisinfection. These data indicate thatM. tuberculosisand its potent TLR2 ligands activate ERK signaling in macrophages to promote anti-inflammatory macrophage responses and blunt Th1 responses against the pathogen.
Glutamate Racemase Mutants of Bacillus anthracis
Authors: Oh So-Young , Richter Stefan G. , Missiakas Dominique M. , Schneewind Olaf
Published: March 2015

d
-Glutamate is an essential component of bacterial peptidoglycan and a building block of the poly-γ-
d
-glutamic acid (PDGA) capsule of
Bacillus anthracis
, the causative agent of anthrax. Earlier work suggested that two glutamate racemases, encoded by
racE1
and
racE2
, are each essential for growth of
B. anthracis
, supplying
d
-glutamic acid for the synthesis of peptidoglycan and PDGA capsule. Earlier work could not explain, however, why two enzymes that catalyze the same reaction may be needed for bacterial growth. Here, we report that deletion of
racE1
or
racE2
did not prevent growth of
B. anthracis
Sterne (pXO1
+
pXO2
−
), the noncapsulating vaccine strain, or of
B. anthracis
Ames (pXO1
+
pXO2
+
), a fully virulent, capsulating isolate. While mutants with deletions in
racE1
and
racE2
were not viable,
racE2
deletion delayed vegetative growth of
B. anthracis
following spore germination and caused aberrant cell shapes, phenotypes that were partially restored by exogenous
d
-glutamate. Deletion of
racE1
or
racE2
from
B. anthracis
Ames did not affect the production or stereochemical composition of the PDGA capsule. A model is presented whereby
B. anthracis
, similar to
Bacillus subtilis
, utilizes two functionally redundant racemase enzymes to synthesize
d
-glutamic acid for peptidoglycan synthesis.

IMPORTANCE
Glutamate racemases, enzymes that convert
l
-glutamate to
d
-glutamate, are targeted for antibiotic development. Glutamate racemase inhibitors may be useful for the treatment of bacterial infections such as anthrax, where the causative agent,
B. anthracis
, requires
d
-glutamate for the synthesis of peptidoglycan and poly-γ-
d
-glutamic acid (PDGA) capsule. Here we show that
B. anthracis
possesses two glutamate racemase genes that can be deleted without abolishing either bacterial growth or PDGA synthesis. These data indicate that drug candidates must inhibit both glutamate racemases, RacE1 and RacE2, in order to block
B. anthracis
growth and achieve therapeutic efficacy.
The Sinorhizobium meliloti SyrM Regulon: Effects on Global Gene Expression Are Mediated by
syrA
and
nodD3
Authors: Barnett Melanie J. , Long Sharon R.
Published: March 2015

In
Sinorhizobium meliloti
, three NodD transcriptional regulators activate bacterial nodulation (
nod
) gene expression. NodD1 and NodD2 require plant compounds to activate
nod
genes. The NodD3 protein does not require exogenous compounds to activate
nod
gene expression; instead, another transcriptional regulator, SyrM, activates
nodD3
expression. In addition, NodD3 can activate
syrM
expression. SyrM also activates expression of another gene,
syrA
, which when overexpressed causes a dramatic increase in exopolysaccharide production. In a previous study, we identified more than 200 genes with altered expression in a strain overexpressing
nodD3
. In this work, we define the transcriptomes of strains overexpressing
syrM
or
syrA
. The
syrM
,
nodD3
, and
syrA
overexpression transcriptomes share similar gene expression changes; analyses imply that
nodD3
and
syrA
are the only targets directly activated by SyrM. We propose that most of the gene expression changes observed when
nodD3
is overexpressed are due to NodD3 activation of
syrM
expression, which in turn stimulates SyrM activation of
syrA
expression. The subsequent increase in SyrA abundance results in broad changes in gene expression, most likely mediated by the ChvI-ExoS-ExoR regulatory circuit.

IMPORTANCE
Symbioses with bacteria are prevalent across the animal and plant kingdoms. Our system of study, the rhizobium-legume symbiosis (
Sinorhizobium meliloti
and
Medicago
spp.), involves specific host-microbe signaling, differentiation in both partners, and metabolic exchange of bacterial fixed nitrogen for host photosynthate. During this complex developmental process, both bacteria and plants undergo profound changes in gene expression. The
S. meliloti
SyrM-NodD3-SyrA and ChvI-ExoS-ExoR regulatory circuits affect gene expression and are important for optimal symbiosis. In this study, we defined the transcriptomes of
S. meliloti
overexpressing SyrM or SyrA. In addition to identifying new targets of the SyrM-NodD3-SyrA regulatory circuit, our work further suggests how it is linked to the ChvI-ExoS-ExoR regulatory circuit.
Has CXCL13 an Added Value in Diagnosis of Neurosyphilis?
Authors: Mothapo Khutso M. , Verbeek Marcel M. , van der Velden Lieven B. , Ang C. Wim , Koopmans Peter P. , van der Ven Andre , Stelma Foekje
Published: March 2015

In patients with syphilis, central nervous system (CNS) involvement is often difficult to determine. In patients who also are infected with human immunodeficiency virus (HIV), this is even more challenging, as cerebrospinal fluid (CSF) pleocytosis can be attributed to HIV, syphilis, or both. Hence, this study investigated (i) CSF chemokine (C-X-C motif) ligand 13 (CXCL13) as a potential marker to diagnose neurosyphilis in HIV-infected individuals and (ii) the added value of CSF CXCL13 to conventional CSF biomarkers, such as the rapid plasma reagin test (RPR), in diagnosing neurosyphilis. We included 103 syphilis patients from two centers in The Netherlands: 47 non-HIV-infected patients and 56 HIV-infected patients. A positive CSF-RPR was regarded as the gold standard for neurosyphilis. CSF CXCL13 levels were significantly higher in neurosyphilis patients when neurosyphilis was diagnosed by CSF-RPR (
P
= 0.0002) than in the syphilis control group. The sensitivity and specificity of CSF CXCL13 (cutoff of 76.3 pg/ml) to diagnose neurosyphilis by using positive CSF-RPR as the gold standard were 50% and 90%, respectively. CSF CXCL13 had an added value to CSF-RPR positivity in 70% of HIV-positive patients and in 33% of HIV-negative patients. Our data show that CSF CXCL13 might be a potential additional marker in neurosyphilis when other markers are not conclusive. The added value of CSF CXCL13 measurement to the current neurosyphilis gold standard appears to benefit HIV-positive patients more than HIV-negative patients.
Macrophages Are Phenotypically and Functionally Diverse across Tissues in Simian Immunodeficiency Virus-Infected and Uninfected Asian Macaques
Authors: Ortiz Alexandra M. , DiNapoli Sarah R. , Brenchley Jason M.
Published: March 2015

Macrophages regulate tissue immunity, orchestrating the initiation and resolution of antimicrobial immune responses and repair of damaged tissue architecture. Their dysfunction can, thus, manifest in either pro- and anti-inflammatory responses. Indeed, despite the importance of macrophage function in health and disease, the role of tissue-resident macrophages in human immunodeficiency virus (HIV) disease progression remains incompletely defined. Here, we use flow cytometry to assess the phenotypes and functions of macrophages isolated from the spleens, axillary lymph nodes, colons, jejuna, and livers of healthy and chronically simian immunodeficiency virus (SIV)-infected Asian macaques, the prominent nonhuman primate model for HIV infection. Our data demonstrate that macrophages from healthy animals exhibit considerable phenotypic and functional heterogeneity across tissues and across a variety of stimuli. Further, our analysis reveals changes in the lipopolysaccharide (LPS) responsiveness of macrophages isolated from SIV-infected animals. We anticipate that our findings will inform future research into macrophage-directed immunity across a variety of primate diseases.

IMPORTANCEThese findings highlight the functional and phenotypic heterogeneity of tissue macrophages in different anatomic sites and as a result of SIV infection. We believe that our data will lead to novel therapeutic interventions aimed at altering the proinflammatory capacity of tissue macrophages in progressively HIV-infected individuals.
A Single Amino Acid Substitution in the NS2A Protein of Japanese Encephalitis Virus Affects Virus Propagation
In Vitro
but Not
In Vivo
Authors: Takamatsu Yuki , Morita Kouichi , Hayasaka Daisuke
Published: March 2015

We identified a unique amino acid of NS2A
113
, phenylalanine, that affects the efficient propagation of two Japanese encephalitis virus strains, JaTH160 and JaOArS982, in neuroblastoma Neuro-2a cells but not in cell lines of extraneural origin. This amino acid did not affect viral loads in the brain or survival curves in mice. These findings suggest that virus propagation
in vitro
may not reflect the level of virus neuroinvasiveness
in vivo
.
What Is the Reservoir of Emergent Human Norovirus Strains?
Authors: Karst Stephanie M. , Baric Ralph S.
Published: March 2015

Since 1996, there have been at least six human norovirus pandemics. All of the pandemic strains are genetically related, segregating in the genogroup II, genotype 4 (GII.4) cluster within the
Norovirus
genus. Evidence indicates that these strains are closely related but antigenically distinct, supporting immune-driven viral evolution. Thus, norovirus vaccines will likely require periodic reformulation to protect from newly emergent strains. A major obstacle is that the reservoir of emergent strains is unknown. Noroviruses display tight species specificity and there is no evidence supporting zoonotic transmission, so an animal reservoir is considered unlikely. Moreover, available data indicate minimal viral diversity in most natural human infections. In this Gem, we discuss the widely speculated idea that chronically infected immunocompromised individuals are norovirus reservoirs and provide a rationale for the theory that elderly and malnourished hosts may also represent norovirus reservoirs.
Genome Diversity of Epstein-Barr Virus from Multiple Tumor Types and Normal Infection
Authors: Palser Anne L. , Grayson Nicholas E. , White Robert E. , Corton Craig , Correia Samantha , Ba abdullah Mohammed M. , Watson Simon J. , Cotten Matthew , Arrand John R. , Murray Paul G. , Allday Martin J. , Rickinson Alan B. , Young Lawrence S. , Farrell Paul J. , Kellam Paul
Published: March 2015

Epstein-Barr virus (EBV) infects most of the world's population and is causally associated with several human cancers, but little is known about how EBV genetic variation might influence infection or EBV-associated disease. There are currently no published wild-type EBV genome sequences from a healthy individual and very few genomes from EBV-associated diseases. We have sequenced 71 geographically distinct EBV strains from cell lines, multiple types of primary tumor, and blood samples and the first EBV genome from the saliva of a healthy carrier. We show that the established genome map of EBV accurately represents all strains sequenced, but novel deletions are present in a few isolates. We have increased the number of type 2 EBV genomes sequenced from one to 12 and establish that the type 1/type 2 classification is a major feature of EBV genome variation, defined almost exclusively by variation of EBNA2 and EBNA3 genes, but geographic variation is also present. Single nucleotide polymorphism (SNP) density varies substantially across all known open reading frames and is highest in latency-associated genes. Some T-cell epitope sequences in EBNA3 genes show extensive variation across strains, and we identify codons under positive selection, both important considerations for the development of vaccines and T-cell therapy. We also provide new evidence for recombination between strains, which provides a further mechanism for the generation of diversity. Our results provide the first global view of EBV sequence variation and demonstrate an effective method for sequencing large numbers of genomes to further understand the genetics of EBV infection.

IMPORTANCE
Most people in the world are infected by Epstein-Barr virus (EBV), and it causes several human diseases, which occur at very different rates in different parts of the world and are linked to host immune system variation. Natural variation in EBV DNA sequence may be important for normal infection and for causing disease. Here we used rapid, cost-effective sequencing to determine 71 new EBV sequences from different sample types and locations worldwide. We showed geographic variation in EBV genomes and identified the most variable parts of the genome. We identified protein sequences that seem to have been selected by the host immune system and detected variability in known immune epitopes. This gives the first overview of EBV genome variation, important for designing vaccines and immune therapy for EBV, and provides techniques to investigate relationships between viral sequence variation and EBV-associated diseases.
Lantibiotic Resistance
Authors: Draper Lorraine A. , Cotter Paul D. , Hill Colin , Ross R. Paul
Published: March 2015

The dramatic rise in the incidence of antibiotic resistance demands that new therapeutic options will have to be developed. One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides. It is interesting that low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Given that there are very few examples of naturally occurring lantibiotic resistance, attempts have been made to deliberately induce resistance phenotypes in order to investigate this phenomenon. Mechanisms that hinder the action of lantibiotics are often innate systems that react to the presence of any cationic peptides/proteins or ones which result from cell well damage, rather than being lantibiotic specific. Such resistance mechanisms often arise due to altered gene regulation following detection of antimicrobials/cell wall damage by sensory proteins at the membrane. This facilitates alterations to the cell wall or changes in the composition of the membrane. Other general forms of resistance include the formation of spores or biofilms, which are a common mechanistic response to many classes of antimicrobials. In rare cases, bacteria have been shown to possess specific antilantibiotic mechanisms. These are often species specific and include the nisin lytic protein nisinase and the phenomenon of immune mimicry.
Psychological interventions for mental health disorders in children with chronic physical illness: a systematic review
Authors: Bennett Sophie , Shafran Roz , Coughtrey Anna , Walker Susan , Heyman Isobel
Published: March 2015

Background

Children with chronic physical illness are significantly more likely to develop common psychiatric symptoms than otherwise healthy children. These children therefore warrant effective integrated healthcare yet it is not established whether the known, effective, psychological treatments for symptoms of common childhood mental health disorders work in children with chronic physical illness.

Methods

EMBASE, MEDLINE, PsycINFO and CINAHL databases were searched with predefined terms relating to evidence-based psychological interventions for psychiatric symptoms in children with chronic physical illness. We included all studies (randomised and non-randomised designs) investigating interventions aimed primarily at treating common psychiatric symptoms in children with a chronic physical illness in the review. Two reviewers independently assessed the relevance of abstracts identified, extracted data and undertook quality analysis.

Results

Ten studies (209 children, including 70 in control groups) met the criteria for inclusion in the review. All studies demonstrated some positive outcomes of cognitive behavioural therapy for the treatment of psychiatric symptoms in children with chronic physical illness. Only two randomised controlled trials, both investigating interventions for symptoms of depression, were found.

Conclusions

There is preliminary evidence that cognitive behavioural therapy has positive effects in the treatment of symptoms of depression and anxiety in children with chronic physical illness. However, the current evidence base is weak and fully powered randomised controlled trials are needed to establish the efficacy of psychological treatments in this vulnerable population.
Acute rheumatic fever and rheumatic heart disease in resource-limited settings
Authors: Watson Gabriella , Jallow Bintou , Le Doare Kirsty , Pushparajah Kuberan , Anderson Suzanne T
Published: March 2015

Poststreptococcal complications, such as acute rheumatic fever (ARF) and rheumatic heart disease (RHD), are common in resource-limited settings, with RHD recognised as the most common cause of paediatric heart disease worldwide. Managing these conditions in resource-limited settings can be challenging. We review the investigation and treatment options for ARF and RHD and, most importantly, prevention methods in an African setting.
Electrical and dielectric properties of Au/1% graphene (GP)+Ca1.9Pr0.1Co4Ox doped poly(vinyl alcohol)/n-Si structures as function of temperature and voltage
Authors: Çetinkaya H.G. , Kaya A. , Altındal Ş. , Koçyiğit S.
Published: March 2015

Electrical and dielectric properties of Au/1% graphene (GP)+Ca1.9Pr0.1Co4Ox doped poly(vinyl alcohol)/n-Si structures have been investigated using the admittance spectroscopy method in the temperature and voltage ranges of 160–300 K and –4 – 5 V, respectively. Experimental results show that both the main electrical and dielectric parameters, such as barrier height (Φb), depletion layer width (Wd), series resistance (Rs) of structure, real and imaginary parts of dielectric constant (ε′, ε″) and electric modulus (M′ and M″), tanδ, and AC conductivity (σac) were found to be strong functions of temperature and applied bias voltage. M′ and M″ versus V plots have a peak at about 1 V. While the peak position shifted towards negative biases, the magnitude of the peak decreases with increasing temperature. Such peak behavior in M′ and M″ can be attributed to the existence of particular density distribution profile interface states at the interfacial layer–n-Si interface and their reordering and restructure under external electric field and interface polarization. These peaks also indicated that the Au/1% GP+Ca1.9Pr0.1Co4Ox doped poly(vinyl alcohol)/n-Si structure exhibits relaxation phenomena.
Ultraviolet light response of electrical and dielectric properties in zinc phthalocyanine and fullerene dispersed liquid crystal composites
Authors: Köysal O. , Gökçen M. , Yıldırım M.
Published: March 2015

Liquid crystal composites form an attractive research area in liquid crystal studies. Among these composites, nematic liquid crystal composited E63 is of particular interest. In the present study, E63 coded liquid crystal composites were dispersed with zinc phthalocyanine (Zn-Pc) and fullerene (C60), and three samples were prepared as E63, E63/Zn-Pc, and E63/Zn-Pc/C60 in indium tin oxide coated cells via capillary action. Later, current and capacitance measurements of the samples were carried out in darkness and under ultraviolet (UV) illumination (365 nm) of 100 mW/cm2 power intensity. It was found that both current and capacitance in the samples are affected by UV light and dispersal of Zn-Pc and C60. Particularly, dispersal of Zn-Pc led to occurrence of photovoltaic properties, which yielded open-circuit voltage of 0.37 V for the E63/Zn-Pc sample. Furthermore, dielectric constant and dielectric anisotropy values were extracted from capacitance values, and UV light was seen to increase the transition frequency of dielectric anisotropy slightly for all samples.
Danhong Injection in the Treatment of Acute Coronary Syndrome: A Systematic Review and Meta-Analysis
Authors: Wu Jia-Rui , Zhang Xiao-Meng , Zhang Bing
Published: March 2015

To systematically evaluate the efficacy and safety of Danhong injection (DH) in treating acute coronary syndrome (ACS), randomized controlled trials (RCTs) regarding ACS treated by DH were searched in Chinese and English electronic databases from inception until June 2013. Two reviewers independently retrieved RCTs and extracted information. The Cochrane risk of bias method was used to assess the quality of the included studies, and a meta-analysis was conducted with Review Manager 5.2 software. About 26 RCTs with 2660 participants were included. The methodological quality was usually not high, and only one study used a randomized, double-blinded method. The meta-analysis indicated that on the basis of conventional therapy with Western medicine (WM), DH was more effective in increasing the total effective rate [RR = 1.24, 95%CI (1.17, 1.32), p < 0.00001]. Additionally, DH can decrease inflammatory cytokines, including high sensitive C-reactive protein (Hs-CRP) and interleukin-6 (IL-6), lower plasma viscosity, plasma endothelin-1 (ET-1) and brain natriuretic peptide (BNP), reduce the generation of myeloperoxidase (MPO), and decrease the number of T-wave inversion. There were no adverse drug reactions (ADR) reported in the experimental group, while one case occurred in the control group. Based on the systematic review, DH combined with WM was effective in the treatment of ACS. However, the safety of DH in the treatment of ACS should be further carefully interpreted by more large-scale and double-blind RCTs.
Hepatoprotective Effect of Kaempferol Against Alcoholic Liver Injury in Mice
Authors: Wang Meng , Sun Jianguo , Jiang Zhihui , Xie Wenyan , Zhang Xiaoying
Published: March 2015

Kaempferol is a biologically active component present in various plants. The hepatoprotective effect of kaempferol in drug-induced liver injury has been proven, while its effect against alcoholic liver injury (ALI) remains unclear. Hence, the present study aimed to evaluate the effect of kaempferol against ALI in mice. The experimental ALI mice model was developed and the mice were treated with different doses of kaempferol for 4 weeks. The liver functions were observed by monitoring the following parameters: Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) levels in serum; histopathological studies of liver tissue; oxidative stress by hydrogen peroxide ( H2O2), superoxide dismutase (SOD) and glutathione (GSH); the lipid peroxidation status by malondialdehyde (MDA) and lipid accumulation by triglyceride (TG) level in serum; and the expression levels and activities of a key microsomal enzyme cytochrome 2E1 (CYP2E1), by both in vitro and in vivo methods. The ALI mice (untreated) showed clear symptoms of liver injury, such as significantly increased levels of oxidative stress, lipid peroxidation and excessive CYP2E1 expression and activity. The mice treated with different kaempferol dosages exhibited a significant decrease in the oxidative stress as well as lipid peroxidation, and increased anti-oxidative defense activity. The kaempferol treatment has significantly reduced the expression level and activity of hepatic CYP2E1, thus indicating that kaempferol could down regulate CYP2E1. These findings show the hepatoprotective properties of kaempferol against alcohol-induced liver injury by attenuating the activity and expression of CYP2E1 and by enhancing the protective role of anti-oxidative defense system.
Structural changes in non-planar octaaryl substituted phthalocyanine phosphorus complexes
Authors: Furuyama Taniyuki , Harako Ryosuke , Kobayashi Nagao
Published: March 2015

Phosphorus complexes of non-planar α-octaaryl phthalocyanine derivatives ((α- Ar )8 Pc ), 3a and 3b have been synthesized by introduction of phosphorus(V) ions into free-base Pcs 2a and 2b. 3a and 3b were characterized by MS, 1 H and 31 P NMR spectra. The solid state structure of 3a indicated a ruffled Pc structure due to the small atomic radius of phosphorus, although the corresponding free-base Pc 2a has a saddled Pc structure. The phosphorus complexes showed intense absorption bands (Q-bands) in the near-IR region, while the introduction of electron-donating groups at the peripheral phenyl groups was efficient for additional red-shifting of the Q-band. Electrochemical data revealed that the red-shift of the Q-band is attributable to a decrease in the HOMO–LUMO gap due to significant and moderate stabilization of the LUMO and HOMO, respectively. MO calculations suggested that the phosphorus(V) ion intensified the electronic interaction between the peripheral aryl moieties and the Pc macrocyclic core.
“Youth Drain” and its Implication for Regional Disparity
Authors: LU Ding
Published: March 2015

China's domestic migration in recent years has featured the migration of working-aged workers from the rural areas to cities and from the poor regions to the rich ones. As a result, the poor regions saw their elderly dependency ratios as well as median population age rise faster than that in the rich regions. This phenomenon of “youth drain” has profound impact on interregional disparity.