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Hearing loss caused by frequent and persistent exposure to loud noise is one of the most common diseases in modern society. Many studies have demonstrated the characteristics of noise-induced hearing loss in human and non-human vertebrate models, including frequency-specific noise-induced hearing loss and sex-biased differences. Zebrafish (Danio rerio) is a useful hearing research model because its lateral line is easy to access and because of its detailed perception of sound. Despite the increasing popularity of zebrafish as a model for NIHL, a better understanding of this model is needed to determine sex differences in NIHL. To study the features of zebrafish as they relate to an NIHL model, we tested various phenotypes after frequency-specific noise stimulation. The degree of damage to hair cells and hearing loss were investigated after exposing zebrafish to 200 Hz and 1 kHz continuous waves and broadband white noise with a bandwidth from 50 Hz to 1 kHz. After exposure to all frequencies, the larvae showed lateral line hair cell damage, which is superficially located. In adult zebrafish, the threshold of auditory-evoked potential signals is elevated. Moreover, the number of hair cells remarkably decreased in the rostral region of the saccule, after exposure to 1 kHz and white noise, whereas zebrafish exposed to 200 Hz noise showed a decrease in hair cells in the caudal region. Moreover, male zebrafish were found to be more vulnerable to noise than female zebrafish, as is the case in humans and other mammals. Cortisol levels also increased in the noise-exposed male group, as compared to the noise-exposed female and control male groups. However, there was no difference in cortisol levels when the noise-exposed female group was compared to the control female group. Our study demonstrates not only that noise-induced hearing loss is frequency-dependent but also that the degree of hearing loss is affected by sex in zebrafish, emphasizing the need to consider sex in NIHL studies.

Zebrafish behavior is influenced by the lateral line hair cells and muscles. Drug-induced behavioral changes can serve as indicators in the evaluation of drug toxicity. The aminoglycoside family of antibiotics comprise a number of agents, including neomycin (NM) and gentamicin (GM). We hypothesized that NM and GM exert different effects on zebrafish larvae through their action on the lateral line and muscle fibers, inducing different swimming behavioral patterns such as locomotor behavior and the startle response. In this study, 125 μM NM and 5, 10, 20 μM GM induced hair cell damage in the anterior and posterior lateral lines of zebrafish larvae. However, unlike GM, 125 μM NM also caused muscle damage. Locomotor behavior was decreased in the 125 μM NM-exposed group compared to the group exposed to GM. Furthermore, 125 μM NM exposure induced significantly different patterns of various indices of startle behavior compared with the GM exposure groups. Additionally, the larvae exhibited different startle responses depending on the concentration of GM. These results suggest that GM may be the drug-of-choice for analyzing behavioral changes in zebrafish caused by damage to the lateral line alone. Our study highlights the importance of confirming muscle damage in behavioral analyses using zebrafish.

Use of rigid endoscopes has become widespread in middle ear surgeries, thereby attracting attention to the safety of antifog agents. However, few studies on the ototoxicity of antifog agents have been conducted. The purpose of this study was to evaluate hair cell damage and the underlying mechanisms caused by antifog agents using zebrafish larvae. We exposed zebrafish larvae at 3 days postfertilization to various concentrations of the antifog agent, Ultrastop (0.01, 0.02, 0.04, and 0.08%) for 72 hours. The average number of hair cells within 4 neuromasts of larvae, including supraorbital (SO1 and SO2), otic (O1), and occipital (OC1), in the control group were compared to those in the exposure groups. Significant hair cell loss was observed in the experimental groups compared to that in the control group ( P < .01; control: 53.88 ± 4.85, 0.01%: 45.08 ± 11.70, 0.02%: 41.36 ± 12.00, 0.04%: 35.36 ± 16.18, and 0.08%: 15.60 ± 7.53 cells). Concentration-dependent increase in hair cell apoptosis by terminal deoxynucleotidyltransferase (TDT)-mediated dUTP-biotin nick end labeling assay (control: 0.00 ± 0.00, 0.01%: 3.48 ± 2.18, 0.02%: 9.64 ± 5.75, 0.04%: 17.72 ± 6.26, and 0.08%: 14.60 ± 8.18 cells) and decrease in the viability of hair cell mitochondria by 2-(4-[dimethylamino] styryl)-N-ethylpyridinium iodide assay (control: 9.61 ± 1.47, 0.01%: 8.28 ± 2.22, 0.02%: 8.45 ± 2.72, 0.04%: 7.25 ± 2.44, and 0.08%: 6.77 ± 3.26 percentage of total area) were observed. Antifog agent exposure can cause hair cell damage in zebrafish larvae, possibly by induction of mitochondrial damage with subsequent apoptosis of hair cells.

Objectives Particulate matter (PM) exposure has become one of the most serious problems. The aim of the present study was to evaluate the hair cell damage and possible developmental toxicity caused by PM2.5 exposure using a zebrafish model. Methods Zebrafish embryos were exposed to various concentrations of PM2.5. Developmental toxicity was evaluated based on general morphology score (GMS) system and Panzica-Kelly score, and by measurement of body length and heart rate. To evaluate hair cell damage, the average number of total hair cells within four neuromasts exposed to various concentrations of PM2.5 was compared with that of the control group. Results Morphological abnormalities evaluated by the GMS system and Panzica-Kelly score were rare and body length tended to be shorter in the PM2.5-exposed groups. Heart rate decreased significantly in the PM2.5-exposed group. Additionally, significant hair cell damage was observed after PM2.5 exposure. It was dose-dependent and more severe after a longer period exposure (10 dpf). Conclusions In zebrafish embryos, exposure of PM2.5 in the early stages of life decreased heart rate and caused significant hair cell damage in a dose-dependent manner.

The site frequency spectrum (SFS) is of primary interest in population genetic studies, because the SFS compresses variation data into a simple summary from which many population genetic inferences can proceed. However, inferring the SFS from sequencing data is challenging because genotype calls from sequencing data are often inaccurate due to high error rates and if not accounted for, this genotype uncertainty can lead to serious bias in downstream analysis based on the inferred SFS. Here, we compare two approaches to estimate the SFS from sequencing data: one approach infers individual genotypes from aligned sequencing reads and then estimates the SFS based on the inferred genotypes (call-based approach) and the other approach directly estimates the SFS from aligned sequencing reads by maximum likelihood (direct estimation approach). We find that the SFS estimated by the direct estimation approach is unbiased even at low coverage, whereas the SFS by the call-based approach becomes biased as coverage decreases. The direction of the bias in the call-based approach depends on the pipeline to infer genotypes. Estimating genotypes by pooling individuals in a sample (multisample calling) results in underestimation of the number of rare variants, whereas estimating genotypes in each individual and merging them later (single-sample calling) leads to overestimation of rare variants. We characterize the impact of these biases on downstream analyses, such as demographic parameter estimation and genome-wide selection scans. Our work highlights that depending on the pipeline used to infer the SFS, one can reach different conclusions in population genetic inference with the same data set. Thus, careful attention to the analysis pipeline and SFS estimation procedures is vital for population genetic inferences.

Received 1 April, 2013; received in revised form 7 May, 2013; accepted 7 May, 2013ABSTRACTThis study focuses on the data schema and data content, which includes maintenance data, datastructures and illustration data relevant with the maintenance process of ship and offshore struc-tures. Product lifecycle management (PLM) is expected to encompass all the product data gen-erated for the operation and maintenance information as well as the design and production. Thispaper introduces a data exchange schema in PLM of ship and offshore, serving as the basis forthe role of standards required by the middle-of- life PLM. Also this paper identifies a typologyof standards relevant to PLM that addresses the schema of evolving standards and identifies aXML schema supporting the exchange of data related with maintenance operations. Technicaldocument based on standards in accordance with S1000D and Shipdex is explained. A casestudy illustrating the use of standard data exchange and technical document is presented. Key Words:Data schema, DEX (Data Exchange), PLM (Product Lifecycle Management), Ship-dex, XML (Extensible Markup Language)

Recently, both the integration of product data during design and production and the effective management of information during full lifecycles have attracted attention from shipyards and ship owners as a result of recycling regulations and a desire for efficient operations. Generally, PLM (Product Lifecycle Management) supports a collaborative environment during the BOL (Beginning of Life) stage, while an ALM (Asset Lifecycle Management) system provides all of the information required to maintain, overhaul, and discard/recycle all or part of a vessel during the MOL (Middle of Life) and EOL (End of Life) stages. The main goal of this paper is to suggest the fundamental configuration of a PALM (Product Asset Lifecylce Management) system and a method that can be used to utilize a marine vessel's lifecycle information during the MOL, emphasizing the maintenance information during the middle of life. The authors also suggest a PALM system configuration in which lifecycle information can be collected by a PEID (Product Embedded Information Device) integrating a microcomputer, sensors, and wireless network communication. Through a prototype PALM system, the suggested features and PALM system configuration are implemented.

International audience; In a series of highly influential publications, Cavalli-Sforza and colleagues used principal component (PC) analysis to produce maps depicting how human genetic diversity varies across geographic space. Within Europe, the first axis of variation (PC1) was interpreted as evidence for the demic diffusion model of agriculture, in which farmers expanded from the Near East approximately 10,000 years ago and replaced the resident hunter-gatherer populations with little or no interbreeding. These interpretations of the PC maps have been recently questioned as the original results can be reproduced under models of spatially covarying allele frequencies without any expansion. Here, we study PC maps for data simulated under models of range expansion and admixture. Our simulations include a spatially realistic model of Neolithic farmer expansion and assume various levels of interbreeding between farmer and resident hunter-gatherer populations. An important result is that under a broad range of conditions, the gradients in PC1 maps are oriented along a direction perpendicular to the axis of the expansion, rather than along the same axis as the expansion. We propose that this surprising pattern is an outcome of the "allele surfing" phenomenon, which creates sectors of high allele-frequency differentiation that align perpendicular to the direction of the expansion.

This study was done for the determination and excretion profile of adrenosterone and its metabolites in human urine using both liquid chromatography with atmospheric pressure chemical ionization mass spectrometry and gas chromatography with mass spectrometry. Adrenosterone and its two metabolites were detected in human urine after administration a healthy volunteer with 75 mg of adrenosterone. We found that adrenosterone-M1 (C19H26O3) was a reduction and adrenosterone-M2 (C19H26O4) was a hydroxylation at C-ring, which did not know the exact position of the C-ring. The adrenosterone parent was detected by GC/TOF-MS, but not detected by LC/APCI/MS because of low intensity. Adrenosterone and its two metabolites were excreted as their glucuronided fractions. The recovery of this method ranged from 100.7 to 118.4% and the reproducibility and accuracy test were 85.5 to 112.0% and 1.1 to 8.4%, respectively. The excretion studies showed that adrenosterone and its metabolites were detectable in human urine during a 48 h period after oral administration, with maximum level of excretion at 4.1 h. The glucuro-/sulfaconjugated ratio of adrenosterone, M1 and M2 was 0.73 ± 0.03, 0.96 ± 0.06 and 0.89 ± 0.03 (n = 6), respectively. The amounts of adrenosterone excreted in urine were 14.75 ng for 48 h. Also, the maximum level of androsterone and 11β-hydroxy androsterone, which were endogenous steroids, were reached 4.1 h after the oral administration of adrenosterone.

Previously we have designed and implemented new image browsing facilities to support effective offline image contents on mobile devices with limited capabilities: low bandwidth, small display, and slow processing. In this letter, we fulfill the automatic production of cartoon contents fitting small-screen display, and introduce a clustering method useful for various types of cartoon images as a prerequisite stage for preserving semantic meaning. The usage of neural networks is to properly cut the various forms of pages. Texture information that is useful for grayscale image segmentation gives us a good clue for page layout analysis using the multilayer perceptron (MLP) based x-y recursive algorithm. We also automatically frame the segment MLP using agglomerative segmentation. Our experimental results show that the combined approaches yield good results of segmentation for several cartoons.

This letter proposes a categorization matrix to analyze the playing style of a computer game player for a shooting game genre. Our aim is to use human-centered modeling as a strategy for adaptive games based on entertainment measure to evaluate the playing experience. We utilized a self-organizing map (SOM) to cluster the player’s style with the data obtained while playing the game. We further argued that style-based adaptation contributes to higher enjoyment, and this is reflected in our experiment using a supervised multilayered perceptron (MLP) network.

Freedman, Adam H. et al., Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rd top hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers., [Author Summary] Identification of the genomic regions under selection during dog domestication is extremely challenging because the demographic fluctuations associated with domestication can produce signals in polymorphism data that mimic those imposed by selective sweeps. We perform the first analysis of selection on the dog lineage that explicitly incorporates a demographic model, that by controlling for the rate of false discovery, more robustly identifies targets of selection. To do so, we conduct a selection scan using three wolf genomes representing the putative centers of dog domestication, two basal dog breeds (Basenji and Dingo), and a golden jackal as outgroup, for which we previously inferred a demographic model. We find that our demographically informed analyses filters out many signals that would be otherwise classified as putative selection signals under an empirical outlier approach. We identify 68 regions of the genome that have likely experienced positive selection. Besides identifying a number of new neurobehavioral candidate genes, our candidate regions contain genes related to lipid metabolism, including CCRN4L, which is centered in the 3rd ranked region. This suggests a previously unreported locus of dietary adaptation, potentially due to the change in diet composition as hunting efficiency increased when proto dogs began hunting alongside hunter-gatherers., The computations in this paper were run on the Hoffmann2 cluster supported by the IDRE Research Technology Group at the University of California, Los Angeles, and the Odyssey cluster supported by the FAS Division of Science, Research Computing Group at Harvard University.

The Tibetan grey wolf (Canis lupus chanco) occupies habitats on the Qinghai-Tibet Plateau, a high altitude (>3000 m) environment where low oxygen tension exerts unique selection pressure on individuals to adapt to hypoxic conditions. To identify genes involved in hypoxia adaptation, we generated complete genome sequences of nine Chinese wolves from high and low altitude populations at an average coverage of 25× coverage. We found that, beginning about 55,000 years ago, the highland Tibetan grey wolf suffered a more substantial population decline than lowland wolves. Positively selected hypoxia-related genes in highland wolves are enriched in the HIF signaling pathway (P = 1.57E-6), ATP binding (P = 5.62E-5), and response to an oxygen-containing compound (P≤5.30E-4). Of these positively selected hypoxia-related genes, three genes (EPAS1, ANGPT1, and RYR2) had at least one specific fixed non-synonymous SNP in highland wolves based on the nine genome data. Our re-sequencing studies on a large panel of individuals showed a frequency difference greater than 58% between highland and lowland wolves for these specific fixed non-synonymous SNPs and a high degree of LD surrounding the three genes, which imply strong selection. Past studies have shown that EPAS1 and ANGPT1 are important in the response to hypoxic stress, and RYR2 is involved in heart function. These three genes also exhibited significant signals of natural selection in high altitude human populations, which suggest similar evolutionary constraints on natural selection in wolves and humans of the Qinghai-Tibet Plateau., Author Summary Understanding the genetic mechanisms that allow some individuals to live at high altitudes under hypoxic conditions can provide insight into the evolutionary constraints of adaptation to extreme conditions and the development of hypoxia-related disease in humans. The Tibetan grey wolf (Canis lupus chanco) has long existed on the Qinghai-Tibet Plateau, where low oxygen tension exerts unique selection pressure on individuals. Comparing the complete genome sequences of 4 grey wolves from high altitude and 5 from low altitude, we identify three candidate genes for high-altitude adaptation (EPAS1, ANGPT1, and RYR2) that show strong signals of selection. The three genes potentially enhance function under hypoxic conditions by increasing oxygen delivery (EPAS1 and ANGPT1) and heart (RYR2) function. These genes also appear under selection in high altitude human populations, which suggesting there may be limited pathways for adapting to high altitude existence.

The past few years of research in human evolutionary genetics have provided novel insights and questions regarding how human adaptations to recent selective pressures have taken place. Here, we review the advances most relevant to understanding human evolution in response to pathogen-induced selective pressures. Key insights come from theoretical models of adaptive evolution, particularly those that consider spatially structured populations, and from empirical population genomic studies of adaptive evolution in humans. We also review theCCR5-Δ32 HIV resistance allele as a case study of pathogen resistance in humans. Taken together, the results make clear that the human response to pathogen-induced selection pressures depends on a complex interplay between the age of the pathogen, the genetic basis of potential resistance phenotypes, and how population structure impacts the adaptive process in humans.

International audience; Advances in genome technology have facilitated a new understanding of the historical and genetic processes crucial to rapid phenotypic evolution under domestication. To understand the process of dog diversification better, we conducted an extensive genome-wide survey of more than 48,000 single nucleotide polymorphisms in dogs and their wild progenitor, the grey wolf. Here we show that dog breeds share a higher proportion of multi-locus haplotypes unique to grey wolves from the Middle East, indicating that they are a dominant source of genetic diversity for dogs rather than wolves from east Asia, as suggested by mitochondrial DNA sequence data. Furthermore, we find a surprising correspondence between genetic and phenotypic/functional breed groupings but there are exceptions that suggest phenotypic diversification depended in part on the repeated crossing of individuals with novel phenotypes. Our results show that Middle Eastern wolves were a critical source of genome diversity, although interbreeding with local wolf populations clearly occurred elsewhere in the early history of specific lineages. More recently, the evolution of modern dog breeds seems to have been an iterative process that drew on a limited genetic toolkit to create remarkable phenotypic diversity.

Emotion gesture art is a new type of user modeling and representation in a form of aesthetic art. It consists of a unique combination of color, sound and animation (shape) that in itself creates the same emotional feeling for spectators. Emotion gesture art takes the body posture expression and remaps the communication of emotions into an aesthetic representation. This paper also presents an emotion gesture art installation (eG-art), a system prototype for affective computing. This installation will allow a smart blend of a system for affective computing with aesthetic art representation.