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Variationist sociolinguistics has not paid much attention to linguistically pathologised groups. This thesis studies pathologised speech from a third-wave variationist perspective, exploring how oral deaf or hard-of-hearing (D/HH) speakers of Taiwan Mandarin invoke variation in spoken Mandarin to embody hearingness or deafness. This thesis is structured into three stand-alone journal articles bookended with introductory and conclusion chapters which tie them together in the broader picture of how disability can mobilise an agentive deployment of linguistic resources. This thesis starts with an examination of how pathologised speech has been approached in linguistics and discusses why we need a third-wave perspective, which foregrounds the agency of languagers, to make a valid sociolinguistic analysis of pathologised speech. The first of the three articles is built upon one of the traditional sociolinguistic methods, minimal pair reading task, to explore how five D/HH speakers perform themselves while being highly conscious of their own speech. Different from how minimal pair reading task is usually adopted in linguistics, this study does not adopt minimal pair reading task to report what a standard speech is, for D/HH speakers. Instead, the participants are informed that their participation in the reading task is to make hearing people recognise D/HH speech, thereby empowering D/HH communities. Results show that while a large portion of the participants believe they should speak like hearing people to empower themselves, not all of them do so in the reading task. The results presented here call for a delicate inspection of the heterogeneity among D/HH people in how they view their relationship with society. The second research reports the results of a "device-on/off'' experiment where 19 participants read aloud the same sentences with and without turning on their assistive devices. Different from how this experiment is usually used in clinical linguistics and audiology, this study takes speaker agency into consideration and considers auditory deprivation as a moment where the body is transformed into a disabled body. Half of the participants report they experience negative psychological feelings during auditory deprivation, while the others report they do not. With the affective displays, we learn that the change in vowel quality during auditory deprivation should not be considered completely driven by mechanistic processes. Instead, results show that participants who display negative affect toward auditory deprivation invoke a greater degree of /i/-backing that the others do, and the negative affective display should be understood as a microcosm of how the participants think of disability in general in everyday life. The final of the three articles explores topic-based linguistic variation in passage reading. 10 participants read aloud two passages: one is not relevant to deaf people, and the other is on the identity politics of D/HH communities, in terms of how hearing people oppress D/HH signers in a fictional kingdom. Rather than seeing passage reading as an activity where speakers neutrally transform written text into spoken language, this study invites the participants to share their thoughts about the identity politics passage. Six of the participants discuss the passage from a third person point of view, distancing themselves from the radical viewpoint of identity politics; the other four participants instead take the opportunity to condemn audism and share experiences with audism. Results show that when reading the deaf people-relevant passage, the former group shift to variants which index hearingness in their stylistic repertoires, and the latter group shift to variants indexing deafness to perform solidarity.

Cloud-to-ground lightning can cause high-temperature and high-pressure deformation features in rock at the strike point, forming fulgurite. Although cloud-to-ground lightning is a frequent phenomenon, rock fulgurites are rarely reported. Here, we present field, optical microscope, X-ray fluorescence, scanning and transmission electron microscope, in situ synchrotron projection X-ray microscopy and X-ray diffraction, and Raman data to investigate the formation and preservation of a recently formed rock fulgurite from Kinmen Island, Taiwan. In the field, the fulgurite is asymmetrically distributed on the surface over an ~ 12 m area. In detail, the fulgurite contains an opaque glassy layer comprised of quartz and feldspar clasts, voids, iron-rich spheres, and barite aggregates that overlies fractured quartz grains and feldspar grains with planar features. Secondary minerals found locally adhering to the glassy layer as greenish patches are mainly jarosite group minerals, which commonly form as a secondary hydrothermal alteration product. We interpret the jarosite to have formed during the solidification of melt in the presence of raindrops, suggesting the rapid alteration of glass and short preservation potential of rock fulgurite. Finally, we estimate the production ratio of fulgurite by calculating the energy required for fulgurite formation and that released to the ground by the lightning event. A calculated energy ratio of 0.026% is within the range of 10 to 10 of the lightning total energy delivered to the strike point. We suggest that the scarcity of rock fulgurite in the geological record may be due to both the low production possibility and rapid alteration., The research was supported by the Taiwan ROC (Republic of China) Ministry of Science and Technology (MOST 110–2116-M-008–002-MY2) and Earthquake-Disaster & Risk Evaluation and Management Center (E-DREaM) from the Ministry of Education (MOE) to Li-Wei Kuo. Dennis Brown acknowledges funding (PGC2018-094227-B-I00) from the Spanish Ministry of Science, Innovation, and Universities, as well as a Chaired Professor stipend from the Department of Earth Sciences at National Central University. Jialiang Si acknowledges funding from the National Natural Science Foundation of China (41872211).

Microbial communities are highly diverse, and understanding the factors that promote and modulate this diversity is a major area of research in microbial ecology. Recent work has proposed a reductionist perspective to microbial coexistence, where pairwise coexistence between strains in isolation is required for their coexistence in a more complex community. In this view, species exclusion in pairwise co-culture would preclude their coexistence in a more complex community too. An alternative view is that coexistence is a more complex property of the entire community, requiring the presence of additional community members. If this view were correct, competitive exclusion in pairwise co-culture would not necessarily preclude species coexistence in more complex community contexts. Empirically testing these alternative hypotheses is complicated by the intractably high microbial diversity of most natural communities, and the challenges of reconstituting every pair of coexisting species under the exact same habitat where their community of origin was assembled. To address this challenge, we have experimentally reconstituted all possible pairwise co-cultures between stably coexisting species from 13 different, low-diversity microbial enrichment communities, which had previously been assembled in a well-controlled synthetic habitat. We find that, when isolated from the rest of their community members, most species pairs fail to coexist. This result highlights the importance of community context for microbial coexistence and indicates that pairwise exclusion may not reflect the ability of species to coexist in more complex, multispecies ecosystems., This work was partially funded by Young Investigator Award RGY0077/2016 from the Human Frontier Science Program (to A.S.). C, C.-Y. was supported by the Graduate Student Fellowship for Studying Abroad from the Ministry of Education, Taiwan.

Cloud-to-ground lightning causes both high-temperature and high-pressure metamorphism of rocks, forming rock fulgurite. We demonstrate that a range of microstructural features indicative of high temperatures and pressures can form in fulgurites at the surface and in fractures up to several meters below the surface. In comparison to a granite reference sample collected from a borehole at a depth of 138 m, microstructures in both the surface and fracture fulgurite are characterized by: (i) the presence of glass, (ii) a phase transformation in K-feldspar with the presence of exsolution lamellae of plagioclase, and (iii) high residual stresses up to 1.5 GPa. Since this is the first time that fracturerelated fulgurite has been described, we also carried out a 1-D numerical model to investigate the processes by which these can form. The model shows that the electric current density in fractures up to 40 m from the landing point can be as high as that on the surface, providing an explanation for the occurrence of fracture-related fulgurites. Our work broadens the near-surface environments in which rock fulgurite has been reported, and provides a detailed description of microstructures that can be compared to those formed during other types of extreme metamorphic events., The research was supported by the Taiwan ROC (Republic of China) Ministry of Science and Technology (MOST 110-2116-M-008-002-MY2) and Earthquake-Disaster & Risk Evaluation and Management Center (E-DREaM) from the Ministry of Education (MOE) to Li-Wei Kuo. Dennis Brown acknowledges funding (PGC2018-094227-B-I00) from the Spanish Ministry of Science, Innovation, and Universities, as well as a Chaired Professor stipend from the Department of Earth Sciences at National Central University. Steven Smith acknowledges funding from the Marsden Fund, administered by the Royal Society of New Zealand (project UOO1829).

International audience; Egg production is an economically critical trait in poultry industry. In order to identify genetic markers and chromosomal regions associated with egg production in tropical climate, we conducted both quantitative trait locus (QTL) mapping and genome-wide association study (GWAS) in an F2 cross set up between the Taiwan Country chicken L2 line and an INRA experimental line of Rhode Island Red layer, R-, by using the chicken 60 K SNP chip. A total of eleven QTL (3 genome-wide and 8 chromosome-wide significant QTL) and 102 single nucleotide polymorphism (SNP) effects (7 genome-wide and 95 suggestive significant SNP effects) were identified. Most of detected QTL regions (exclude a QTL on GGA23) and SNPs overlapped with previously published QTL for egg production or quality, providing the evidences to the relationship for the studied traits. The list of QTL and SNPs reported in present study could be contributed to a better comprehension of the genetic control for egg production which is useful for future functional studies.

24 pages, 16 figures, 3 tables, supplementary data https://doi.org/10.1016/j.geobios.2018.06.002, Despite extensive studies on the taxonomy of fossil otoliths, the diversity of late Quaternary to Recent sea bottom otolith assemblages remains largely unexplored. Otolith assemblages from bottom sediments of the North-eastern Atlantic (NE Atlantic), central Mediterranean, and Red Sea were described based on a dataset of 9696 identifiable otoliths. Diversity estimators were computed and taxonomic compositions were compared against geographical site and depth gradient. Several species from the Red Sea show previously unnoticed range extensions or ancient occurrences, suggesting that the otolith assemblage requires further exploration in this region. The diversity is high in the NE Atlantic and central Mediterranean, whereas Red Sea assemblages are dominated by few taxa. We find that, departing from Modern fish communities, the richness of otolith taxa peaks at mid-water depths (500–1500 m) and decreases at depths > 2000 m. The lower diversity at shallow water suggests environments not favorable for otolith preservation. The assemblages are geographically distinct, due to unique combinations of mesopelagic taxa specific to each sample area, though areas in the central Mediterranean and middle-latitude NE Atlantic share many taxa. Depth does not seem to structure otolith assemblages in the central Mediterranean because the otolith composition in this region is highly variable at depths < 500 m but poorly variable at greater depths. The discrepancies between otolith thanatocoenoses and fossil assemblages and the potential application for reconstructing ancient fish communities are discussed. Illustrating otoliths that are rarely found in the literature, this study is the first descriptive and comparative diversity analysis on Recent otolith assemblages for the regions of interest, Chien-Hsiang Lin was financially supported by the Ministry of Education, Taiwan, under the title “Government scholarship for overseas study” during his Ph.D. studies. The microscope laboratory at the Dipartimento di Scienze della Terra and Geoambientali, University of Bari Aldo Moro was funded by Potenziamento Strutturale PONa3_00369 “Laboratorio per lo Sviluppo Integrato delle Scienze e delle Tecnologie dei Materiali Avanzati e per dispositivi innovativi (SISTEMA)”

Full author list: A J Shajib, S Birrer, T Treu, A Agnello, E J Buckley-Geer, J H H Chan, L Christensen, C Lemon, H Lin, M Millon, J Poh, C E Rusu, D Sluse, C Spiniello, G C-F Chen, T Collett, F Courbin, C D Fassnacht, J Frieman, A Galan, D Gilman, A More, T Anguita, M W Auger, V Bonvin, R McMahon, G Meylan, K C Wong, T M C Abbott, J Annis, S Avila, K Bechtol, D Brooks, D Brout, D L Burke, A Carnero Rosell, M Carrasco Kind, J Carretero, F J Castander, M Costanzi, L N da Costa, J De Vicente, S Desai, J P Dietrich, P Doel, A Drlica-Wagner, A E Evrard, D A Finley, B Flaugher, P Fosalba, J García-Bellido, D W Gerdes, D Gruen, R A Gruendl, J Gschwend, G Gutierrez, D L Hollowood, K Honscheid, D Huterer, D J James, T Jeltema, E Krause, N Kuropatkin, T S Li, M Lima, N MacCrann, M A G Maia, J L Marshall, P Melchior, R Miquel, R L C Ogando, A Palmese, F Paz-Chinchón, A A Plazas, A K Romer, A Roodman, M Sako, E Sanchez, B Santiago, V Scarpine, M Schubnell, D Scolnic, S Serrano, I Sevilla-Noarbe, M Smith, M Soares-Santos, E Suchyta, G Tarle, D Thomas, A R Walker, Y Zhang, We present a blind time-delay cosmographic analysis for the lens system DES J0408-5354. This system is extraordinary for the presence of two sets of multiple images at different redshifts, which provide the opportunity to obtain more information at the cost of increased modelling complexity with respect to previously analysed systems. We perform detailed modelling of the mass distribution for this lens system using three band Hubble Space Telescope imaging. We combine the measured time delays, line-of-sight central velocity dispersion of the deflector, and statistically constrained external convergence with our lens models to estimate two cosmological distances. We measure the 'effective' time-delay distance corresponding to the redshifts of the deflector and the lensed quasar DΔ t eff=3382-115+146 Mpc and the angular diameter distance to the deflector Dd = 1711-280+376 Mpc, with covariance between the two distances. From these constraints on the cosmological distances, we infer the Hubble constant H0= 74.2-3.0+2.7 km s-1 Mpc-1 assuming a flat ΛCDM cosmology and a uniform prior for ωm as \Omega m ∼ \mathcal {U(0.05, 0.5). This measurement gives the most precise constraint on H0 to date from a single lens. Our measurement is consistent with that obtained from the previous sample of six lenses analysed by the H0 Lenses in COSMOGRAIL's Wellspring (H0LiCOW) collaboration. It is also consistent with measurements of H0 based on the local distance ladder, reinforcing the tension with the inference from early Universe probes, for example, with 2.2σ discrepancy from the cosmic microwave background measurement., TT acknowledges support by the Packard Foundation through a Packard Research fellowship and by the National Science Foundation through NSF grants AST-1714953 and AST-1906976. This project is partly funded by the Danish council for independent research under the project ‘Fundamentals of Dark Matter Structures’, DFF - 6108-00470. AA was supported by a grant from VILLUM FONDEN (project number 16599). JHHC, MM, CL, DS, FC, and AG acknowledge support from the Swiss National Science Foundation (SNSF) and by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (COSMICLENS: grant agreement No 787866). CS has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie actions grant agreement No 664931. GCFC acknowledges support from the Ministry of Education in Taiwan via Government Scholarship to Study Abroad (GSSA). CDF and GCFC acknowledge support for this work from the National Science Foundation under Grant No AST-1715611. TA acknowledges support from Proyecto FONDECYT N○ 1190335. KCW was supported by World Premier International Research Center Initiative (WPI Initiative), MEXT, Japan. This work used computational and storage services associated with the Hoffman2 Shared Cluster provided by UCLA Institute for Digital Research and Education’s Research Technology Group. This work used the Extreme Science and Engineering Discovery Environment (XSEDE) through allocation TG-AST190038, which is supported by National Science Foundation grant number ACI-1548562 (Towns et al. 2014). Specifically, this work used the Comet and Oasis system at the San Diego Supercomputer Center (SDSC), and the Bridges system, which is supported by NSF award number ACI-1445606, at the Pittsburgh Supercomputing Center (PSC, Nystrom et al. 2015). AJS thanks Smadar Naoz for providing access to additional computing nodes on the Hoffman2 Shared Cluster and Khalid Jawed for assisting with additional computational resources from the Structures–Computer Interaction Laboratory at UCLA. The DES data management system is supported by the National Science Foundation under Grant Numbers AST-1138766 and AST-1536171. The DES participants from Spanish institutions are partially supported by MINECO under grants AYA2015-71825, ESP2015-66861, FPA2015-68048, SEV-2016-0588, SEV-2016-0597, and MDM-2015-0509, some of which include ERDF funds from the European Union. IFAE is partially funded by the CERCA program of the Generalitat de Catalunya. Research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP7/2007-2013) including ERC grant agreements 240672, 291329, and 306478. We acknowledge support from the Australian Research Council Centre of Excellence for All-sky Astrophysics (CAASTRO), through project number CE110001020, and the Brazilian Instituto Nacional de Ciência e Tecnologia (INCT) e-Universe (CNPq grant 465376/2014-2).

The levels of the four deoxynucleoside triphosphates (dNTPs) are under strict control in the cell, as improper or imbalanced dNTP pools may lead to growth defects and oncogenesis. Upon treatment of cancer cells with therapeutic agents, changes in the canonical dNTPs levels may provide critical information for evaluating drug response and mode of action. The radioisotope-labeling enzymatic assay has been commonly used for quantitation of cellular dNTP levels. However, the disadvantage of this method is the handling of biohazard materials. Here, we described the use of click chemistry to replace radioisotope-labeling in template-dependent DNA polymerization for quantitation of the four canonical dNTPs. Specific oligomers were designed for dCTP, dTTP, dATP and dGTP measurement, and the incorporation of 5-ethynyl-dUTP or C8-alkyne-dCTP during the polymerization reaction allowed for fluorophore conjugation on immobilized oligonucleotides. The four reactions gave a linear correlation coefficient >0.99 in the range of the concentration of dNTPs present in 106 cells, with little interference of cellular rNTPs. We present evidence indicating that data generated by this methodology is comparable to radioisotope-labeling data. Furthermore, the design and utilization of a robust microplate assay based on this technology evidenced the modulation of dNTPs in response to different chemotherapeutic agents in cancer cells., We thank Hsin-Yen Wang for maintaining K562 cells. This study was financially supported by the “Center of Precision Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan and by the grant, MOST 107-3017-F-002-002, MOST 107-2321-B-002-041, and MOST 106-2113-M-002-021-MY3 from the Ministry of Science and Technology, Taiwan, (R.O.C.).

International audience; Extracellular nucleotides are important mediators of cell activation and trigger multiple responses via membrane receptors known as purinergic receptors (P2). P2X receptors are ligand-gated ion channels, activated by extracellular ATP. P2X4 is one of the most sensitive purinergic receptors, that is typically expressed by neurons, microglia, and some epithelial and endothelial cells. P2X4 mediates neuropathic pain via brain-derived neurotrophic factor and is also involved in inflammation in response to high ATP release. It is therefore involved in multiple inflammatory pathologies as well as neurodegenerative diseases. We have produced monoclonal antibodies (mAb) directed against this important human P2X4 receptor. Focusing on two mAbs, we showed that they also recognize mouse and rat P2X4. We demonstrated that these mAbs can be used in flow cytometry, immunoprecipitation and immunohistochemistry, but not in Western blot assays, indicating that they target conformational epitopes. We also characterised the expression of P2X4 receptor on mouse and human peripheral blood lymphocytes (PBL). We showed that P2X4 is expressed at the surface of several leukocyte cell types, with the highest expression level on eosinophils, making them potentially sensitive to adenosine triphosphate (ATP). P2X4 is expressed by leucocytes, in human and mouse, with a significant gender difference, males having higher surface expression levels than females. Our findings reveal that PBL express significant levels of P2X4 receptor, and suggest an important role of this receptor in leukocyte activation by ATP, particularly in P2X4high expressing eosinophils.

Tissue engineering research has opened a new chapter in modern medicine since it emerged as a mainstream research field in the early 90s. Until now, however, effective strategies to fully emulate the complexity of natural tissue remain elusive. One of the key features in the development of complex tissue structures is the presence of morphogen gradients during development. In nature, from squid beaks to human teeth, gradients are preserved in many structures after evolution. In a living organism, gradients play an essential role in defining the physiological function. The formation of these gradients is often largely dictated by an anisotropic distribution of different morphogens present during development. The spatial difference in concentration of different morphogens results a spatial variance in cell signalling, patterning the development of tissue and leading to the formation of heterogeneous structure. Although these principles of development are well-established, the overwhelming majority of in vitro engineering strategies use uniform scaffolds and spatially invariant growth factor delivery to produce homogeneous tissue constructs. It is clear that more sophisticated fabrication processes are required to replicate the native complexity and fulfil the functional requirements of tissue grafts. A few material strategies have been developed that can heterogeneously deliver biological or mechanical cues; however, most of them are limited by complex fabrication procedures or restricted compatibility with different material systems. By establishing signaling factor gradients within tissue engineering scaffolds, the formation of heterogeneous tissue interfaces can be achieved. This thesis will demonstrate two gradient casting strategies to emulate physiological gradients, exploiting magnetism and buoyancy to distribute growth factors. These strategies are shown to be capable of establishing gradients in different materials, and are used to engineer osteochondral tissue. The strategies proposed in this research are designed to be widely applicable and easy to reproduce. It is hoped that these strategies may be adapted and tailored for wider use by the tissue engineering field, allowing development of complex, functional tissue by mimicking the processes used by nature. Open Access

Proliferative kidney disease (PKD) is a widespread disease caused by the endoparasite Tetracapsuloides bryosalmonae (Myxozoa: Malacosporea). Clinical disease, provoked by the proliferation of extrasporogonic parasite stages, is characterized by a chronic kidney pathology with underlying transcriptional changes indicative of altered B cell responses and dysregulated T­helper cell­like activities. Despite the relevance of PKD to European and North American salmonid aquaculture, no studies, to date, have focused on further characterizing the B cell response during the course of this disease. Thus, in this work, we have studied the behavior of diverse B cell populations in rainbow trout (Oncorhynchus mykiss) naturally infected with T. bryosalmonae at different stages of preclinical and clinical disease. Our results show a clear upregulation of all trout immunoglobulins (Igs) (IgM, IgD, and IgT) demonstrated by immunohistochemistry and Western blot analysis, suggesting the alteration of diverse B cell populations that coexist in the infected kidney. Substantial changes in IgM, IgD, and IgT repertoires were also identified throughout the course of the disease further pointing to the involvement of the three Igs in PKD through what appear to be independently regulated mechanisms. Thus, our results provide strong evidence of the involvement of IgD in the humoral response to a specific pathogen for the first time in teleosts. Nevertheless, it was IgT, a fish­specific Ig isotype thought to be specialized in mucosal immunity, which seemed to play a prevailing role in the kidney response to T. bryosalmonae. We found that IgT was the main Ig coating extrasporogonic parasite stages, IgT+ B cells were the main B cell subset that proliferated in the kidney with increasing kidney pathology, and IgT was the Ig for which more significant changes in repertoire were detected. Hence, although our results demonstrate a profound dysregulation of different B cell subsets during PKD, they point to a major involvement of IgT in the immune response to the parasite. These results provide further insights into the pathology of PKD that may facilitate the future development of control strategies., This work was supported by the European Research Council (ERC Consolidator Grant 2016 725061 TEMUBLYM) and the European Commission under the H2020 Programme (Grant H2020-634429 ParaFishControl). IE was recipient of APOSTD/2016/037 grant by the “Generalitat Valenciana” and YH was recipient of a PhD Studentship from the Ministry of Education, Republic of China (Taiwan). JWH was supported by BBSRC grant BB/K009125/1 and SNSF grant CRSII3_147649-1. PDR was funded by grant T1-BIO-1672 from the “Comunidad de Madrid”.

Drawing on recent discussions of relational embeddedness and socio-technical agencement, this thesis analyses the relationship between stock trading and lay investors’ daily lives, including their social relations, activities, events, devices, places, work and ways of thinking. Taiwan’s stock market provides an appropriate location for investigation because of the dominance of lay investors in the market and the high proportion of Taiwan’s adult population who engage in stock trading. The data were obtained from three main sets of sources: in-depth interviews, document analysis and ethnographic observation. I argue that lay market actors are not only framed by the market’s mechanisms, but also by daily-life structures. The Taiwan Stock Exchange, as an electronic, anonymous financial market, has been a challenge to the embeddedness approach due to the absence of direct interaction between the parties to transactions. This study presents another aspect of socio-economic relationships in the market: the role of financial-market activity in wider social interactions. Like taking part in any popular social activity, lay investors’ social ties are maintained and expended by engaging in stock trading. Social relations and stock trading are woven together and form a largely seamless whole, part of lay investors’ daily life. The socio-technical agencements of lay investors contain distinctive features: diversity, bricolage, use of non-professional ‘devices’, action in non-financial places, everyday means of controlling market risk and association with everyday events. The differences between the agencements of lay investors and professional practitioners produce an asymmetry of calculative capabilities between market actors. Superior calculative capabilities tend to give an advantage to professional practitioners in the market, but these strengths are constrained by political and economic factors. This study sheds light on micro social factors, which are comparable with economic, institutional and psychological explanations, in accounting for lay investors’ behaviours in financial markets. The analysis also suggests the compatibility of the three important social science approaches to economic agents: Granovetter’s embeddedness, Zelizer’s relational work and Callon’s agencement.