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The translation of taboo words has attracted scholars’ interest in studying it in the audiovisual context over the last decades. The surge of research on this predominant form of translation in everyday life has brought to light the communicative, pragmatic, and semiotic aspects as well as the technical constraints for subtitling taboo words. Previous research has primarily taken a quantitative method, discussed issues that justify their results, and suggested possible outcomes from a potential receiver’s point of view. While contributing to existing related literature, this paper argues that there is a need for a thorough, detailed examination of translation options in subtitling taboo words. The paper presents a three-layered typology of methods, strategies, and techniques, which provides a comprehensive description of audiovisual translators’ options. Following a bottom-up/top-down approach, the proposed typography is then put to the test in a corpus-based case study comprising six movies and their professional subtitles broadcast on Portuguese televisions.

The Ceará’s state coast belongs to one of the most important areas of the South Atlantic for migration and feeding of sea turtles. Thus, the present study observed (1) which species occur in Fortaleza, (2) which species and sex are beached the most, (3) the life stage and (4) season that they most strand. We aimed to update existing information regarding the occurrence of sea turtles in Fortaleza, evaluate if seasonality influences beaching behavior, register the beached species on the coast of Fortaleza, and investigate the beaching behavior. This study was carried out in Fortaleza, Brazil. Data were obtained through monitoring and reports provided by the local community, from January/16 to December/19. A total of 112 beached turtles of four species were observed, and younger specimens were more observed. No significant differences appeared between the years, months, and the rainy/dry seasons on the number of the strandings. Females were observed more than males for all species, perhaps due to the use of the region as a migratory route for breeding and foraging. This is the first data for Ceará State published in a scientific paper, which can be used as the basis to raise awareness in the general population, and government, regarding the vulnerability of these organisms. Keywords: Chelonia mydas, juvenile turtles, female turtles, human activities, northeastern.

Human CD20 expression on hCD20pos B16 cells was analyzed by flow cytometry. A) 2 x 105 Daudi cells or (B) hCD20pos B16 cells were incubated with 10 µg of Rituximab for 1h at 4{degree sign}C. After washing the cells, Rituximab binding was detected by adding 1 µg of human anti-IgG1 PE mAb (clone IS11-12E4.23.20, Miltenyi Biotec) for 30 min at 4{degree sign}C. After washing, mean fluorescence intensity (MFI) was measured using a FACS Canto Flow Cytometer (BD) and analyzed with Flow Jo 7 software (Tree Star Inc., Ashland, Oregon, USA). Background controls included: unstained Daudi and hCD20pos B16 cells, and Daudi and hCD20pos B16 cells incubated with anti-HER2 Trastuzumab mAb (isotype control) and further processed as described above. C) hCD20-expression was similar for both Daudi and hCD20pos B16 cells.

Ex vivo biodistribution of 68Ga-NOTA-sdAb 9077, 9079 and non-target control sdAb (68Ga-NOTA-ctrl sdAb) at 1.5 h p.i., in hCD20 B16 tumor mouse model. Results are presented as mean % IA/g {plus minus} SD (n = 3 per sdAb).

Anti-CD20 radioimmunotherapy is an effective approach for therapy of relapsed or refractory CD20pos lymphomas, but faces limitations due to poor tumor penetration and undesirable pharmacokinetics of full antibodies. Camelid single-domain Ab fragments (sdAb) might circumvent some of the limitations of radiolabeled full antibodies. In this study, a set of hCD20-targeting sdAbs was generated, and their capacity to bind hCD20 was evaluated in vitro and in vivo. A lead sdAb, sdAb 9079, was selected on the basis of its specific tumor targeting and significant lower kidney accumulation compared with other sdAbs. SdAb 9079 was then radiolabeled with 68Ga and 177Lu for PET imaging and targeted therapy. The therapeutic potential of 177Lu-DTPA-sdAb was compared with that of 177Lu-DTPA-rituximab and unlabeled rituximab in mice bearing hCD20pos tumors. Radiolabeled with 68Ga, sdAb 9079 showed specific tumor uptake, with very low accumulation in nontarget organs, except kidneys. The tumor uptake of 177Lu-DTPA-sdAb 9079 after 1.5 h was 3.4 ± 1.3% ID/g, with T/B and T/M ratios of 13.3 ± 4.6 and 32.9 ± 15.6. Peak tumor accumulation of 177Lu-DTPA-rituximab was about 9 times higher, but concomitantly with high accumulation in nontarget organs and very low T/B and T/M ratios (0.8 ± 0.1 and 7.1 ± 2.4). Treatment of mice with 177Lu-DTPA-sdAb 9079 significantly prolonged median survival compared with control groups and was as effective as treatment with rituximab or its 177Lu-labeled variant. Taken together, sdAb 9079 displays promising features as a theranostic drug to treat CD20pos lymphomas. Mol Cancer Ther; 16(12); 2828–39. ©2017 AACR.

Supplementary Table S5 shows the ex vivo biodistribution of 131I-2Rs15d after 1h in mice with BT474/M1 xenografts that were pre-treated 72h earlier with a 100-fold molar excess of trastuzumab, pertuzumab or a combination of both.

Purpose: Camelid single-domain antibody-fragments (sdAb) have beneficial pharmacokinetic properties, and those targeted to HER2 can be used for imaging of HER2-overexpressing cancer. Labeled with a therapeutic radionuclide, they may be used for HER2-targeted therapy. Here, we describe the generation of a 131I-labeled sdAb as a theranostic drug to treat HER2-overexpressing cancer.Experimental Design: Anti-HER2 sdAb 2Rs15d was labeled with 131I using [131I]SGMIB and evaluated in vitro. Biodistribution was evaluated in two HER2+ murine xenograft models by micro-SPECT/CT imaging and at necropsy, and under challenge with trastuzumab and pertuzumab. The therapeutic potential of [131I]SGMIB-2Rs15d was investigated in two HER2+ tumor mouse models. A single-dose toxicity study was performed in mice using unlabeled [127I]SGMIB-sdAb at 1.4 mg/kg. The structure of the 2Rs15d–HER2 complex was determined by X-ray crystallography.Results: [131I]SGMIB-2Rs15d bound specifically to HER2+ cells (Kd = 4.74 ± 0.39 nmol/L). High and specific tumor uptake was observed in both BT474/M1 and SKOV-3 tumor xenografted mice and surpassed kidney levels by 3 hours. Extremely low uptake values were observed in other normal tissues at all time points. The crystal structure revealed that 2Rs15d recognizes HER2 Domain 1, consistent with the lack of competition with trastuzumab and pertuzumab observed in vivo. [131I]SGMIB-2Rs15d alone, or in combination with trastuzumab, extended median survival significantly. No toxicity was observed after injecting [127I]SGMIB-2Rs15d.Conclusions: These findings demonstrate the theranostic potential of [131I]SGMIB-2Rs15d. An initial scan using low radioactive [*I]SGMIB-2Rs15d allows patient selection and dosimetry calculations for subsequent therapeutic [131I]SGMIB-2Rs15d and could thereby impact therapy outcome on HER2+ breast cancer patients. Clin Cancer Res; 23(21); 6616–28. ©2017 AACR.

A detailed description of the materials and methods used for the HER2-2Rs15d structure determination, the radioiodination of sdAbs, and all flow cytometry experiments.

Supplementary figure S1 details the HER2-epitope recognized by 2Rs15d compared to those reported for other described HER2-binders and a view of HER2-ÂÃ,â­2Rs15d interactions.

Iris melanocytoma (IM) is a rare variant of iris nevus with distinctive clinical and histopathological features. A 66-year-old woman, with a history of right eye pigmented iris nevus, presented to us with a recent onset of visual acuity decrease in that eye. She had a melanocytic iris lesion with iridocorneal angle invasion, peripheral corneal adhesion, pupil corectopia, sectorial cataract and high intraocular pressure. Ultrasound biomicroscopy did not exclude malignant transformation, so excisional biopsy was performed revealing the presence of IM without signs of atypia. Subsequently, the patient underwent cataract surgery combined with iridoplasty and later an ab externo trabeculectomy. Most cases of IM remain stable and require no intervention, but in cases of unusual clinical course, with rapid growth or secondary glaucoma, surgical treatment is indicated as a diagnostic and therapeutic measure. This case report highlights the importance of a timely and multidisciplinary ophthalmological approach for a better visual outcome.

Lyophilization is commonly used in the production of pharmaceutical compounds to increase the stability of the Active Pharmaceutical Ingredient (API) by removing solvents. This study investigates the possibility to lyophilize an anti-HER2 and an anti-MMR single-domain antibody fragment (sdAb)-based precursor as a first step in the development of a diagnostic kit for PET imaging. Methods NOTA-sdAb precursors have been lyophilized with the following formulation: 100 µg NOTA-sdAb in 0.1 M NaOAc (NaOAc), 5% (w/v%) mannitol-sucrose mix at a 2:1 ratio and 0.1 mg/mL polysorbate 80. During development of the formulation and drying cycle, factors such as cake appearance, glass transition temperature and residual moisture were analyzed to ensure qualitative and stable lyophilized samples. Stability studies of lyophilized precursor were conducted up to 18 months after storage at 2–8 °C by evaluating the precursor integrity, aggregation, functionality and 68Ga-labeling efficiency. A comparative biodistribution study (lyophilized vs non-lyophilized precursor) was conducted in wild type mice (n = 3) and in tumor bearing mice (n = 6). Results The lyophilized NOTA-anti-HER2 precursor shows consistent stability data in vitro for up to 12 months at 2–8 °C in three separate batches, with results indicating stability even for up to T18m. No aggregation, degradation or activity loss was observed. Radiochemical purity after 68Ga-labeling is consistent over a period of 12 months (RCP ≥ 95% at T12m). In vivo biodistribution analyses show a typical [68Ga]Ga-NOTA-anti-HER2 sdAb distribution profile and a comparable tumor uptake for the lyophilized compound vs non-lyophilized (5.5% vs 5.7 %IA/g, respectively). In vitro results of lyophilized NOTA-anti-MMR precursor indicates stability for up to 18 months, while in vivo data show a comparable tumor uptake (2.5% vs 2.8 %IA/g, respectively) and no significant difference in kidney retention (49.4% vs 47.5 %IA/g, respectively). Conclusion A formulation and specific freeze-drying cycle were successfully developed to lyophilize NOTA-sdAb precursors for long-term storage at 2–8 °C. In vivo data show no negative impact of the lyophilization process on the in vivo behavior or functionality of the lyophilized precursor. These results highlight the potential to develop a kit for the preparation of 68Ga-sdAb-based radiopharmaceuticals.

Within Audiovisual Translation Studies, many studies have been dedicated to the subtitling of taboo words. Most of this research has been restricted to quantitative and qualitative data about translation strategies, with comparably less attention given to translation norms. As norms cannot be directly observed, their investigation raises methodological challenges for empirical studies. This paper proposes a model for the investigation of translation norms by triangulating data on observed regularities in the English to Portuguese subtitling of taboo words in a corpus of movies broadcast on Portuguese FTA (free-to-air, open-signal) television between 2001 and 2015, with questionnaire data on subtitlers’ attitudes towards the subtitling of taboo words on television. The results enable the identification of the most frequent subtitling strategies, their possible motivations, and the relevance of two contextual variables (time period and channel typology). Using the results, a (potential) norm regarding the subtitling of taboo words in Portugal is formulated. However, some of the data, both textual and extratextual, raise the question of whether there is also a competing norm at play.

Submitted by Maria da Luz Antunes (mluz.antunes@estesl.ipl.pt) on 2021-08-04T14:37:34Z No. of bitstreams: 1 Corneal subbasal nerve plexus evaluation by in vivo confocal microscopy in multiple sclerosis.pdf: 1317032 bytes, checksum: 86be831615d41642d36aa9409b5f2dd8 (MD5) Made available in DSpace on 2021-08-04T14:37:34Z (GMT). No. of bitstreams: 1 Corneal subbasal nerve plexus evaluation by in vivo confocal microscopy in multiple sclerosis.pdf: 1317032 bytes, checksum: 86be831615d41642d36aa9409b5f2dd8 (MD5) Previous issue date: 2021-04 info:eu-repo/semantics/publishedVersion

The maternal mode of mitochondrial DNA (mtDNA) inheritance is central to human genetics. Recently, evidence for bi-parental inheritance of mtDNA was claimed for individuals of three pedigrees that suffered mitochondrial disorders. We sequenced mtDNA using both direct Sanger and Massively Parallel Sequencing in several tissues of eleven maternally related and other affiliated healthy individuals of a family pedigree and observed mixed mitotypes in eight individuals. Cells without nuclear DNA, i.e. thrombocytes and hair shafts, only showed the mitotype of haplogroup (hg) V. Skin biopsies were prepared to generate ρ° cells void of mtDNA, sequencing of which resulted in a hg U4c1 mitotype. The position of the Mega-NUMT sequence was determined by fluorescence in situ hybridization and two different quantitative PCR assays were used to determine the number of contributing mtDNA copies. Thus, evidence for the presence of repetitive, full mitogenome Mega-NUMTs matching haplogroup U4c1 in various tissues of eight maternally related individuals was provided. Multi-copy Mega-NUMTs mimic mixtures of mtDNA that cannot be experimentally avoided and thus may appear in diverse fields of mtDNA research and diagnostics. We demonstrate that hair shaft mtDNA sequencing provides a simple but reliable approach to exclude NUMTs as source of misleading results.

Introduction Human coronavirus (HCoVs) are a group of viruses with recognized neurotropic and neuroinvasive capabilities. The reports on the neurological and ocular findings are increasing day after day and several central and peripheral neurological manifestations are already described. However, none specifically describes the neuro-ophthalmological manifestation of HCoVs. This is the first article specifically reviewing neuro-ophthalmological manifestations of HCoVs infection. Methods PubMed and Google Scholar databases were searched using the keywords: coronaviridae, coronavirus, COVID-19, SARS-CoV-2, SARS-CoV-1, MERS, ocular, ophthalmology, ophthalmological, neuro-ophthalmology, neurological, manifestations. A manual search through the reference lists of relevant articles was also performed. There were no restrictions concerning language or study type and publications not yet printed but available online were considered. Results Coronavirus eye involvement is not frequent and includes mostly a typical viral follicular conjunctivitis. Recently, retinal anatomical alterations were described using optic coherence tomography. Neuro-ophthalmological symptoms and signs can appear isolated or associated with neurological syndromes. The manifestations include headache, ocular pain, visual impairment, diplopia, and cranial nerve palsies secondary to Miller Fisher syndrome, Guillain-Barre syndrome, or encephalitis, and nystagmus. Conclusion Neurological and neuro-ophthalmological syndromes, symptoms, and signs should not be neglected and a complete ophthalmological examination of these patients should be performed to fully describe ocular manifestations related to HCoVs. We believe that major ocular and neuro-ophthalmological manifestations reports lack due to safety issues concerning detailed ophthalmological examination; on the other hand, in a large number of cases, the presence of life-threatening coronavirus disease hinders ocular examination and ophthalmologist's visit to the intensive care unit.

Targeted alpha-particle therapy (TAT) might be a relevant therapeutic strategy to circumvent resistance to conventional therapies in the case of HER2-positive metastatic cancer. Single-domain antibody fragments (sdAb) are promising vehicles for TAT because of their excellent in vivo properties, high target affinity, and fast clearance kinetics. This study combines the cytotoxic α-particle emitter bismuth-213 (213Bi) and HER2-targeting sdAbs. The in vitro specificity, affinity, and cytotoxic potency of the radiolabeled complex were analyzed on HER2pos cells. Its in vivo biodistribution through serial dissections and via Cherenkov and micro-single-photon emission computed tomography (CT)/CT imaging was evaluated. Finally, the therapeutic efficacy and potential associated toxicity of [213Bi]Bi-DTPA-2Rs15d were evaluated in a HER2pos tumor model that manifests peritoneal metastasis. In vitro, [213Bi]Bi-DTPA-2Rs15d bound HER2pos cells in a HER2-specific way. In mice, high tumor uptake was reached already 15 min after injection, and extremely low uptake values were observed in normal tissues. Co-infusion of gelofusine resulted in a 2-fold reduction in kidney uptake. Administration of [213Bi]Bi-DTPA-2Rs15d alone and in combination with trastuzumab resulted in a significant increase in median survival. We describe for the very first time the successful labeling of an HER2-sdAb with the α-emitter 213Bi, and after intravenous administration, revealing high in vivo stability and specific accumulation in target tissue and resulting in an increased median survival of these mice especially in combination with trastuzumab. These results indicate the potential of [213Bi]Bi-DTPA-sdAb as a new radioconjugate for TAT, alone and as an add-on to trastuzumab for the treatment of HER2pos metastatic cancer.

Nanobodies (Nbs) are 15 kDa recombinant, single-domain, antigen-specific fragments derived from heavy-chain only antibodies (HCAbs) occurring naturally in species of Camelidae. The beneficial properties of Nbs make them suitable tracers for diagnostic and therapeutic purposes. Whereas Nbs with a terminal hexa-histidine tag (His-tag) are easily purified via immobilized metal affinity chromatography, previous studies revealed a negative impact of the His-tag on the biodistribution of Nb-based tracers. Thus, it is important to develop alternative purification methods for Nbs without a His-tag. Protein A (SpA), a surface protein of Staphylococcus aureus, binds the Fc-region of IgG molecules and also to a lesser extent human heavy chain family-3 variable (VH) regions. Nbs also belong to this VH family, although many fail to be recognized by SpA. Here it is demonstrated that non-SpA binding Nbs can be mutagenized for purification by SpA affinity chromatography and that these Nb variants retain their thermostability and antigen affinity, while biodistribution remains unaffected.

Horizontal gaze palsy and progressive scoliosis (HGPPS) is a rare autosomal recessive disorder caused by mutations in the

The high number of matching haplotypes of the most common mitochondrial (mt)DNA lineages are considered to be the greatest limitation for forensic applications. This study investigates the potential to solve this constraint by massively parallel sequencing a large number of mitogenomes that share the most common West Eurasian mtDNA control region (CR) haplotype motif (263G 315.1C 16519C). We augmented a pilot study on 29 to a total of 216 Italian mitogenomes that represents the largest set of the most common CR haplotype compiled from a single country. The extended population sample confirmed and extended the huge coding region diversity behind the most common CR motif. Complete mitogenome sequencing allowed for the detection of 163 distinct haplotypes, raising the power of discrimination from 0 (CR) to 99.6% (mitogenome). The mtDNAs were clustered into 61 named clades of haplogroup H and did not reveal phylogeographic trends within Italy. Rapid individualization approaches for investigative purposes are limited to the most frequent H clades of the dataset, viz. H1, H3, and H7.

Immigrants from diverse origins have arrived in Paraguay and produced important demographic changes in a territory initially inhabited by indigenous Guarani. Few studies have been performed to estimate the proportion of Native ancestry that is still preserved in Paraguay and the role of females and males in admixture processes. Therefore, 548 individuals from eastern Paraguay were genotyped for three marker sets: mtDNA, Y-SNPs and autosomal AIM-InDels. A genetic homogeneity was found between departments for each set of markers, supported by the demographic data collected, which showed that only 43% of the individuals have the same birthplace as their parents. The results show a sex-biased intermarriage, with higher maternal than paternal Native American ancestry. Within the native mtDNA lineages in Paraguay (87.2% of the total), most haplogroups have a broad distribution across the subcontinent, and only few are concentrated around the Paraná River basin. The frequency distribution of the European paternal lineages in Paraguay (92.2% of the total) showed a major contribution from the Iberian region. In addition to the remaining legacy of the colonial period, the joint analysis of the different types of markers included in this study revealed the impact of post-war migrations on the current genetic background of Paraguay.

The emergence of Massively Parallel Sequencing technologies enabled the analysis of full mitochondrial (mt)DNA sequences from forensically relevant samples that have, so far, only been typed in the control region or its hypervariable segments. In this study, we evaluated the performance of a commercially available multiplex-PCR-based assay, the Precision ID mtDNA Whole Genome Panel (Thermo Fisher Scientific), for the amplification and sequencing of the entire mitochondrial genome (mitogenome) from even degraded forensic specimens. For this purpose, more than 500 samples from 24 different populations were selected to cover the vast majority of established superhaplogroups. These are known to harbor different signature sequence motifs corresponding to their phylogenetic background that could have an effect on primer binding and, thus, could limit a broad application of this molecular genetic tool. The selected samples derived from various forensically relevant tissue sources and were DNA extracted using different methods. We evaluated sequence concordance and heteroplasmy detection and compared the findings to conventional Sanger sequencing as well as an orthogonal MPS platform. We discuss advantages and limitations of this approach with respect to forensic genetic workflow and analytical requirements.

Most studies on maternal lineages of South America populations are restricted to control region (CR) markers and, for some geographical regions, the number of studied samples does not adequately represent the existing diversity. This is the case of mitochondrial DNA (mtDNA) studies on Paraguay that are limited to two Native ethnic groups. To overcome this deficiency, we analysed the mitogenomes from 105 individuals living in Alto Parana, the second most populated department of the country. Using the Precision ID mtDNA Whole Genome Panel, the molecule was sequenced on Ion S5. The majority of the haplotypes belong to the Native American lineages A, B, C and D. Analyses of maximum parsimony using mitogenome data retrieved from publications and in The 1000 Genomes Project showed a high number of new native American subclades in Paraguay. Also, none of the haplotypes found in Alto Parana match the remaining South American samples, which include admixed populations from Colombia, Peru and Ecuador, and natives from Colombia and Ecuador. FST genetic distance analysis showed that the native genetic background of Alto Parana has an intermediate position between the Amazonian groups and the admixed populations from Peru and Ecuador, supporting the theory about the Amazonian origin of the Tupi-Guarani and, at the same time, showing the influence of other linguistic groups.

During the preparation of [68Ga]Ga-NOTA-sdAb at high activity, degradation of the tracers was observed, impacting the radiochemical purity (RCP). Increasing starting activities in radiolabelings is often paired with increased degradation of the tracer due to the formation of free radical species, a process known as radiolysis. Radical scavengers and antioxidants can act as radioprotectant due to their fast interaction with formed radicals and can therefore reduce the degree of radiolysis. This study aims to optimize a formulation to prevent radiolysis during the labeling of NOTA derivatized single domain antibody (sdAbs) with 68Ga. Gentisic acid, ascorbic acid, ethanol and polyvinylpyrrolidone were tested individually or in combination to find an optimal mix able to prevent radiolysis without adversely influencing the radiochemical purity (RCP) or the functionality of the tracer. RCP and degree of radiolysis were assessed via thin layer chromatography and size exclusion chromatography for up to three hours after radiolabeling. Individually, the radioprotectants showed insufficient efficacy in reducing radiolysis when using high activities of 68Ga, while being limited in amount due to negative impact on radiolabeling of the tracer. A combination of 20% ethanol (VEtOH/VBuffer%) and 5 mg ascorbic acid proved successful in preventing radiolysis during labeling with starting activities up to 1–1.2 GBq of 68Ga, and is able to keep the tracer stable for up to at least 3 h after labeling at room temperature. The prevention of radiolysis by the combination of ethanol and ascorbic acid potentially allows radiolabeling compatibility of NOTA-sdAbs with all currently available 68Ge/68Ga generators. Additionally, a design is proposed to allow the incorporation of the radioprotectant in an ongoing diagnostic kit development for 68Ga labeling of NOTA-sdAbs.

Lyophilization is commonly used in the production of pharmaceutical compounds to increase the stability of the Active Pharmaceutical Ingredient (API) by removing solvents. This study investigates the possibility to lyophilize an anti-HER2 and an anti-MMR single-domain antibody fragment (sdAb)-based precursor as a first step in the development of a diagnostic kit for PET imaging.NOTA-sdAb precursors have been lyophilized with the following formulation: 100 µg NOTA-sdAb in 0.1 M NaOAc (NaOAc), 5% (w/v%) mannitol-sucrose mix at a 2:1 ratio and 0.1 mg/mL polysorbate 80. During development of the formulation and drying cycle, factors such as cake appearance, glass transition temperature and residual moisture were analyzed to ensure qualitative and stable lyophilized samples. Stability studies of lyophilized precursor were conducted up to 18 months after storage at 2-8 °C by evaluating the precursor integrity, aggregation, functionality andThe lyophilized NOTA-anti-HER2 precursor shows consistent stability data in vitro for up to 12 months at 2-8 °C in three separate batches, with results indicating stability even for up to T18m. No aggregation, degradation or activity loss was observed. Radiochemical purity afterA formulation and specific freeze-drying cycle were successfully developed to lyophilize NOTA-sdAb precursors for long-term storage at 2-8 °C. In vivo data show no negative impact of the lyophilization process on the in vivo behavior or functionality of the lyophilized precursor. These results highlight the potential to develop a kit for the preparation of

RESUMO Os falantes interagem através dos recursos linguísticos ao seu dispor para produzir significados ao nível da compreensão do mundo que os rodeia e dos restantes falantes (EGGINS, [1994] 2004, p. 11). O falante conhece, então, um código para cada situação comunicativa e adequa as suas seleções estilísticas ao contexto em que as produz. Neste enquadramento, este artigo exploratório investiga a linguagem tabu do ponto de vista das variáveis do contexto situacional, como propostas por Halliday (1978, [1985] 2014). Segue, por um lado, uma abordagem teórica onde propõe o cruzamento das variáveis do registro com os conceitos de uso marcado e não marcado (HYMES, 1974); e, por outro, aplica esta proposta num corpus escolhido para o efeito. Os resultados, de ordem quantitativa, demonstram o predomínio do uso não marcado da linguagem tabu no corpus. ABSTRACT Language users make use of several linguistic resources to make meanings regarding the world around them as well as others (EGGINS, [1994] 2004, p. 11). The user then recognizes a specific code for each communicative situation and selectively adapts his/her options to the particular context. Against this background, this article sets out to investigate taboo language from the standpoint of Register variables, proposed by Halliday (1978; [1985] 2014). On the one hand, we follow a theoretical approach by proposing an intersection between the register variables and the concept of markedness (HYMES, 1974). On the other hand, we make use of this proposal in a purpose-built corpus. Results show the predominance of the unmarked use of taboo in the corpus.

Although taboo has become an ever-increasing widespread linguistic resource within audiovisual contexts (Sapolsky et al. 2010; Bednarek 2019), and despite the importance sociolinguistic profiles hold in cinematic products, little research has been carried out on the topic.Thus, this study aims at examining the role taboo language plays in the movies. In order to do so, the presentation will combine a theoretical approach - geared towards the cinematic tradition of how taboo is used in the movies, the stereotyping of fictional characters through taboo and the relationship established between the use of taboo and the multimodal and ephemeral nature of cinematic products, with an applied approach – which presents the frequency of taboo words in six North-American movies as well as their functions. Based on the findings, this study suggests that taboo in cinema discourse can be disclosed in two different layers of functions: an intratextual function, concerning the role taboo plays within the narrative; and an extratextual function, related to the role taboo plays beyond the story, i.e. between the movie and the receivers. Further, more detailed, analysis showed that taboo is used intratextually, with an expletive, offensive, social or stylistic function, and, extratextually, with a mimetic, comic or ideological function; the frequency of each will help us characterize taboo in this audiovisual corpus.

DNA methylation is known as a biomarker for age with applications in forensics. Here we describe the VISAGE (VISible Attributes through GEnomics) Consortium’s enhanced tool for epigenetic age estimation in somatic tissues. The tool is based on eight DNA methylation markers (44 CpGs), bisulfite multiplex PCR followed by sequencing on the MiSeq FGx platform, and three statistical prediction models for blood, buccal cells and bones. The model for blood is based on six CpGs from ELOVL2, MIR29B2CHG, KLF14, FHL2, TRIM59 and PDE4C, and predicts age with a mean absolute error (MAE) of 3.2 years, while the model for buccal cells includes five CpGs from PDE4C, MIR29B2CHG, ELOVL2, KLF14 and EDARADD and predicts age with MAE of 3.7 years, and the model for bones has six CpGs from ELOVL2, KLF14, PDE4C and ASPA and predicts age with MAE of 3.4 years. The VISAGE enhanced tool for age estimation in somatic tissues enables reliable collection of DNA methylation data from small amounts of DNA using a sensitive multiplex MPS assay that provides accurate estimation of age in blood, buccal swabs, and bones using the statistical model tailored to each tissue.

Clinical molecular imaging aims to detect particular biological processes, molecules, or cells in the body in a noninvasive manner. Frequently, it employs an imaging device that detects signals that are emitted by tracers. The tracer typically consists of a targeting vehicle that is connected, through a chosen linker chemistry to an imaging moiety. Frequently, the vehicle is of proteinaceous nature, such as a peptide, a small protein, or an antibody. This chapter provides an overview of newer methods to (bio-)conjugate imaging moieties such as chelated radionuclides, to protein vehicles. The focus will be both on the introduction of a conjugation handle on the proteins as well as on the chemistry to link it to the imaging moiety.