Co-evolution of mutagenic genome deditors and vertebrate adaptive immunity

The adaptive immune systems of all vertebrates rely on self-DNA mutating enzymes to assemble their antigen receptors in lymphocytes of their two principal lineages. In jawed vertebrates, the RAG1/2 recombinase directs V(D)J recombination of B cell and T cell receptor genes, whereas the activation-induced cytidine deaminase AID engages in their secondary modification. The recombination activating genes (RAG) 1 and 2 evolved from an ancient transposon-encoded genome modifier into a self-DNA mutator serving adaptive immunity; this was possible as a result of domestication, involving several changes in RAG1 and RAG2 proteins suppressing transposition and instead facilitating-coupled cleavage and recombination. By contrast, recent evidence supports the notion that the antigen receptors of T-like and B-like cells of jawless vertebrates, designated variable lymphocyte receptors (VLRs), are somatically assembled through a process akin to gene conversion that is believed to be dependent on the activities of distant relatives of AID, the cytidine deaminases CDA1 and CDA2, respectively. It appears, therefore, that the precursors of AID and CDAs underwent a domestication process that changed their target range from foreign nucleic acids to self-DNA; this multi-step evolutionary process ensured that the threat to host genome integrity was minimized. Here, we review recent findings illuminating the evolutionary steps associated with the domestication of the two groups of genome editors, RAG1/2 and cytidine deaminases, indicating how they became the driving forces underlying the emergence of vertebrate adaptive immune systems

Prosodic exercises for children with ASD via virtual therapy

which means that there is a wide degree of variation in the way it affects people. It is known that, even though it has a huge spectrum, the characterization of the speech of autistic children has been consensual in the literature as devoid of wealth prosodic parameters manifested by healthy children, such as the emotional aspects that are reflected in communicative interaction. The use of technology as a teaching tool has been growing and the presentation of educational exercises through electronic devices reveals itself as more attractive and captivating for children when compared with traditional methods. In this project, we developed prosodic exercises for intonation assessment in an imitation task, where the main focus is the development and enrichment of prosodic abilities of children with autism spectrum disorders, as a complement to therapy sessions.We evaluated the intonation assessment method, achieving accuracy values between 70%and 83.3%, depending on the feature set adapted (pitch, energy, Mel-Frequency Cepstral features, and pseudo-syllable information), and also by making a fusion of all features. Although the original intention was to integrate these exercises in an existing platform for children diagnosed with ASD, the current implementation is a stand-alone mobile application.info:eu-repo/semantics/publishedVersio

Recovering capitalization and punctuation marks for automatic speech recognition: case study for Portuguese broadcast news

The following material presents a study about recovering punctuation marks, and capitalization information from European Portuguese broadcast news speech transcriptions. Different approaches were tested for capitalization, both generative and discriminative, using: finite state transducers automatically built from language models; and maximum entropy models. Several resources were used, including lexica, written newspaper corpora and speech transcriptions. Finite state transducers produced the best results for written newspaper corpora, but the maximum entropy approach also proved to be a good choice, suitable for the capitalization of speech transcriptions, and allowing straightforward on-the-fly capitalization. Evaluation results are presented both for written newspaper corpora and for broadcast news speech transcriptions. The frequency of each punctuation mark in BN speech transcriptions was analyzed for three different languages: English, Spanish and Portuguese. The punctuation task was performed using a maximum entropy modeling approach, which combines different types of information both lexical and acoustic. The contribution of each feature was analyzed individually and separated results for each focus condition are given, making it possible to analyze the performance differences between planned and spontaneous speech. All results were evaluated on speech transcriptions of a Portuguese broadcast news corpus. The benefits of enriching speech recognition with punctuation and capitalization are shown in an example, illustrating the effects of described experiments into spoken texts.info:eu-repo/semantics/acceptedVersio

Extending automatic transcripts in a unified data representation towards a prosodic-based metadata annotation and evaluation

This paper describes a framework that extends automatic speech transcripts in order to accommodate relevant information coming from manual transcripts, the speech signal itself, and other resources, like lexica. The proposed framework automatically collects, relates, computes, and stores all relevant information together in a self-contained data source, making it possible to easily provide a wide range of interconnected information suitable for speech analysis, training, and evaluating a number of automatic speech processing tasks. The main goal of this framework is to integrate different linguistic and paralinguistic layers of knowledge for a more complete view of their representation and interactions in several domains and languages. The processing chain is composed of two main stages, where the first consists of integrating the relevant manual annotations in the speech recognition data, and the second consists of further enriching the previous output in order to accommodate prosodic information. The described framework has been used for the identification and analysis of structural metadata in automatic speech transcripts. Initially put to use for automatic detection of punctuation marks and for capitalization recovery from speech data, it has also been recently used for studying the characterization of disfluencies in speech. It was already applied to several domains of Portuguese corpora, and also to English and Spanish Broadcast News corpora

Acoustic-prosodic entrainment in structural metadata events

This paper presents an acoustic-prosodic analysis of entrain- ment in a Portuguese map-task corpus. Our aim is to ana- lyze how turn-by-turn entrainment varies with distinct structural metadata events: types of sentence-like units (SU) in consecu- tive turns (e.g. interrogatives followed by declaratives, or both declaratives), and with the presence of discourse markers, affir- mative cue words, and disfluencies in the beginning of turns. Entrainment at turn-exchanges may be observed in terms of pitch, energy, duration, and voice quality. Regarding SU types, question-answer turns are the ones with stronger similarity, and declarative-interrogative pairs are the ones where less entrain- ment occurs, as expected. Moreover, in question-answer pairs, there is also stronger evidence of entrainment with Yes/No and Tag questions than with Wh- questions. In fact, these subtypes are coded in distinctive prosodic ways (moreover, the first sub- type has no associated lexical-syntactic cues in Portuguese, only prosodic). As for turn-initial structures, entrainment is stronger when the second turn begins with an affirmative cue word; less strong with ambiguous structures (such as ‘OK’), emphatic af- firmative answers, and negative answers; and scarce with dis- fluencies and discourse markers. The different degrees of local entrainment may be related with the informative structure of distinct structural metadata events.info:eu-repo/semantics/publishedVersio

Reconstruction of delayed scleral flap melting with bovine pericardium after trabeculectomy with mitomycin C.

Aim: To present a challenging case of hypotony after trabeculectomy and its treatment. Case description: A 22-year-old woman with juvenile glaucoma underwent a conventional trabeculectomy with mitomycin C on the right eye (OD). In the immediate postoperative period, we observed a hyperfiltration bleb with hypotony refractory to conservative measures leading to hypotony maculopathy. A surgical revision with scleral flap resuture and conjunctival graft was performed with a satisfactory result and resolution of hypotony maculopathy. After two years, the patient complained of low visual acuity (VA) of the OD. During examination, we observed a fine and avascular bleb with Seidel and visualization of the underlying uveal tissue, an intraocular pressure (IOP) of 5 mmHg, and chorioretinal folds. A new revision of the trabeculectomy was performed. During the procedure, it was not possible to identify the scleral flap, so the fistula was closed with a patch of collagenous membrane derived from bovine pericardium (Tutopatch® graft). A good clinical evolution occurred. After 2 months, IOP was 15 mmHg without Seidel or changes in the fundus and VA was 20/20. After 8 months of follow-up, the IOP remains stable without further complaints. Conclusion: This case illustrates the difficulties faced in the management of a common complication of trabeculectomy and highlights some of the options available for its treatment. There are few reports of scleral melting after trabeculectomy. However, trauma and scleral necrosis associated with mitomycin are listed as the main causes. The use of a scleral patch derived from bovine pericardium allows effective suturing and closure of the aqueous leak.info:eu-repo/semantics/publishedVersio

Comparing different machine learning approaches for disfluency structure detection in a corpus of university lectures

This paper presents a number of experiments focusing on assessing the performance of different machine learning methods on the identification of disfluencies and their distinct structural regions over speech data. Several machine learning methods have been applied, namely Naive Bayes, Logistic Regression, Classification and Regression Trees (CARTs), J48 and Multilayer Perceptron. Our experiments show that CARTs outperform the other methods on the identification of the distinct structural disfluent regions. Reported experiments are based on audio segmentation and prosodic features, calculated from a corpus of university lectures in European Portuguese, containing about 32h of speech and about 7.7% of disfluencies. The set of features automatically extracted from the forced alignment corpus proved to be discriminant of the regions contained in the production of a disfluency. This work shows that using fully automatic prosodic features, disfluency structural regions can be reliably identified using CARTs, where the best results achieved correspond to 81.5% precision, 27.6% recall, and 41.2% F-measure. The best results concern the detection of the interregnum, followed by the detection of the interruption point.info:eu-repo/semantics/publishedVersio

Speaker age estimation for elderly speech recognition in European Portuguese

Phone-like acoustic models (AMs) used in large-vocabulary automatic speech recognition (ASR) systems are usually trained with speech collected from young adult speakers. Using such models, ASR performance may decrease by about 10% absolute when transcribing elderly speech. Ageing is known to alter speech production in ways that require ASR systems to be adapted, in particular at the level of acoustic modeling. In this study, we investigated automatic age estimation in order to select age-specific adapted AMs. A large corpus of read speech from European Portuguese speakers aged 60 or over was used. Age estimation (AE) based on i-vectors and support vector regression achieved mean error rates of about 4.2 and 4.5 years for males and females, respectively. Compared with a baseline ASR system with AMs trained using young adult speech and a WER of 13.9%, the selection of five-year-range adapted AMs, based on the estimated age of the speakers, led to a decrease in WER of about 9.3% relative (1.3% absolute). Comparable gains in ASR performance were observed when considering two larger age ranges (60-75 and 76-90) instead of six five-year ranges, suggesting that it would be sufficient to use the two large ranges only.info:eu-repo/semantics/acceptedVersio

Cross-domain analysis of discourse markers in European Portuguese

This paper presents an analysis of discourse markers in two spontaneous speech corpora for European Portuguese - university lectures and map-task dialogues - and also in a collection of tweets, aiming at contributing to their categorization, scarcely existent for European Portuguese. Our results show that the selection of discourse markers is domain and speaker dependent. We also found that the most frequent discourse markers are similar in all three corpora, despite tweets containing discourse markers not found in the other two corpora. In this multidisciplinary study, comprising both a linguistic perspective and a computational approach, discourse markers are also automatically discriminated from other structural metadata events, namely sentence-like units and disfluencies. Our results show that discourse markers and disfluencies tend to co-occur in the dialogue corpus, but have a complementary distribution in the university lectures. We used three acoustic-prosodic feature sets and machine learning to automatically distinguish between discourse markers, disfluencies and sentence-like units. Our in-domain experiments achieved an accuracy of about 87% in university lectures and 84% in dialogues, in line with our previous results. The eGeMAPS features, commonly used for other paralinguistic tasks, achieved a considerable performance on our data, especially considering the small size of the feature set. Our results suggest that turn-initial discourse markers are usually easier to classify than disfluencies, a result also previously reported in the literature. We conducted a cross-domain evaluation in order to evaluate the robustness of the models across domains. The results achieved are about 11%-12% lower, but we conclude that data from one domain can still be used to classify the same events in the other. Overall, despite the complexity of this task, these are very encouraging state-of-the-art results. Ultimately, using exclusively acoustic-prosodic cues, discourse markers can be fairly discriminated from disfluencies and SUs. In order to better understand the contribution of each feature, we have also reported the impact of the features in both the dialogues and the university lectures. Pitch features are the most relevant ones for the distinction between discourse markers and disfluencies, namely pitch slopes. These features are in line with the wide pitch range of discourse markers, in a continuum from a very compressed pitch range to a very wide one, expressed by total deaccented material or H+L* L* contours, with upstep H tones.info:eu-repo/semantics/publishedVersio

Evolution of thymopoietic microenvironments

In vertebrates, the development of lymphocytes from undifferentiated haematopoietic precursors takes place in so-called primary lymphoid organs, such as the thymus. Therein, lymphocytes undergo a complex differentiation and selection process that culminates in the generation of a pool of mature T cells that collectively express a self-tolerant repertoire of somatically diversified antigen receptors. Throughout this entire process, the microenvironment of the thymus in large parts dictates the sequence and outcome of the lymphopoietic activity. In vertebrates, direct genetic evidence in some species and circumstantial evidence in others suggest that the formation of a functional thymic microenvironment is controlled by members of the Foxn1/4 family of transcription factors. In teleost fishes, both Foxn1 and Foxn4 contribute to thymopoietic activity, whereas Foxn1 is both necessary and sufficient in the mammalian thymus. The evolutionary history of Foxn1/4 genes suggests that an ancient Foxn4 gene lineage gave rise to the Foxn1 genes in early vertebrates, raising the question of the thymopoietic capacity of the ancestor common to all vertebrates. Recent attempts to reconstruct the early events in the evolution of thymopoietic tissues by replacement of the mouse Foxn1 gene by Foxn1-like genes isolated from various chordate species suggest a plausible scenario. It appears that the primordial thymus was a bi-potent lymphoid organ, supporting both B cell and T cell development; however, during the course of vertebrate, evolution B cell development was gradually diminished converting the thymus into a site specialized in T cell development