The influence of actions on auditory perception: cognitive and neural mechanisms

It is well known that self-generated stimuli are processed differently from externally generated stimuli. For example, many people have noticed since childhood that it is very difficult to make a self-tickling. In the auditory domain, self-generated sounds elicit smaller brain responses as compared to externally generated sounds, known as the sensory attenuation (SA) effect. SA is manifested in reduced amplitudes of evoked responses as measured through MEEG, decreased firing rates of neurons and a lower level of perceived loudness for self-generated sounds. The predominant explanation for SA is based on the idea that self-generated stimuli are predicted (e.g., the forward model account). It is the nature of their predictability that is crucial for SA. On the contrary, the sensory gating account emphasizes a general suppressive effect of actions on sensory processing, regardless of the predictability of the stimuli. Both accounts have received empirical support, which suggests that both mechanisms may exist. In chapter 2, three behavioural studies concerning the influence of motor activation on auditory perception were presented. Study 1 compared the effect of SA and attention in an auditory detection task and showed that SA was present even when substantial attention was paid to unpredictable stimuli. Study 2 compared the loudness perception of tones generated by others between Chinese and British participants. Compared to externally generated tones, a decrease in perceived loudness for others generated tones was found among Chinese but not among the British. In study 3, partial evidence was found that even when reading words that are related to action, auditory detection performance was impaired. In chapter 3, the classic SA effect of M100 suppression was replicated with MEG in study 4. With time-frequency analysis, a potential neural information processing sequence was found in auditory cortex. Prior to the onset of self-generated tones, there was an increase of oscillatory power in the alpha band. After the stimulus onset, reduced gamma power and alpha/beta phase locking were found. The three temporally segregated oscillatory events correlated with each other and with SA effect, which may be the underlying neural implementation of SA. In chapter 4, a TMS-MEG study was presented investigating the role of the cerebellum in adapting to delayed presentation of self-generated tones (study 5). It demonstrated that in sham stimulation condition, the brain can adapt to the delay (about 100 ms) within 300 trials of learning by showing a significant increase of SA effect in the suppression of M100, but not M200 component. Whereas after stimulating the cerebellum with a suppressive TMS protocol, the adaptation in M100 suppression disappeared and the pattern of M200 suppression reversed to M200 enhancement. These data support the idea that the suppressive effect of actions on auditory processing is a consequence of both motor driven sensory predictions and general sensory gating. The results also demonstrate the importance of neural oscillations in implementing SA effect and the critical role of the cerebellum in learning sensory predictions under sensory perturbation.

Determining conservation priority areas for Palearctic passerine migrant birds in sub-Saharan Africa

Migratory bird species breeding in the Palearctic and overwintering in sub-Saharan Africa face multiple conservation challenges. As a result, many of these species have declined in recent decades, some dramatically. We therefore used the best available database for the distribution of 68 passerine migrants in sub-Saharan Africa to determine priority regions for their conservation. After modeling each species’ distribution using BIOMOD software, we entered the resulting species distributions at a 1° × 1° grid resolution into MARXAN software. We then used several different selection procedures that varied the boundary length modifier, species penalty factor, and the inclusion of grid cells with high human footprint and with protected areas. While results differed between selection procedures, four main regions were regularly selected: (1) one centered on southern Mali; (2) one including Eritrea, central Sudan, and northern Ethiopia; (3) one encompassing southwestern Kenya and much of Tanzania and Uganda; and (4) one including much of Zimbabwe and southwestern Zambia. We recommend that these four regions become priority regions for research and conservation efforts for the bird species considered in this study.

Design and synthesis of E3 ligase RNF5 inhibitors as innovative strategy to trigger mutant CFTR rescue in Cystic Fibrosis

In Cystic Fibrosis (CF) the deletion of phenylalanine 508 (F508del) in the CFTR anion channel is associated to misfolding and defective gating of the mutant protein. Among the known proteins involved in CFTR processing, one of the most promising drug target is the ubiquitin ligase RNF5, which normally promotes F508del-CFTR degradation. In this context, a small molecule RNF5 inhibitor is expected to chemically mimic a condition of RNF5 silencing, thus preventing mutant CFTR degradation and causing its stabilization and plasma membrane trafficking. Hence, by exploiting a virtual screening (VS) campaign, the hit compound inh-2 was discovered as the first-in-class inhibitor of RNF5. Evaluation of inh-2 efficacy on CFTR rescue showed that it efficiently decreases ubiquitination of mutant CFTR and increases chloride current in human primary bronchial epithelia. Based on the promising biological results obtained with inh-2, this thesis reports the structure-based design of potential RNF5 inhibitors having improved potency and efficacy. The optimization of general synthetic strategies gave access to a library of analogues of the 1,2,4-thiadiazol-5-ylidene inh-2 for SAR investigation. The new analogues were tested for their corrector activity in CFBE41o- cells by using the microfluorimetric HS-YFP assay as a primary screen. Then, the effect of putative RNF5 inhibitors on proliferation, apoptosis and the formation of autophagic vacuoles was evaluated. Some of the new analogs significantly increased the basal level of autophagy, reproducing RNF5 silencing effect in cell. Among them, one compound also displayed a greater rescue of the F508del-CFTR trafficking defect than inh-2. Our preliminary results suggest that the 1,2,4-thiadiazolylidene could be a suitable scaffold for the discovery of potential RNF5 inhibitors able to rescue mutant CFTRs. Biological tests are still ongoing to acquire in-depth knowledge about the mechanism of action and therapeutic relevance of this unprecedented pharmacological strategy.

Nodi sensori LoRaWAN a micropotenze: progettazione hardware, firmware e a livello di applicazione

L'elaborato parte da una scheda di sviluppo commerciale per arrivare a realizzare una rete LoRaWAN comprensiva di End-Node, Gateway e Application Server. In maniera specifica, l'elaborato affronta il problema della progettazione di end-node a micropotenze. Dopo aver studiato e collaudato la piattaforma di sviluppo, è stata affrontata la problematica dell'ottimizzazione energetica a diversi livelli: scelta di componenti con correnti di perdita estremamente ridotte, tecniche di power gating temporizzato, comportamento adattativo del nodo, impostazione dei consumi del nodo mediante i server della rete. L'elaborato presenta infine il layout del PCB progettato, pronto per la fabbricazione, insieme a stime del tempo di vita dell'end-node in funzione della frequenza di trasmissione e della capacità delle batterie utilizzate.

Ampliamento del corpus EPTIC e studio di caso sulla combinazione inglese-finlandese

The goal of this dissertation is both to expand EPTIC, the European Parliament Translation and Interpreting Corpus containing EU Parliament plenary speeches in five different languages, and to carry out a case study on the corpus. The corpus was expanded by adding 52 new speeches in both oral and written form in a language that was not hitherto represented in the corpus i.e., Finnish. The case study focuses on the analysis of the English structure “head noun + of + modifier” interpreted into Finnish with the use of the genitive case. As for several previous case studies, this dissertation shows the potential of a corpus such as EPTIC, despite its limited size. It can be used to expand research in the fields of translation and interpreting, but also for didactic purposes. The dissertation is divided into three chapters. The first offers a theoretical background, by presenting the notion of “corpus,” the different types of corpora – particularly focusing on intermodal corpora – and an overview of corpus-based translation and interpreting studies. The second chapter focuses on the EPTIC corpus i.e., on its development and structure, and it then describes all phases of the construction of the corpus. Finally, the third chapter presents the case study, which is introduced by a description of the genitive case in Finnish and of several strategies used by interpreters to face certain difficulties in simultaneous interpreting. The case study highlights two dimensions of the EPTIC corpus. Each original speech was compared with its interpreted version (parallel dimension), and each interpreted speech was compared with its verbatim report, the written version of the oral speech (intermodal dimension). The results confirm the initial assumption of higher accuracy in translation compared to interpreting of the “of structure” from English into Finnish. Moreover, the use of the genitive case in Finnish is higher among translators than interpreters.

Development of wearable electrochemical sensors for the determination of biological analytes

Wearable biosensors are attracting interest due to their potential to provide continuous, real-time physiological information via dynamic, non-invasive measurements of biochemical markers in biofluids, such as interstitial fluid (ISF). One notable example of their applications is for glycemic monitoring in diabetic patients, which is typically carried out either by direct measurement of blood glucose via finger pricking or by wearable sensors that can continuously monitor glucose in ISF by sampling it from below the skin with a microneedle. In this context, the development of a new and minimally invasive multisensing tattoo-based platform for the monitoring of glucose and other analytes in ISF extracted through reverse iontophoresis in proposed by the GLUCOMFORT project. This elaborate describes the in-vitro development of flexible electrochemical sensors based on inkjet-printed PEDOT:PSS and metal inks that are capable of determining glucose and chloride at biologically relevant concentrations, making them good candidates for application in the GLUCOMFORT platform. In order to make PEDOT:PSS sensitive to glucose at micromolar concentrations, a biocompatible functionalization based on immobilized glucose oxidase and electrodeposited platinum was developed. This functionalization was successfully applied to bulk and flexible amperometric devices, the design of which was also optimized. Using the same strategy, flexible organic electrochemical transistors (OECTs) for glucose sensing were also made and successfully tested. For the sensing of chloride ions, an organic charge-modulated field-effect transistor (OCMFET) featuring a silver/silver chloride modified floating gate electrode was developed and tested.