Morphological and functional study of cerebral aging in rat

Aging is a physiological process characterized by a progressive decline of the “cellular homeostatic reserve”, refereed as the capability to respond suitably to exogenous and endogenous stressful stimuli. Due to their high energetic requests and post-mitotic nature, neurons are peculiarly susceptible to this phenomenon. However, the aged brain maintains a certain level of adaptive capacities and if properly stimulated may warrant a considerable functional recovery. Aim of the present research was to verify the plastic potentialities of the aging brain of rats subjected to two kind of exogenous stimuli: A) the replacement of the standard diet with a ketogenic regimen (the change forces the brain to use ketone bodies (KB) in alternative to glucose to satisfy the energetic needs) and B) a behavioural task able to induce the formation of inhibitory avoidance memory. A) Fifteen male Wistar rats of 19 months of age were divided into three groups (average body weight pair-matched), and fed for 8 weeks with different dietary regimens: i) diet containing 10% medium chain triglycerides (MCT); ii) diet containing 20% MCT; iii) standard commercial chow. Five young (5 months of age) and five old (26-27 months of age) animals fed with the standard diet were used as further controls. The following morphological parameters reflecting synaptic plasticity were evaluated in the stratum moleculare of the hippocampal CA1 region (SM CA1), in the outer molecular layer of the hippocampal dentate gyrus (OML DG), and in the granule cell layer of the cerebellar cortex (GCL-CCx): average area (S), numeric density (Nvs), and surface density (Sv) of synapses, and average volume (V), numeric density (Nvm), and volume density (Vv) of synaptic mitochondria. Moreover, succinic dehydrogenase (SDH) activity was cytochemically determined in Purkinje cells (PC) and V, Nvm, Vv, and cytochemical precipitate area/mitochondrial area (R) of SDH-positive mitochondria were evaluated. In SM CA1, MCT-KDs induced the early appearance of the morphological patterns typical of old animals: higher S and V, and lower Nvs and Nvm. On the contrary, in OML DG, Sv and Vv of MCT-KDs-fed rats were higher (as a result of higher Nvs and Nvm) vs. controls; these modifications are known to improve synaptic function and metabolic supply. The opposite effects of MCT-KDs might reflect the different susceptibility of these brain regions to the aging processes: OML DG is less vulnerable than SM CA1, and the reactivation of ketone bodies uptake and catabolism might occur more efficiently in this region, allowing the exploitation of their peculiar metabolic properties. In GCL-CCx, the results described a new scenario in comparison to that found in the hippocampal formation: 10%MCT-KD induced the early appearance of senescent patterns (decreased Nvs and Nvm; increased V), whereas 20%MCT-KD caused no changes. Since GCL-CCx is more vulnerable to age than DG, and less than CA1, these data further support the hypothesis that MCT-KDs effects in the aging brain critically depend on neuronal vulnerability to age, besides MCT percentage. Regarding PC, it was decided to evaluate only the metabolic effect of the dietetic regimen (20%MCT-KD) characterized by less side effects. KD counteracted age-related decrease in numeric density of SDH-positive mitochondria, and enhanced their energetic efficiency (R was significantly higher in MCT-KD-fed rats vs. all the controls). Since it is well known that Purkinje and dentate gyrus cells are less vulnerable to aging than CA1 neurons, these results corroborate our previous hypothesis. In conclusion, the A) experimental line provides the first evidence that morphological and functional parameters reflecting synaptic plasticity and mitochondrial metabolic competence may be modulated by MCT-KDs in the pre-senescent central nervous system, and that the effects may be heterogeneous in different brain regions. MCT-KDs seem to supply high energy metabolic intermediates and to be beneficial (“anti-aging”) for those neurons that maintain the capability to exploit them. This implies risks but also promising potentialities for the therapeutic use of these diets during aging B) Morphological parameters of synapses and synaptic mitochondria in SM CA1 were investigated in old (26-27 month-old) female Wistar rats following a single trial inhibitory avoidance task. In this memory protocol animals learn to avoid a dark compartment in which they received a mild, inescapable foot-shock. Rats were tested 3 and 6 or 9 hours after the training, divided into good and bad responders according to their performance (retention times above or below 100 s, respectively) and immediately sacrificed. Nvs, S, Sv, Nvm, V, and Vv were evaluated. In the good responder group, the numeric density of synapses and mitochondria was significantly higher and the average mitochondrial volume was significantly smaller 9 hours vs. 6 hours after the training. No significant differences were observed among bad responders. Thus, better performances in passive avoidance memory task are correlated with more efficient plastic remodeling of synaptic contacts and mitochondria in hippocampal CA1. These findings indicate that maintenance of synaptic plastic reactivity during aging is a critical requirement for preserving long-term memory consolidation.

Adaptive wireless multimedia communication systems

In recent years, due to the rapid convergence of multimedia services, Internet and wireless communications, there has been a growing trend of heterogeneity (in terms of channel bandwidths, mobility levels of terminals, end-user quality-of-service (QoS) requirements) for emerging integrated wired/wireless networks. Moreover, in nowadays systems, a multitude of users coexists within the same network, each of them with his own QoS requirement and bandwidth availability. In this framework, embedded source coding allowing partial decoding at various resolution is an appealing technique for multimedia transmissions. This dissertation includes my PhD research, mainly devoted to the study of embedded multimedia bitstreams in heterogenous networks, developed at the University of Bologna, advised by Prof. O. Andrisano and Prof. A. Conti, and at the University of California, San Diego (UCSD), where I spent eighteen months as a visiting scholar, advised by Prof. L. B. Milstein and Prof. P. C. Cosman. In order to improve the multimedia transmission quality over wireless channels, joint source and channel coding optimization is investigated in a 2D time-frequency resource block for an OFDM system. We show that knowing the order of diversity in time and/or frequency domain can assist image (video) coding in selecting optimal channel code rates (source and channel code rates). Then, adaptive modulation techniques, aimed at maximizing the spectral efficiency, are investigated as another possible solution for improving multimedia transmissions. For both slow and fast adaptive modulations, the effects of imperfect channel estimation errors are evaluated, showing that the fast technique, optimal in ideal systems, might be outperformed by the slow adaptive modulation, when a real test case is considered. Finally, the effects of co-channel interference and approximated bit error probability (BEP) are evaluated in adaptive modulation techniques, providing new decision regions concepts, and showing how the widely used BEP approximations lead to a substantial loss in the overall performance.

Study of molecular mechanisms in cardio- and neuroprotection and possibility of modulation by nutraceutical phytocomponents

Ischemic preconditioning is a complex cardioprotective phenomenon that involves adaptive changes in cells and molecules. This adaptation occurs in a biphasic pattern: an early phase which develops after 1-2 h, and a late phase that develops after 12-24 h. While it is widely accepted that reactive oxygen species (ROS) are strongly involved in triggering ischemic preconditiong, it is not clear if they play a major role in the early or late phase of preconditioning and which are the mechanisms involved. Methylglyoxal, a metabolic compound formed mainly from the glycolytic intermediate glyceraldehyde-3-phosphate., is a precursor of advanced glycation end product (AGEs) .It is more reactive than glucose and shows a stronger ability to cross-link with protein amino groups to form AGEs. Methylglyoxal induced cytotoxicity may be at least partially responsible for cardiovascular and Alzheimer diseases. Methylglyoxal omeostasis is controlled by the glyoxalase system that consists of two enzyme, glyoxalase 1 (GLO1) and glyoxalase 2. In a recent study it was demonstrated that the transcriptional levels of GLO1 are controlled by NF-E2-related factor 2 (Nrf2). The isothiocyanate sulforaphane, derived from the hydrolysis of glucoraphanin abundantly present in broccoli, represents one of the most potent inducers of phase II enzymes through the Keap1–Nrf2 pathway. The aim of this thesis was evaluated molecular mechanisms in cardio- and neuroprotection and the possibility of modulation by nutraceutical phytocomponents This thesis show to one side that the protection induced by H2O2 is mediated by detoxifying and antioxidant phase II enzymes induction, regulated, not only by transcriptional factor Nrf2, but also by Nrf1; on the other side our data represent an innovative result because for the first time it was demonstrated the possibility of inducing GLO1 by SF supplementation.

The phenomenological experiences of Autobiographical Memory: A cross-sectional and a longitudinal study

Phenomenology is a critical component of autobiographical memory retrieval. Some memories are vivid and rich in sensory details whereas others are faded; some memories are experienced as emotionally intense whereas others are not. Sutin and Robins (2007) identified 10 dimensions in which a memory may vary—i.e., Vividness, Coherence, Accessibility, Sensory Details, Emotional Intensity, Visual Perspective, Time Perspective, Sharing, Distancing, and Valence—and developed a comprehensive psychometrically sound measure of memory phenomenology, the Memory Experiences Questionnaire (MEQ). Phenomenology has been linked to underlining stable dispositions—i.e. personality, as well as to a variety of positive/negative psychological outcomes—well-being and life satisfaction, depression and anxiety, among others. Using the MEQ, a cross-sectional and a longitudinal study were conducted on a large sample of American and Italian adults. In both studies, participants retrieved two ‘key’ personal memories, a Turning Point and a Childhood Memory, and rated the affect and phenomenology of each memory. Participants also completed self-reported measures of personality (i.e. Neuroticism and Conscientiousness), and measures of depression, well-being and life satisfaction. The present research showed that phenomenological ratings tend (a) to cross-sectionally increase across adulthood (Study 1), and (b) to be moderately stable over time, regardless the contents of the memories (Study 2). Interrelations among memory phenomenology, personality and psychological outcome variables were also examined (Study 1 and Study 2). In particular, autobiographical memory phenomenology was proposed as a dynamic expression of personality functioning that partially explains adaptive/maladaptive psychological outcomes. In fact, the findings partially supported the hypothesized mediating effect of phenomenology on the personality association with psychological outcomes. Implications of the findings are discussed proposing future lines of research. In particular, the need for more longitudinal studies is highlighted, along with the combined application of both self-report questionnaires and narrative measures.

Adaptive Neural Translation for Enterprises (ANTE). La traduzione automatica neurale a sostegno delle imprese emiliano-romagnole

Il progetto ANTE riguarda i nuovi sistemi di traduzione automatica (TA) e la loro applicazione nel mondo delle imprese. Lo studio prende spunto dai recenti sviluppi legati all’intelligenza artificiale e ai Big Data che negli ultimi anni hanno permesso alla TA di raggiungere livelli qualitativi molto elevati, al punto tale da essere impiegata da grandi multinazionali per raggiungere nuove quote di mercato. La TA può rispondere positivamente anche ai bisogni delle imprese di piccole dimensioni e a basso tenore tecnologico, migliorando la qualità delle comunicazioni multilingue attraverso delle traduzioni in tempi brevi e a costi contenuti. Lo studio si propone quindi di contribuire al rafforzamento della competitività internazionale delle piccole e medie imprese (PMI) emiliano- romagnole, migliorando la loro capacità di comunicazione in una o più lingue straniere attraverso l’introduzione e l’utilizzo efficace e consapevole di soluzioni ICT di ultima generazione e fornire, così, nuove opportunità di internazionalizzazione.

1° level of automation: the effectiveness of adaptive cruise control on driving and visual behaviour

The research activities have allowed the analysis of the driver assistance systems, called Advanced Driver Assistance Systems (ADAS) in relation to road safety. The study is structured according to several evaluation steps, related to definite on-site tests that have been carried out with different samples of users, according to their driving experience with the ACC. The evaluation steps concern: •The testing mode and the choice of suitable instrumentation to detect the driver’s behaviour in relation to the ACC. •The analysis modes and outputs to be obtained, i.e.: - Distribution of attention and inattention; - Mental workload; - The Perception-Reaction Time (PRT), the Time To Collision (TTC) and the Time Headway (TH). The main purpose is to assess the interaction between vehicle drivers and ADAS, highlighting the inattention and variation of the workloads they induce regarding the driving task. The research project considered the use of a system for monitoring visual behavior (ASL Mobile Eye-XG - ME), a powerful GPS that allowed to record the kinematic data of the vehicle (Racelogic Video V-BOX) and a tool for reading brain activity (Electroencephalographic System - EEG). Just during the analytical phase, a second and important research objective was born: the creation of a graphical interface that would allow exceeding the frame count limit, making faster and more effective the labeling of the driver’s points of view. The results show a complete and exhaustive picture of the vehicle-driver interaction. It has been possible to highlight the main sources of criticalities related to the user and the vehicle, in order to concretely reduce the accident rate. In addition, the use of mathematical-computational methodologies for the analysis of experimental data has allowed the optimization and verification of analytical processes with neural networks that have made an effective comparison between the manual and automatic methodology.

Response times in computerized adaptive testing: a method for cheating detection

In the field of educational and psychological measurement, the shift from paper-based to computerized tests has become a prominent trend in recent years. Computerized tests allow for more complex and personalized test administration procedures, like Computerized Adaptive Testing (CAT). CAT, following the Item Response Theory (IRT) models, dynamically generates tests based on test-taker responses, driven by complex statistical algorithms. Even if CAT structures are complex, they are flexible and convenient, but concerns about test security should be addressed. Frequent item administration can lead to item exposure and cheating, necessitating preventive and diagnostic measures. In this thesis a method called "CHeater identification using Interim Person fit Statistic" (CHIPS) is developed, designed to identify and limit cheaters in real-time during test administration. CHIPS utilizes response times (RTs) to calculate an Interim Person fit Statistic (IPS), allowing for on-the-fly intervention using a more secret item bank. Also, a slight modification is proposed to overcome situations with constant speed, called Modified-CHIPS (M-CHIPS). A simulation study assesses CHIPS, highlighting its effectiveness in identifying and controlling cheaters. However, it reveals limitations when cheaters possess all correct answers. The M-CHIPS overcame this limitation. Furthermore, the method has shown not to be influenced by the cheaters’ ability distribution or the level of correlation between ability and speed of test-takers. Finally, the method has demonstrated flexibility for the choice of significance level and the transition from fixed-length tests to variable-length ones. The thesis discusses potential applications, including the suitability of the method for multiple-choice tests, assumptions about RT distribution and level of item pre-knowledge. Also limitations are discussed to explore future developments such as different RT distributions, unusual honest respondent behaviors, and field testing in real-world scenarios. In summary, CHIPS and M-CHIPS offer real-time cheating detection in CAT, enhancing test security and ability estimation while not penalizing test respondents.