Chronic Intermittent Hypoxia Depresses Afferent Neurotransmission in NTS Neurons by a Reduction in the Number of Active Synapses

Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autonomic regulation. Here we identified the synaptic mechanisms of CIH-induced depression of the afferent neurotransmission in NTS neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes were observed in release probability, evidenced by absence of any CIH-elicited effects on short-term depression and failures in EPSCs evoked in low calcium. CIH also produced no changes in TS-eEPSC quantal size, since the amplitudes of both low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of Sr2+) were unchanged. Using single TS afferent fiber stimulation in slices from control and CIH rats we clearly show that CIH reduced the quantal content of the TS-eEPSCs without affecting the quantal size or release probability, suggesting a reduction in the number of active synapses as the mechanism of CIH induced TS-eEPSC depression. In accordance with this concept, the input-output relationship of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH animals. These findings open new perspectives for a better understanding of the mechanisms underlying the synaptic plasticity in the brainstem sensory neurons under challenges such as those produced by CIH in experimental and pathological conditions.

Statistical physics approach to dendritic computation: The excitable-wave mean-field approximation

We analytically study the input-output properties of a neuron whose active dendritic tree, modeled as a Cayley tree of excitable elements, is subjected to Poisson stimulus. Both single-site and two-site mean-field approximations incorrectly predict a nonequilibrium phase transition which is not allowed in the model. We propose an excitable-wave mean-field approximation which shows good agreement with previously published simulation results [Gollo et al., PLoS Comput. Biol. 5, e1000402 (2009)] and accounts for finite-size effects. We also discuss the relevance of our results to experiments in neuroscience, emphasizing the role of active dendrites in the enhancement of dynamic range and in gain control modulation.

Exercise training normalizes an increased neuronal excitability of NTS-projecting neurons of the hypothalamic paraventricular nucleus in hypertensive rats

Stern JE, Sonner PM, Son SJ, Silva FC, Jackson K, Michelini LC. Exercise training normalizes an increased neuronal excitability of NTS-projecting neurons of the hypothalamic paraventricular nucleus in hypertensive rats. J Neurophysiol 107: 2912-2921, 2012. First published February 22, 2012; doi:10.1152/jn.00884.2011.-Elevated sympathetic outflow and altered autonomic reflexes, including impaired baroreflex function, are common findings observed in hypertensive disorders. Although a growing body of evidence supports a contribution of preautonomic neurons in the hypothalamic paraventricular nucleus (PVN) to altered autonomic control during hypertension, the precise underlying mechanisms remain unknown. Here, we aimed to determine whether the intrinsic excitability and repetitive firing properties of preautonomic PVN neurons that innervate the nucleus tractus solitarii (PVN-NTS neurons) were altered in spontaneously hypertensive rats (SHR). Moreover, given that exercise training is known to improve and/or correct autonomic deficits in hypertensive conditions, we evaluated whether exercise is an efficient behavioral approach to correct altered neuronal excitability in hypertensive rats. Patch-clamp recordings were obtained from retrogradely labeled PVN-NTS neurons in hypothalamic slices obtained from sedentary (S) and trained (T) Wistar-Kyoto (WKY) and SHR rats. Our results indicate an increased excitability of PVN-NTS neurons in SHR-S rats, reflected by an enhanced input-output function in response to depolarizing stimuli, a hyperpolarizing shift in Na+ spike threshold, and smaller hyperpolarizing afterpotentials. Importantly, we found exercise training in SHR rats to restore all these parameters back to those levels observed in WKY-S rats. In several cases, exercise evoked opposing effects in WKY-S rats compared with SHR-S rats, suggesting that exercise effects on PVN-NTS neurons are state dependent. Taken together, our results suggest that elevated preautonomic PVN-NTS neuronal excitability may contribute to altered autonomic control in SHR rats and that exercise training efficiently corrects these abnormalities.

Plantar flexion force induced by amplitude-modulated tendon vibration and associated soleus V/F-waves as an evidence of a centrally-mediated mechanism contributing to extra torque generation in humans

Background: High-frequency trains of electrical stimulation applied over the human muscles can generate forces higher than would be expected by direct activation of motor axons, as evidenced by an unexpected relation between the stimuli and the evoked contractions, originating what has been called “extra forces”. This phenomenon has been thought to reflect nonlinear input/output neural properties such as plateau potential activation in motoneurons. However, more recent evidence has indicated that extra forces generated during electrical stimulation are mediated primarily, if not exclusively, by an intrinsic muscle property, and not from a central mechanism as previously thought. Given the inherent differences between electrical and vibratory stimuli, this study aimed to investigate: (a) whether the generation of vibration-induced muscle forces results in an unexpected relation between the stimuli and the evoked contractions (i.e. extra forces generation) and (b) whether these extra forces are accompanied by signs of a centrally-mediated mechanism or whether intrinsic muscle properties are the redominant mechanisms. Methods: Six subjects had their Achilles tendon stimulated by 100 Hz vibratory stimuli that linearly increased in amplitude (with a peak-to-peak displacement varying from 0 to 5 mm) for 10 seconds and then linearly decreased to zero for the next 10 seconds. As a measure of motoneuron excitability taken at different times during the vibratory stimulation, short-latency compound muscle action potentials (V/F-waves) were recorded in the soleus muscle in response to supramaximal nerve stimulation. Results: Plantar flexion torque and soleus V/F-wave amplitudes were increased in the second half of the stimulation in comparison with the first half. Conclusion: The present findings provide evidence that vibratory stimuli may trigger a centrally-mediated mechanism that contributes to the generation of extra torques. The vibration-induced increased motoneuron excitability (leading to increased torque generation) presumably activates spinal motoneurons following the size principle, which is a desirable feature for stimulation paradigms involved in rehabilitation programs and exercise training.

Sviluppo di metodologie per l'analisi in tempo reale delle prestazioni di un motore automobilistico

Durante il periodo di dottorato, l’attività di ricerca di cui mi sono occupato è stata finalizzata allo sviluppo di metodologie per la diagnostica e l’analisi delle prestazioni di un motore automobilistico. Un primo filone di ricerca è relativo allo sviluppo di strategie per l’identificazione delle mancate combustioni (misfires) in un motore a benzina. La sperimentazione si è svolta nella sala prove della Facoltà di Ingegneria dell’Università di Bologna, nei quali è presente un motore Fiat 1.200 Fire, accoppiato ad un freno a correnti parassite, e comandato da una centralina virtuale, creata mediante un modello Simulink, ed interfacciata al motore tramite una scheda di input/output dSpace. Per quanto riguarda la campagna sperimentale, sono stati realizzati delle prove al banco in diverse condizioni di funzionamento (sia stazionarie, che transitorie), durante le quali sono stati indotti dei misfires, sia singoli che multipli. Durante tali test sono stati registrati i segnali provenienti sia dalla ruota fonica usata per il controllo motore (che, nel caso in esame, era affacciata al volano), sia da quella collegata al freno a correnti parassite. Partendo da tali segnali, ed utilizzando un modello torsionale del sistema motoregiunto-freno, è possibile ottenere una stima sia della coppia motrice erogata dal motore, sia della coppia resistente dissipata dal freno. La prontezza di risposta di tali osservatori è tale da garantirci la possibilità di effettuare una diagnosi misfire. In particolare, si è visto che l’indice meglio correlato ala mancata combustione risultaessere la differenza fra la coppia motrice e la coppia resistente; tale indice risulta inoltre essere quello più semplice da calibrare sperimentalmente, in quanto non dipende dalle caratteristiche del giunto, ma solamente dalle inerzie del sistema. Una seconda attività della quale mi sono occupato è relativa alla stima della coppia indicata in un motore diesel automobilistico. A tale scopo, è stata realizzata una campagna sperimentale presso i laboratori della Magneti Marelli Powertrain (Bologna), nella quale sono state effettuati test in molteplici punti motori, sia in condizioni di funzionamento “nominale”, sia variando artificiosamente alcuni dei fattori di controllo (quali Start of Injection, pressione nel rail e, nei punti ove è stato possibile, tasso di EGR e pressione di sovralimentazione), sia effettuando degli sbilanciamenti di combustibile fra un cilindro e l’altro. Utilizzando il solo segnale proveniente da una ruota fonica posta sul lato motore, e sfruttando un modello torsionale simile a quello utilizzato nella campagna di prove relativa alla diagnosi del misfire, è possibile correlare la componente armonica con frequenza di combustione della velocità all’armonica di pari ordine della coppia indicata; una volta stimata tale componente in frequenza, mediante un’analisi di tipo statistico, è possibile eseguire una stima della coppia indicata erogata dal motore. A completamento dell’algoritmo, sfruttando l’analisi delle altre componenti armoniche presenti nel segnale, è possibile avere una stima dello sbilanciamento di coppia fra i vari cilindri. Per la verifica dei risultati ottenuti, sono stati acquisiti i segnali di pressione provenienti da tutti e quattro i cilindri del motore in esame.

I dati metereologici per applicazioni energetiche e ambientali

Many energetic and environmental evaluations need appropriate meteorological data, as input to analysis and prevision softwares. In Italy there aren't adeguate meteorological data because, in many cases, they are incomplete, incorrect and also very expensive for a long-term analysis (that needs multi-year data sets). A possible solution to this problem is the use of a Typical Meteorological Year (TRY), generated for specific applications. Nowadays the TRYs have been created, using statistical criteria, just for the analysis of solar energy systems and for predicting the thermal performance of buildings, applying it also to the study of photovoltaic plants (PV), though not specifically created for this type of application. The present research has defined the methodology for the creation of TRYs for different applications. In particular TRYs for environmental and wind plant analysis have been created. This is the innovative aspect of this research, never explored before. In additions, the methodology of the generation for the PV TRYs has been improved. The results are very good and the TRYs generated for these applications are adeguate to characterize the climatic condition of the place over a long period and can be used for energetic and environmental studies.

Sicurezza di rete, analisi del traffico e monitoraggio.

Il lavoro è stato suddiviso in tre macro-aree. Una prima riguardante un'analisi teorica di come funzionano le intrusioni, di quali software vengono utilizzati per compierle, e di come proteggersi (usando i dispositivi che in termine generico si possono riconoscere come i firewall). Una seconda macro-area che analizza un'intrusione avvenuta dall'esterno verso dei server sensibili di una rete LAN. Questa analisi viene condotta sui file catturati dalle due interfacce di rete configurate in modalità promiscua su una sonda presente nella LAN. Le interfacce sono due per potersi interfacciare a due segmenti di LAN aventi due maschere di sotto-rete differenti. L'attacco viene analizzato mediante vari software. Si può infatti definire una terza parte del lavoro, la parte dove vengono analizzati i file catturati dalle due interfacce con i software che prima si occupano di analizzare i dati di contenuto completo, come Wireshark, poi dei software che si occupano di analizzare i dati di sessione che sono stati trattati con Argus, e infine i dati di tipo statistico che sono stati trattati con Ntop. Il penultimo capitolo, quello prima delle conclusioni, invece tratta l'installazione di Nagios, e la sua configurazione per il monitoraggio attraverso plugin dello spazio di disco rimanente su una macchina agent remota, e sui servizi MySql e DNS. Ovviamente Nagios può essere configurato per monitorare ogni tipo di servizio offerto sulla rete.

Role of nitric oxide and endocannabinoids in synaptic plasticity in the perirhinal cortex and in visual recognition memory

Introduction and aims of the research Nitric oxide (NO) and endocannabinoids (eCBs) are major retrograde messengers, involved in synaptic plasticity (long-term potentiation, LTP, and long-term depression, LTD) in many brain areas (including hippocampus and neocortex), as well as in learning and memory processes. NO is synthesized by NO synthase (NOS) in response to increased cytosolic Ca2+ and mainly exerts its functions through soluble guanylate cyclase (sGC) and cGMP production. The main target of cGMP is the cGMP-dependent protein kinase (PKG). Activity-dependent release of eCBs in the CNS leads to the activation of the Gαi/o-coupled cannabinoid receptor 1 (CB1) at both glutamatergic and inhibitory synapses. The perirhinal cortex (Prh) is a multimodal associative cortex of the temporal lobe, critically involved in visual recognition memory. LTD is proposed to be the cellular correlate underlying this form of memory. Cholinergic neurotransmission has been shown to play a critical role in both visual recognition memory and LTD in Prh. Moreover, visual recognition memory is one of the main cognitive functions impaired in the early stages of Alzheimer’s disease. The main aim of my research was to investigate the role of NO and ECBs in synaptic plasticity in rat Prh and in visual recognition memory. Part of this research was dedicated to the study of synaptic transmission and plasticity in a murine model (Tg2576) of Alzheimer’s disease. Methods Field potential recordings. Extracellular field potential recordings were carried out in horizontal Prh slices from Sprague-Dawley or Dark Agouti juvenile (p21-35) rats. LTD was induced with a single train of 3000 pulses delivered at 5 Hz (10 min), or via bath application of carbachol (Cch; 50 μM) for 10 min. LTP was induced by theta-burst stimulation (TBS). In addition, input/output curves and 5Hz-LTD were carried out in Prh slices from 3 month-old Tg2576 mice and littermate controls. Behavioural experiments. The spontaneous novel object exploration task was performed in intra-Prh bilaterally cannulated adult Dark Agouti rats. Drugs or vehicle (saline) were directly infused into the Prh 15 min before training to verify the role of nNOS and CB1 in visual recognition memory acquisition. Object recognition memory was tested at 20 min and 24h after the end of the training phase. Results Electrophysiological experiments in Prh slices from juvenile rats showed that 5Hz-LTD is due to the activation of the NOS/sGC/PKG pathway, whereas Cch-LTD relies on NOS/sGC but not PKG activation. By contrast, NO does not appear to be involved in LTP in this preparation. Furthermore, I found that eCBs are involved in LTP induction, but not in basal synaptic transmission, 5Hz-LTD and Cch-LTD. Behavioural experiments demonstrated that the blockade of nNOS impairs rat visual recognition memory tested at 24 hours, but not at 20 min; however, the blockade of CB1 did not affect visual recognition memory acquisition tested at both time points specified. In three month-old Tg2576 mice, deficits in basal synaptic transmission and 5Hz-LTD were observed compared to littermate controls. Conclusions The results obtained in Prh slices from juvenile rats indicate that NO and CB1 play a role in the induction of LTD and LTP, respectively. These results are confirmed by the observation that nNOS, but not CB1, is involved in visual recognition memory acquisition. The preliminary results obtained in the murine model of Alzheimer’s disease indicate that deficits in synaptic transmission and plasticity occur very early in Prh; further investigations are required to characterize the molecular mechanisms underlying these deficits.

A new 3D modelling paradigm for discrete model

Until few years ago, 3D modelling was a topic confined into a professional environment. Nowadays technological innovations, the 3D printer among all, have attracted novice users to this application field. This sudden breakthrough was not supported by adequate software solutions. The 3D editing tools currently available do not assist the non-expert user during the various stages of generation, interaction and manipulation of 3D virtual models. This is mainly due to the current paradigm that is largely supported by two-dimensional input/output devices and strongly affected by obvious geometrical constraints. We have identified three main phases that characterize the creation and management of 3D virtual models. We investigated these directions evaluating and simplifying the classic editing techniques in order to propose more natural and intuitive tools in a pure 3D modelling environment. In particular, we focused on freehand sketch-based modelling to create 3D virtual models, interaction and navigation in a 3D modelling environment and advanced editing tools for free-form deformation and objects composition. To pursuing these goals we wondered how new gesture-based interaction technologies can be successfully employed in a 3D modelling environments, how we could improve the depth perception and the interaction in 3D environments and which operations could be developed to simplify the classical virtual models editing paradigm. Our main aims were to propose a set of solutions with which a common user can realize an idea in a 3D virtual model, drawing in the air just as he would on paper. Moreover, we tried to use gestures and mid-air movements to explore and interact in 3D virtual environment, and we studied simple and effective 3D form transformations. The work was carried out adopting the discrete representation of the models, thanks to its intuitiveness, but especially because it is full of open challenges.

Tecniche di inserimento e visualizzazione di formule matematiche

La tesi enuncia e spiega i vari metodi e le varie tecnologie utilizzate dalle applicazioni web per inserire i dati e visualizzare i risultati. Per ciò che concerne i metodi vengono considerati l'input dei dati (come tastiera, fotocamera, disegni geometrici e scrittura a mano) e la loro renderizzazione (visuale, testuale, grafico, ecc). Vengono infine evidenziate le principali tecnologie relative all'input dei dati (come tastiere virtuali, OCR e inchiostro digitale) e all'output (LaTeX, MathML, MathJax, ecc).

Progetto di un sistema di collaudo per un tag RFID uwb integrato

La tesi è incentrata sul progetto di un PCB in grado di testare il corretto funzionamento del chip GRETA, un integrato dedicato, che implementa un nodo intelligente basato su harvesting RF. L'integrato implementa un sistema innovativo di comunicazione per RFID, che sfrutta la metodologia Green Tagging, per la trasmissione di sequenze RF. Vengono elaborate le diverse fasi di progettazione e di design pcb attraverso un programma di cad. Lo scopo è quello di realizzare un unico sistema perfettamente controllabile dall'utente, che attraverso i componenti messi a disposizione dalla scheda di testing, permetta di ricevere, inviare o escludere i segnali che afferiscono ai pin di Input/output del chip integrato. E' stata introdotta la possibilità di pilotare/testare separatamente le sottoparti interne al chip, con lo scopo di isolare eventuali malfunzionamenti.

Multi-software modeling technique for field distribution propagation through an optical vertical interconnect assembly

Embedded siloxane polymer waveguides have shown promising results for use in optical backplanes. They exhibit high temperature stability, low optical absorption, and require common processing techniques. A challenging aspect of this technology is out-of-plane coupling of the waveguides. A multi-software approach to modeling an optical vertical interconnect (via) is proposed. This approach utilizes the beam propagation method to generate varied modal field distribution structures which are then propagated through a via model using the angular spectrum propagation technique. Simulation results show average losses between 2.5 and 4.5 dB for different initial input conditions. Certain configurations show losses of less than 3 dB and it is shown that in an input/output pair of vias, average losses per via may be lower than the targeted 3 dB.

MARVIN: a medical research application framework based on open source software

This paper describes the open source framework MARVIN for rapid application development in the field of biomedical and clinical research. MARVIN applications consist of modules that can be plugged together in order to provide the functionality required for a specific experimental scenario. Application modules work on a common patient database that is used to store and organize medical data as well as derived data. MARVIN provides a flexible input/output system with support for many file formats including DICOM, various 2D image formats and surface mesh data. Furthermore, it implements an advanced visualization system and interfaces to a wide range of 3D tracking hardware. Since it uses only highly portable libraries, MARVIN applications run on Unix/Linux, Mac OS X and Microsoft Windows.

Transfer Functions in Artificial Neural Networks - A Simulation-Based Tutorial

Artificial neural networks are based on computational units that resemble basic information processing properties of biological neurons in an abstract and simplified manner. Generally, these formal neurons model an input-output behaviour as it is also often used to characterize biological neurons. The neuron is treated as a black box; spatial extension and temporal dynamics present in biological neurons are most often neglected. Even though artificial neurons are simplified, they can show a variety of input-output relations, depending on the transfer functions they apply. This unit on transfer functions provides an overview of different transfer functions and offers a simulation that visualizes the input-output behaviour of an artificial neuron depending on the specific combination of transfer functions.

Tree species and diversity effects on soil water seepage in a tropical plantation

Plant diversity has been shown to influence the water cycle of forest ecosystems by differences in water consumption and the associated effects on groundwater recharge. However, the effects of biodiversity on soil water fluxes remain poorly understood for native tree species plantations in the tropics. Therefore, we estimated soil water fluxes and assessed the effects of tree species and diversity on these fluxes in an experimental native tree species plantation in Sardinilla (Panama). The study was conducted during the wet season 2008 on plots of monocultures and mixtures of three or six tree species. Rainfall and soil water content were measured and evapotranspiration was estimated with the Penman-Monteith equation. Soil water fluxes were estimated using a simple soil water budget model considering water input, output, and soil water and groundwater storage changes and in addition, were simulated using the physically based one-dimensional water flow model Hydrus-1D. In general, the Hydrus simulation did not reflect the observed pressure heads, in that modeled pressure heads were higher compared to measured ones. On the other hand, the results of the water balance equation (WBE) reproduced observed water use patterns well. In monocultures, the downward fluxes through the 200 cm-depth plane were highest below Hura crepitans (6.13 mm day−1) and lowest below Luehea seemannii (5.18 mm day−1). The average seepage rate in monocultures (±SE) was 5.66 ± 0.18 mm day−1, and therefore, significantly higher than below six-species mixtures (5.49 ± 0.04 mm day−1) according to overyielding analyses. The three-species mixtures had an average seepage rate of 5.63 ± 0.12 mm day−1 and their values did not differ significantly from the average values of the corresponding species in monocultures. Seepage rates were driven by the transpiration of the varying biomass among the plots (r = 0.61, p = 0.017). Thus, a mixture of trees with different growth rates resulted in moderate seepage rates compared to monocultures of either fast growing or slow growing tree species. Our results demonstrate that tree-species specific biomass production and tree diversity are important controls of seepage rates in the Sardinilla plantation during the wet season.