A high energy perspective of the co-evolution of black holes and their host galaxies

Thanks to the Chandra and XMM–Newton surveys, the hard X-ray sky is now probed down to a flux limit where the bulk of the X-ray background is almost completely resolved into discrete sources, at least in the 2–8 keV band. Extensive programs of multiwavelength follow-up observations showed that the large majority of hard X–ray selected sources are identified with Active Galactic Nuclei (AGN) spanning a broad range of redshifts, luminosities and optical properties. A sizable fraction of relatively luminous X-ray sources hosting an active, presumably obscured, nucleus would not have been easily recognized as such on the basis of optical observations because characterized by “peculiar” optical properties. In my PhD thesis, I will focus the attention on the nature of two classes of hard X-ray selected “elusive” sources: those characterized by high X-ray-to-optical flux ratios and red optical-to-near-infrared colors, a fraction of which associated with Type 2 quasars, and the X-ray bright optically normal galaxies, also known as XBONGs. In order to characterize the properties of these classes of elusive AGN, the datasets of several deep and large-area surveys have been fully exploited. The first class of “elusive” sources is characterized by X-ray-to-optical flux ratios (X/O) significantly higher than what is generally observed from unobscured quasars and Seyfert galaxies. The properties of well defined samples of high X/O sources detected at bright X–ray fluxes suggest that X/O selection is highly efficient in sampling high–redshift obscured quasars. At the limits of deep Chandra surveys (∼10−16 erg cm−2 s−1), high X/O sources are generally characterized by extremely faint optical magnitudes, hence their spectroscopic identification is hardly feasible even with the largest telescopes. In this framework, a detailed investigation of their X-ray properties may provide useful information on the nature of this important component of the X-ray source population. The X-ray data of the deepest X-ray observations ever performed, the Chandra deep fields, allows us to characterize the average X-ray properties of the high X/O population. The results of spectral analysis clearly indicate that the high X/O sources represent the most obscured component of the X–ray background. Their spectra are harder (G ∼ 1) than any other class of sources in the deep fields and also of the XRB spectrum (G ≈ 1.4). In order to better understand the AGN physics and evolution, a much better knowledge of the redshift, luminosity and spectral energy distributions (SEDs) of elusive AGN is of paramount importance. The recent COSMOS survey provides the necessary multiwavelength database to characterize the SEDs of a statistically robust sample of obscured sources. The combination of high X/O and red-colors offers a powerful tool to select obscured luminous objects at high redshift. A large sample of X-ray emitting extremely red objects (R−K >5) has been collected and their optical-infrared properties have been studied. In particular, using an appropriate SED fitting procedure, the nuclear and the host galaxy components have been deconvolved over a large range of wavelengths and ptical nuclear extinctions, black hole masses and Eddington ratios have been estimated. It is important to remark that the combination of hard X-ray selection and extreme red colors is highly efficient in picking up highly obscured, luminous sources at high redshift. Although the XBONGs do not present a new source population, the interest on the nature of these sources has gained a renewed attention after the discovery of several examples from recent Chandra and XMM–Newton surveys. Even though several possibilities were proposed in recent literature to explain why a relatively luminous (LX = 1042 − 1043erg s−1) hard X-ray source does not leave any significant signature of its presence in terms of optical emission lines, the very nature of XBONGs is still subject of debate. Good-quality photometric near-infrared data (ISAAC/VLT) of 4 low-redshift XBONGs from the HELLAS2XMMsurvey have been used to search for the presence of the putative nucleus, applying the surface-brightness decomposition technique. In two out of the four sources, the presence of a nuclear weak component hosted by a bright galaxy has been revealed. The results indicate that moderate amounts of gas and dust, covering a large solid angle (possibly 4p) at the nuclear source, may explain the lack of optical emission lines. A weak nucleus not able to produce suffcient UV photons may provide an alternative or additional explanation. On the basis of an admittedly small sample, we conclude that XBONGs constitute a mixed bag rather than a new source population. When the presence of a nucleus is revealed, it turns out to be mildly absorbed and hosted by a bright galaxy.

Revisione critica dei risultati e nuovi algoritmi decisionali sulla chirurgia dell'OSAS

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is the periodic reduction or cessation of airflow during sleep. The syndrome is associated whit loud snoring, disrupted sleep and observed apnoeas. Surgery aims to alleviate symptoms of daytime sleepiness, improve quality of life and reduce the signs of sleep apnoea recordered by polysomnography. Surgical intervention for snoring and OSAHS includes several procedures, each designed to increase the patency of the upper airway. Procedures addressing nasal obstruction include septoplasty, turbinectomy, and radiofrequency ablation (RF) of the turbinates. Surgical procedures to reduce soft palate redundancy include uvulopalatopharyngoplasty with or without tonsillectomy, uvulopalatal flap, laser-assisted uvulopalatoplasty, and RF of the soft palate. More significant, however, particularly in cases of severe OSA, is hypopharyngeal or retrolingual obstruction related to an enlarged tongue, or more commonly due to maxillomandibular deficiency. Surgeries in these cases are aimed at reducing the bulk of the tongue base or providing more space for the tongue in the oropharynx so as to limit posterior collapse during sleep. These procedures include tongue-base suspension, genioglossal advancement, hyoid suspension, lingualplasty, and maxillomandibular advancement. We reviewed 269 patients undergoing to osas surgery at the ENT Department of Forlì Hospital in the last decade. Surgery was considered a success if the postoperative apnea/hypopnea index (AHI) was less than 20/h. According to the results, we have developed surgical decisional algorithms with the aims to optimize the success of these procedures by identifying proper candidates for surgery and the most appropriate surgical techniques. Although not without risks and not as predictable as positive airway pressure therapy, surgery remains an important treatment option for patients with obstructive sleep apnea (OSA), particularly for those who have failed or cannot tolerate positive airway pressure therapy. Successful surgery depends on proper patient selection, proper procedure selection, and experience of the surgeon. The intended purpose of medical algorithms is to improve and standardize decisions made in the delivery of medical care, assist in standardizing selection and application of treatment regimens, to reduce potential introduction of errors. Nasal Continuous Positive Airway Pressure (nCPAP) is the recommended therapy for patients with moderate to severe OSAS. Unfortunately this treatment is not accepted by some patient, appears to be poorly tolerated in a not neglible number of subjects, and the compliance may be critical, especially in the long term if correctly evaluated with interview as well with CPAP smart cards analysis. Among the alternative options in Literature, surgery is a long time honoured solution. However until now no clear scientific evidence exists that surgery can be considered a really effective option in OSAHS management. We have design a randomized prospective study comparing MMA and a ventilatory device (Autotitrating Positive Airways Pressure – APAP) in order to understand the real effectiveness of surgery in the management of moderate to severe OSAS. Fifty consecutive previously full informed patients suffering from severe OSAHS were enrolled and randomised into a conservative (APAP) or surgical (MMA) arm. Demographic, biometric, PSG and ESS profiles of the two group were statistically not significantly different. One year after surgery or continuous APAP treatment both groups showed a remarkable improvement of mean AHI and ESS; the degree of improvement was not statistically different. Provided the relatively small sample of studied subjects and the relatively short time of follow up, MMA proved to be in our adult and severe OSAHS patients group a valuable alternative therapeutical tool with a success rate not inferior to APAP.

Entrepreneurial opportunities, capability development and the performance of new firms

This study aims at providing a theoretical framework encompassing the two approaches towards entrepreneurial opportunity (opportunity discovery and opportunity creation) by outlining a trajectory from firm creation to capability development, to firm performance in the short term (firm survival) and the medium/long term (growth rate). A set of empirically testable hypotheses is proposed and tested by performing qualitative analyses on interviews on a small sample of entrepreneurs and event history analysis on a large sample of firms founded in the United States in 2004.

Development of muliplexed analytical methods based on bioluminescent whole-cell biosensors

The subject of this Ph.D. research thesis is the development and application of multiplexed analytical methods based on bioluminescent whole-cell biosensors. One of the main goals of analytical chemistry is multianalyte testing in which two or more analytes are measured simultaneously in a single assay. The advantages of multianalyte testing are work simplification, high throughput, and reduction in the overall cost per test. The availability of multiplexed portable analytical systems is of particular interest for on-field analysis of clinical, environmental or food samples as well as for the drug discovery process. To allow highly sensitive and selective analysis, these devices should combine biospecific molecular recognition with ultrasensitive detection systems. To address the current need for rapid, highly sensitive and inexpensive devices for obtaining more data from each sample,genetically engineered whole-cell biosensors as biospecific recognition element were combined with ultrasensitive bioluminescence detection techniques. Genetically engineered cell-based sensing systems were obtained by introducing into bacterial, yeast or mammalian cells a vector expressing a reporter protein whose expression is controlled by regulatory proteins and promoter sequences. The regulatory protein is able to recognize the presence of the analyte (e.g., compounds with hormone-like activity, heavy metals…) and to consequently activate the expression of the reporter protein that can be readily measured and directly related to the analyte bioavailable concentration in the sample. Bioluminescence represents the ideal detection principle for miniaturized analytical devices and multiplexed assays thanks to high detectability in small sample volumes allowing an accurate signal localization and quantification. In the first chapter of this dissertation is discussed the obtainment of improved bioluminescent proteins emitting at different wavelenghts, in term of increased thermostability, enhanced emission decay kinetic and spectral resolution. The second chapter is mainly focused on the use of these proteins in the development of whole-cell based assay with improved analytical performance. In particular since the main drawback of whole-cell biosensors is the high variability of their analyte specific response mainly caused by variations in cell viability due to aspecific effects of the sample’s matrix, an additional bioluminescent reporter has been introduced to correct the analytical response thus increasing the robustness of the bioassays. The feasibility of using a combination of two or more bioluminescent proteins for obtaining biosensors with internal signal correction or for the simultaneous detection of multiple analytes has been demonstrated by developing a dual reporter yeast based biosensor for androgenic activity measurement and a triple reporter mammalian cell-based biosensor for the simultaneous monitoring of two CYP450 enzymes activation, involved in cholesterol degradation, with the use of two spectrally resolved intracellular luciferases and a secreted luciferase as a control for cells viability. In the third chapter is presented the development of a portable multianalyte detection system. In order to develop a portable system that can be used also outside the laboratory environment even by non skilled personnel, cells have been immobilized into a new biocompatible and transparent polymeric matrix within a modified clear bottom black 384 -well microtiter plate to obtain a bioluminescent cell array. The cell array was placed in contact with a portable charge-coupled device (CCD) light sensor able to localize and quantify the luminescent signal produced by different bioluminescent whole-cell biosensors. This multiplexed biosensing platform containing whole-cell biosensors was successfully used to measure the overall toxicity of a given sample as well as to obtain dose response curves for heavy metals and to detect hormonal activity in clinical samples (PCT/IB2010/050625: “Portable device based on immobilized cells for the detection of analytes.” Michelini E, Roda A, Dolci LS, Mezzanotte L, Cevenini L , 2010). At the end of the dissertation some future development steps are also discussed in order to develop a point of care (POCT) device that combine portability, minimum sample pre-treatment and highly sensitive multiplexed assays in a short assay time. In this POCT perspective, field-flow fractionation (FFF) techniques, in particular gravitational variant (GrFFF) that exploit the earth gravitational field to structure the separation, have been investigated for cells fractionation, characterization and isolation. Thanks to the simplicity of its equipment, amenable to miniaturization, the GrFFF techniques appears to be particularly suited for its implementation in POCT devices and may be used as pre-analytical integrated module to be applied directly to drive target analytes of raw samples to the modules where biospecifc recognition reactions based on ultrasensitive bioluminescence detection occurs, providing an increase in overall analytical output.

L'efficienza degli indici azionari: un'analisi empirica

La studio dell’efficienza di un indice azionario ha accresciuto la propria importanza nell’industria dell’asset management a seguito della diffusione dell’utilizzo di benchmark e investimenti indicizzati. Il presente lavoro valuta il livello di efficienza dei principali indici del mercato azionario statunitense, dell’Area Euro e italiano. Lo studio empirico ricorre a quattro misure di efficienza: il GRS, un test small-sample multivariato fondato sul CAPM; il test large sample di Wald, implementato tramite una simulazione bootstrap; il test GMM, che è stato applicato in una cornice non-gaussiana attraverso una simulazione block bootstrap; la misura di efficienza relativa di Kandel e Stambaugh. I risultati empirici forniscono una prova evidente della superiore efficienza degli indici equiponderati. Questa conclusione è interpretata sulla base della letteratura scientifica esistente, analizzando le diverse cause di ordine teorico ed empirico che sono state proposte.

Nonverbal emotional regulation in psychotherapy process according to an intersubjective perspective

In recent decades fascinating studies in developmental psychology, especially in infant research (for review see Lavelli, 2007) and recent discoveries in neuroscience (Welsh, et al, 2007; Siegel, 2001; Pally, 2007) have brought great interest to study the mode of sharing subjective experiences (affective states, intentions and attentional focus) in children and adults.It therefore appears today in the clinic is a growing consensus about the fact that the psychological disorder can be read as a deficit in intersubjective processes of affect regulation (see Benecke C. et al 2005; psychodynamic Diagnostic Manual-PDM, 2006) leading many authors to assume the centrality of affect regulation in the construction of the psychotherapeutic process of change (just to name a few Tronick, Greenberg, Stern, Sander, Fonagy, Beebe, Philippot, Rimé etc..). As previously stated, this study has led us to hypothesize that the long process of therapy is to assist with the sessions continue, a growing "emotional attunement" between the communication styles of both patient and therapist. And also to speculate that this synchronization can represent the existence of a significant positive correlation between the increased level of "emotional synchronization" and increased capacity for regulation of emotions by the patient.The research results despite the limitations of small sample showed encouraging results about the verification of the existence of an increasing degree of attunement between therapist and patient long psychotherapy sessions and also showed a good degree of positive correlation between the increase the latter construct and emotional regulation through the implicit mode of expression and nonverbal communication.

Essays in Macroecometrics: methodological aspects and empirical applications

In the first chapter, I develop a panel no-cointegration test which extends Pesaran, Shin and Smith (2001)'s bounds test to the panel framework by considering the individual regressions in a Seemingly Unrelated Regression (SUR) system. This allows to take into account unobserved common factors that contemporaneously affect all the units of the panel and provides, at the same time, unit-specific test statistics. Moreover, the approach is particularly suited when the number of individuals of the panel is small relatively to the number of time series observations. I develop the algorithm to implement the test and I use Monte Carlo simulation to analyze the properties of the test. The small sample properties of the test are remarkable, compared to its single equation counterpart. I illustrate the use of the test through a test of Purchasing Power Parity in a panel of EU15 countries. In the second chapter of my PhD thesis, I verify the Expectation Hypothesis of the Term Structure in the repurchasing agreements (repo) market with a new testing approach. I consider an "inexact" formulation of the EHTS, which models a time-varying component in the risk premia and I treat the interest rates as a non-stationary cointegrated system. The effect of the heteroskedasticity is controlled by means of testing procedures (bootstrap and heteroskedasticity correction) which are robust to variance and covariance shifts over time. I fi#nd that the long-run implications of EHTS are verified. A rolling window analysis clarifies that the EHTS is only rejected in periods of turbulence of #financial markets. The third chapter introduces the Stata command "bootrank" which implements the bootstrap likelihood ratio rank test algorithm developed by Cavaliere et al. (2012). The command is illustrated through an empirical application on the term structure of interest rates in the US.

Multimodal (EEG-fMRI) functional connectivity study of levodopa effect in Parkinson’s disease

Aim: To assess if the intake of levodopa in patients with Parkinson’s Disease (PD) changes cerebral connectivity, as revealed by simultaneous recording of hemodynamic (functional MRI, or fMRI) and electric (electroencephalogram, EEG) signals. Particularly, we hypothesize that the strongest changes in FC will involve the motor network, which is the most impaired in PD. Methods: Eight patients with diagnosis of PD “probable”, therapy with levodopa exclusively, normal cognitive and affective status, were included. Exclusion criteria were: moderate-severe rest tremor, levodopa induced dyskinesia, evidence of gray or white matter abnormalities on structural MRI. Scalp EEG (64 channels) were acquired inside the scanner (1.5 Tesla) before and after the intake of levodopa. fMRI functional connectivity was computed from four regions of interest: right and left supplementary motor area (SMA) and right and left precentral gyrus (primary motor cortex). Weighted partial directed coherence (w-PDC) was computed in the inverse space after the removal of EEG gradient and cardioballistic artifacts. Results and discussion: fMRI group analysis shows that the intake of levodopa increases hemodynamic functional connectivity among the SMAs / primary motor cortex and: sensory-motor network itself, attention network and default mode network. w-PDC analysis shows that EEG connectivity among regions of the motor network has the tendency to decrease after the intake the levodopa; furthermore, regions belonging to the DMN have the tendency to increase their outflow toward the rest of the brain. These findings, even if in a small sample of patients, suggest that other resting state physiological functional networks, beyond the motor one, are affected in patients with PD. The behavioral and cognitive tasks corresponding to the affected networks could benefit from the intake of levodopa.

A spectroscopic and photometric study of stellar populations in a sample of clusters in the Magellanic Clouds

This Ph.D. Thesis has been carried out in the framework of a long-term and large project devoted to describe the main photometric, chemical, evolutionary and integrated properties of a representative sample of Large and Small Magellanic Cloud (LMC and SMC respectively) clusters. The globular clusters system of these two Irregular galaxies provides a rich resource for investigating stellar and chemical evolution and to obtain a detailed view of the star formation history and chemical enrichment of the Clouds. The results discussed here are based on the analysis of high-resolution photometric and spectroscopic datasets obtained by using the last generation of imagers and spectrographs. The principal aims of this project are summarized as follows: • The study of the AGB and RGB sequences in a sample of MC clusters, through the analysis of a wide near-infrared photometric database, including 33 Magellanic globulars obtained in three observing runs with the near-infrared camera SOFI@NTT (ESO, La Silla). • The study of the chemical properties of a sample of MCs clusters, by using optical and near-infrared high-resolution spectra. 3 observing runs have been secured to our group to observe 9 LMC clusters (with ages between 100 Myr and 13 Gyr) with the optical high-resolution spectrograph FLAMES@VLT (ESO, Paranal) and 4 very young (<30 Myr) clusters (3 in the LMC and 1 in the SMC) with the near-infrared high-resolution spectrograph CRIRES@VLT. • The study of the photometric properties of the main evolutive sequences in optical Color- Magnitude Diagrams (CMD) obtained by using HST archive data, with the final aim of dating several clusters via the comparison between the observed CMDs and theoretical isochrones. The determination of the age of a stellar population requires an accurate measure of the Main Sequence (MS) Turn-Off (TO) luminosity and the knowledge of the distance modulus, reddening and overall metallicity. For this purpose, we limited the study of the age just to the clusters already observed with high-resolution spectroscopy, in order to date only clusters with accurate estimates of the overall metallicity.