Probing the innermost regions of AGN via time-resolved spectral analysis

The dynamics and geometry of the material inflowing and outflowing close to the supermassive black hole in active galactic nuclei are still uncertain. X-rays are the most suitable way to study the AGN innermost regions because of the Fe Kα emission line, a proxy of accretion, and Fe absorption lines produced by outflows. Winds are typically classified as Warm Absorbers (slow and mildly ionized) and Ultra Fast Outflows (fast and highly ionized). Transient Obscurers -optically thick winds that produce strong spectral hardening in X-rays, lasting from days to months- have been observed recently. Emission and absorption features vary on time-scales from hours to years, probing phenomena at different distances from the SMBH. In this work, we use time-resolved spectral analysis to investigate the accretion and ejection flows, to characterize them individually and search for correlations. We analyzed XMM-Newtomn data of a set of the brightest Seyfert 1 galaxies that went through an obscuration event: NGC 3783, NGC 3227, NGC 5548, and NGC 985. Our aim is to search for emission/absorption lines in short-duration spectra (∼ 10ks), to explore regions as close as the SMBH as the statistics allows for, and possibly catch transient phenomena. First we run a blind search to detect emission/absorption features, then we analyze their evolution with Residual Maps: we visualize simultaneously positive and negative residuals from the continuum in the time-energy plane, looking for patterns and relative time-scales. In NGC 3783 we were able to ascribe variations of the Fe Kα emission line to absorptions at the same energy due to clumps in the obscurer, whose presence is detected at >3σ, and to determine the size of the clumps. In NGC 3227 we detected a wind at ∼ 0.2c at ∼ 2σ, briefly appearing during an obscuration event.

Interconnection systems for highly integrated computation devices

The sustained demand for faster,more powerful chips has beenmet by the availability of chip manufacturing processes allowing for the integration of increasing numbers of computation units onto a single die. The resulting outcome, especially in the embedded domain, has often been called SYSTEM-ON-CHIP (SOC) or MULTI-PROCESSOR SYSTEM-ON-CHIP (MPSOC). MPSoC design brings to the foreground a large number of challenges, one of the most prominent of which is the design of the chip interconnection. With a number of on-chip blocks presently ranging in the tens, and quickly approaching the hundreds, the novel issue of how to best provide on-chip communication resources is clearly felt. NETWORKS-ON-CHIPS (NOCS) are the most comprehensive and scalable answer to this design concern. By bringing large-scale networking concepts to the on-chip domain, they guarantee a structured answer to present and future communication requirements. The point-to-point connection and packet switching paradigms they involve are also of great help in minimizing wiring overhead and physical routing issues. However, as with any technology of recent inception, NoC design is still an evolving discipline. Several main areas of interest require deep investigation for NoCs to become viable solutions: • The design of the NoC architecture needs to strike the best tradeoff among performance, features and the tight area and power constraints of the on-chip domain. • Simulation and verification infrastructure must be put in place to explore, validate and optimize the NoC performance. • NoCs offer a huge design space, thanks to their extreme customizability in terms of topology and architectural parameters. Design tools are needed to prune this space and pick the best solutions. • Even more so given their global, distributed nature, it is essential to evaluate the physical implementation of NoCs to evaluate their suitability for next-generation designs and their area and power costs. This dissertation focuses on all of the above points, by describing a NoC architectural implementation called ×pipes; a NoC simulation environment within a cycle-accurate MPSoC emulator called MPARM; a NoC design flow consisting of a front-end tool for optimal NoC instantiation, called SunFloor, and a set of back-end facilities for the study of NoC physical implementations. This dissertation proves the viability of NoCs for current and upcoming designs, by outlining their advantages (alongwith a fewtradeoffs) and by providing a full NoC implementation framework. It also presents some examples of additional extensions of NoCs, allowing e.g. for increased fault tolerance, and outlines where NoCsmay find further application scenarios, such as in stacked chips.

Nonlinear / electromagnetic co-simulation and co-design of microwave links in highly polluted and / or strongly inhomogeneous environments

The objective of the Ph.D. thesis is to put the basis of an all-embracing link analysis procedure that may form a general reference scheme for the future state-of-the-art of RF/microwave link design: it is basically meant as a circuit-level simulation of an entire radio link, with – generally multiple – transmitting and receiving antennas examined by EM analysis. In this way the influence of mutual couplings on the frequency-dependent near-field and far-field performance of each element is fully accounted for. The set of transmitters is treated as a unique nonlinear system loaded by the multiport antenna, and is analyzed by nonlinear circuit techniques. In order to establish the connection between transmitters and receivers, the far-fields incident onto the receivers are evaluated by EM analysis and are combined by extending an available Ray Tracing technique to the link study. EM theory is used to describe the receiving array as a linear active multiport network. Link performances in terms of bit error rate (BER) are eventually verified a posteriori by a fast system-level algorithm. In order to validate the proposed approach, four heterogeneous application contexts are provided. A complete MIMO link design in a realistic propagation scenario is meant to constitute the reference case study. The second one regards the design, optimization and testing of various typologies of rectennas for power generation by common RF sources. Finally, the project and implementation of two typologies of radio identification tags, at X-band and V-band respectively. In all the cases the importance of an exhaustive nonlinear/electromagnetic co-simulation and co-design is demonstrated to be essential for any accurate system performance prediction.

Natural compounds Camptothecin and Triptolide: highly specific enzyme inhibitors and tools to dissect transcriptional functions

With this work I elucidated new and unexpected mechanisms of two strong and highly specific transcription inhibitors: Triptolide and Campthotecin. Triptolide (TPL) is a diterpene epoxide derived from the Chinese plant Trypterigium Wilfoordii Hook F. TPL inhibits the ATPase activity of XPB, a subunit of the general transcription factor TFIIH. In this thesis I found that degradation of Rbp1 (the largest subunit of RNA Polymerase II) caused by TPL treatments, is preceded by an hyperphosphorylation event at serine 5 of the carboxy-terminal domain (CTD) of Rbp1. This event is concomitant with a block of RNA Polymerase II at promoters of active genes. The enzyme responsible for Ser5 hyperphosphorylation event is CDK7. Notably, CDK7 downregulation rescued both Ser5 hyperphosphorylation and Rbp1 degradation triggered by TPL. Camptothecin (CPT), derived from the plant Camptotheca acuminata, specifically inhibits topoisomerase 1 (Top1). We first found that CPT induced antisense transcription at divergent CpG islands promoter. Interestingly, by immunofluorescence experiments, CPT was found to induce a burst of R loop structures (DNA/RNA hybrids) at nucleoli and mitochondria. We then decided to investigate the role of Top1 in R loop homeostasis through a short interfering RNA approach (RNAi). Using DNA/RNA immunoprecipitation techniques coupled to NGS I found that Top1 depletion induces an increase of R loops at a genome-wide level. We found that such increase occurs on the entire gene body. At a subset of loci R loops resulted particularly stressed after Top1 depletion: some of these genes showed the formation of new R loops structures, whereas other loci showed a reduction of R loops. Interestingly we found that new peaks usually appear at tandem or divergent genes in the entire gene body, while losses of R loop peaks seems to be a feature specific of 3’ end regions of convergent genes.