Synthesis And Biological Evaluation Of 1 5 Diphenylpyrrole Derivatives As Cox 2 Selective Inhibitors And No Releasing Agents And Development Of A Novel Brd9 Chemical Probe

This PhD thesis consists of three projects: the first and the second ones, carried out at Sapienza University of Rome, deal with the design and synthesis of novel COX-2 selective inhibitors and dual COX-2 inhibitors/NO-releasing agents, respectively. The third project concerns the development of a novel BRD9 chemical probe and was realized at the University of Oxford (Department of Chemistry).

The topic of proactivity of brain functions has become of growing interest in the cognitive neuroscience. Brain activity is no longer described solely in a reactive way, but also as preparatory and predictive of future events. This volume focuses especially on the neurocognitive activities associated with anticipatory processes of perceptual decision-making. What does the brain do to prevent mistakes? Is it possible to prevent speed and accuracy of a decision even before it is made? Why do some people perform better or worse than others? The volume answers these and other questions through the description of some original research. In particular, electroencephalographic investigations are illustrated which allowed to define a first version of the model known as “preparation-perception-action cycle”. Present findings reveal theoretical and practical implications which constitute a useful reference for researchers and scholars interested in discovering the aware and unaware ways in which our brain anticipates the future.

Considering the seismic behaviour of cultural heritage buildings, recent earthquakes have emphasised the high vulnerability of vaulted structures. In this regard, the present thesis deals with masonry cross vaults, among the most diffused and fascinating structural typologies of the European cultural heritage. After a thorough review of cross vault historical developments, the focus is shifted to the shaking table tests of a scaled arch. These two points provided valuable information to calibrate the finite element model of cross vault, discussed next. Finally, the influence of the main geometrical and mechanical parameters on the seismic capacity of cross vaults are examined by means of a sensitivity analysis.

This volume collects the main results of the Author’s Ph.D. course in Electromagnetics and Mathematical Models for Engineering, attended at ‘Sapienza’ University of Rome from November 2011 to February 2015, in the Electromagnetic Fields 1 Lab of the Department of Information Engineering, Electronics and Telecommunications, under the tutoring of Prof. Alessandro Galli.

Living organisms are adapted to their environment. Modern compilers and runtime systems for computer software are no different: as part of a continuous optimization process, they can adapt the execution cycle of a program to the workload it operates on. This thesis brings novel ideas to the software optimization domain. It illustrates methodological and practical contributions that advance the state of the art for performance profiling techniques and adaptive runtime designs, backed by promising experimental results on industrial-strength benchmarks. Part of the results has been presented in flagship programming language venues.

Neuropathic pain is a common problem in clinical practice, which affects patients quality of life. The more recent approach to this peculiar type of pain is based on the “sensory profiles theory”. According to this theory, neuropathic pain manifests with different combinations of sensory abnormalities, which in turn arise through different pathophysiological mechanisms. Convincing evidence now suggests that the classification of neuropathic pain according to a mechanism-based approach rather than etiology could help in targeting the therapy for the individual patient and would be useful for testing new drugs. My work has therefore focused on disclosing the pathophysiological mechanisms underlying neuropathic pain and how they translate into symptoms.

Within the past few years, it has become recognized that the immune system communicates to the brain. Substances released from activated immune cells (cytokines) stimulate peripheral nerves, thereby signaling the brain and spinal cord that infection/inflammation has occurred. Additionally, peripheral infection/inflammation leads to de novo synthesis and release of cytokines within the brain and spinal cord. Thus, cytokines effect neural activation both peripherally and centrally. Through this communication pathway, cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor markedly alter brain function, physiology and behavior. One important but underrecognized aspect of this communication is the dramatic impact that immune activation has on pain modulation. The purpose of this book is to examine, for the first time, immune-to-brain communication from the viewpoint of its effect on pain processing. It is aimed both at the basic scientist and health care providers, in order to clarify the major role that substances released by immune cells play in pain modulation. This book contains chapters contributed by all of the major laboratories focused on understanding how cytokines modulate pain. These chapters provide a unique vantage point from which to examine this question, as the summarized work ranges from evolutionary approaches across diverse species, to the basics of the immune response, to the effect of cytokines on peripheral and central nervous system sites, to therapeutic potential in humans.

This text provides an overview of the pathogenesis, pathophysiology and treatment of trigeminal neuralgia, and correlates experimental data with clinical obervations. Current knowledge and the latest treatments are discussed by the pioneers who developed them.