Alterations of brain eicosanoid synthetic pathway in multiple sclerosis and in animal models of demyelination: Role of cyclooxygenase-2

Inflammation is a physiological response to exogenous and endogenous stimuli and, together with demyelination and immune system activation, is one of the key features of multiple sclerosis (MS). Arachidonic acid (AA) metabolism by cyclooxygenase (COX) and lipoxygenase (LO) enzymes leads to the production of proinflammatory eicosanoids, and stimulates cytokine production and activation of microglia and astrocytes, thereby contributing to MS pathology. Current therapies target the immune system but do not specifically target AA-related inflammatory pathway. Corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently associated with immunomodulatory therapies to treat flu-like adverse effects. Few clinical and mounting preclinical data in MS show that AA metabolism contributes to immune system activation, demyelination and motor disabilities, and administration of NSAIDs reduces these symptoms. The beneficial effect of NSAIDs seems to be a prerogative of COX-2 selective inhibitors and suggests that NSAIDs selective for COX-2 may be more effective than mixed COX-1/2 inhibitors

Automated power gating methodology for dataflow-based reconfigurable systems

Modern embedded systems designers are required to implement efficient multi-functional applications, over portable platforms under strong energy and resources constraints. Automatic tools may help them in challenging such a complex scenario: to develop complex reconfigurable systems while reducing time-to-market. At the same time, automated methodologies can aid them to manage power consumption. Dataflow models of computation, thanks to their modularity, turned out to be extremely useful to these purposes. In this paper, we will demonstrate as they can be used to automatically achieve power management since the earliest stage of the design flow. In particular, we are focussing on the automation of power gating. The methodology has been evaluated on an image processing use case targeting an ASIC 90 nm CMOS technology

Generation of Efficient High-Level Hardware Code from Dataflow Programs

High-level synthesis (HLS) aims at reducing the time-to-market by providing an automated design process that interprets and compiles high-level abstraction programs into hardware. However, HLS tools still face limitations regarding the performance of the generated code, due to the difficulties of compiling input imperative languages into efficient hardware code. Moreover the hardware code generated by the HLS tools is usually target-dependant and at a low level of abstraction (i.e. gate-level). A generated code at a high-level of abstraction (i.e. chip-level) is better suited to the needs of systems' architects because they can understand and control all of the design processes. We propose in this paper a new approach to HLS to generate efficient, high-level hardware code from Dataflow Programs. Implementation results (from two dynamic dataflow programs) on Xilinx, Altera and Latice FPGAs and on ASIC targeting 90nm CMOS technology are also presented

Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL)

The Hedgehog (HH) signaling network is one of the main regulators of invertebrate and vertebrate embryonic development. Along with other networks, such as NOTCH and WNT, HH signaling specifies both the early patterning and the polarity events as well as the subsequent organ formation via the temporal and spatial regulation of cell proliferation and differentiation. However, aberrant activation of HH signaling has been identified in a broad range of malignant disorders, where it positively influences proliferation, survival, and therapeutic resistance of neoplastic cells. Inhibitors targeting the HH pathway have been tested in preclinical cancer models. The HH pathway is also overactive in other blood malignancies, including T-cell acute lymphoblastic leukemia (T-ALL). This review is intended to summarize our knowledge of the biological roles and pathophysiology of the HH pathway during normal T-cell lymphopoiesis and in T-ALL. In addition, we will discuss potential therapeutic strategies that might expand the clinical usefulness of drugs targeting the HH pathway in T-ALL

SPECT and PET serve as molecular imaging techniques and in vivo biomarkers for brain metastases

Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET) represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI) is discussed

Modelling and Automated Implementation of Optimal Power Saving Strategies in Coarse-Grained Reconfigurable Architectures

This paper focuses on how to efficiently reduce power consumption in coarse-grained reconfigurable designs, to allow their effective adoption in heterogeneous architectures supporting and accelerating complex and highly variable multifunctional applications. We propose a design flow for this kind of architectures that, besides their automatic customization, is also capable of determining their optimal power management support. Power and clock gating implementation costs are estimated in advance, before their physical implementation, on the basis of the functional, technological, and architectural parameters of the baseline design. Experimental results, on 90 and 45 nm CMOS technologies, demonstrate that the proposed approach guides the designer towards optimal implementation