A Sensitivity-Based Design Space Exploration Methodology for Embedded Systems

In this paper, we propose a system-level design methodology for the efficient exploration of the architectural parameters of the memory sub-systems, from the energy-delay joint perspective. The aim is to find the best configuration of the memory hierarchy without performing the exhaustive analysis of the parameters space. The target system architecture includes the processor, separated instruction and data caches, the main memory, and the system buses. To achieve a fast convergence toward the near-optimal configuration, the proposed methodology adopts an iterative local-search algorithm based on the sensitivity analysis of the cost function with respect to the tuning parameters of the memory sub-system architecture. The exploration strategy is based on the Energy-Delay Product (EDP) metric taking into consideration both performance and energy constraints. The effectiveness of the proposed methodology has been demonstrated through the design space exploration of a real-world case study: the optimization of the memory hierarchy of a MicroSPARC2-based system executing the set of Mediabench benchmarks for multimedia applications. Experimental results have shown an optimization speedup of 2 orders of magnitude with respect to the full search approach, while the near-optimal system-level configuration is characterized by a distance from the optimal full search configuration in the range of 2%.     

Podocyte-Related Mechanisms Underlying Survival Benefit of Long-Term Angiotensin Receptor Blocker

We previously found that short-term treatment (week 8 to 12 after injury) with high-dose angiotensin receptor blocker (ARB) induced the regression of existing glomerulosclerosis in 5/6 nephrectomy rats. We therefore assessed the effects of long-term intervention with ARB vs. nonspecific antihypertensives in this study. Adult rats underwent 5/6 nephrectomy and renal biopsy 8 weeks later. The rats were then divided into three groups with equivalent renal function and glomerular sclerosis and treated with high-dose losartan (ARB), nonspecific antihypertensive triple-therapy (TRX), or left untreated (Control) until week 30. We found that blood pressure, serum creatinine levels, and glomerulosclerosis were lower at sacrifice in ARB and TRX vs. Control. Only ARB reduced proteinuria and maintained the density of WT-1-positive podocytes. Glomerular tufts showed more double-positive cells for CD44, a marker of activated parietal epithelial cells, and synaptopodin after ARB vs. TRX or Control. ARB treatment reduced aldosterone levels. ARB-treated rats had significantly improved survival when compared with TRX or Control. We conclude that both long-term ARB and triple-therapy ameliorate progression, but do not sustain the regression of glomerulosclerosis. ARB resulted in the superior preservation of podocyte integrity and decreased proteinuria and aldosterone, linked to increased survival in the uremic environment.     

Clean seas: a North Sea test site

The Clean Seas project focused on the role that existing Earth observing satellites might play in monitoring marine pollution. Results are presented here from August 1997, for the North Sea test site, using sea surface temperature (SST), colour and synthetic aperture radar (SAR) images in conjunction with a hydrodynamic model. There was good correlation between data sources, e.g. between SST and ERS-2 SAR images. Both datasets showed the development of fine plume structures close to the Rhine outflow, apparently associated with the outflow, and possibly caused by tidal pulsing of the Rhine Plume.

The model reproduced general temperature and sediment distributions well, but fine structures were not reproduced. Model sediment distribution patterns were verified using ‘chlorophyll concentration’ data from colour sensors, representative of sediment concentration in turbid water. In conjunction with the visible channels of the Advanced Very High Resolution Radiometer and Along-Track Scanning Radiometer, they give an uncalibrated measure of the sediment load. The model gives a more complete picture of the temporal dispersion of the Rhine Plume over time than is evident from the remotely sensed data alone.     

MERIS potential for ocean colour studies in the open ocean

The interest of space observations of ocean colour for determining variations in phytoplankton distribution and for deriving primary production (via models) has been largely demonstrated by the Coastal Zone Color Scanner (CZCS) which operated from 1978 to 1986. The capabilities of this pioneer sensor, however, were limited both in spectral resolution and radiometric accuracy. The next generation of ocean colour sensors will benefit from major improvements. The Medium Resolution Imaging Spectrometer (MERIS), planned by the European Space Agency (ESA) for the Envisat platform, has been designed to measure radiances in 15 visible and infrared channels. Three infrared channels will allow aerosol characterization, and therefore accurate atmospheric corrections, to be performed for each pixel. For the retrieval of marine parameters, nine channels between 410 and 705nm will be available (as opposed to only four with the CZCS). In coastal waters this should, in principle, allow a separate quantification of different substances (phytoplankton, mineral particles, yellow substance) to be performed. In open ocean waters optically dominated by phytoplankton and their associate detrital matter, the basic information (i.e. the concentration of phytoplanktonic pigments) will be retrieved with improved accuracy due to the increased radiometric performances of MERIS. The adoption of multi-wavelength algorithms could also lead to additional information concerning auxiliary pigments and taxonomic groups. Finally, MERIS will be one of the first sensors to allow measurements of Sun-induced chlorophyll a in vivo fluorescence, which could provide a complementary approach for the assessment of phytoplankton abundance. The development of these next-generation algorithms, however, requires a number of fundamental studies.     

Emerging specializations,competences and firms' proximity in digital industries: The case of London

In order to overcome the limitations of defining industrial specializations in digital industries through SIC codes, this paper suggests measuring the specializations and competences of these industries on the basis of the degree of digital technologies present in the products and services supplied. Metadata from CrunchBase are employed, as proxies of firms' specializations and competences which are defined as the fields of activity in which firms are involved. Applying a network analysis, these specializations and competences are linked to the recognition of emerging digital technologies and the strongest combinations of products and services. We tested the proposed methodology on London, a leading centre for the digital economy.     

Evaluation of 4-(4-Fluorobenzyl)piperazin-1-yl]-Based Compounds as Competitive Tyrosinase Inhibitors Endowed with Antimelanogenic Effects

There is a considerable attention for the development of inhibitors of tyrosinase (TYR) as therapeutic strategy for the treatment of hyperpigmentation disorders in humans. Continuing in our efforts to identify TYR inhibitors, we describe the design, synthesis and pharmacophore exploration of new small molecules structurally characterized by the presence of the 4-fluorobenzylpiperazine moiety as key pharmacophoric feature for the inhibition of TYR from Agaricus bisporus (AbTYR). Our investigations resulted in the discovery of the competitive inhibitor [4-(4-fluorobenzyl)piperazin-1-yl]-(3-chloro-2-nitro-phenyl)methanone 26 (IC₅₀=0.18 μM) that proved to be ∼100-fold more active than reference compound kojic acid (IC₅₀=17.76 μM). Notably, compound 26 exerted antimelanogenic effect on B16F10 cells in absence of cytotoxicity. Docking analysis suggested its binding mode into AbTYR and into modelled human TYR.     

miRNA Expression Profiling in Subcutaneous Adipose Tissue of Monozygotic Twins Discordant for HIV Infection: Validation of Differentially Expressed miRNA and Bioinformatic Analysis

Combined AntiRetroviral Treatments (cARTs) used for HIV infection may result in varied metabolic complications, which in some cases, may be related to patient genetic factors, particularly microRNAs. The use of monozygotic twins, differing only for HIV infection, presents a unique and powerful model for the controlled analysis of potential alterations of miRNAs regulation consequent to cART treatment. Profiling of 2578 mature miRNA in the subcutaneous (SC) adipose tissue and plasma of monozygotic twins was investigated by the GeneChip^® miRNA 4.1 array. Real-time PCR and ddPCR experiments were performed in order to validate differentially expressed miRNAs. Target genes of deregulated miRNAs were predicted by the miRDB database (prediction score > 70) and enrichment analysis was carried out with g:Profiler. Processes in SC adipose tissue most greatly affected by miRNA up-regulation included (i) macromolecular metabolic processes, (ii) regulation of neurogenesis, and (iii) protein phosphorylation. Furthermore, KEGG analysis revealed miRNA up-regulation involvement in (i) insulin signaling pathways, (ii) neurotrophin signaling pathways, and (iii) pancreatic cancer. By contrast, miRNA up-regulation in plasma was involved in (i) melanoma, (ii) p53 signaling pathways, and (iii) focal adhesion. Our findings suggest a mechanism that may increase the predisposition of HIV⁺ patients to insulin resistance and cancer.