Symbolic generation of constrained random logic cells Costa, R.; Curatelli, F.; Caviglia, D.D. ...
IEEE transactions on computer-aided design of integrated circuits and systems,
02/1991, Volume:
10, Issue:
2
Journal Article
Peer reviewed
A symbolic cell generator (SYC) that can generate the symbolic layout of a generic CMOS logic cell is presented. It accepts as input a SPICE-like netlist describing circuit components, connectivity, ...and the list of the I/O pins. Using this generator, the user can specify topological constraints on pin and transistor positions, the maximum lengths of polysilicon and diffusion wires, and a preferred layer for each electrical node. Cells are generated according to optimization criteria that take into account not only geometric factors, such as cell area, aspect ratio, and wirelength, but also electrical features, namely capacitance to the substrate and contact and via minimization. The generator's placement strategy includes transistor clustering into regions, global region placement by linear ordering, and two-dimensional local transistor placement. The routing combines Steiner trees and Lee algorithms. Object-oriented programming paradigms were used in the implementation of the program, written in C++ language. Experimental results for small and medium-sized cells are presented.< >
We report the electrocardiographic and electrophysiologic effects of magnesium (Mg) sulfate infusion in 25 normomagnesemic patients (16 men and 9 women, aged 22-74 years; mean +/− SD, 60.4 +/− 11.9) ...with different cardiac conduction impairments. Ten patients had chronic ischemic heart disease, two had idiopathic dilated cardiomyopathy, two had hypertensive heart disease, three had valvular heart disease, five had sclerodegenerative heart disease and three had no clinical evidence of cardiac disease. Five patients had trifascicular block first degree atrioventricular (A-V) block+right bundle branch block (RBBB)+left anterior hemiblock (LAH), eight had bifascicular block (6 RBBB+LAH, 2 first degree A-V block+RBBB), four had isolated first degree A-V block and eight had bundle branch block 5 RBBB, 3 left bundle branch block (LBBB). Before and during Mg infusion (50 mg/min/60 min) we evaluated the A-V (P-R), intraatrial (P-A), suprahisian (A-H), infrahisian (H-V) conduction times, electrical ventricular systole (Q-T), Q-T index (Q-Tc) intraventricular conduction time (QRS) and heart rate. At the end of infusion the P-R, P-A, A-H, H-V increased from 215.4 +/− 36.6, 33.6 +/− 9.1, 112.8 +/− 37.3, 69.0 +/− 12.8 ms to 217.6 +/− 37.1 (p less than 0.002), 33.8 +/− 9.4 (NS), 114.2 +/− 38.1 (p less than 0.005), 69.6 +/− 13.3 (NS) ms. QRS complex did not change (125 +/− 16.9 ms).
A tool capable of synthesizing the symbolic layout of a CMOS cell from its circuit descriptions is presented. The synthesis process is guided by topological constraints on pin and transistor ...positions, maximum lengths of poly and diffusion wires, and the specification of a preferred layer for each electrical node. The optimization criteria, take into account cell area and aspect ratio, wire length, capacitance to the substrate, and contact and via minimization. The novel placement strategy includes transistor clustering into regions, global region placement by linear ordering, and two-dimensional local transistor placement. The routing combines Steiner trees and Lee algorithms. The program is fast and has been thoroughly tested on small and medium-sized cells.< >
Climate change and the overexploitation of natural resources increase the need to integrate sustainable development policies at both national and international levels to fit the demands of a growing ...population. In 2015 the United Nations (UN) established the 2030 Agenda for sustainable development with the aim of eradicating extreme poverty, reducing inequality and protecting the planet. The Agenda 2030 highlights the importance of biodiversity and the functioning of ecosystems to maintain economic activities and the well-being of local communities. Nature Based Solutions (NBS) support biodiversity conservation and the functioning of ecosystems. NBS are increasingly seen as innovative solutions to manage water-related risks while transforming natural capital into a source of green growth and sustainable development. In this context, NBS could potentially contribute to the achievement of several Sustainable Development Goals (SDGs) by promoting the delivery of bundles of ecosystem services together generating various social, economic and environmental co-benefits. However, to achieve the full potential of NBS, it is necessary to recognize the trade-offs and synergies of the co-benefits associated with their implementation. To this aim, we have adopted a system perspective and a multi-sectoral approach to analyse the potential of NBS to deliver co-benefits while at the same time reducing the negative effects of water-related hazards. Using the case study of Copenhagen, we have analysed the relationships between the co-benefits associated with the scenario of the restoration of the Ladegaardsaa urban river. Our hypothesis is that enhancing the understanding of the social, economic and environmental factors of the system, including mutual influences and trade-offs, could improve the decision-making process and thereby enhance the capability of NBS to contribute to the achievement of the SDGs.
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•Evidence regarding the contribution of NBS to SDGs is needed.•Understanding the dynamic evolution of co-benefits increases NBS effectiveness.•The capacity of NBS for addressing SDGs is highly dependent on NBS multifunctionality.•Engaging stakeholders in the first stages of NBS design and implementation is key.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mutations of the mitochondrial genome (mtDNA) underlie a substantial portion of mitochondrial disease burden. These disorders are currently incurable and effectively untreatable, with heterogeneous ...penetrance, presentation and prognosis. To address the lack of effective treatment for these disorders, we exploited a recently developed mouse model that recapitulates common molecular features of heteroplasmic mtDNA disease in cardiac tissue: the m.5024C>T tRNA
mouse. Through application of a programmable nuclease therapy approach, using systemically administered, mitochondrially targeted zinc-finger nucleases (mtZFN) delivered by adeno-associated virus, we induced specific elimination of mutant mtDNA across the heart, coupled to a reversion of molecular and biochemical phenotypes. These findings constitute proof of principle that mtDNA heteroplasmy correction using programmable nucleases could provide a therapeutic route for heteroplasmic mitochondrial diseases of diverse genetic origin.
Understanding the relationship between heat wave occurrence and wildfire spread represents a key priority in global change studies due to the significant threats posed on natural ecosystems and ...society. Previous studies have not explored the spatial and temporal mechanism underlying the relationship between heat waves and wildfires occurrence, especially over large geographical regions. This study seeks to investigate such a relationship with a focus on 37 ecoregions within a Eurasia longitudinal gradient. The analysis is based on the wildfire dataset provided by the GlobFire Final Fire Event Detection and the meteorological dataset ERA5-land from Copernicus Climate service. In both cases we focused on the 2001–2019 timeframe. By means of a 12 km square grid, three wildfire metrics, i.e., density, seasonality, and severity of wildfires, were computed as proxy of fire regime. Heat waves were also characterized in terms of periods, duration, and intensity for the same period. Statistical tests were performed to evaluate the different patterns of heat wave and wildfire occurrence in the 37 ecoregions within the study area. By using Geographically Weighted Regression (GWR) we modeled the spatial varying relationships between heat wave characteristics and wildfire metrics. As expected, our results suggest that the 37 ecoregions identified within the Eurasia longitudinal gradient differ in terms of fire regimes. However, the occurrence of heat waves did not show significant differences among ecoregions, but a more evident variability in terms of relationship between fire regime metrics and heat waves within the study area. The outcome of the GWR analysis allowed us to identify the spatial locations (i.e., hotspot areas) where the relationship between heat waves and wildfires is positive and significant. Hence, in hotspots the presence of heat waves can be seen as a driver of wildfire occurrence in forest and steppe ecosystems. The findings from this study could contribute to a more comprehensive assessment of wildfire patterns in this geographical region, thus supporting cross-regional prevention strategies for disaster risk mitigation.
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•Characterization of heatwaves (HWs) and fire regime metrics in 37 ecoregions•No significant differences in terms of intensity, duration and periods of HWs•High spatial variability of the relationships between fire regime metrics and HWs•Hotspot areas found in ecoregions characterized by mixed forest ecosystems•The main HWs metrics guiding the coupling occurrence are the intensity and duration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes ...and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miRNA signatures in plasma derived LEVs and SEVs of Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD) patients. LEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and differential centrifugation and RNA was extracted. Small RNAs libraries were carried out by Next Generation Sequencing (NGS). MiRNAs discriminate all NDs diseases from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were instead linked to ubiquitin mediated proteolysis and Toll-like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway. LEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading of the disease. The study of common and different miRNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Since Italian liver allocation policy was last revised (in 2012), relevant critical issues and conceptual advances have emerged, calling for significant improvements. We report the results of a ...national consensus conference process, promoted by the Italian College of Liver Transplant Surgeons (for the Italian Society for Organ Transplantation) and the Italian Association for the Study of the Liver, to review the best indicators for orienting organ allocation policies based on principles of urgency, utility, and transplant benefit in the light of current scientific evidence. MELD exceptions and hepatocellular carcinoma were analyzed to construct a transplantation priority algorithm, given the inequity of a purely MELD‐based system for governing organ allocation. Working groups of transplant surgeons and hepatologists prepared a list of statements for each topic, scoring their quality of evidence and strength of recommendation using the Centers for Disease Control grading system. A jury of Italian transplant surgeons, hepatologists, intensivists, infectious disease specialists, epidemiologists, representatives of patients’ associations and organ‐sharing organizations, transplant coordinators, and ethicists voted on and validated the proposed statements. After carefully reviewing the statements, a critical proposal for revising Italy's current liver allocation policy was prepared jointly by transplant surgeons and hepatologists.
The authors present a critical proposal for the implementation of the current liver allocation policy in Italy developed following the results of a national Consensus Conference process aimed to revise, on the basis of scientific evidence, the best indicators for guiding organ allocation policies in the urgency, utility, and benefit models. See the editorial from Berg on page 2537.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Behçet’s disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure ...vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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