High performance and energy-efficient instruction cache design and optimisation for ultra-low-power multi-core clusters

High Energy efficiency and high performance are the key regiments for Internet of Things (IoT) end-nodes. Exploiting cluster of multiple programmable processors has recently emerged as a suitable solution to address this challenge. However, one of the main bottlenecks for multi-core architectures is the instruction cache. While private caches fall into data replication and wasting area, fully shared caches lack scalability and form a bottleneck for the operating frequency. Hence we propose a hybrid solution where a larger shared cache (L1.5) is shared by multiple cores connected through a low-latency interconnect to small private caches (L1). However, it is still limited by large capacity miss with a small L1. Thus, we propose a sequential prefetch from L1 to L1.5 to improve the performance with little area overhead. Moreover, to cut the critical path for better timing, we optimized the core instruction fetch stage with non-blocking transfer by adopting a 4 x 32-bit ring buffer FIFO and adding a pipeline for the conditional branch. We present a detailed comparison of different instruction cache architectures' performance and energy efficiency recently proposed for Parallel Ultra-Low-Power clusters. On average, when executing a set of real-life IoT applications, our two-level cache improves the performance by up to 20% and loses 7% energy efficiency with respect to the private cache. Compared to a shared cache system, it improves performance by up to 17% and keeps the same energy efficiency. In the end, up to 20% timing (maximum frequency) improvement and software control enable the two-level instruction cache with prefetch adapt to various battery-powered usage cases to balance high performance and energy efficiency.

Landslide activity in contrasting land-cover settings constrained by multi-temporal inventorying

This doctoral thesis focuses on the study of historical shallow landslide activity over time in response to anthropogenic forcing on land use, through the compilation of multi-temporal landslide inventories. The study areas, located in contrasting settings and characterized by different history of land-cover changes, include the Sillaro River basin (Italy) and the Tsitika and Eve River basins (coastal British Columbia). The Sillaro River basin belongs to clay-dominated settings, characterized by extensive badland development, and dominated by earth slides and earthflows. Here, forest removal began in the Roman period and has been followed by agricultural land abandonment and natural revegetation in recent time. By contrast, the Tsitika-Eve River basins are characterized by granitic and basaltic lithologies, and dominated by debris slides, debris flows and debris avalanches. In this setting, anthropogenic impacts started in 1960’s and have involved logging operation. The thesis begins with an introductory chapter, followed by a methodological section, where a multi-temporal mapping approach is proposed and tested at four landslide sites of the Sillaro River basin. Results, in terms of inventory completeness in time and space, are compared against the existing region-wide Emilia-Romagna inventory. This approach is then applied at the Sillaro River basin scale, where the multi-temporal inventory obtained is used to investigate the landslide activity in relation to historical land cover changes across geologic domains and in relation to hydro-meteorological forcing. Then, the impact of timber harvesting and road construction on landslide activity and sediment transfer in the Tsitika-Eve River basins is investigated, with a focus on the controls that interactions between landscape morphometry and cutblock location may have on landslide size-frequency relations. The thesis ends with a summary of the main findings and discusses advantages and limitations associated with the compilation of multi-temporal inventories in the two settings during different periods of human-driven, land-cover dynamics.

User scheduling for low earth orbit multi-user multiple-input-multiple-output non-terrestrial network systems

In rural and isolated areas without cellular coverage, Satellite Communication (SatCom) is the best candidate to complement terrestrial coverage. However, the main challenge for future generations of wireless networks will be to meet the growing demand for new services while dealing with the scarcity of frequency spectrum. As a result, it is critical to investigate more efficient methods of utilizing the limited bandwidth; and resource sharing is likely the only choice. The research community’s focus has recently shifted towards the interference management and exploitation paradigm to meet the increasing data traffic demands. In the Downlink (DL) and Feedspace (FS), LEO satellites with an on-board antenna array can offer service to numerous User Terminals (UTs) (VSAT or Handhelds) on-ground in FFR schemes by using cutting-edge digital beamforming techniques. Considering this setup, the adoption of an effective user scheduling approach is a critical aspect given the unusually high density of User terminals on the ground as compared to the on-board available satellite antennas. In this context, one possibility is that of exploiting clustering algorithms for scheduling in LEO MU-MIMO systems in which several users within the same group are simultaneously served by the satellite via Space Division Multiplexing (SDM), and then these different user groups are served in different time slots via Time Division Multiplexing (TDM). This thesis addresses this problem by defining a user scheduling problem as an optimization problem and discusses several algorithms to solve it. In particular, focusing on the FS and user service link (i.e., DL) of a single MB-LEO satellite operating below 6 GHz, the user scheduling problem in the Frequency Division Duplex (FDD) mode is addressed. The proposed State-of-the-Art scheduling approaches are based on graph theory. The proposed solution offers high performance in terms of per-user capacity, Sum-rate capacity, SINR, and Spectral Efficiency.

Doehlert Design-desirability Function Multi-criteria Optimal Separation Of 17 Phenolic Compounds From Extra-virgin Olive Oil By Capillary Zone Electrophoresis.

In Brazil, the consumption of extra-virgin olive oil (EVOO) is increasing annually, but there are no experimental studies concerning the phenolic compound contents of commercial EVOO. The aim of this work was to optimise the separation of 17 phenolic compounds already detected in EVOO. A Doehlert matrix experimental design was used, evaluating the effects of pH and electrolyte concentration. Resolution, runtime and migration time relative standard deviation values were evaluated. Derringer's desirability function was used to simultaneously optimise all 37 responses. The 17 peaks were separated in 19min using a fused-silica capillary (50μm internal diameter, 72cm of effective length) with an extended light path and 101.3mmolL(-1) of boric acid electrolyte (pH 9.15, 30kV). The method was validated and applied to 15 EVOO samples found in Brazilian supermarkets.

Elevated Micronucleus Frequency In Patients With Type 2 Diabetes, Dyslipidemia And Periodontitis.

The over-production of reactive oxygen species (ROS) can cause oxidative damage to a large number of molecules, including DNA, and has been associated with the pathogenesis of several disorders, such as diabetes mellitus (DM), dyslipidemia and periodontitis (PD). We hypothesise that the presence of these diseases could proportionally increase the DNA damage. The aim of this study was to assess the micronucleus frequency (MNF), as a biomarker for DNA damage, in individuals with type 2 DM, dyslipidemia and PD. One hundred and fifty patients were divided into five groups based upon diabetic, dyslipidemic and periodontal status (Group 1 - poor controlled DM with dyslipidemia and PD; Group 2 - well-controlled DM with dyslipidemia and PD; Group 3 - without DM with dyslipidemia and PD; Group 4 - without DM, without dyslipidemia and with PD; and Group 5 - without DM, dyslipidemia and PD). Blood analyses were carried out for fasting plasma glucose, HbA1c and lipid profile. Periodontal examinations were performed, and venous blood was collected and processed for micronucleus (MN) assay. The frequency of micronuclei was evaluated by cell culture cytokinesis-block MN assay. The general characteristics of each group were described by the mean and standard deviation and the data were submitted to the Mann-Whitney, Kruskal-Wallis, Multiple Logistic Regression and Spearman tests. The Groups 1, 2 and 3 were similarly dyslipidemic presenting increased levels of total cholesterol, low density lipoprotein cholesterol and triglycerides. Periodontal tissue destruction and local inflammation were significantly more severe in diabetics, particularly in Group 1. Frequency of bi-nucleated cells with MN and MNF, as well as nucleoplasmic bridges, were significantly higher for poor controlled diabetics with dyslipidemia and PD in comparison with those systemically healthy, even after adjusting for age, and considering Bonferroni's correction. Elevated frequency of micronuclei was found in patients affected by type 2 diabetes, dyslipidemia and PD. This result suggests that these three pathologies occurring simultaneously promote an additional role to produce DNA impairment. In addition, the micronuclei assay was useful as a biomarker for DNA damage in individuals with chronic degenerative diseases.

Frequency Of The Allelic Variant C.1150t > C In Exon 10 Of The Fibroblast Growth Factor Receptor 3 (fgfr3) Gene Is Not Increased In Patients With Pathogenic Mutations And Related Chondrodysplasia Phenotypes.

Mutations in the FGFR3 gene cause the phenotypic spectrum of FGFR3 chondrodysplasias ranging from lethal forms to the milder phenotype seen in hypochondroplasia (Hch). The p.N540K mutation in the FGFR3 gene occurs in ∼70% of individuals with Hch, and nearly 30% of individuals with the Hch phenotype have no mutations in the FGFR3, which suggests genetic heterogeneity. The identification of a severe case of Hch associated with the typical mutation c.1620C > A and the occurrence of a c.1150T > C change that resulted in a p.F384L in exon 10, together with the suspicion that this second change could be a modulator of the phenotype, prompted us to investigate this hypothesis in a cohort of patients. An analysis of 48 patients with FGFR3 chondrodysplasia phenotypes and 330 healthy (control) individuals revealed no significant difference in the frequency of the C allele at the c.1150 position (p = 0.34). One patient carrying the combination `pathogenic mutation plus the allelic variant c.1150T > C' had a typical achondroplasia (Ach) phenotype. In addition, three other patients with atypical phenotypes showed no association with the allelic variant. Together, these results do not support the hypothesis of a modulatory role for the c.1150T > C change in the FGFR3 gene.

Behavior Of Listeria Monocytogenes In A Multi-species Biofilm With Enterococcus Faecalis And Enterococcus Faecium And Control Through Sanitation Procedures.

The formation of mono-species biofilm (Listeria monocytogenes) and multi-species biofilms (Enterococcus faecium, Enterococcus faecalis, and L. monocytogenes) was evaluated. In addition, the effectiveness of sanitation procedures for the control of the multi-species biofilm also was evaluated. The biofilms were grown on stainless steel coupons at various incubation temperatures (7, 25 and 39°C) and contact times (0, 1, 2, 4, 6 and 8days). In all tests, at 7°C, the microbial counts were below 0.4 log CFU/cm(2) and not characteristic of biofilms. In mono-species biofilm, the counts of L. monocytogenes after 8days of contact were 4.1 and 2.8 log CFU/cm(2) at 25 and 39°C, respectively. In the multi-species biofilms, Enterococcus spp. were present at counts of 8 log CFU/cm(2) at 25 and 39°C after 8days of contact. However, the L. monocytogenes in multi-species biofilms was significantly affected by the presence of Enterococcus spp. and by temperature. At 25°C, the growth of L. monocytogenes biofilms was favored in multi-species cultures, with counts above 6 log CFU/cm(2) after 8days of contact. In contrast, at 39°C, a negative effect was observed for L. monocytogenes biofilm growth in mixed cultures, with a significant reduction in counts over time and values below 0.4 log CFU/cm(2) starting at day 4. Anionic tensioactive cleaning complemented with another procedure (acid cleaning, disinfection or acid cleaning+disinfection) eliminated the multi-species biofilms under all conditions tested (counts of all micro-organisms<0.4 log CFU/cm(2)). Peracetic acid was the most effective disinfectant, eliminating the multi-species biofilms under all tested conditions (counts of the all microorganisms <0.4 log CFU/cm(2)). In contrast, biguanide was the least effective disinfectant, failing to eliminate biofilms under all the test conditions.

Prospects For Early Investigational Therapies For Sickle Cell Disease.

Sickle cell disease (SCD) is a genetic disorder characterized by the production of abnormal hemoglobin that polymerizes at low oxygen concentrations, causing the erythrocyte to adopt a sickle-shaped morphology. SCD pathophysiology is extremely complex and can lead to numerous clinical complications, including painful vaso-occlusive crises (VOC), end-organ damage, and a shortened lifespan. An impressive number of investigational drugs are currently in early stages of clinical development with prospects for use either as chronic therapies to reduce VOC frequency and end-organ damage in SCD or for use at the time of VOC onset. Many of these agents have been developed using a pathophysiological-based approach to SCD, targeting one or more of the mechanisms that contribute to the disease process. It is plausible that a multi-drug approach to treating the disease will evolve in the coming years, whereby hydroxyurea (HU) (the only drug currently FDA-approved for SCD) is used in combination with drugs that amplify nitric oxide signaling and/or counteract hemolytic effects, platelet activation and inflammation.

Explosive Synchronization With Partial Degree-frequency Correlation.

Networks of Kuramoto oscillators with a positive correlation between the oscillators frequencies and the degree of their corresponding vertices exhibit so-called explosive synchronization behavior, which is now under intensive investigation. Here we study and discuss explosive synchronization in a situation that has not yet been considered, namely when only a part, typically a small part, of the vertices is subjected to a degree-frequency correlation. Our results show that in order to have explosive synchronization, it suffices to have degree-frequency correlations only for the hubs, the vertices with the highest degrees. Moreover, we show that a partial degree-frequency correlation does not only promotes but also allows explosive synchronization to happen in networks for which a full degree-frequency correlation would not allow it. We perform a mean-field analysis and our conclusions were corroborated by exhaustive numerical experiments for synthetic networks and also for the undirected and unweighed version of a typical benchmark biological network, namely the neural network of the worm Caenorhabditis elegans. The latter is an explicit example where partial degree-frequency correlation leads to explosive synchronization with hysteresis, in contrast with the fully correlated case, for which no explosive synchronization is observed.

Enhanced D1 And D2 Inhibitions Induced By Low-frequency Trains Of Conditioning Stimuli: Differential Effects On H- And T-reflexes And Possible Mechanisms.

Mechanically evoked reflexes have been postulated to be less sensitive to presynaptic inhibition (PSI) than the H-reflex. This has implications on investigations of spinal cord neurophysiology that are based on the T-reflex. Preceding studies have shown an enhanced effect of PSI on the H-reflex when a train of ~10 conditioning stimuli at 1 Hz was applied to the nerve of the antagonist muscle. The main questions to be addressed in the present study are if indeed T-reflexes are less sensitive to PSI and whether (and to what extent and by what possible mechanisms) the effect of low frequency conditioning, found previously for the H-reflex, can be reproduced on T-reflexes from the soleus muscle. We explored two different conditioning-to-test (C-T) intervals: 15 and 100 ms (corresponding to D1 and D2 inhibitions, respectively). Test stimuli consisted of either electrical pulses applied to the posterior tibial nerve to elicit H-reflexes or mechanical percussion to the Achilles tendon to elicit T-reflexes. The 1 Hz train of conditioning electrical stimuli delivered to the common peroneal nerve induced a stronger effect of PSI as compared to a single conditioning pulse, for both reflexes (T and H), regardless of C-T-intervals. Moreover, the conditioning train of pulses (with respect to a single conditioning pulse) was proportionally more effective for T-reflexes as compared to H-reflexes (irrespective of the C-T interval), which might be associated with the differential contingent of Ia afferents activated by mechanical and electrical test stimuli. A conceivable explanation for the enhanced PSI effect in response to a train of stimuli is the occurrence of homosynaptic depression at synapses on inhibitory interneurons interposed within the PSI pathway. The present results add to the discussion of the sensitivity of the stretch reflex pathway to PSI and its functional role.

Frequency of the different mutations causing spinocerebellar ataxia (SCA1, SCA2, MJD/SCA3 and DRPLA) in a large group of Brazilian patients

Spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2) and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA) caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes. Another related disease, dentatorubropallidoluysian atrophy (DRPLA) is also caused by an unstable triplet repeat and can present as SCA in late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3 and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated families with various patterns of inheritance and originating in different geographic regions of Brazil. We found mutations in 35 families (39%), 32 of them with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation was 3% of all patients; and 6 % in the dominantly inherited SCAs. We identified the SCA2 mutation in 6% of all families and in 9% of the families with autosomal dominant inheritance. The MJD/SCA3 mutation was detected in 30 % of all patients; and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In addition, we observed variability in the frequency of the different mutations according to geographic origin of the patients, which is probably related to the distinct colonization of different parts of Brazil. These results suggest that SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian population, and that the MJD/SCA3 mutation is the most common cause of dominantly inherited SCA in Brazil.

Recalled and recorded bowel habits confirm early onset and high frequency of constipation in day-care nursery children

CONTEXT: Mothers recall early-onset constipation in children attending gastroenterology clinics. OBJECTIVES: To study the bowel habit of young children in the community to determine, first, whether early-onset constipation is confirmed in this setting and, second, the agreement between recalled and recorded bowel habit. METHODS:Defecation data of 57 children aged 6.0-40.7 mo were obtained by maternal recall (questionnaire on predominant stool characteristics) and by record (1,934 defecations registered prospectively at home and in the nursery). The bowel habit was classified according to stool frequency and proportion of stool characteristics (soft, hard and/or runny). Two criteria were used to classify recorded data, since the cutoff point for hard stools to identify constipation is undefined in children: predominant criterion and adult criterion, respectively with >50% and >25% of stools with altered consistency. Bowel habit categories were: adequate, constipation, functional diarrhea and "other bowel habit". Nonparametric statistics, and the Kappa index for agreement between recalled and recorded bowel habit, were used. RESULTS: Constipation occurred in 17.5%, 10.5%, 19.3% of the children by recall, the predominant and the adult criteria, respectively. Constipation was the main recalled alteration, vs 12.3% "other bowel habit". Only one child classified as having functional diarrhea (by the adult criterion). Agreement between recalled and recorded bowel habit was fair for constipation, by the predominant and the adult criteria (K = 0.28 and 0.24, respectively), but only slight (K <0.16) for other bowel habit categories. Individual data, however, pointed to a better relationship between recalled constipation and the adult rather than the predominant criterion. CONCLUSIONS: Frequent early-onset constipation was confirmed. Fair agreement between recalled and recorded constipation by the two used criteria indicates that recalled data are quite reliable to detect constipation.

A multi-screening approach for marine-derived fungal metabolites and the isolation of cyclodepsipeptides from Beauveria felina

Extracts obtained from 57 marine-derived fungal strains were analyzed by HPLC-PDA, TLC and ¹H NMR. The analyses showed that the growth conditions affected the chemical profile of crude extracts. Furthermore, the majority of fungal strains which produced either bioactive of chemically distinctive crude extracts have been isolated from sediments or marine algae. The chemical investigation of the antimycobacterial and cytotoxic crude extract obtained from two strains of the fungus Beauveria felina have yielded cyclodepsipeptides related to destruxins. The present approach constitutes a valuable tool for the selection of fungal strains that produce chemically interesting or biologically active secondary metabolites.

A hybrid heuristic for the multi-plant capacitated lot sizing problem with setup carry-over

This paper addresses the capacitated lot sizing problem (CLSP) with a single stage composed of multiple plants, items and periods with setup carry-over among the periods. The CLSP is well studied and many heuristics have been proposed to solve it. Nevertheless, few researches explored the multi-plant capacitated lot sizing problem (MPCLSP), which means that few solution methods were proposed to solve it. Furthermore, to our knowledge, no study of the MPCLSP with setup carry-over was found in the literature. This paper presents a mathematical model and a GRASP (Greedy Randomized Adaptive Search Procedure) with path relinking to the MPCLSP with setup carry-over. This solution method is an extension and adaptation of a previously adopted methodology without the setup carry-over. Computational tests showed that the improvement of the setup carry-over is significant in terms of the solution value with a low increase in computational time.

Validation of a food frequency questionnaire to assess the consumption of carotenoids, fruits and vegetables among adolescents: the method of triads

The aim of this study was to validate the intake of carotenoids, fruits and vegetables estimated by the Food Frequency Questionnaire for Adolescents (FFQA) using the method of triads. Blood samples were collected from 80 elementary school adolescents to assess serum levels of β-carotene. Partial correlation coefficients (r) were calculated between an estimated intake of carotenoids, fruits and vegetables and the serum levels of β-carotene. Validity coefficients were calculated using the method of triads. With the exception of carotenoids, partial r from the food frequency questionnaire (FFQ) were greater than those of the 24-hour recall (24hR). The fruit/vegetable group showed the highest partial r for the FFQ (r = 0.235) and the 24hR (r = 0.137). The highest validity coefficient was obtained for the vegetable group, as assessed by the FFQ (r = 0.873). On average, the validity coefficient values for the FFQ were greater than those obtained for the 24hR or the β-carotene serum levels. The FFQA is an accurate tool for estimating the intake of carotenoids, fruits and vegetables in this population group.