Exploiting FPGA-aware merging of custom instructions for runtime reconfiguration

Runtime reconfiguration is a promising solution for reducing hardware cost in embedded systems, without compromising on performance. We present a framework that aims to increase the performance benefits of reconfigurable processors that support full or partial runtime reconfiguration. The proposed framework achieves this by: (1) providing a means for choosing suitable custom instruction selection heuristics, (2) leveraging FPGA-aware merging of custom instructions to maximize the reconfigurable logic block utilization in each configuration, and (3) incorporating a hierarchical loop partitioning strategy to reduce runtime reconfiguration overhead. We show that the performance gain can be improved by employing suitable custom instruction selection heuristics that, in turn, depend on the reconfigurable resource constraints and the merging factor (extent to which the selected custom instructions can be merged). The hierarchical loop partitioning strategy leads to an average performance gain of over 31% and 46% for full and partial runtime reconfiguration, respectively. Performance gain can be further increased to over 52% and 70% for full and partial runtime reconfiguration, respectively, by exploiting FPGA-aware merging of custom instructions.</jats:p

Existence of a Strong Correlation of Biomarkers and Mirna in Females With Metabolic Syndrome and Obesity in a Population of West Virginia

Objectives: Metabolic syndrome causes complications like cardiovascular disease and type 2 diabetes mellitus (T2DM). As metabolic syndrome develops, altered levels of cytokines and microRNAs (miRNA) are measurable in the circulation. We aimed to construct a panel detecting abnormal levels of cytokines and miRNAs in patients at risk for metabolic syndrome. Methods: Participants included 54 patients from a Family Medicine Clinic at Marshall University School of Medicine, in groups of: Control, Obese, and Metabolic Syndrome (MetS). Results: Serum levels of leptin, adiponectin, leptin: adiponectin ratio, IL-6, six miRNAs (320a, 197-3p, 23-3p, 221-3p, 27a-3p, and 130a-3p), were measured. Among the three groups, leptin, and leptin: adiponectin ratio, and IL-6 levels were highest in MetS, and levels in Obese were greater than Control (p\u3e0.05). Adiponectin levels were lower in Obese compared to Control, but lowest in MetS (p0.05). Conclusion: Our results support the clinical application of biomarkers in diagnosing early stage MetS, which will enable attenuation of disease progression before onset of irreversible complications. Since West Virginians are high-risk for developing MetS, our biomarker panel could reduce the disease burden on our population

Longevity Framework: Leveraging Online Integrated Aging-Aware Hierarchical Mapping and VF-Selection for Lifetime Reliability Optimization in Manycore Processors

Rapid device aging in the nano era threatens system lifetime reliability, posing a major intrinsic threat to system functionality. Traditional techniques to overcome the aging-induced device slowdown, such as guardbanding are static and incur performance, power, and area penalties. In a manycore processor, the system-level design abstraction offers dynamic opportunities through the control of task-to-core mappings and per-core operation frequency towards more balanced core aging profile across the chip, optimizing the system lifetime reliability while meeting the application performance requirements. This article presents Longevity Framework (LF) that leverages online integrated aging-aware hierarchical mapping and voltage frequency (VF)-selection for lifetime reliability optimization in manycore processors. The mapping exploration is hierarchical to achieve scalability. The VF-selection builds on the trade-offs involved between power, performance, and aging as the VF is scaled while leveraging the per-core DVFS capabilities. The methodology takes the chip-wide process variation into account. Extensive experimentation, comparing the proposed approach with two state-of-the-art methods, for 64-core and 256-core systems running applications from PARSEC and SPLASH-2 benchmark suites, show an improvement of up to 3.2 years in the system lifetime reliability and 4× improvement in the average core health

Intra-alveolar neutrophil-derived microvesicles are associated with disease severity in COPD

Despite advances in the pathophysiology of Chronic Obstructive Pulmonary Disease (COPD), there is a distinct lack of biochemical markers to aid clinical management. Microvesicles (MVs) have been implicated in the pathophysiology of inflammatory diseases including COPD but their association to COPD disease severity remains unknown. We analysed different MV populations in plasma and bronchoalveolar lavage fluid (BALF) taken from sixty-two patients with mild to very severe COPD (51% male; mean age: 65.9 years). These patients underwent comprehensive clinical evaluation (symptom scores, lung function, exercise testing) and the capacity of MVs to be clinical markers of disease severity was assessed. We successfully identified various MV subtype populations within BALF (leukocyte, PMN (polymorphonuclear leukocyte i.e. neutrophil), monocyte, epithelial and platelet MVs) and plasma (leukocyte, PMN, monocyte and endothelial MVs), and compared each MV population to disease severity. BALF neutrophil MVs were the only population to significantly correlate with the clinical evaluation scores including FEV1, mMRC dyspnoea score, 6-minute walk test, hyperinflation and gas transfer. BALF neutrophil MVs, but not neutrophil cell numbers, also strongly correlated with BODE index. We have undertaken, for the first time, a comprehensive evaluation of MV profiles within BALF/plasma of COPD patients. We demonstrate that BALF levels of neutrophil-derived MVs are unique in correlating with a number of key functional and clinically-relevant disease severity indices. Our results show the potential of BALF neutrophil MVs for a COPD biomarker that tightly links a key pathophysiological mechanism of COPD (intra-alveolar neutrophil activation) with clinical severity/outcome

pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57BI6 and ApoE Knockout Mice Fed a Western Diet

We have previously reported that the alpha1 subunit of sodium potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a western diet containing high amounts of fat and fructose. The administration of pNaKtide reduced obesity as well as hepatic steatosis, inflammation and fibrosis. Of interest, we also noted marked improvement in mitochondrial fatty acid oxidation, insulin sensitivity, dyslipidemia and aortic streaking in this mouse model. To further elucidate the effects of pNaKtide on atherosclerosis, similar studies were performed in ApoE knockout mice also exposed to the western diet. In these mice, pNaKtide not only improved steatohepatitis, dyslipidemia, and insulin sensitivity, but also ameliorated significant aortic atherosclerosis. Collectively, this study demonstrates that the Na/K-ATPase/ROS amplification loop contributes significantly to the development and progression of steatohepatitis and atherosclerosis. And furthermore, this study presents a potential treatment, the pNaKtide, for the metabolic syndrome phenotype

Symptomatic, biochemical and radiographic recovery in patients with Covid-19

Background: The symptoms, radiography, biochemistry and healthcare utilisation of patients with COVID-19 following discharge from hospital have not been well described. Methods: Retrospective analysis of 401 adult patients attending a clinic following an index hospital admission or emergency department attendance with COVID-19. Regression models were used to assess the association between characteristics and persistent abnormal chest radiographs or breathlessness. Results: 75.1% of patients were symptomatic at a median of 53 days post discharge and 72 days after symptom onset and chest radiographs were abnormal in 47.4%. Symptoms and radiographic abnormalities were similar in PCR-positive and PCR-negative patients. Severity of COVID-19 was significantly associated with persistent radiographic abnormalities and breathlessness. 18.5% of patients had unscheduled healthcare visits in the 30 days post discharge. Conclusions: Patients with COVID-19 experience persistent symptoms and abnormal blood biomarkers with a gradual resolution of radiological abnormalities over time. These findings can inform patients and clinicians about expected recovery times and plan services for follow-up of patients with COVID-19

Sarcopenia Exacerbates Obesity-Associated Insulin Resistance and Dysglycemia: Findings from the National Health and Nutrition Examination Survey III

Sarcopenia often co-exists with obesity, and may have additive effects on insulin resistance. Sarcopenic obese individuals could be at increased risk for type 2 diabetes. We performed a study to determine whether sarcopenia is associated with impairment in insulin sensitivity and glucose homeostasis in obese and non-obese individuals.We performed a cross-sectional analysis of National Health and Nutrition Examination Survey III data utilizing subjects of 20 years or older, non-pregnant (N = 14,528). Sarcopenia was identified from bioelectrical impedance measurement of muscle mass. Obesity was identified from body mass index. Outcomes were homeostasis model assessment of insulin resistance (HOMA IR), glycosylated hemoglobin level (HbA1C), and prevalence of pre-diabetes (6.0≤ HbA1C<6.5 and not on medication) and type 2 diabetes. Covariates in multiple regression were age, educational level, ethnicity and sex.Sarcopenia was associated with insulin resistance in non-obese (HOMA IR ratio 1.39, 95% confidence interval (CI) 1.26 to 1.52) and obese individuals (HOMA-IR ratio 1.16, 95% CI 1.12 to 1.18). Sarcopenia was associated with dysglycemia in obese individuals (HbA1C ratio 1.021, 95% CI 1.011 to 1.043) but not in non-obese individuals. Associations were stronger in those under 60 years of age. We acknowledge that the cross-sectional study design limits our ability to draw causal inferences.Sarcopenia, independent of obesity, is associated with adverse glucose metabolism, and the association is strongest in individuals under 60 years of age, which suggests that low muscle mass may be an early predictor of diabetes susceptibility. Given the increasing prevalence of obesity, further research is urgently needed to develop interventions to prevent sarcopenic obesity and its metabolic consequences

Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism

Background & aims: β-hydroxy-β-methylbutyrate (HMB) is purported as a key nutritional supplement for the preservation of muscle mass in health, disease and as an ergogenic aid in exercise. Of the two available forms of HMB (calcium (Ca-HMB) salt or free acid (FA-HMB)) – differences in plasma bioavailability have been reported. We previously reported that ∼3 g oral FA-HMB increased muscle protein synthesis (MPS) and reduced muscle protein breakdown (MPB). The objective of the present study was to quantify muscle protein metabolism responses to oral Ca-HMB. Methods: Eight healthy young males received a primed constant infusion of 1,2 13C2 leucine and 2H5 phenylalanine to assess MPS (by tracer incorporation in myofibrils) and MPB (via arterio-venous (A-V) dilution) at baseline and following provision of ∼3 g of Ca-HMB; muscle anabolic (MPS) and catabolic (MPB) signalling was assessed via immunoblotting. Results: Ca-HMB led a significant and rapid (<60 min) peak in plasma HMB concentrations (483.6 ± 14.2 μM, p < 0.0001). This rise in plasma HMB was accompanied by increases in MPS (PA: 0.046 ± 0.004%/h, CaHMB: 0.072 ± 0.004%/h, p < 0001) and suppressions in MPB (PA: 7.6 ± 1.2 μmol Phe per leg min−1, Ca-HMB: 5.2 ± 0.8 μmol Phe per leg min−1, p < 0.01). Increases in the phosphorylation of mTORc1 substrates i.e. p70S6K1 and RPS6 were also observed, with no changes detected in the MPB targets measured. Conclusions: These findings support the pro-anabolic properties of HMB via mTORc1, and show that despite proposed differences in bioavailability, Ca-HMB provides a comparable stimulation to MPS and suppression of MPB, to FA-HMB, further supporting its use as a pharmaconutrient in the modulation of muscle mass