1.5V fully programmable CMOS Membership Function Generator Circuit with proportional DC-voltage control

A Membership Function Generator Circuit (MFGC) with bias supply of 1.5 Volts and independent DC-voltage programmable functionalities is presented. The realization is based on a programmable differential current mirror and three compact voltage-to-current converters, allowing continuous and quasi-linear adjustment of the center position, height, width and slopes of the triangular/trapezoidal output waveforms. HSPICE simulation results of the proposed circuit using the parameters of a double-poly, three metal layers, 0.5 μm CMOS technology validate the functionality of the proposed architecture, which exhibits a maximum deviation of the linearity in the programmability of 7 %

Ultra Low-Power Analog Median Filters

The design and implementation of three analog median filter topologies, whose transistors operate in the deep weak-inversion region, is described. The first topology is a differential pairs array, in which drain currents are driven into two nodes in a differential fashion, while the second topology is based on a wide range OTA, which is used to maximize the dynamic range. Finally, the third topology uses three range-extended OTAs. The proposed weak-inversion filters were designed and fabricated in ON Semiconductor 0.5 micrometer technology through MOSIS. Experimental results of three-input fabricated prototypes for all three topologies are show, where power consumptions of 90nW in the first case, and 270nW in the other two cases can be noticed. A dual power supply +/-1.5 Volts were used

Numerical analysis of interlaminar stresses in open-hole laminates under compression

In this paper, the interlaminar stresses in open-hole laminates subjected to compressive loads are analysed using a numerical model. This model implements the Serial/Parallel Mixing Theory (S/PMT) and a Continuum Damage Mechanics (CDM) approach. The S/PMT estimates the global stiffness in the laminate from fibre and matrix properties. The CDM approach models the damage initiation due to fibre microbuckling. The global response estimated by the model was verified with experimental data from the literature. The model predicts that the damage initiates in the laminate middle-plane where the thickest block of plies oriented in the load direction is located, and progressively propagates to the nearest block of layers with the same orientation. Two laminate stacking sequences were analysed. The interlaminar stresses around the hole presented symmetry with respect to the load direction and the perpendicular axis, being located the maximum and minimum values in different angular positions for each stress component and laminate.Postprint (published version

Improving Mechanical Properties and Reaction to Fire of EVA/LLDPE Blends for Cable Applications with Melamine Triazine and Bentonite Clay

The high flame-retardant loading required for ethylene-vinyl acetate copolymer blends with polyethylene (EVA-PE) employed for insulation and sheathing of electric cables represents a significant limitation in processability and final mechanical properties. In this work, melamine triazine (TRZ) and modified bentonite clay have been investigated in combination with aluminum trihydroxide (ATH) for the production of EVA-PE composites with excellent fire safety and improved mechanical properties. Optimized formulations with only 120 parts per hundred resin (phr) of ATH can achieve self-extinguishing behavior according to the UL94 classification (V0 rating), as well as reduced combustion kinetics and smoke production. Mechanical property evaluation shows reduced stiffness and improved elongation at break with respect to commonly employed EVA-PE/ATH composites. The reduction in filler content also provides improved processability and cost reductions. The results presented here allow for a viable and halogen-free strategy for the preparation of high performing EVA-PE composites

Keratin fibres derived from tannery industry wastes for flame retarded PLA composites

In this work, keratin fibres (KFs) were recovered from tannery industry wastes and reused for preparing completely green materials based on poly(lactic acid) (PLA) composites. A specific process for extracting and treating KFs as reinforcing and flame retardant agents for PLA was used. KFs were characterised by scanning electron microscopy, thermogravimetric analysis (TGA) and total nitrogen content by Kjeldahl method. PLA was compounding using both KFs at different contents and KFs in combination with a traditional flame retardant, namely, aluminium trihydroxide (ATH), in order to exploit the joint action between these two species. PLA composites were studied by scanning electron microscopy, thermogravimetry in nitrogen and air, UL94 classification, dynamical-mechanical, mechanical and rheological measurements. As a result, a good KF/polymer matrix adhesion was observed. Thus, PLA passes from V2 with only KFs (3 phr) to V0 classification when KFs are added in combination with 30 phr ATH. Tensile strength was increased by 16%, strain at break by 40% and tenacity by 66% when ATH content was reduced from 50 phr to 30 phr in joint combination with 3\ua0phr\ua0KF content. Rheological measurements in simple and oscillatory shear flows showed that KFs reduced the viscosity of the investigated materials, improving the processability of composites

Antigen-Induced IL-1RA Production Discriminates Active and Latent Tuberculosis Infection

The IGRA (Interferon Gamma Release Assays) test is currently the standard specific test for Mycobacterium tuberculosis infection status. However, a positive test cannot distinguish between active tuberculosis disease (ATBD) and latent tuberculosis infection (LTBI). Developing a test with this characteristic is needed. We conducted longitudinal studies to identify a combination of antigen peptides and cytokines to discriminate between ATBD and LTBI. We studied 54 patients with ATBD disease and 51 with LTBI infection. Cell culture supernatant from cells stimulated with overlapping Mycobacterium tuberculosis novel peptides and 40 cytokines/chemokines were analyzed using the Luminex technology. To summarize longitudinal measurements of analyte levels, we calculated the area under the curve (AUC). Our results indicate that in vitro cell stimulation with a novel combination of peptides (Rv0849-12, Rv2031c-14, Rv2031c-5, and Rv2693-06) and IL-1RA detection in culture supernatants can discriminate between LTBI and ATBD

Cellular and Molecular Mechanisms of Liver Fibrosis in Patients with NAFLD

The expression of immune- and cancer-related genes was measured in liver biopsies from 107 NAFLD patients. The strongest difference in overall gene expression was between liver fibrosis stages F3 and F4, with 162 cirrhosis-associated genes identified. Strong correlations with fibrosis progression from F1 to F4 were observed for 91 genes, including CCL21, CCL2, CXCL6, and CCL19. In addition, the expression of 21 genes was associated with fast progression to F3/F4 in an independent group of eight NAFLD patients. These included the four chemokines, SPP1, HAMP, CXCL2, and IL-8. A six-gene signature including SOX9, THY-1, and CD3D had the highest performance detecting the progressors among F1/F2 NAFLD patients. We also characterized immune cell changes using multiplex immunofluorescence platforms. Fibrotic areas were strongly enriched in CD3+ T cells compared to CD68+ macrophages. While the number of CD68+ macrophages increased with fibrosis severity, the increase in CD3+ T-cell density was more substantial and progressive from F1 to F4. The strongest correlation with fibrosis progression was observed for CD3+CD45R0+ memory T cells, while the most significant increase in density between F1/F2 and F3/F4 was for CD3+CD45RO+FOXP3+CD8- and CD3+CD45RO-FOXP3+CD8- regulatory T cells. A specific increase in the density of CD68+CD11b+ Kupffer cells with liver fibrosis progression was also observed

Spatial Molecular and Cellular Determinants of STAT3 Activation in Liver Fibrosis Progression in Non-alcoholic Fatty Liver Disease

BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is increasing. Individuals with NASH often develop liver fibrosis and advanced liver fibrosis is the main determinant of mortality in individuals with NASH. We and others have reported that STAT3 contributes to liver fibrosis and hepatocellular carcinoma in mice. METHODS: Here, we explored whether STAT3 activation in hepatocyte and non-hepatocyte areas, measured by phospho-STAT3 (pSTAT3), is associated with liver fibrosis progression in 133 patients with NAFLD. We further characterized the molecular and cellular determinants of STAT3 activation by integrating spatial distribution and transcriptomic changes in fibrotic NAFLD livers.Results: pSTAT3 scores in non-hepatocyte areas progressively increased with fibrosis severity (r = 0.53, CONCLUSION: Increased understanding of the spatial dependence of STAT3 signaling in NASH and liver fibrosis progression could lead to novel targeted treatment approaches. IMPACT AND IMPLICATIONS: Advanced liver fibrosis is the main determinant of mortality in patients with NASH. This study showed using liver biopsies from 133 patients with NAFLD, that STAT3 activation in non-hepatocyte areas is strongly associated with fibrosis severity, inflammation, and progression to NASH. STAT3 activation was enriched in hepatic progenitor cells (HPCs) and sinusoidal endothelial cells (SECs), as determined by innovative technologies interrogating the spatial distribution of pSTAT3. Finally, STAT3 inhibition in mice resulted in reduced liver fibrosis and depletion of HPCs, suggesting that STAT3 activation in HPCs contributes to their expansion and fibrogenesis in NAFLD

Impact of prematurity and perinatal antibiotics on the developing intestinal microbiota: A functional inference study

The microbial colonization of the neonatal gut provides a critical stimulus for normal maturation and development. This process of early microbiota establishment, known to be affected by several factors, constitutes an important determinant for later health. Methods: We studied the establishment of the microbiota in preterm and full-term infants and the impact of perinatal antibiotics upon this process in premature babies. To this end, 16S rRNA gene sequence-based microbiota assessment was performed at phylum level and functional inference analyses were conducted. Moreover, the levels of the main intestinal microbial metabolites, the short-chain fatty acids (SCFA) acetate, propionate and butyrate, were measured by Gas-Chromatography Flame ionization/Mass spectrometry detection. Results: Prematurity affects microbiota composition at phylum level, leading to increases of Proteobacteria and reduction of other intestinal microorganisms. Perinatal antibiotic use further affected the microbiota of the preterm infant. These changes involved a concomitant alteration in the levels of intestinal SCFA. Moreover, functional inference analyses allowed for identifying metabolic pathways potentially affected by prematurity and perinatal antibiotics use. Conclusion: A deficiency or delay in the establishment of normal microbiota function seems to be present in preterm infants. Perinatal antibiotic use, such as intrapartum prophylaxis, affected the early life microbiota establishment in preterm newborns, which may have consequences for later healt

Elderly hypertensive patients: Silent white matter lesions, blood pressure variability, baroreflex impairment and cognitive deterioration

Introduction: Hypertension may increase the risk for stroke and is frequently associated with subcortical and periventricular white matter lesions (WML). This is considered a prognostic factor for the development of stroke and cognitive impairment, particularly in attention processes. Additionally, in elderly subjects, it is known the implications of alterations in the neural cardiovascular regulation and the cardiovascular risk. Aims: To evaluate, in asymptomatic elderly hypertensives, the association of ambulatory blood pressure values and autonomic activity with neurocognitive impairment and WML. In addition, we also evaluated the role of the autonomic nervous system particularly the vagal component, in the pathogenesis of white matter lesions. Methods: We studied 22 elderly essential hypertensive patients (69±1.1y) and as control group, 16 normotensive elderly subjects (age 67±3.2y) were also enrolled. To each one of them, a cerebral MRI was performed to classify them, by a neuro-radiologist blinded of the subject clinical status, using a 0 to 9 scale where 0 denoted no WML and 9 the most severe lesions. Twenty four hours arterial blood pressure monitoring was performed to each one of the subjects under study. Office blood pressure was measured 3 times and the mean value reported. Beat to beat finger arterial pressure monitoring (Finapres) was performed for a 2h period. During the first hour the patient remained lying supine in a quiet darkened room and during the second hour four manoeuvres: stand-up, cold pressor test, handgrip and quiet activity were randomly performed. Mean blood pressure and pulse interval values, from the two periods, and their respective variabilities, baroreflex sensitivity and power spectral analysis were calculated. Regarding neuropsychological assessment: Minimental test, attention evaluation, RAVLT, visual memory, language and executive function, geriatric depression scale, cognitive deficit rate tests were performed in all subject. Results: We found a closer correlation of WML with 24hs ABPM than with office BP readings being more evident with systolic blood pressure during the night time period. WML failed to show any correlation with SBP average values derived from the Finapres recordings in either the supine or the upright position, while it was positively and significantly related to PP in both conditions. However, beat to beat SBP variability, either in the supine or in the upright position, showed a positive and significant correlation with WML. During the resting period, BRS calculated through the sequence method (Time Domain) was similar in HT and NT subjects. However when BRS was assessed in the frequency domain a significant reduction was observed in HT compared with NT. In addition, At the time of laboratory manoeuvres implying sympathetic activation, BRS was significantly reduced as compared to the resting values being particularly evident for the HF values. In hypertensive subjects, only semantic fluency showed a significant difference (p=0.01), when compared to normotensives. When the patients were divided in older and younger than 75 years, a significant difference was observed in the delayed analysis of words, and in the phonological fluency showing a significant higher rate of pathological results in the group of patients older than 75 years. Conclusions: As previously shown, incidental WML, suggestive of silent cerebrovascular disease, is a frequent finding in elderly hypertensives. Night-time BP mean values and SBP variability in upright position seems to be the best predictor on silent cerebral WML. The vagal component of the autonomic nervous system seems to be involved in the pathogenesis of these lesions. Finally, the neurocognitive alterations are multifactorial in origin where the aging process seems to be the principal component.Fil: Ramírez, Agustín José. Fundación Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Parati, Gianfranco. San Gerardo Hospital; Italia. University of Milan-Bicocca; ItaliaFil: Castiglioni, Paolo. Fondazione Don Gnocchi; ItaliaFil: Consalvo, Damian. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Solis, Patricia Cristina Lourdes. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Risk, Marcelo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Waissman, Paola. Fundación Favaloro; ArgentinaFil: di Rienzo, Marco. Fondazione Don Gnocchi; ItaliaFil: Mancia, Giusepe. San Gerardo Hospital; Italia. University of Milan-Bicocca; ItaliaFil: Sanchez, Ramiro A.. Fundación Favaloro; Argentin