Effect of olmesartan and amlodipine on serum angiotensin-(1–7) levels and kidney and vascular function in patients with type 2 diabetes and hypertension

Background Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) [Ang-(1–7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1–7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension. Methods This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20mg of olmesartan (N = 40) or 5mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1–7) from baseline to week 24. Results Both olmesartan and amlodipine treatment for 24weeks decreased systolic and diastolic blood pressures significantly by > 18mmHg and > 8mmHg, respectively. Serum Ang-(1–7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5pg/mL → 46.2 ± 59.4pg/mL) than by amlodipine treatment (29.2 ± 38.9pg/mL → 31.7 ± 26.0pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42ng/mL → 6.74 ± 0.39ng/mL by olmesartan treatment vs. 6.43 ± 0.23ng/mL → 6.61 ± 0.42ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1–7) levels (r =  − 0.252 and r =  − 0.299, respectively). The change in Ang-(1–7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1–7) levels were an independent predictor of a reduction in albuminuria. Conclusions These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1–7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease. Trial registration: ClinicalTrials.gov NCT05189015.This research was funded by Daiichi Sankyo Co., Seoul, South Korea through a subcontract with SNUBH (Seongnam, Republic of Korea). The funding agency had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Type I IFNs and TNF cooperatively reprogram the macrophage epigenome to promote inflammatory activation

Cross-regulation of Toll-like receptor responses by cytokines is essential for effective host defense, avoidance of toxicity, and homeostasis, but the underlying mechanisms are not well understood. A comprehensive epigenomic approach in human macrophages showed that the proinflammatory cytokines TNF and type I IFNs induce transcriptional cascades that alter chromatin states to broadly reprogram TLR4-induced responses. TNF tolerized inflammatory genes to prevent toxicity, while preserving antiviral and metabolic gene induction. Type I IFNs potentiated TNF inflammatory function by priming chromatin to prevent silencing of inflammatory NF-κB target genes. Priming of chromatin enabled robust transcriptional responses to weak upstream signals. Similar chromatin regulation occurred in human diseases. Our findings reveal that signaling crosstalk between IFNs and TNF is integrated at the level of chromatin to reprogram inflammatory responses, and identify new functions and mechanisms of action of these cytokines

A genome-wide scan for signatures of directional selection in domesticated pigs

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background Animal domestication involved drastic phenotypic changes driven by strong artificial selection and also resulted in new populations of breeds, established by humans. This study aims to identify genes that show evidence of recent artificial selection during pig domestication. Results Whole-genome resequencing of 30 individual pigs from domesticated breeds, Landrace and Yorkshire, and 10 Asian wild boars at ~16-fold coverage was performed resulting in over 4.3 million SNPs for 19,990 genes. We constructed a comprehensive genome map of directional selection by detecting selective sweeps using an F ST-based approach that detects directional selection in lineages leading to the domesticated breeds and using a haplotype-based test that detects ongoing selective sweeps within the breeds. We show that candidate genes under selection are significantly enriched for loci implicated in quantitative traits important to pig reproduction and production. The candidate gene with the strongest signals of directional selection belongs to group III of the metabolomics glutamate receptors, known to affect brain functions associated with eating behavior, suggesting that loci under strong selection include loci involved in behaviorial traits in domesticated pigs including tameness. Conclusions We show that a significant proportion of selection signatures coincide with loci that were previously inferred to affect phenotypic variation in pigs. We further identify functional enrichment related to behavior, such as signal transduction and neuronal activities, for those targets of selection during domestication in pigs

Load Tests on Pipe Piles for Development of CPT-Based Design Method

This research focused on the drivability and load-carrying capacity of both open and closed-ended steel pipe piles. Two pipe piles (one open-ended, the other closed-ended) were installed in a sandy soil to the same depth. The site was extensively characterized. SPT and CPT tests were performed both before and after pile installation. A variety of soil indices and shear strength parameters (such as the constant-volume friction angle) were measured in the laboratory. The piles were fully instrumented, permitting separate measurement of shaft and base capacity for the closed-ended pile and shaft, annulus and soil plug capacities for the open-ended pile. The results are presented in a variety of ways. In particular, values of pile resistance are presented normalized with respect to CPT cone resistance values both along the shaft and base of the piles for quick reference. The test results for the openended piles are quite unique. Two design methods are proposed for open-ended piles based on the field load test as well as on results found in the literature. In one method, pile resistances are referred to either the soil plug length or incremental filling ratio. In the other method, pile resistances are correlated to the CPT cone resistance. Comparisons of the proposed methods with the load test results and with methods currently in use are quite favorable. The present research suggests current pile design methods may be excessively conservative. It seems that cost savings from similar research, where complete measurement of all variables of interest both for the piles and for the soil deposit where the piles are installed are done, can be very substantial if the methods proposed here are validated further. It appears that such savings would be in the interest of DOT\u27s and the FHWA

IJTC2006-12158 Stability Analyses on Flexure Pivot Tilting Pad Gas Bearings for Microturbomachinery

ABSTRACT Presented are stability analyses of a flexure pivot tilting pad gas bearing with radial compliance using linearized perturbation method. The radial compliance was intended to accommodate large rotor centrifugal growth at high speeds. The rotor centrifugal growth was considered in the perturbation analyses as a physical mechanism that reduces the gas film thickness. The rotor growth reduces effective bearing clearance and could be a stabilizing mechanism at intermediate speed ranges as well as a limiting factor to the maximum achievable rotor speed for given bearing clearance and pad radial stiffness. The bearing stability was very sensitive to the bearing clearance. The smaller clearance is desirable to achieve higher stability margin at low speed ranges below 100 krpm. However, at higher speeds above 100 krpm, the larger clearances provide more stability margins. The cross-coupled stiffnesses and damping coefficients become near zero at resonance frequency of pad tilting motion, and direct stiffnesses become near zero as excitation frequency approaches the resonance frequency of pad radial motion. NOMENCLATURE INTRODUCTION Small turbomachinery require very high-speed operations to achieve meaningful power and efficiency. The high-speed operations can cause significant rotor centrifugal and thermal growth, requiring well-designed gas bearings that can absorb the rotor growths very effectively. Foil gas bearings have been sought for decades as promising bearings for various highspeed micro turbomachinery. Current applications of the gas bearings include: oil-free micro gas turbines for solid oxide fuel cell (SOFC)-micro gas turbine (MGT) hybrids [1], oil-free turbo pumps/compressors, small gas turbine generators (50~200kW), oil-free turbo chargers, etc. In this paper, flexure pivot tilting pad gas bearings with radial compliance are introduced as alternative bearings to the foil gas bearings for various micro turbomachinery applications. Tilting pad gas bearings with ball-socket joints or axial pin have very small cross-coupled stiffness [2], rendering very small cross-coupled stiffnesses. However, these tilting pad bearings cannot accommodate rotor centrifugal and thermal growth because the pivot design doesn&apos;t allow pads to move in the radial direction. Furthermore, the pivot structure is vulnerable to pivot wear due to continuous sliding contact and manufacturing cost is high. Flexure pivot tilting pad gas bearings Previous design studies In this paper, linearized perturbation analyses are introduced to provide a new insight to the complicated rotordynamics behavior which the orbit method cannot provide. Stability analyses are compared with the results from the orbit method. Dynamic force coefficients are evaluated up to 350 krpm, and effect of pad inertias and radial compliance on the force coefficients are investigated

Rotordynamic Analysis of Piezoelectric Gas Foil Bearings with a Mechanical Preload Control Based on Structural Parameter Identifications

This paper presents a rotordynamic analysis and experimental characterization of a novel concept of a controllable gas foil bearing (C-GFB) with piezoelectric (PZT) actuators. The C-GFB consists of bump foil structures and three PZT actuators, and the PZT actuators push the bump foil structures in different displacements according to the driving voltage, enabling preload control. In order to predict the piezoelectric preload according to the driving voltage, an equivalent spring model for PZT actuators and foil structures is introduced. In addition, PZT parameters (a piezoelectric constant and stiffness) are measured through parameter identification tests using a latch. Next, static lubrication analysis for C-GFB reveals that the gas-film pressure reduces the effect of piezoelectric preload by up to a maximum of 11%, because the piezoelectric actuator has structural compliance so that it is structurally deformed by the pressure. Finally, nonlinear orbit simulation is performed, and the performance of real-time vibration control of C-GFB is evaluated. The real-time preload control is carried out at ~32.6 krpm, where the rotordynamic instability sufficiently occurs. As the driving voltage increases, the instability suppression and delay effect increase. In particular, when controlled at 150 V, the onset speed of the instability increases to 79.1 krpm. Consequently, this study demonstrates that the GFB with piezoelectric preloads is a simple, effective, and real-time method to improve the rotordynamic stability

Development and Performance Measurements of Gas Foil Polymer Bearings with a Dual-Rotor Test Rig Driven by Permanent Magnet Electric Motor

The rotordynamic stability of journal gas foil&ndash;polymer bearings (GFPBs) applied to a dual-rotor bearing system was investigated. The GFPB has a high damping structure, i.e., it has an additional polymer layer, and top/bump/bottom foil structures. Test GFPBs were fabricated with nitrile butadiene rubber polymer layers with a thickness of 2 mm. Static-load-deflection tests of test gas foil bearings (GFBs) and GFPBs were performed to estimate the geometric bearing clearance (200 &micro;m). The dual-rotor rotordynamic test rig consisted of a motor rotor, test rotor, and beam-type coupling. Two journal test bearings were installed on both the drive-end and non-drive-end sides of the test rotor. Predicting and testing the natural mode characteristics of the dual rotors revealed that the relative error between them was less than 7%, indicating that the first and second natural frequencies were 15 Hz and 160 Hz, respectively, and the third natural frequency was 1835 Hz in the tests. Based on the API 612 standard, the upper limit of the rotating speed for the test rig was limited to be approximately 92 krpm with a separation margin of 26%. Rotordynamic tests were conducted to examine the stability performance of GFBs and GFPBs, where the adjusted bearing clearance was 150 &micro;m. The test results indicate that GFPBs have better stability performance in terms of delaying and suppressing unstable vibrations than GFBs. Specifically, GFPBs showed stable synchronous and subsynchronous responses up to a maximum rotating speed of 80 krpm. As a result, GFPB is a reliable lubricating element that can be used for vibration dampening in machines operating at relatively low temperatures

An Adaptive User Tracking Algorithm Using Irregular Data Frames for Passive Fingerprint Positioning

Wi-Fi fingerprinting is the most popular indoor positioning method today, representing received signal strength (RSS) values as vector-type fingerprints. Passive fingerprinting, unlike the active fingerprinting method, has the advantage of being able to track location without user participation by utilizing the signals that are naturally emitted from the user&rsquo;s smartphone. However, since signals are generated depending on the user&rsquo;s network usage patterns, there is a problem in that data are irregularly collected according to the patterns. Therefore, this paper proposes an adaptive algorithm that shows stable tracking performances for fingerprints generated at irregular time intervals. The accuracy and stability of the proposed tracking method were verified by experiments conducted in three scenarios. Through the proposed method, it is expected that the stability of indoor positioning and the quality of location-based services will improve

Development and Performance Measurements of Gas Foil Polymer Bearings with a Dual-Rotor Test Rig Driven by Permanent Magnet Electric Motor

The rotordynamic stability of journal gas foil–polymer bearings (GFPBs) applied to a dual-rotor bearing system was investigated. The GFPB has a high damping structure, i.e., it has an additional polymer layer, and top/bump/bottom foil structures. Test GFPBs were fabricated with nitrile butadiene rubber polymer layers with a thickness of 2 mm. Static-load-deflection tests of test gas foil bearings (GFBs) and GFPBs were performed to estimate the geometric bearing clearance (200 µm). The dual-rotor rotordynamic test rig consisted of a motor rotor, test rotor, and beam-type coupling. Two journal test bearings were installed on both the drive-end and non-drive-end sides of the test rotor. Predicting and testing the natural mode characteristics of the dual rotors revealed that the relative error between them was less than 7%, indicating that the first and second natural frequencies were 15 Hz and 160 Hz, respectively, and the third natural frequency was 1835 Hz in the tests. Based on the API 612 standard, the upper limit of the rotating speed for the test rig was limited to be approximately 92 krpm with a separation margin of 26%. Rotordynamic tests were conducted to examine the stability performance of GFBs and GFPBs, where the adjusted bearing clearance was 150 µm. The test results indicate that GFPBs have better stability performance in terms of delaying and suppressing unstable vibrations than GFBs. Specifically, GFPBs showed stable synchronous and subsynchronous responses up to a maximum rotating speed of 80 krpm. As a result, GFPB is a reliable lubricating element that can be used for vibration dampening in machines operating at relatively low temperatures