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At least 37 records · Page 2

FOXM1-activated SIRT4 inhibits NF-κB signaling and NLRP3 inflammasome to alleviate kidney injury and podocyte pyroptosis in diabetic nephropathy

Highlights: • FOXM1 is downregulated in kidney tissues of patients with DN. • Overexpression of FOXM1 alleviates kidney injury in DN modeled mice. • Overexpression of FOXM1 reduces pyroptosis of HG-treated podocytes. • FOXM1 activates SIRT4 to inhibit the NFκB pathway and the NLRP3 inflammasome. • Downregulation of SIRT4 blocks the protective roles of FOXM1 in podocytes and mice. Forkhead box M1 (FOXM1) has been reported to play a protective role against acute kidney injury by driving tubular regeneration. This study aims to probe the function of FOXM1 in diabetic nephropathy (DN) and the molecules involved. FOXM1 was poorly expressed in DN-diseased kidney tissues. A murine model of DN was established, and podocytes cells (MPC5) were treated with high-glucose (HG) for in vitro studies. FOXM1 overexpression improved kidney function and reduced pathological changes in mice, and it increased the expression of the podocyte marker Nephrin in kidney tissues. In vitro, FOXM1 increased viability and reduced pyroptosis of the HG-treated MPC5 cells, and it elevated the expression of the podocyte marker Nephrin whereas reduced the expression of pyroptosis-related NLRP3 inflammasome and cleaved caspase 1. FOXM1 bound to the promoter of sirtuin 4 (SIRT4) to induce transcriptional activation. Downregulation of SIRT4 blocked the protective roles of FOXM1 both in vivo and in vitro. Phosphorylation of nuclear factor-kappa B (NF-κB) in HG-treated cells was suppressed by FOXM1 but restored after SIRT4 inhibition. In conclusion, this study suggested that FOXM1 transcriptionally activates SIRT4 and inhibits NF-κB signaling and the NLRP3 inflammasome to alleviate kidney injury and podocyte pyroptosis in DN.

60 APPLIED LIFE SCIENCES↗

IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1

Localized synthesis of insulin-like growth factors (IGFs) has been broadly implicated in skeletal muscle growth, hypertrophy and regeneration. Virally delivered IGF-1 genes induce local skeletal muscle hypertrophy and attenuate age-related skeletal muscle atrophy, restoring and improving muscle mass and strength in mice. Here we show that the molecular pathways underlying the hypertrophic action of IGF-1 in skeletal muscle are similar to those responsible for cardiac hypertrophy. Transfected IGF-1 gene expression in postmitotic skeletal myocytes activates calcineurin-mediated calcium signalling by inducing calcineurin transcripts and nuclear localization of calcineurin protein. Expression of activated calcineurin mimics the effects of IGF-1, whereas expression of a dominant-negative calcineurin mutant or addition of cyclosporin, a calcineurin inhibitor, represses myocyte differentiation and hypertrophy. Either IGF-1 or activated calcineurin induces expression of the transcription factor GATA-2, which accumulates in a subset of myocyte nuclei, where it associates with calcineurin and a specific dephosphorylated isoform of the transcription factor NF-ATc1. Thus, IGF-1 induces calcineurin-mediated signalling and activation of GATA-2, a marker of skeletal muscle hypertrophy, which cooperates with selected NF-ATc isoforms to activate gene expression programs.

Non-NASA Center↗

Removal of organic contaminants by RO and NF membranes

Rejection characteristics of organic and inorganic compounds were examined for six reverse osmosis (RO) membranes and two nanofiltration (NF) membranes that are commercially available. A batch stirred-cell was employed to determine the membrane flux and the solute rejection for solutions at various concentrations and different pH conditions. The results show that for ionic solutes the degree of separation is influenced mainly by electrostatic exclusion, while for organic solutes the removal depends mainly upon the solute radius and molecular structure. In order to provide a better understanding of rejection mechanisms for the RO and NF membranes, the ratio of solute radius (r(i,s)) to effective membrane pore radius (r(p)) was employed to compare rejections. An empirical relation for the dependence of the rejection of organic compounds on the ratio r(i,s)/r(p) is presented. The rejection for organic compounds is over 75% when r(i,s)/r(p) is greater than 0.8. In addition, the rejection of organic compounds is examined using the extended Nernst-Planck equation coupled with a steric hindrance model. The transport of organic solutes is controlled mainly by diffusion for the compounds that have a high r(i,s)/r(p) ratio, while convection is dominant for compounds that have a small r(i,s)/r(p) ratio. c2005 Elsevier B.V. All rights reserved.

NASA Discipline Life Sciences Technologies↗

Flight Test of an Adaptive Controller and Simulated Failure/Damage on the NASA NF-15B

The method of flight-testing the Intelligent Flight Control System (IFCS) Second Generation (Gen-2) project on the NASA NF-15B is herein described. The Gen-2 project objective includes flight-testing a dynamic inversion controller augmented by a direct adaptive neural network to demonstrate performance improvements in the presence of simulated failure/damage. The Gen-2 objectives as implemented on the NASA NF-15B created challenges for software design, structural loading limitations, and flight test operations. Simulated failure/damage is introduced by modifying control surface commands, therefore requiring structural loads measurements. Flight-testing began with the validation of a structural loads model. Flight-testing of the Gen-2 controller continued, using test maneuvers designed in a sequenced approach. Success would clear the new controller with respect to dynamic response, simulated failure/damage, and with adaptation on and off. A handling qualities evaluation was conducted on the capability of the Gen-2 controller to restore aircraft response in the presence of a simulated failure/damage. Control room monitoring of loads sensors, flight dynamics, and controller adaptation, in addition to postflight data comparison to the simulation, ensured a safe methodology of buildup testing. Flight-testing continued without major incident to accomplish the project objectives, successfully uncovering strengths and weaknesses of the Gen-2 control approach in flight.

Buschbacher, Mark↗

nf-core/proteinfamilies: a scalable pipeline for the generation of protein families

The growth of metagenomics-derived amino acid sequence data has transformed our understanding of protein function, microbial diversity, and evolutionary relationships. However, the vast majority of these proteins remain functionally uncharacterized. Grouping the millions of such uncharacterized sequences with the few experimentally characterized ones allows the transfer of annotations, while the inspection of conserved residues with multiple sequence alignments can provide clues to function, even in the absence of existing functional information. To address the challenges associated with this data surge and the need to group sequences, we present a scalable, open-source, parametrizable Nextflow pipeline (nf-core/proteinfamilies) that generates nascent protein families or assigns new proteins to existing families. The computational benchmarks demonstrated that resource usage scales approximately linearly with input size, and the biological benchmarks showed that the generated protein families closely resemble manually curated families in widely used databases.

Nextflow↗

Materials Data on NF by Materials Project

NF is Wurtzite structured and crystallizes in the orthorhombic Cmc2_1 space group. The structure is zero-dimensional and consists of four monofluoroamine molecules. N1+ is bonded in a single-bond geometry to one F1- atom. The N–F bond length is 1.33 Å. F1- is bonded in a single-bond geometry to one N1+ atom.

36 MATERIALS SCIENCE↗

Materials Data on La2Cu(NF)2 by Materials Project

La2Cu(NF)2 crystallizes in the tetragonal I4/mmm space group. The structure is three-dimensional. La3+ is bonded in a body-centered cubic geometry to four equivalent N3- and four equivalent F1- atoms. All La–N bond lengths are 2.58 Å. All La–F bond lengths are 2.62 Å. Cu2+ is bonded in a square co-planar geometry to four equivalent N3- atoms. All Cu–N bond lengths are 2.02 Å. N3- is bonded to four equivalent La3+ and two equivalent Cu2+ atoms to form NLa4Cu2 octahedra that share corners with two equivalent NLa4Cu2 octahedra, corners with twelve equivalent FLa4 tetrahedra, edges with two equivalent NLa4Cu2 octahedra, edges with two equivalent FLa4 tetrahedra, and faces with four equivalent NLa4Cu2 octahedra. The corner-sharing octahedral tilt angles are 0°. F1- is bonded to four equivalent La3+ atoms to form FLa4 tetrahedra that share corners with twelve equivalent NLa4Cu2 octahedra, corners with four equivalent FLa4 tetrahedra, edges with two equivalent NLa4Cu2 octahedra, and edges with four equivalent FLa4 tetrahedra. The corner-sharing octahedra tilt angles range from 1–67°.

36 MATERIALS SCIENCE↗

Materials Data on ScRu(NF)6 by Materials Project

ScRu(NF)6 crystallizes in the cubic Pa-3 space group. The structure is three-dimensional. Sc3+ is bonded to six equivalent N+0.33- and six equivalent F1- atoms to form ScN6F6 cuboctahedra that share corners with six equivalent RuN6 octahedra. The corner-sharing octahedral tilt angles are 11°. All Sc–N bond lengths are 2.47 Å. All Sc–F bond lengths are 2.26 Å. Ru5+ is bonded to six equivalent N+0.33- atoms to form RuN6 octahedra that share corners with six equivalent ScN6F6 cuboctahedra. All Ru–N bond lengths are 2.01 Å. N+0.33- is bonded in a 2-coordinate geometry to one Sc3+, one Ru5+, and one F1- atom. The N–F bond length is 1.47 Å. F1- is bonded in a 1-coordinate geometry to one Sc3+ and one N+0.33- atom.

36 MATERIALS SCIENCE↗

Materials Data on FeRu(NF)6 by Materials Project

RuFe(NF)6 crystallizes in the cubic Pa-3 space group. The structure is three-dimensional. Ru5+ is bonded in an octahedral geometry to six equivalent N+0.33- atoms. All Ru–N bond lengths are 1.95 Å. Fe3+ is bonded in an octahedral geometry to six equivalent F1- atoms. All Fe–F bond lengths are 2.04 Å. N+0.33- is bonded in a 2-coordinate geometry to one Ru5+ and one F1- atom. The N–F bond length is 1.55 Å. F1- is bonded in a distorted bent 120 degrees geometry to one Fe3+ and one N+0.33- atom.

36 MATERIALS SCIENCE↗

Highly selective Si 3 N 4 /SiO 2 etching using an NF 3 /N 2 /O 2 /H 2 remote plasma. II. Surface reaction mechanism

Developing processes for highly selective etching of silicon nitride (Si 3 N 4 ) with respect to silicon dioxide (SiO 2 ) is a major priority for semiconductor fabrication processing. In this paper and in Paper I [Volynets et al., J. Vac. Sci. Technol. A 38, 023007 (2020)], mechanisms are discussed for highly selective Si3N4 etching in a remote plasma based on experimental and theoretical investigations. The Si 3 N 4 /SiO 2 etch selectivity of up to 380 was experimentally produced using a remote plasma sustained in NF 3 /N 2 /O 2 /H 2 mixtures. A selectivity strongly depends on the flow rate of H 2 , an effect attributed to the formation of HF molecules in vibrationally excited states that accelerate etching reactions. Based on experimental measurements and zero-dimensional plasma simulations, an analytical etching model was developed for etch rates as a function of process parameters. Reaction rates and sticking coefficients were provided by quantum chemistry models and also fitted to the experimental results. Etch rates from the analytical model show good agreement with the experimental results and demonstrate why certain etchants accelerate or inhibit the etch process. In particular, the modeling shows the important role of HF molecules in the first vibrationally excited state [HF( v = 1)] in achieving high Si 3 N 4 /SiO 2 selectivity.

42 ENGINEERING↗

ExpM+NF MIMIC III experiments

This code allows reproduction of results in the paper "Are Normalizing Flows the Key to Unlocking the Exponential Mechanism? " https://arxiv.org/abs/2311.09200 The code here provides implementation of our experiments where we test if we can training models with ExpM+NF alongside and in comparison with DPSGD and non-private training.

Tombs, VandyJ↗

Overexpression of the Mas1 gene mitigated LPS-induced inflammatory injury in mammary epithelial cells by inhibiting the NF-κB/MAPKs signaling pathways

Breast infection is the primary etiology of mastitis in dairy cows, leading to a reduction in the quality of dairy products and resulting in substantial economic losses for animal husbandry. Although antibiotic treatment can eliminate the pathogenic microorganisms that induce mastitis, it cannot repair the inflammatory damage of mammary epithelial cells and blood milk barrier. Mas1 is a G protein-coupled receptor, and its role in lipopolysaccharide (LPS) -induced inflammatory injury to mammary epithelial cells has not been studied. LPS treatment of EpH4 EV cells led to a significant downregulation of Mas1 transcript levels, which attracted our great interest, suggesting that Mas1 may be an important target for the treatment of mastitis. Therefore, this study intends to verify the role of Mas1 in the inflammatory injury of EpH4 EV cells by gene overexpression technology and gene silencing technology. The findings demonstrated that the overexpression of the Mas1 gene effectively reversed the activation of the nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) signaling pathways induced by LPS, while also suppressing the upregulation of pro-inflammatory mediators. Furthermore, overexpression of the Mas1 gene reversed the downregulation of zonula occludens 1 (ZO-1), Occludin, and Claudin-3 caused by LPS, suggesting that Mas1 could promote to repair the blood-milk barrier. However, the silencing of the Mas1 gene using siRNA resulted in a contrasting effect. These results indicated that Mas1 alleviated the inflammatory injury of mammary epithelial cells induced by LPS.

Yan, Shuping↗

Development and Flight Testing of a Neural Network Based Flight Control System on the NF-15B Aircraft

The Intelligent Flight Control System (IFCS) project at the NASA Dryden Flight Research Center, Edwards AFB, CA, has been investigating the use of neural network based adaptive control on a unique NF-15B test aircraft. The IFCS neural network is a software processor that stores measured aircraft response information to dynamically alter flight control gains. In 2006, the neural network was engaged and allowed to learn in real time to dynamically alter the aircraft handling qualities characteristics in the presence of actual aerodynamic failure conditions injected into the aircraft through the flight control system. The use of neural network and similar adaptive technologies in the design of highly fault and damage tolerant flight control systems shows promise in making future aircraft far more survivable than current technology allows. This paper will present the results of the IFCS flight test program conducted at the NASA Dryden Flight Research Center in 2006, with emphasis on challenges encountered and lessons learned.

Bomben, Craig R.↗

Flight Test Results from the NF-15B Intelligent Flight Control System (IFCS) Project with Adaptation to a Simulated Stabilator Failure

Adaptive flight control systems have the potential to be more resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane and subjected to an inflight simulation of a failed (frozen) (unmovable) stabilator. Formation flight handling qualities evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to decouple the roll and pitch response and reestablish good onboard model tracking. Flight evaluation with the simulated stabilator failure and adaptation engaged showed that there was generally improvement in the pitch response; however, a tendency for roll pilot-induced oscillation was experienced. A detailed discussion of the cause of the mixed results is presented.

Bosworth, John T.↗

Flight Test Results from the NF-15B Intelligent Flight Control System (IFCS) Project with Adaptation to a Simulated Stabilator Failure

Adaptive flight control systems have the potential to be more resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane and subjected to an inflight simulation of a failed (frozen) (unmovable) stabilator. Formation flight handling qualities evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to decouple the roll and pitch response and reestablish good onboard model tracking. Flight evaluation with the simulated stabilator failure and adaptation engaged showed that there was generally improvement in the pitch response; however, a tendency for roll pilot-induced oscillation was experienced. A detailed discussion of the cause of the mixed results is presented.

Bosworth, John T.↗

Flight Results of the NF-15B Intelligent Flight Control System (IFCS) Aircraft with Adaptation to a Longitudinally Destabilized Plant

Adaptive flight control systems have the potential to be resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. The goal for the adaptive system is to provide an increase in survivability in the event that these extreme changes occur. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane. The adaptive element was incorporated into a dynamic inversion controller with explicit reference model-following. As a test the system was subjected to an abrupt change in plant stability simulating a destabilizing failure. Flight evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to stabilize the vehicle and reestablish good onboard reference model-following. Flight evaluation with the simulated destabilizing failure and adaptation engaged showed improvement in the vehicle stability margins. The convergent properties of this initial system warrant additional improvement since continued maneuvering caused continued adaptation change. Compared to the non-adaptive system the adaptive system provided better closed-loop behavior with improved matching of the onboard reference model. A detailed discussion of the flight results is presented.

Bosworth, John T.↗

Flight Test Results from the NF-15B Intelligent Flight Control System (IFCS) Project with Adaptation to a Simulated Stabilator Failure

Adaptive flight control systems have the potential to be more resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane and subjected to an inflight simulation of a failed (frozen) (unmovable) stabilator. Formation flight handling qualities evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to decouple the roll and pitch response and reestablish good onboard model tracking. Flight evaluation with the simulated stabilator failure and adaptation engaged showed that there was generally improvement in the pitch response; however, a tendency for roll pilot-induced oscillation was experienced. A detailed discussion of the cause of the mixed results is presented.

Bosworth, John T.↗