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At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Momentum shift and on-shell recursion relation for electroweak theory

We study the all-line transverse (ALT) shift which we developed for on-shell recursion of amplitudes for particles of any mass. We discuss the validity of the shift for general theories of spin ≤1, and illustrate the connection between Ward identity and constructibility for massive spin-1 amplitude under the ALT shift. We apply the shift to the electroweak theory, and various four-point scattering amplitudes among electroweak gauge bosons and fermions are constructed. We show explicitly that the four-point gauge boson contact terms in massive electroweak theory automatically arise after recursive construction, independent of UV completion, and they automatically cancel the terms growing as (energy) 4 at high energy. We explore UV completion of the electroweak theory that cancels the remaining (energy) 2 terms and impose unitarity requirements to constrain additional couplings. The ALT shift framework allows consistent treatment in dealing with contact term ambiguities for renormalizable massive and massless theories, which we show can be useful in studying real-world amplitudes with massive spinors.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2015

°Enhancing High Temperature Anode Performance with 2° Anchoring Phases

Project accomplishments included developing and optimizing strength testing of aluminum titanate (ALT)-doped Ni-YSZ materials and identified the dopant levels that optimized mechanical strength and enhanced electrochemical performance. We also optimized our ability to fabricate electrolyte supported button cells with anodes consisting of powders provided by Fuel Cell Energy. In several instances, those anodes were infiltrated with ALT and tested with hydrogen for 30 hours at 800°C at an applied potential of 0.4 V. Our research activities were focused in three areas: 1) mechanical strength testing on as prepared and reducced nickel-YSZ structures that were either free of a dopant or prepared by mechanically mixing in ALT at various weight percents (up to 10 wt%); 2) 24-hour electrochemical testing of electroylte supported cells having anodes made from Ni/YSZ and Ni/YSZ/ALT anodes with specific attention focused on modeling degradation rates; and 3) operando EIS and optical testing of both in-house fabricated devices as well as membrane electrode assemblies that were acquired from commercial vendors.

25 ENERGY STORAGE↗
DOE OSTI2015

Using field observations to inform thermal hydrology models of permafrost dynamics with ATS (v0.83)

Climate change is profoundly transforming the carbon-rich Arctic tundra landscape, potentially moving it from a carbon sink to a carbon source by increasing the thickness of soil that thaws on a seasonal basis. Thus, the modeling capability and precise parameterizations of the physical characteristics needed to estimate projected active layer thickness (ALT) are limited in Earth system models (ESMs). In particular, discrepancies in spatial scale between field measurements and Earth system models challenge validation and parameterization of hydrothermal models. A recently developed surface–subsurface model for permafrost thermal hydrology, the Advanced Terrestrial Simulator (ATS), is used in combination with field measurements to achieve the goals of constructing a process-rich model based on plausible parameters and to identify fine-scale controls of ALT in ice-wedge polygon tundra in Barrow, Alaska. An iterative model refinement procedure that cycles between borehole temperature and snow cover measurements and simulations functions to evaluate and parameterize different model processes necessary to simulate freeze–thaw processes and ALT formation. After model refinement and calibration, reasonable matches between simulated and measured soil temperatures are obtained, with the largest errors occurring during early summer above ice wedges (e.g., troughs). The results suggest that properly constructed and calibrated one-dimensional thermal hydrology models have the potential to provide reasonable representation of the subsurface thermal response and can be used to infer model input parameters and process representations. The models for soil thermal conductivity and snow distribution were found to be the most sensitive process representations. However, information on lateral flow and snowpack evolution might be needed to constrain model representations of surface hydrology and snow depth.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2015

Using field observations to inform thermal hydrology models of permafrost dynamics with ATS (v0.83)

Climate change is profoundly transforming the carbon-rich Arctic tundra landscape, potentially moving it from a carbon sink to a carbon source by increasing the thickness of soil that thaws on a seasonal basis. However, the modeling capability and precise parameterizations of the physical characteristics needed to estimate projected active layer thickness (ALT) are limited in Earth System Models (ESMs). In particular, discrepancies in spatial scale between field measurements and Earth System Models challenge validation and parameterization of hydrothermal models. A recently developed surface/subsurface model for permafrost thermal hydrology, the Advanced Terrestrial Simulator (ATS), is used in combination with field measurements to calibrate and identify fine scale controls of ALT in ice wedge polygon tundra in Barrow, Alaska. An iterative model refinement procedure that cycles between borehole temperature and snow cover measurements and simulations functions to evaluate and parameterize different model processes necessary to simulate freeze/thaw processes and ALT formation. After model refinement and calibration, reasonable matches between simulated and measured soil temperatures are obtained, with the largest errors occurring during early summer above ice wedges (e.g. troughs). The results suggest that properly constructed and calibrated one-dimensional thermal hydrology models have the potential to provide reasonable representation of the subsurface thermal response and can be used to infer model input parameters and process representations. The models for soil thermal conductivity and snow distribution were found to be the most sensitive process representations. However, information on lateral flow and snowpack evolution might be needed to constrain model representations of surface hydrology and snow depth.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS1975

An evaluation of the MSBLS/nose boom interference for the approach and landing test

An analysis was performed to investigate whether or not the obstruction caused by boom-mounted probes forward of the Orbiter nose could cause Microwave Scan Beam Landing System (MSBLS) data dropout during the autoland flight phase of the Approach and Landing Test (ALT). The results indicate that there will be no interference from the nose boom to cause MSBLS data dropout for the flight conditions under which the ALT is to be performed. Additional analysis considering approach trajectories in more extreme wind conditions than anticipated for the ALT also indicates that the nose boom creates no interference.

Tate, J. M.↗
NASA NTRS1981

Global satellite measurements of water vapour, wind speed and wave height

The results of global measurements of atmospheric water vapor by the Seasat Scanning Multichannel Microwave Radiometer and wave height and wind speed by the Seasat altimeter (ALT) are reported. The 13.5 GHz ALT has a 3.125 ns pulsewidth and 1022 Hz repetition rate, and measures surface height to a resolution exceeding 10 cm celative to a reference ellipsoid. Full ALT data comprise 135 km equatorial groundtracks, with about a 50 cm difference of sea wave height compared to buoy reference measurements, and windspeed accuracy to within 0.25-1.58 m/sec up to 20 m/sec. Highest water vapor concentrations were observed in the tropics and the lowest at high latitudes. Wind speeds were highest for the north-east and south-east tradewinds in both the Atlantic and Pacific oceans. Average wave height is small in the summer North Hemisphere and the largest waves are in the winter Southern ocean, and lowest in western Atlantic and Pacific ocean areas where winds are lightest.

Chelton, D. B.↗
NASA NTRS1982

Intercomparison of wind speeds inferred by the SASS, altimeter, and SMMR

The operational theory, control algorithms, and comparisons with surface-determined wind speeds for the scatterometer (SASS), altimeter (ALT), and passive microwave radiometer (SMMR) on board the Seasat satellite are presented. Radiative scattering combining specular reflections and Bragg resonance scattering are noted to occur at tilting waves and sea foam, two conditions highly correlated with wind speed. SASS scans swaths of 70, 200, and 700 km from nadir, the SMMR covers a 150 km strip. Normalized radar sections are derived from the SASS and ALT telemetry, and brightness temperature from the SMMR. ALT winds were found to be biased about 3 m/sec low, while intercomparison between the SMMR and SASS data showed a mean difference of 0.3 m/sec with a standard deviation from measured winds of 1.7 m/sec or less. The effects of land thermal emissions, rain, and sun glint are discussed, and good viewing conditions are concluded to result in 2 m/sec accuracy.

Wentz, F. J.↗
NASA NTRS2005

The Mega Mesospheric Parachute

The current understanding and modeling of the upper reaches of the atmosphere is incomplete. Upper atmospheric interactions with the lower atmosphere, effects of ionizing radiation, high altitude cloud phenomena, and the dynamical interaction with the magnetosphere require greater definition. The scientific objective of obtaining a greater understanding of the upper atmosphere can be achieved by designing, implementing, testing, and utilizing a facility that provides long period in-situ measurements of the mesosphere. Current direct sub-sonic measurements of the upper atmosphere are hampered by the approximately one minute sub-sonic observation window of a ballistic sounding rocket regardless of the launch angle. In-situ measurements at greater than transonic speeds impart energy into the molecular atmospheric system and distort the true atmospheric chemistry. A long duration, sub-sonic capability will significantly enhance our ability to observe and measure: (1) mesospheric lightning phenomena (sprites and blue jets) (2) composition, structure and stratification of noctilucent clouds (3) physics of seasonal radar echoes, gravity wave phenomena (4) chemistry of mesospheric gaseous ratio mixing (5) mesospheric interaction of ionizing radiation (6) dynamic electric and magnetic fields This new facility will also provide local field measurements which complement those that can be obtained through external measurements from satellite and ground-based platforms. The 400 foot (approximately 130 meter) diameter lightweight mega-mesospheric parachute system, deployed with a sounding rocket, is proposed herein as a method to increase sub-sonic mesospheric measurement time periods by more than an order of magnitude. The report outlines a multi-year evolving science instrumentation suite in parallel with the development of the mega meso-chute facility. The developmental issues surrounding the meso-chute are chiefly materials selection (thermal and structural) and deployment mechanism physics. Three mission cases were conceived and developed to include cost and schedules estimates. Each scenario has increasing scientific utility with paralleling launch weight, parachute hang-time, deployment altitude, and parachute size: (1) Case #1: $8.4M@24 months, 6kg payload, 20 min., 50km alt., 80 m. dia. (2) Case #2: $10.4M@24 months, 6kg payload, 20 min., 60km alt, 130m. dia. (3) Case #3: $13.6M@36 months, 30kg payload, 30 min., 90km alt., 200m. dia. The initial breakout cost for the parachute system is approximately $2M@24 months. This report identifies that although the challenges of the mega-meso-chute may be difficult, they can be surmounted and valuable results can be achieved.

Kloesel, Kurt J.↗
DOE OSTI2014

New understandings of failure modes in SSL luminaires

As SSL products are being rapidly introduced into the market, there is a need to develop standard screening and testing protocols that can be performed quickly and provide data surrounding product lifetime and performance. These protocols, derived from standard industry tests, are known as ALTs (accelerated life tests) and can be performed in a timeframe of weeks to months instead of years. Accelerated testing utilizes a combination of elevated temperature and humidity conditions as well as electrical power cycling to control aging of the luminaires. In this study, we report on the findings of failure modes for two different luminaire products exposed to temperature-humidity ALTs. LEDs are typically considered the determining component for the rate of lumen depreciation. However, this study has shown that each luminaire component can independently or jointly influence system performance and reliability. Material choices, luminaire designs, and driver designs all have significant impacts on the system reliability of a product. From recent data, it is evident that the most common failure modes are not within the LED, but instead occur within resistors, capacitors, and other electrical components of the driver. Insights into failure modes and rates as a result of ALTs are reported with emphasis on component influence on overall system reliability.

Shepherd, Sarah D↗
DOE OSTI2026

Bemnifosbuvir: An HCV NS5B Inhibitor With Multiple Modes of Action

Bemnifosbuvir (BEM) is a potent, pan-genotypic inhibitor targeting the hepatitis C virus (HCV) NS5B polymerase. Its antiviral activity was evaluated in an ascending dose phase I clinical trial involving 30 patients treated once a day for 7 days. After treatment initiation, plasma HCV RNA declined in a biphasic manner with a mean reduction of 2.3 log 10 IU/mL after 24 hours and 4.4 log10 IU/mL by day 7 for the highest dose. Alanine aminotransferase (ALT) also normalized in most patients. We employed a multiscale mathematical model fitted to the HCV RNA and ALT dynamics to quantify the antiviral activity and evaluate the modes of action of BEM. We found that models in which BEM only acted as a typical HCV RNA polymerase inhibitor and reduced the intracellular production of HCV RNA did not fit the data as well as models in which BEM had multiple modes of action, including suppressing viral assembly and secretion and enhancing intracellular HCV RNA degradation. BEM's effectiveness in inhibiting intracellular HCV RNA production increased with dose (150 mg/day: 88.2%, 300 mg/day: 98.8%, 600 mg/day: 99.5%), while inhibition of viral assembly and release was ~95% effective regardless of dose. We observed a dose-dependent enhancement in the degradation of intracellular HCV RNA, with degradation rates 1.5-fold higher in patients receiving 300 mg/day and 2.7-fold higher in those receiving 600 mg/day than in patients receiving 150 mg/day. No significant differences in antiviral activity were detected between HCV genotypes 1b and 3 or between patients with and without compensated cirrhosis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Improved ambient-stable perovskite solar cells enabled by a hybrid polymeric electron-transporting layer

In this study, an efficient inverted perovskite solar cell with decent ambient stability is successfully demonstrated by employing an n-type polymer, poly{[ N,N’ -bis(2-octyldodecyl)- 1,4,5,8-naphthalene diimide-2,6-diyl]- alt -5,5’-(2,2’-bithiophene)} (N2200), as the electron-transporting layer (ETL). The device performance can be further enhanced from a power conversion efficiency (PCE) of 15 to 16.8% by tailoring the electronic properties of N2200 with a polymeric additive, poly[9,9-bis(6’- ( N,N’ -diethylamino)propyl)-fluorene- alt -9,9-bis(3-ethyl(oxetane- 3-ethyloxy)-hexyl) fluorene] (PFN-Ox). More importantly, the device derived from this hybrid ETL can maintain good ambient stability inherent from the pristine N2200 ETL, for which 60–70% of initial PCE can be retained after being stored in air with 10–20% humidity for 45 days.

14 SOLAR ENERGY↗
DOE OSTI2016

Cryoablation of Hepatocellular Carcinoma with High-Risk for Percutaneous Ablation: Safety and Efficacy

PurposeThe aim of this study was to evaluate the safety and effectiveness of cryoablation in the treatment of subcapsular hepatocellular carcinoma (HCC) adjacent to various organs.Materials and MethodsTwenty-eight patients with subcapsular HCC were treated with cryoablation in our institution. The degree of peri-procedural pain was measured using the visual analog scale (VAS). Technical success, local tumor progression, and overall disease progression rates were calculated. Procedure-related complications were identified by reviewing electronic medical records. Biochemical data, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels before and after the procedure were collected.ResultsSubcapsular HCC tumors were located near the gallbladder, colon, stomach, kidney, diaphragm, or abdominal wall. The technical success rate of cryoablation was 96.4 % (27/28). Local recurrence- and progression-free survival rates were 96 and 84 % at 6 months, and 82 and 43 % at 1 year, respectively. All patients survived during the follow-up period. The VAS pain score ranged from 0 to 3 (mean, 1.57). A major complication occurred in one patient (3.6 %) and minor complications occurred at a rate of 17.9 %. Transient elevations of serum AST, ALT, and bilirubin levels were observed.ConclusionCryoablation is a safe and an effective procedure for the treatment of subcapsular HCC adjacent to various major organs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Suppression of telomere-binding protein TPP1 resulted in telomere dysfunction and enhanced radiation sensitivity in telomerase-negative osteosarcoma cell line

Highlights: • Down-regulation of TPP1 shortened telomere length in telomerase-negative cells. • Down-regulation of TPP1 induced cell apoptosis in telomerase-negative cells. • Down-regulation of TPP1 increased radiosensitivity in telomerase-negative cells. - Abstract: Mammalian telomeres are protected by the shelterin complex that contains the six core proteins POT1, TPP1, TIN2, TRF1, TRF2 and RAP1. TPP1, formerly known as TINT1, PTOP, and PIP1, is a key factor that regulates telomerase recruitment and activity. In addition to this, TPP1 is required to mediate the shelterin assembly and stabilize telomere. Previous work has found that TPP1 expression was elevated in radioresistant cells and that overexpression of TPP1 led to radioresistance and telomere lengthening in telomerase-positive cells. However, the exact effects and mechanism of TPP1 on radiosensitivity are yet to be precisely defined in the ALT cells. Here we report on the phenotypes of the conditional deletion of TPP1 from the human osteosarcoma U2OS cells using ALT pathway to extend the telomeres.TPP1 deletion resulted in telomere shortening, increased apoptosis and radiation sensitivity enhancement. Together, our findings show that TPP1 plays a vital role in telomere maintenance and protection and establish an intimate relationship between TPP1, telomere and cellular response to ionizing radiation, but likely has the specific mechanism yet to be defined.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Protective effects of Sapindus mukorossi Gaertn against fatty liver disease induced by high fat diet in rats

Highlights: • AESM is able to prevent the elevation of ALT and AST, and to decreased LDL-C level. • AESM demonstrates the effects of down-regulating blood fat level and protecting liver. • AESM consistent with the efficacy of simvastatin in NAFLD. - Abstract: Objectives: Study the effects of alcohol extract of Sapindus mukorossi Gaertn (AESM) on the metabolism of blood fat, morphology of fenestrated liver sinusoidal endothelial cells (LSEC), and the ultrastructure of liver cells of the rats with non-alcoholic fatty liver disease (NAFLD). Methods: Divide SD rats into control group, model group, simvastatin (7.2 mg/kg) group, and S.mukorossi Gaertn group with high dosage (0.5 g/kg), moderate dosage (0.1 g/kg), and low dosage (0.05 g/kg). After feeding with fat-rich nutrients for 3 weeks and establishing the model of hepatic adipose, conduct intragastric administration and provide the rats with fat-rich nutrients at the same time. At the 43rd day, take blood sample and measure aminotransferase and different indexes of blood fat; take hepatic tissue for pathological section, and observe the hepatic morphological patterns under light microscope; obtain and fix the hepatic tissue after injecting perfusate into the body, and observe the changes of fenestrated LSEC under scanning electron microscope; observe the ultrastructure of liver cells under transmission electron microscope. Results: High-dosage alcohol extracts of S.mukorossi Gaertn can alleviate the AST, ALT, TC, TG, LDL, γ-GT, and ALP level, as well as raise the HDL and APN level in the serum of NAFLD-rat model. In addition, through the observation from light microscope and electron microscopes, the morphology of the hepatic tissue and liver cells as well as the recovery of the fenestrated LSEC in the treatment group has become normal. Conclusions: Alcohol extracts of S.mukorossi Gaertn can regulate the level of blood fat and improve the pathological changes of the hepatic tissues in NAFLD-rat model, which demonstrates the effects of down-regulating fat level and protecting liver.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Adaptive harnessing damping in hydrokinetic energy conversion by two rough tandem-cylinders using flow-induced vibrations

Alternating lift technology (ALT) harnesses hydrokinetic energy from currents and tides and is different from conventional steady lift technologies (turbines). ALT is still under development with an important research issue being the mitigation of wake effect on downstream cylinders in Flow Induced Oscillations (FIO) of multi-cylinder Current Energy Converters (CEC). Rather than adjust the configuration/parameters of the converter, a more direct and effective way is to actively adjust the harnessed power. In this paper, a hydrokinetic energy converter using FIO of two cylinders in tandem in one-degree-of-freedom oscillators, with nonlinear adaptive damping and linear spring stiffness, is tested experimentally. FIO include Vortex Induced Vibrations (VIV), galloping, and their coexistence. Introducing adaptive damping into the tandem cylinders overcomes the shielding effect, which previous research on two tandem cylinders has shown to reduce power output by the downstream cylinder. Shielding along with fixed damping result either in ceasing motion due to excessive damping, or in low harnessed energy due to insufficient damping. In this experimental study, damping-to-velocity rate, linear spring-stiffness, cylinder spacing, and flow-velocity are the parameters with Reynolds number 30,000 ≤ Re ≤ 120,000. Comparison to linear-oscillators in FIO shows that this nonlinear converter, with velocity-proportional damping coefficient, is more effective over the entire FIO range but especially in galloping, where both flow and cylinder speeds are higher. Experimental results for energy harvesting, efficiency and instantaneous energy of the converter are presented and discussed supported by amplitude and frequency response data. Here the results show that the nonlinear, adaptive, velocity-proportional damping coefficient is an effective way to increase the overall harnessed power and the power of downstream cylinder. The harnessed power in the VIV to galloping transition increases by up to 94%. The most significant improvement is in the galloping region, where the increase in harnessed power and efficiency is around 33%.

13 HYDRO ENERGY↗
DOE OSTI2021

A comprehensive review of nonlinear oscillators in hydrokinetic energy harnessing using flow-induced vibrations

A comprehensive review of hydrokinetic energy converters based on alternating lift technology (ALT) is provided. Emphasis is on nonlinear oscillators based on Flow Induced Vibration (FIV) or Oscillation (FIO). Due to strong coupling in Fluid-Structure Interaction (FSI), and in order to maximize the hydrokinetic harnessed energy, design of nonlinear oscillators and analysis by model tests or computational fluid dynamics dominates this area. Research confirmed that the nonlinear oscillator can harvest energy from a stochastic excitation modeled by a generic wide spectrum, and overcome the most severe oscillator limitations: specifically, the need for continuous frequency tuning due to the narrow bandwidth response, and low efficiency outside the narrow bandwidth oscillator response. This review covers the following aspects of nonlinear oscillators in ALT converters: (1) Geometric changes in oscillator cross-section; e.g., circular, square, rectangular, or trilateral shapes. (2) Passive turbulence control of FIV/FIO. (3) Position based nonlinear stiffness. (4) Multi-cylinder synergistic FIV/FIO. (5) Mechanically linked oscillators. (6) Velocity-based, nonlinear, adaptive harnessing damping.

42 ENGINEERING↗
DOE OSTI2012

Thromboxane A{sub 2} receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment

It is thought that thromboxane A{sub 2} (TxA{sub 2}) contributes to the progression of inflammation during acute hepatic injury; however, it is still unknown whether TxA{sub 2} is involved in liver repair. The objective of the present study was to examine the role of TxA{sub 2} receptor (TP) signaling in liver injury and repair in response to toxic injury. Carbon tetrachloride (CCl{sub 4}) was used to induce liver injury in TP knockout (TP{sup −/−}) mice and wild-type (WT) mice. In WT mice, serum levels of alanine aminotransferase (ALT) and the size of the necrotic area peaked at 24 and 48 h, respectively, and then declined. In TP{sup −/−} mice, the changes in ALT levels were similar to WT mice, but liver regeneration was impaired as evidenced by remained elevated levels of hepatic necrosis and by delayed hepatocyte proliferation, which was associated with the reduced expression of growth factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and hepatocyte growth factor (HGF). In TP{sup −/−} mice, the accumulation of hepatic CD11b{sup +}/F4/80{sup +} macrophages in injured livers was attenuated, and the hepatic expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, the C―C chemokine receptor (CCR2), was reduced compared to WT. Additionally, the application of the TP receptor agonist, U-46619, enhanced the expression of MCP-1/CCL2 and CCR2 in peritoneal macrophages, which was associated with increased levels of IL-6, TNFα and HGF. These results suggested that TP receptor signaling facilitates liver recovery following CCl{sub 4}-induced hepatotoxicity by affecting the expression of hepatotrophic growth factors, and through the recruitment of macrophages mediated by MCP-1/CCL2-CCR2 expression. -- Highlights: ► TP enhances liver regeneration by CCl{sub 4}. ► TP accumulates macrophages. ► TP up-regulates MCP-1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Nrf2 activation prevents cadmium-induced acute liver injury

Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H{sub 2}DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice were resistant to cadmium-induced liver injury. ► Cadmium increased ROS in hepatocytes isolated from Nrf2-null and wild-type mice. ► Mt-1 and Mt‐2 were induced over 200-fold in both Nrf2-null and Nrf2-enhanced mice. ► Gclc, Gpx2, and Srxn-1 were induced in Nrf2-enhanced mice, not in Nrf2-null mice.

60 APPLIED LIFE SCIENCES↗