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At least 631 records · Page 35
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Coordination and Control of Building HVAC Systems to Provide Frequency Regulation to the Electric Grid

Buildings consume 73% of electricity produced in the United States and, currently, they are largely passive participants in the electric grid. However, the flexibility in building loads can be exploited to provide ancillary services to enhance the grid reliability. In this paper, we investigate two control strategies that allow Heating, Ventilation and Air-Conditioning (HVAC) systems in commercial and residential buildings to provide frequency regulation services to the grid while maintaining occupants comfort. The first optimal control strategy is based on model predictive control acting on a variable air volume HVAC system (continuously variable HVAC load), which is available in large commercial buildings. The second strategy is rule-based control acting on an aggregate of on/off HVAC systems, which are available in residential buildings in addition to many small to medium size commercial buildings. Hardware constraints that include limiting the switching between the different states for on/off HVAC units to maintain their lifetimes are considered. Furthermore, simulations illustrate that the proposed control strategies provide frequency regulation to the grid, without affecting the indoor climate significantly.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2013

High Penetration Photovoltaic Case Study Report

Technical concerns with integrating higher penetrations of photovoltaic (PV) systems include grid stability, voltage regulation, power quality (voltage rise, sags, flicker, and frequency fluctuations), and protection and coordination. The current utility grid was designed to accommodate power flows from the central generation source to the transmission system and eventually to the distribution feeders. At the distribution level, the system was designed to carry power from the substation toward the load. Renewable distributed generation, particularly solar PV, provides power at the distribution level challenging this classical paradigm. As these resources become more commonplace the nature of the distribution network and its operation is changing to handle power flow in both directions. A large portion of distribution system components, including voltage regulators and protection systems, were not designed to coordinate with bidirectional power flow and bidirectional fault currents from distributed generation and PV systems in particular. Coordinating these devices in the presence of high penetration PV areas introduces additional challenges to feasibility and system impact studies. Some cases require modification of existing protection schemes, additional distribution equipment, or reactive power requirements on the PV inverters. This report is focused on large PV installations in which penetration is significantly greater than 15% of maximum daytime feeder load. To date the impact on the electric utility and its customers has not been problematic in any of these cases. The PV system installations described in this report exceeds what most experts consider high penetration scenarios. The voltage, power quality, and other operating parameters have been maintained within the required ranges with minimal negative impact on distribution operations and utility customers. These case studies are intended to demonstrate success stories with integration of large PV plants at the distribution level as well as some of the solutions used by the utility to ensure safe, reliable operation of both the PV system and the distribution network.

14 SOLAR ENERGY↗
DOE OSTI2020

Middlesex South FUSRAP Site: Collaboration Towards Beneficial Reuse - 20338

The US Department of Energy (DOE) Office of Legacy Management (LM) manages DoE's post-closure responsibilities and ensures the future protection of human health and the environment with respect to sites that have no continuing DOE mission after undergoing remediation. LM's beneficial reuse program promotes the LM strategic goal to sustainably manage and optimize use of public lands. The beneficial reuse program aims to repurpose former contaminated sites to restore the environment, protect the public health, revitalize communities, and spur economic growth. Benefits from the reuse of a site may increase the local tax base, facilitate job growth, utilize existing infrastructure, and enhance or protect natural resources. Beneficial reuse also promotes protectiveness by ensuring activities are compatible with long-term maintenance and protection of public health and the environment, as well as by retaining good stewardship of natural resources. LM actively participates in promoting the economic development vision of the surrounding communities by collaborating with local communities to promote regional or municipal initiatives. The Borough of Middlesex, New Jersey, has prepared the Lincoln Boulevard Redevelopment Plan, which will reinvent a once-viable downtown and enhance the quality of life for the community. The Middlesex South, New Jersey, Formerly Utilized Sites Remedial Action Program (FUSRAP) site lies within the boundaries of this redevelopment area. In support of this development plan, the Borough is interested in acquiring the site for its Department of Public Works and to increase street access in the future commercial district to be built near adjacent properties. The opportunity to put the FUSRAP site into productive use aligns with LM's mission and strategic goals. In support of beneficial reuse activities, DOE can dispose of excess real property using several mechanisms. The two disposal options applicable to the Middlesex south site include (1) utilizing the US General Services Administration (GSA) or (2) using the Title 10 Code of Federal Regulations Section 770, 'Transfer of Real Property at Defense Nuclear Facilities for Economic Development' (known as a '770 transfer') process. Using the 770 transfer requires economic development as the primary driver, and a specific redevelopment proposal must be submitted. If there is no interest in specific economic development, the GSA option becomes the default mechanism for disposal of the property. In the case of the Middlesex south site, the 770 transfer process is being utilized and the Borough has submitted its economic development proposal to LM. Although LM is encouraged by the opportunity to put the site into productive use, the Middlesex south site is currently on the US Environmental Protection Agency (EPA) National Priorities List and remediation is being performed by the US Army Corp of Engineers (USACE) under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Consequently, any property transfer must meet the requirements under CERCLA Section 120(h), 'Property Transferred by Federal Agencies.' As the groundwater remedy will not be in place for several years, approval would be required from the US EPA administrator and the governor of the state of New Jersey to perform an early transfer of the site (before all response actions have been completed). The time frame for these approvals to occur under the normal process conflicts with the proposed redevelopment schedule; therefore, various options for expedited sale, transfer, or lease of portions of the site to the Borough were evaluated. The subsequent decision on a mutually beneficial path forward was the result of a collaborative effort between LM, USACE, the Borough and its redevelopment team, EPA, and the New Jersey Department of Environmental Protection. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2017

Hydrological Drought in the Anthropocene: Impacts of Local Water Extraction and Reservoir Regulation in the U.S.

Hydrological drought is a substantial negative deviation from normal hydrologic conditions and is influenced by climate and human activities such as water management. By perturbing the streamflow regime, climate change and water management may significantly alter drought characteristics in the future. Here we utilize a high-resolution integrated modeling framework that represents water management in terms of both local surface water extraction and reservoir regulation, and use the Standardized Streamflow Index (SSI) to quantify hydrological drought. We explore the impacts of water management on hydrological drought over the contiguous US in a warming climate with and without emissions mitigation. Despite the uncertainty of climate change impacts, local surface water extraction consistently intensifies drought that dominates at the regional to national scale. However, reservoir regulation alleviates drought by enhancing summer flow downstream of reservoirs. The relative dominance of drought intensification or relief is largely determined by the water demand, with drought intensification dominating in regions with intense water demand such as the Great Plains and California, while drought relief dominates in regions with low water demand. Here, at the national level, water management increases the spatial extent of extreme drought despite some alleviations of moderate to severe drought. In an emissions mitigation scenario with increased irrigation demand for bioenergy production, water management intensifies drought more than the business-as-usual scenario at the national level, so the impacts of emissions mitigation must be evaluated by considering its benefit in reducing warming and evapotranspiration against its effects on increasing water demand and intensifying drought.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2012

Impact of ArcA loss in Shewanella oneidensis revealed by comparative proteomics under aerobic and anaerobic conditions

Shewanella inhabit a wide variety of niches in nature and can utilize a broad spectrum of electron acceptors under anaerobic conditions. How they modulate their gene expression to adapt is poorly understood. ArcA, homologue of a global regulator controlling hundreds of genes involved in aerobic and anaerobic respiration in E. coli, was shown to be important in aerobiosis/anaerobiosis of S. oneidensis as well. Loss of ArcA, in addition to altering transcription of many genes, resulted in impaired growth under aerobic condition, which was not observed in E. coli. To further characterize the impact of ArcA loss on gene expression on the level of proteome under aerobic and anaerobic conditions, liquid-chromatography-mass-spectrometry (LC-MS) based proteomic approach was employed. Results show that ArcA loss led to globally altered gene expression, generally consistent with that observed with transcripts. Comparison of transcriptomic and proteomic data permitted identification of 17 high-confidence ArcA targets. Moreover, our data indicate that ArcA is required for regulation of cytochrome c proteins, and the menaquinone level may play a role in regulating ArcA as in E. coli. Proteomic-data-guided growth assay revealed that the aerobic growth defect of ArcA mutant is presumably due to impaired peptide utilization.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2012

Reducing Conservatism in Aircraft Engine Response Using Conditionally Active Min-Max Limit Regulators

Current aircraft engine control logic uses a Min-Max control selection structure to prevent the engine from exceeding any safety or operational limits during transients due to throttle commands. This structure is inherently conservative and produces transient responses that are slower than necessary. In order to utilize the existing safety margins more effectively, a modification to this architecture is proposed, referred to as a Conditionally Active (CA) limit regulator. This concept uses the existing Min-Max architecture with the modification that limit regulators are active only when the operating point is close to a particular limit. This paper explores the use of CA limit regulators using a publicly available commercial aircraft engine simulation. The improvement in thrust response while maintaining all necessary safety limits is demonstrated in a number of cases.

May, Ryan D.↗
DOE OSTI2017

Potential For Plug-In Electric Vehicles To Provide Grid Support Services

Since the modern-day introduction of plug-in electric vehicles (PEVs), scientists have proposed leveraging PEV battery packs as distributed energy resources for the electric grid. PEV charging can be controlled not only to provide energy for transportation but also to provide grid services and to facilitate the integration of renewable energy generation. With renewable generation increasing at an unprecedented rate, most of which is non-dispatchable and intermittent, the concept of using PEVs as controllable loads is appealing to electric utilities. This additional functionality could also provide value to PEV owners and drive PEV adoption. It has been widely proposed that PEVs can provide valuable grid services, such as load shifting to provide voltage regulation. The objective this work is to address the degree to which PEVs can provide grid services and mutually benefit the electric utilities, PEV owners, and auto manufacturers.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2024

PV-BESS DC-Series Integration for Regulated DC Systems

DC-series integration introduces a novel approach to seamlessly integrate a solar photovoltaic (PV) array and a battery energy storage (BES) in series. This system, referred to as the PV-integrated battery energy storage system—dc series (PVBESS-DCS), simplifies integration and enhances power density by leveraging the inherent voltage-source characteristics of batteries and adopting the concept of partial power processing. However, addressing voltage variations of a PV array and a BES under different operational conditions remains a challenge to apply the PVBESS-DCS to a regulated dc system, where the dc-bus voltage is fixed. This article proposes a PVBESS-DCS solution tailored for regulated dc systems. Within this framework, we present a controllable series voltage source compensating for the voltage differences between the PV and BES sources and the dc bus. Thus, the system can perform PV maximum power point tracking and curtailment control while charging and discharging BES and connected to a regulated dc bus. Additionally, we present a single-stage multiport partial power processing dc–dc converter designed for the proposed PVBESS-DCS. It utilizes a triple active bridge dc–dc converter topology. Finally, this article presents operating principles, control strategies, simulation results, and experimental findings of the proposed PVBESS-DCS for regulated dc systems.

25 ENERGY STORAGE↗
NASA NTRS1997

Gene Regions Responding to Skeletal Muscle Atrophy

Our stated specific aims for this project were: 1) Identify the region(s) of the mouse IIb myosin heavy chain (MHC) promoter necessary for in vivo expression in mouse fast-twitch muscle, and 2) Identify the region(s) of the mouse IIb MHC promoter responsive to immobilization in mouse slow-twitch muscle in vivo. We sought to address these specific aims by introducing various MHC IIb promoter/reporter gene constructs directly into the tibialis anterior and gastrocnemius muscles of living mice. Although the method of somatic gene transfer into skeletal muscle by direct injection has been successfully used in our laboratory to study the regulation of the skeletal alpha actin gene in chicken skeletal muscle, we had many difficulties utilizing this procedure in the mouse. Because of the small size of the mouse soleus and the difficulty in obtaining consistent results, we elected not to study this muscle as first proposed. Rather, our MHC IIb promoter deletion experiments were performed in the gastrocnemius. Further, we decided to use hindlimb unloading via tail suspension to induce an upregulation of the MHC IIb gene, rather than immobilization of the hindlimbs via plaster casts. This change was made because tail suspension more closely mimics spaceflight, and this procedure in our lab results in a smaller loss of overall body mass than the mouse hindlimb immobilization procedure. This suggests that the stress level during tail suspension is less than during immobilization. This research has provided an important beginning point towards understanding the molecular regulation of the MHC lIb gene in response to unweighting of skeletal muscle Future work will focus on the regulation of MHC IIb mRNA stability in response to altered loading of skeletal muscle

Booth, Frank W.↗
DOE OSTI2022

Implementation of a Model Predictive Control Strategy to Regulate Temperature Inside Plug-Flow Solar Reactor With Countercurrent Flow

Abstract Solar-driven thermochemical energy storage systems are proven to be promising energy carriers (solar fuels) to utilize solar energy by using reactive solid-state pellets. However, the production of solar fuel requires a quasi-steady-state process temperature, which represents the main challenge due to the transient nature of solar power. In this work, an adaptive model predictive controller (MPC) is presented to regulate the temperature inside a tubular solar reactor to produce solid-state solar fuel for long-term thermal storage systems. The solar reactor system consists of a vertical tube heated circumferentially over a segment of its length by concentrated solar power, and the reactive pellets (MgMn2O4) are fed from the top end and flow downwards through the heated tube. A countercurrent flowing gas supplied from the lower end interacts with flowing pellets to reduce it thermochemically at a temperature range of 1000—1500 °C. A low-order physical model was developed to simulate the dynamics of the solar reactor including the reaction kinetics, and the proposed model was validated numerically by using a 7-kW electric furnace. The numerical model then was utilized to design the MPC controller, where the control system consists of an MPC code linked to an adaptive system identification code that updates system parameters online to ensure system robustness against external disturbances (sudden change in the flow inside the reactor), model mismatches, and uncertainty. The MPC controller parameters are tuned to enhance the system performance with minimum steady-state error and overshoot. The controller is tested to track different temperature ranges between 500 °C and 1400 °C with different particles/gas mass flowrates and ramping temperature profiles. Results show that the MPC controller successfully regulated the reactor temperature within ± 1 °C of its setpoint and maintained robust performance with minimum input effort when subjected to sudden changes in the amount of flowing media and the presence of chemical reaction.

Engineering↗
DOE OSTI2018

Distributed Control Strategy to Achieve Synchronized Operation of an Islanded MG

To seamlessly transition a microgrid (MG) from islanded to grid-connected mode, it is necessary to synchronize the magnitude, frequency, and phase of the MG voltage to the voltage of the main grid. In this paper, we present a distributed control strategy to achieve synchronized operation of an islanded MG supported by multiple controllable distributed generators (DGs). The proposed method utilizes pinning-based consensus algorithm to ensure explicit coordination between magnitude, frequency and phase angle regulation, while ensuring proportional power sharing. System frequency is regulated by all the DGs in proportion to their capacity, while a selected DG eliminates the phase and magnitude regulation errors. Controller design criteria is based on small-signal stability analysis. Here, the proposed control strategy is implemented in hardware controllers and its effectiveness is demonstrated using a real-time hardware-in-the-loop MG testbed.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2023

Faster-than-real-time Simulation with Demonstration for Resilient DER Integration

The US electric grid is facing operational, stability, and security challenges. Transmission system operators need some measure of visibility into distribution system renewable generation. Distribution system generation needs to support transmission system voltage. The grid is experiencing an expansion in measurement systems. How to take full advantage of this expansion and defend against attacks, both cyber and physical, poses additional challenges. The Faster-than-real-time Simulation with demonstration for Resilient DER Integration project set out to do the following: a. Flatten the voltage profile through the feeders and system for cost saving and voltage stabilization needs. b. Increase the amount of intermittent distributed energy resources (IDERs) that could be deployed on a utility feeder and provide 100% or more energy needed for the demands on that feeder, and c. based on an accurate model (Digital Twin) of the utilities system, be able to detect any abnormalities on the utilities distribution system. To manage the voltage and increase IDER penetration (a,b), Graph Trace Analysis is employed in a time-series, optimal power flow to coordinate the time-varying feedback control setpoints of a distribution feeder’s utility control devices. Under the coordinated control are a Load Tap Changing Transformer, a voltage regulator, and five switched capacitor banks. The feeder serves over 2000 customers, the feeder secondaries are modeled, and the feeder has 2.3 MW of PV generation, corresponding to a 17.4% penetration of PV generation. The feeder model has over 12,000 components, where every customer load bus and PV generator are modeled. The accuracy of the power flow solution is compared against historical meter voltage measurements, the improvement in conservation voltage reduction energy savings as a function of the coordinated control desired voltage profile is investigated, and the increase in PV penetration of the coordinated control over the existing control is presented. To achieve improved control performance while observing system operation constraints, bellwether Advanced Metering Infrastructure (AMI) voltage measurements are used to adjust the desired voltage profile used by the optimal power flow analysis. To detect and alleviate or negate attacks or failures on the distribution and transmission utility grids (c) the grid needs to be resilient and self-healing. In this project software was designed to do just that. At the center of the software is an Integrated System Model (ISM) that spans from transmission to secondary distribution. The ISM is employed in real-time abnormality detection, voltage stability forecasting, and multi-mode control. Testing results are presented for: 1—attacks on utility infrastructure; 2—energy savings from optimal control; 3—distribution system control response during a low voltage transmission system event; 4—cyber-attacks on PV inverters, where physical inverters are used in hard-ware-in-the-simulation-loop studies. Contributions of this work include real-time analysis that spans from three-phase transmission through secondary distribution; an approach for detecting abnormalities that employs measurements from three independent measurement systems; and a multi-mode distribution system control that responds to cyber-attacks, physical attacks, equipment failures, and transmission system needs.

Integrated System Model, Graph Trace Analysis, Adv↗
NASA NTRS1973

An advanced regulator for the helium pressurization systems of the Space Shuttle OMS and RCS

The Space Shuttle Orbit Maneuvering System and Reaction Control System are pressure-fed rocket propulsion systems utilizing earth storable hypergolic propellants and featuring engines of 6000 lbs and 900 lbs thrust, respectively. The helium pressurization system requirements for these propulsion systems are defined and the current baseline pressurization systems are described. An advanced helium pressure regulator capable of meeting both OMS and RCS helium pressurization system requirements is presented and its operating characteristics and predicted performance characteristics are discussed.

Wichmann, H.↗
NASA NTRS1978

Multivariable quadratic synthesis of an advanced turbofan engine controller

A digital controller for an advanced turbofan engine utilizing multivariate feedback is described. The theoretical background of locally linearized control synthesis is reviewed briefly. The application of linear quadratic regulator techniques to the practical control problem is presented. The design procedure has been applied to the F100 turbofan engine, and details of the structure of this system are explained. Selected results from simulations of the engine and controller are utilized to illustrate the operation of the system. It is shown that the general multivariable design procedure will produce practical and implementable controllers for modern, high-performance turbine engines.

Dehoff, R. L.↗
DOE OSTI2014

Keap1 redox-dependent regulation of doxorubicin-induced oxidative stress response in cardiac myoblasts

Doxorubicin (DOX) is a widely prescribed treatment for a broad scope of cancers, but clinical utility is limited by the cumulative, dose-dependent cardiomyopathy that occurs with repeated administration. DOX-induced cardiotoxicity is associated with the production of reactive oxygen species (ROS) and oxidation of lipids, DNA and proteins. A major cellular defense mechanism against such oxidative stress is activation of the Keap1/Nrf2-antioxidant response element (ARE) signaling pathway, which transcriptionally regulates expression of antioxidant genes such as Nqo1 and Gstp1. In the present study, we address the hypothesis that an initial event associated with DOX-induced oxidative stress is activation of the Keap1/Nrf2-dependent expression of antioxidant genes and that this is regulated through drug-induced changes in redox status of the Keap1 protein. Incubation of H9c2 rat cardiac myoblasts with DOX resulted in a time- and dose-dependent decrease in non-protein sulfhydryl groups. Associated with this was a near 2-fold increase in Nrf2 protein content and enhanced transcription of several of the Nrf2-regulated down-stream genes, including Gstp1, Ugt1a1, and Nqo1; the expression of Nfe2l2 (Nrf2) itself was unaltered. Furthermore, both the redox status and the total amount of Keap1 protein were significantly decreased by DOX, with the loss of Keap1 being due to both inhibited gene expression and increased autophagic, but not proteasomal, degradation. These findings identify the Keap1/Nrf2 pathway as a potentially important initial response to acute DOX-induced oxidative injury, with the primary regulatory events being the oxidation and autophagic degradation of the redox sensor Keap1 protein. - Highlights: • DOX caused a ∼2-fold increase in Nrf2 protein content. • DOX enhanced transcription of several Nrf2-regulated down-stream genes. • Redox status and total amount of Keap1 protein were significantly decreased by DOX. • Loss of Keap1 protein was due to inhibited gene expression and increased autophagy. • Keap1/Nrf2 pathway is an important initial response to DOX-induced oxidative injury.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Applying the Transactive Systems Business Value Model to IRP

As part of the Transactive Systems Program at Pacific Northwest National Laboratory, a value modeling system was developed to support the evaluation of transactive systems. The technique is general enough to be applied outside transactive systems and to demonstrate this capability, a project was undertaken to use this value modeling technique as a means for modeling the valuation process undertaken by vertically integrated utilities when undergoing integrated resource planning (IRP). IRP is the process by which vertically integrated utilities (those that both serve customers directly as well as manage and run generation assets to do so) regularly go through to demonstrate to their regulators that they have a plan to meet the expected future load of their customers in a least cost and compliant manner. Traditionally this has been primarily an issue of how many and of which types of power plants to build but increasingly has included alternative measures such as demand response programs. Increasingly, environmental regulations play a significant role in both determine what types of power plants can be built under current regulations as well as what retrofits or upgrades need to be made to existing plants to allow them to continue to operate. Two use-case diagrams were constructed, one showing the showing the process by which IRP is carried out and another showing how a vertically integrated utility procures the resources it requires to meet load now and in the future. These diagrams help clarify the difference and provide a high-level outline of the two processes. A class diagram was constructed to clearly define the types of actors that would be considered in this model and the relationships between them. This diagram tacitly indicates which types of actors are and are not included in the model which provides significant guidance in defining the scope of the model. The relationship between the classes/actors provides further indication of what areas of the model have higher levels of detail and by implication bear more significance in modeling the system. Using the classes/actors defined in the class diagram, a business value diagram was constructed that defines the key value streams exchanged between the actors. This diagram provides a clear expression of the business case of the vertically integrated utility and who its counterparties are during the process of meeting load. These value streams have not only to do with meeting the load but doing so in a manner that meets environmental regulations. Increasingly, IRPs have three key metrics to evaluate a given plant to meet load: net present value of revenue required, emissions, and renewable energy credits. From this business value diagram, more detailed activity diagrams were formed that focus on a few of the key value stream exchanges, showing the process by which each party accrues value. These diagrams provide insight into the timing and sequence of the interactions in a way that the business value diagrams did not. The transactive value model was found to be highly compatible with IRP and provided a clear, simple model of the analysis done during IRP and key metrics driving IRP decisions. In particular it highlighted a few key items that may or may not have been as clear prior to the development of the model. Specifically, the role of the environmental regulations has become increasingly important and two of the three key metrics by which IRPs are typically evaluated are environmentally focused. Additionally, though generally not acknowledged, the role of the investor was included in this model as they are an essential source of capital in building new power plants and cannot be ignored when defining the business case of the vertically integrated utility.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2015

Cancer–Osteoblast Interaction Reduces Sost Expression in Osteoblasts and Up-Regulates lncRNA MALAT1 in Prostate Cancer

Dynamic interaction between prostate cancer and the bone microenvironment is a major contributor to metastasis of prostate cancer to bone. In this study, we utilized an in vitro co-culture model of PC3 prostate cancer cells and osteoblasts followed by microarray based gene expression profiling to identify previously unrecognized prostate cancer–bone microenvironment interactions. Factors secreted by PC3 cells resulted in the up-regulation of many genes in osteoblasts associated with bone metabolism and cancer metastasis, including Mmp13, Il-6 and Tgfb2, and down-regulation of Wnt inhibitor Sost. To determine whether altered Sost expression in the bone microenvironment has an effect on prostate cancer metastasis, we co-cultured PC3 cells with Sost knockout (Sost KO ) osteoblasts and wildtype (WT) osteoblasts and identified several genes differentially regulated between PC3-Sost KO osteoblast co-cultures and PC3-WT osteoblast co-cultures. Co-culturing PC3 cells with WT osteoblasts up-regulated cancer-associated long noncoding RNA (lncRNA) MALAT1 in PC3 cells. MALAT1 expression was further enhanced when PC3 cells were co-cultured with Sost KO osteoblasts and treatment with recombinant Sost down-regulated MALAT1 expression in these cells. Our results suggest that reduced Sost expression in the tumor microenvironment may promote bone metastasis by up-regulating MALAT1 in prostate cancer.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Chitosan oligosaccharides enhance lipid droplets via down-regulation of PCSK9 gene expression in HepG2 cells

Highlights: • COS enhance lipid droplets in HepG2 cells. • COS down-regulate the expression of PCSK9 to maintain hepatic LDLR abundance and activity. • COS inhibit HNF1α and SREBP-2 activity leading to down-regulation of PCSK9. Chitosan oligosaccharides (COS), linear polymers of N-acetyl-D-glucosamine and deacetylated glucosamine, exhibit diverse pharmacological effects such as antimicrobial, antitumor, antioxidant and anti-inflammatory activities. Here, we explored their hypocholesterolemic effects in vivo and the molecular mechanisms of COS in hepatic cells. Our in vivo study of dyslipidemic ApoE{sup -/-} male mice showed that COS treatment of 500 mg kg{sup −1} d{sup −1} for 4 weeks clearly reduced the lipid deposits in the aorta and significantly decreased the hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) protein levels versus HFD groups (p < 0.05). To elucidate the mechanisms behind these effects, the HepG2 cell line was treated with COS. We found that COS (200 μg/ml) increased the amount of cell-surface low-density lipoprotein receptor (LDLR) and enhanced the lipid droplets in HepG2 cells (p < 0.05). The mRNA levels of LDLR and HMG-CoA protein levels were not altered, and the mRNA levels of PCSK9 were down-regulated by COS treatment for 24 h. We also observed that the expression levels of SREBP-2 (125 kD) and HNF-1α were increased in total cell lysates, but nuclear SREBP-2 (nSREBP-2, 68 kD, the active subunit of SREBP-2) levels were decreased and FOXO3a levels increased in nuclear lysates after COS treatment for 24 h. We demonstrated that one of the reasons for regulation of lipid transfer with COS is that FOXO3a levels are up-regulated by COS, leading to a reduction in the PCSK9 promoter binding capacity of HNF-1α and thus suppressing PCSK9 gene expression, up-regulating LDLR levels, and enhancing the lipid droplets in HepG2 cells. In addition, decreased expression of the PCSK9 gene was also contributed to by down-regulation of SREBP-2 by COS. We further confirmed the effect of suppression of PCSK9 expression by COS by utilizing RNA interference to silence HNF-1α and SREBP-2. Finally, to the best of our knowledge, we are the first to demonstrate that PCSK9 expression and LDLR activity are synergistically changed by a combination of HNF-1α and SREBP-2 after COS treatment. Our findings indicate that COS may regulate PCSK9 to modulate hepatic LDLR abundance and activity.

60 APPLIED LIFE SCIENCES↗