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At least 1,495 records · Page 83

Thermal Transport Model for Heat Sink Design

A document discusses the development of a finite element model for describing thermal transport through microcalorimeter arrays in order to assist in heat-sinking design. A fabricated multi-absorber transition edge sensor (PoST) was designed in order to reduce device wiring density by a factor of four. The finite element model consists of breaking the microcalorimeter array into separate elements, including the transition edge sensor (TES) and the silicon substrate on which the sensor is deposited. Each element is then broken up into subelements, whose surface area subtends 10 10 microns. The heat capacity per unit temperature, thermal conductance, and thermal diffusivity of each subelement are the model inputs, as are the temperatures of each subelement. Numerical integration using the Finite in Time Centered in Space algorithm of the thermal diffusion equation is then performed in order to obtain a temporal evolution of the subelement temperature. Thermal transport across interfaces is modeled using a thermal boundary resistance obtained using the acoustic mismatch model. The document concludes with a discussion of the PoST fabrication. PoSTs are novel because they enable incident x-ray position sensitivity with good energy resolution and low wiring density.

Chervenak, James A.↗

Testing and Results of Vacuum Swing Adsorption Units for Spacesuit Carbon Dioxide and Humidity Control

A principal concern for extravehicular activity (EVA) space suits is the capability to control carbon dioxide (CO2) and humidity (H2O) for the crewmember. The release of CO2 in a confined or unventilated area is dangerous for human health and leads to asphyxiation; therefore, CO2 and H2O become leading factors in the design and development of the spacesuit. An amine-based CO2 and H2O vapor sorbent for use in pressure-swing re-generable beds has been developed by Hamilton Sundstrand. The application of solid-amine materials with vacuum swing adsorption technology has shown the capacity to concurrently manage CO2 and H2O levels through a fully regenerative cycle eliminating mission constraints imposed with non-regenerative technologies. Two prototype solid amine-based systems, known as rapid cycle amine (RCA), were designed to continuously remove CO2 and H2O vapor from a flowing ventilation stream through the use of a two-bed amine based, vacuum-swing adsorption system. The Engineering and Science Contract Group (ESCG) RCA is the first RCA unit implementing radial flow paths, whereas the Hamilton Sundstrand RCA was designed with linear flow paths. Testing was performed in a sea-level pressure environment and a reduced-pressure environment with simulated human metabolic loads in a closed-loop configuration. This paper presents the experimental results of laboratory testing for a full-size and a sub-scale test article. The testing described here characterized and evaluated the performance of each RCA unit at the required Portable Life Support Subsystem (PLSS) operating conditions. The test points simulated a range of crewmember metabolic rates. The experimental results demonstrate the ability of each RCA unit to sufficiently remove CO2 and H2O from a closed loop ambient or subambient atmosphere.

McMillin, Summer↗

Thermal link design for conduction cooling of SRF cavities using cryocoolers

Superconducting radio frequency (SRF) cavities with quality factors ~1010 near 4 K have potential to be cooled using re-generative-cycle cryocoolers. Contrary to using liquid helium, cry-ogen-free operation can be realized by conductively linking a cavity to a cryocooler. The cavity-cryocooler thermal link needs careful design for balancing cooling capacity of the cryocooler with the dissipation rate in the cavity. We present a thermal analysis of a conduction-cooled SRF cavity that identifies the link thermal con-ductance requirement. The analysis uses published or expected RF dissipation characteristics of an Nb3Sn coated niobium cavity and in-house measured cooling capacity of a commercial pulse tube cryocooler. We describe mechanical design of a link that is con-structed using commercial high-purity aluminum and facilitates bolted-connection to elliptical SRF cavities. The thermal perfor-mance of the link is assessed by finite element simulations, taking into account temperature dependent thermal conductivities and measured thermal contact resistance of aluminum and niobium. The link is shown to support operation at an accelerating gradient of 10 MV/m with the lowest-known ‘perfect’ Nb3Sn surface re-sistance (10 nΩ) and also under non-ideal cases that assume certain static heat leak into the system and non-perfect Nb3Sn coatings

43 PARTICLE ACCELERATORS↗

Selective Shielding Bone Marrow: An Approach to Create Personal Protective Equipment for Gamma Radiation

Many casualties of the Hiroshima and Nagasaki atomic bombs, and many of the firefighters who first responded to the Chernobyl nuclear power plant accident, became ill with acute radiation syndrome (ARS). Most of the people who do not recover from ARS will die within a few weeks to a few months after exposure, with the primary cause of death being the destruction of the body's bone marrow (BM). This is exemplified by the Chernobyl firefighters, the majority of whom received whole body doses between 0.8 and 10 Gy, and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) final report on the disaster concluded that the underlying cause of death of all 28 firefighters who succumbed to ARS was from bone marrow failure. BM is comprised of hematopoietic stem cells (HSCs) which are responsible for the constant renewal of blood cells. Due to their high rate of proliferation, HSCs are especially vulnerable to ionizing radiation, but are endowed with remarkable regenerative potential. Owing to their central role in blood production, lethal irradiation of HSCs leads to death from severe anemia, infection and internal bleeding. This relationship between high doses of radiation and HSC apoptosis has led to the use of HSC transplantation as a life-saving intervention in cases of acute exposure. This is demonstrable in medical practice, where thousands of individuals have undergone supra-lethal Total Body Irradiation (TBI) for purposes of cancer therapy, and were rescued by well-matched BM transplantation. Indeed, life-threatening damage may be reversed by BM transplantation in individuals receiving doses of radiation of up to 10 Gy. At doses > 10 Gy, damage to gastrointestinal (GI) tissue may become a limiting factor in survival. Remarkably, in the common procedure of BM transplantation, the number of HSCs extracted from a single active BM site containing less than 5% of the donor's BM tissue is sufficient to support the complete reconstitution of the HSC compartment in a lethally irradiated recipient. This capacity of BM to expand and replenish is due to the high regenerative potential of the HSCs it harbors. In contrast to mature blood cells, which are dispersed throughout the body, HSCs are confined to the bones, allowing for effective targeted shielding. This has been confirmed in several animal models, where sparing the HSC-rich area of a subject receiving otherwise full-body irradiation is sufficient to support hematopoietic functions and allow survival. Approximately 48% of the human body's active BM is contained within the lumbar vertebrae and the pelvic region. This high concentration of BM makes the pelvic region an ideal area to shield for preventing the serious hematopoietic effects of radiation exposure. Stem-cell rich tissues like active BM are also more sensitive to the stochastic effects (i.e. cancer) of radiation exposure. The high amount of BM in the pelvic region, combined with the presence of the sensitive gastrointestinal system and female gonads in this same area of the body allows for the possibility of significantly reducing stochastic effects of radiation by limiting radiation exposure to this vital area. Thus, shielding this region holds great promise for both acute and protracted exposures. Thus, a specialized radiation shielding device for the protection of active BM concentrations is presented here. This belt-like selective shielding device focuses on the protection of BM that is present in the pelvis and hip bones, protecting the medullary volume from which BM is commonly extracted for transplantation (i.e. the iliac bones) while allowing relatively unhindered movement of the wearer. In order to optimize the use of shielding materials towards the protection of active BM, the shielding uniquely brings into account the natural shielding properties of human tissue, with thickness being inversely related to the thickness and radiation attenuation of the underlying tissue at each point surrounding the area being protected. The findings resulting from both experimental and simulation testing of this selective shielding device are presented here.

61 RADIATION PROTECTION AND DOSIMETRY↗

VTO_2021_APR_LLNL_Ye

Traditional batteries are composed of two-dimensional films that are stacked and/or rolled. Thin film batteries display high power density while their thick film counterparts show good energy density, but it has proven difficult to concurrently achieve both within these planar form factors. In addition, conventional Li-ion batteries based on liquid organic electrolytes or gel polymer electrolytes have raised severe safety concerns due to the intrinsic flammable properties of the organic electrolytes. They are also not ideal for the use of high energy density metallic lithium (Li) anodes due to Li dendrite growth, or sulfur cathodes due to shuttling effects that result in fast capacity fade. There is an urgent need to develop safe, high-performance solid-state batteries (SSBs) with advanced electrolyte and separator technologies. Although in recent years a series of superionic conductors have been developed for electrolytes and separators, their performance does not satisfy demanding criteria due to large impedance from poor solid electrolyte-electrode contact and questionable electrochemical and mechanical stability. Unlike the well-established roll-to-roll fabrication of conventional Li-ion batteries, the processing of SSBs is unique due to the brittleness of solid-state electrolytes (SSEs). The commercially available or lab-developed SSE discs are usually very thick (hundreds of micrometers to millimeters) to overcome their brittle nature, which unfortunately increases the cell impedance and accounts for the majority of the overall cell weight and volume, leading to dramatically decreased power and energy densities. In this project, we will investigate 3D printing techniques to overcome safety, fabrication, mechanical, and electrochemical issues in SSBs. 3D printing builds complex structures in a layer-by-layer fashion, which allows rapid production of hierarchical architectures, gradient and multi-material structures, and multi-component assemblies. 3D printing is an emerging area that could fundamentally transform energy storage devices. For example, 3D printing can produce batteries with arbitrary form factors to fit a product’s specific volume requirements and can create interwoven electrode arrangements over a wide range of length scales to improve transport and increase power density for a given energy density. For SSBs, 3D printing may dramatically reduce the separator thickness from ~1 mm (by hydraulic pressing) to tens of micrometers or less. In addition, the interfacial contact area between the electrolyte and the electrode may be increased via 3D interdigitated designs. Hence, we expect a significant reduction of the overall cell impedance and enhancement of both energy and power densities of SSBs by harnessing an array of 3D printing technologies being developed at Lawrence Livermore National Laboratory (LLNL).

25 ENERGY STORAGE↗

Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

In Brachypodium a complex signaling is actuated to protect cells from proteotoxic stress and facilitate seed filling

A conserved UPR machinery is necessary for Brachypodium ER stress resistance and grain filling. Human and livestock diets depend on the accumulation of cereal storage proteins and carbohydrates, including mixed-linkage glucan (MLG), in the endosperm during seed development. Storage proteins and proteins responsible for the production of carbohydrates are synthesized in the endoplasmic reticulum (ER). Unfavorable conditions during growth that hamper the ER biosynthetic capacity, such as heat, can cause a potentially lethal condition known as ER stress, which activates the unfolded protein response (UPR), a signaling response designed to mitigate ER stress. The UPR relies primarily on a conserved ER-associated kinase and ribonuclease, IRE1, which splices the mRNA of a transcription factor (TF), such as bZIP60 in plants, to produce an active TF that controls the expression of ER resident chaperones. Here, we investigated activation of the UPR in Brachypodium, as a model to study the UPR in seeds of a monocotyledon species, as well as the consequences of heat stress on MLG deposition in seeds. We identified a Brachypodium bZIP60 orthologue and determined a positive correlation between bZIP60 splicing and ER stress induced by chemicals and heat. Each stress condition led to transcriptional modulation of several BiP genes, supporting the existence of condition-specific BiP regulation. Finally, we found that the UPR is elevated at the early stage of seed development and that MLG production is negatively affected by heat stress via modulation of MLG synthase accumulation. We present that successful accomplishment of seed filling is strongly correlated with the ability of the plant to sustain ER stress via the UPR.

59 BASIC BIOLOGICAL SCIENCES↗

Water Availability for Biorefineries in the Contiguous United States and the Implications for Bioenergy Production Distribution

Renewable biofuel production depends on many factors, including feedstock availability, refinery and shipment infrastructure, and in particular, water availability. This study assesses water requirement and availability for mainstream biorefinery technologies in the contiguous United States (CONUS). The assessment is conducted in newly defined spatial units, namely, biorefinery planning boundaries, considering feedstock availability, transportation cost, and refinery capacity requirement for cost-effectiveness. The results suggest that the total biorefinery water use in the CONUS by 2030 will be low compared to the total water availability. However, biorefinery water requirements can aggravate the water stress situation in many regions, including the Great Plains, California Central Valley, and the upper Columbia-Snake River basin in Washington. Bioenergy productions in these regions can be largely constrained by water. Here, it is projected that biofuel production will concentrate in Northern Plains, Lake States, and Corn Belt regions, which contribute 94.4% of the conventional, 86.1% of biodiesel, and 54.8% of cellulosic biofuel production mandated by the renewable fuel standard. If biorefineries are constrained to use less than 10% of the locally available water, up to 7% of planned cellulosic biofuel production will be affected. Findings from this study can aid the sustainable planning of national bioenergy production.

54 ENVIRONMENTAL SCIENCES↗

Insights into Supramolecular Sites Responsible for Complete Separation of Biomass-Derived Phenolics and Glucose in Metal–Organic Framework NU-1000

The molecular origins of adsorption of lignin-derived phenolics to metal–organic framework NU-1000 are investigated from aqueous solution as well as in competitive mode with glucose present in the same aqueous mixture. A comparison of adsorption equilibrium constants ($K_{ads}$) for phenolics functionalized with either carboxylic acid or aldehyde substituents demonstrated only a slight increase (less than a factor of 6) for the former according to both experiments and calculations. This small difference in $K_{ads}$ between aldehyde and carboxylic-acid substituted adsorbates is consistent with the pyrene unit of NU-1000 as the adsorption site, rather than the zirconia nodes, while at saturation coverage, the adsorption capacity suggests multiple guests per pyrene. Experimental standard free energies of adsorption directly correlated with the molecular size and electronic structure calculations confirmed this direct relationship, with the pyrene units as adsorption site. The underlying origins of this relationship are grounded in noncovalent $π–π$ interactions as being responsible for adsorption, the same interactions present in the condensed phase of the phenolics, which to a large extent govern their heat of vaporization. Thus, NU-1000 acts as a preformed aromatic cavity for driving aromatic guest adsorption from aqueous solution and does so specifically without causing detectable glucose adsorption from aqueous solution, thereby achieving complete glucose–phenolics separations. The reusability of NU-1000 during an adsorption/desorption cycle was good, even with some of the phenolic compounds with greatest affinity not easiliy removed with water and ethanol washes at room temperature. A competitive adsorption experiment gave an upper bound for $K_{ads}$ for glucose of at most 0.18 M –1 , which can be compared with $K_{ads}$ for the phenolics investigated here, which fell in the range of 443–42 639 M –1 . The actual value of $K_{ads}$ for glucose may be much closer to zero given the lack of observed glucose uptake with NU-1000 as adsorbent.

09 BIOMASS FUELS↗

Fracture-matrix fluid exchange in oil-bearing unconventional mudstones

The poromechanical properties of unconventional reservoir materials are in large part dictated by their mineralogy. Since these properties govern the response to stress experienced during hydraulic fracturing, fluid production, and fluid injection, they play a central role in the formation of microcracks or bedding delaminations which ultimately dominate mass transport. In this work we study access to the porosity of end member unconventional reservoir materials, where the end members are predominantly dictated by carbonate content. Access to the porosity is quantified using state of the art 3D x-ray computed tomography coupled with physics informed data analytics. Xenon gas, which attenuates x-rays, provides a spatiotemporal map of access to the porosity. The accessible porosity is quantified over a range of net confining stress relevant to the manmade disturbances listed above. These experiments demonstrate that heavily carbonated mudstones are nearly impermeable at the core (~ cm) scale, while carbonate free analogues afford better access to the microstructure. Consistent with previous qualitative 2D radiographs, access to the interior of the clastic mudstones is first observed along planar microcracks, followed by slow penetration into the surrounding matrix. Physics informed data analytics of the 3D tomography measurements presented here show that these microcracks do not permit uniform access to the adjacent rock matrix. In addition, variation of the effective pressure elucidates the mechanisms that govern fracture/matrix fluid exchange. Under conditions consistent with hydrocarbon production fluid accumulates in the immediate vicinity of the nearest microcrack. While there is clear evidence that, as intended, part of this accumulation is from the more distant matrix, fluid is also squeezed out of the microcrack. The fluid build-up at the microcrack indicates that migration out of the rock is hindered by the coupled poroelastic response of the microcrack and adjacent rock matrix. We show that these mechanisms ultimately account for the meager oil recovery factors realized in practice. These insights have implications for making reservoir scale predictions based on core scale observations, and provide a basis for devising new asset development techniques to access more porosity, and enhance fluid extraction. Finally, these findings shed light on key features and mechanisms that govern shale storage capacity, with relevance to other important industrial processes, such as geologic CO 2 storage.

58 GEOSCIENCES↗

Triacylglycerol stability limits futile cycles and inhibition of carbon capture in oil-accumulating leaves

Engineering plant vegetative tissue to accumulate triacylglycerols (TAG, e.g. oil) can increase the amount of oil harvested per acre to levels that exceed current oilseed crops. Engineered tobacco (Nicotiana tabacum) lines that accumulate 15% to 30% oil of leaf dry weight resulted in starkly different metabolic phenotypes. In-depth analysis of the leaf lipid accumulation and 14 CO 2 tracking describe metabolic adaptations to the leaf oil engineering. An oil-for-membrane lipid tradeoff in the 15% oil line (referred to as HO) was surprisingly not further exacerbated when lipid production was enhanced to 30% (LEAFY COTYLEDON 2 (LEC2) line). The HO line exhibited a futile cycle that limited TAG yield through exchange with starch, altered carbon flux into various metabolite pools and end products, and suggested interference of the glyoxylate cycle with photorespiration that limited CO 2 assimilation by 50%. In contrast, inclusion of the LEC2 transcription factor in tobacco improved TAG stability, alleviated the TAG-to-starch futile cycle, and recovered CO 2 assimilation and plant growth comparable to wild type but with much higher lipid levels in leaves. Thus, the unstable production of storage reserves and futile cycling limit vegetative oil engineering approaches. The capacity to overcome futile cycles and maintain enhanced stable TAG levels in LEC2 demonstrated the importance of considering unanticipated metabolic adaptations while engineering vegetative oil crops.

59 BASIC BIOLOGICAL SCIENCES↗

Community Centered Solar Development (CCSD) Case Study Interviews [Slides]

Large-scale solar (LSS, defined here as ground-mounted photovoltaic projects ≥1 MWDC) has grown rapidly in the U.S., accounting for nearly half of new electric generating capacity added to the U.S. grid in 2022. All sources of electricity bring positive and negative impacts to hosting communities and the rapid growth of LSS has increased the urgency to understand those impacts. Yet, information about the potential positive and negative impacts of LSS on host communities, and the factors or drivers leading to support or opposition to a project, is lacking. This information gap limits how project developers, municipalities, and local siting authorities can address community concerns and appropriately align proposed projects to best suit and benefit local communities. As part of Berkeley Lab’s Community-Centered Solar Development (CCSD) project, this research set out to explore deep insights and perceptions from LSS stakeholders that only qualitative data can provide to identify key factors driving project success or threatened failure. Case studies, such as those utilized in this research, are uniquely adept at capturing the subjective experience of individuals and at identifying variables, structures, and interactions between stakeholders. Our case studies included 54 semi-structured interviews across 7 different LSS sites, representing a diversity of geographies, project sizes (MW), site types (i.e., greenfield, agrivoltaic, and brownfield / contaminated sites), zoning jurisdiction types, and more (Table 1). In addition to local residents living in close proximity to these LSS sites, we interviewed other key stakeholders involved in the projects such as developers, decision-makers, utility representatives, landowners, and individuals from community-based organizations. The overarching aim of this case study research was two-fold: (1) to inform subsequent tasks in the CCSD research project (including an upcoming national survey of LSS neighbors), and (2) to provide insights into the following set of research questions: -What are the key positive and negative drivers leading to support and opposition to LSS projects? -To what extent do LSS projects exacerbate or mitigate perceived inequities and marginalization within hosting communities and how can those inequities be mitigated going forward? -What strategies can communities employ to align LSS development with local land-use plans and community needs and values? The research findings and next steps are described in this slide deck report.

14 SOLAR ENERGY↗

DOE Zero Energy Ready Manufactured Housing: Subject Matter Expert Technical Assistance Summary

Manufactured homes offer American consumers an affordable option for decent single-family detached housing. For working-class American families in many U.S. markets, manufactured homes are the first step toward home ownership. They now make up 10% of all new homes constructed in the United States, with higher percentages in the south and in rural communities. To help encourage the production of homes that are more durable, healthy, efficient, and disaster resistant, the U.S. Department of Energy is bringing its building science research to the manufactured housing industry through DOE’s Zero Energy Ready Manufactured Home (ZER-MH) program, which provides technical assistance and voluntary guidelines to manufactured home builders. Homes built to these guidelines are better able to handle power outages and less likely to experience moisture issues, offering a better product option for American families. This higher quality is evidenced by energy modeling which shows homes manufactured to these voluntary guidelines will typically use half the energy of manufactured homes built to the current minimum requirements of the U.S. Department of Housing and Urban Development (HUD)’s Manufactured Housing and Construction Safety Standard (MHCSS). These homes can also reduce critical energy demand during the busiest hours of the day, typically late afternoon and early evening in the summer when air conditioning demand is highest and mornings in the winter when furnaces and heaters are heating up. Reducing electricity demand during these peak periods when electricity rates are at their highest reduces costs for American families while freeing up capacity on overburdened energy distribution networks. Builders participating in the DOE ZER-MH program are eligible for a tax incentive via the 45L tax credit, which helps to offset the costs of ZER-MH upgrades, enabling builders to offer these certified homes at no additional cost. Together these factors enable manufactured homes to offer home buyers a housing option that is both affordable to finance and affordable to operate, with lower monthly mortgage payments and lower monthly energy bills.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Technology and politics: The regional airport experience

The findings of a comparative study of the following six regional airports were presented: Dallas/Fort Worth, Kansas City, Washington, D.C., Montreal, Tampa, and St. Louis. Each case was approached as a unique historical entity, in order to investigate common elements such as: the use of predictive models in planning, the role of symbolism to heighten dramatic effects, the roles of community and professional elites, and design flexibility. Some of the factors considered were: site selection, consolidation of airline service, accessibility, land availability and cost, safety, nuisance, and pollution constraints, economic growth, expectation of regional growth, the demand forecasting conundrum, and design decisions. The hypotheses developed include the following: the effect of political, social, and economic conflicts, the stress on large capacity and dramatic, high-technology design, projections of rapid growth to explain the need for large capital outlays.

Starling, J. D.↗

Intelligent monitoring system applied to super long distance telerobotic tasks

Time delay and small capacity of communication are the primary constraint in super long distance telerobotic systems such as astronautical robotic tasks. Intelligent telerobotics is thought to break this constraint. We aim to realize this super long distance telerobotic system with object handling knowledge base and intelligent monitoring. We will discuss physical and technical factors for this purpose.

Wakita, Yujin↗

Cannabidiol restores differentiation capacity of LPS exposed adipose tissue mesenchymal stromal cells

Highlights: • LPS increases amount of oxidized proteins and lipids in homogenisates of MSCs. • LPS inhibits MSC adipogenic and chondrogenic differentiation. • CBD reduces oxidative stress and restores adipogenesis and chondrogenesis of MSCs upon LPS exposure. Multipotent mesenchymal stromal cells (MSCs) support wound healing processes. These cells express toll-like receptors (TLRs). TLRs perform important key functions when the immune system is confronted with danger signals. TLR ligation by lipopolysaccharides (LPS) activates MSCs and induces intracellular signaling cascades, which affect their differentiation profile, increase the release of inflammatory cytokines and the production of reactive oxygen species. Continuing exposure to LPS triggers prolonged inflammatory reactions, which may lead to deleterious conditions, e.g. non-healing wounds. Cannabidiol (CBD) exerts anti-inflammatory processes through cannabinoid receptor dependent and independent mechanisms. In the present study, we examined whether CBD could influence the inflammatory MSC phenotype. Exposure to LPS increased the release of IL-6, as well as other soluble factors, and elevated levels of oxidized macromolecules found in cell homogenisates. While the amount of IL-6 was unaffected, co-treatment with CBD reduced the oxidative stress acting on the cells. LPS inhibited adipogenic as well as chondrogenic differentiation, which was attenuated by CBD treatment. In the case of adipogenesis, the disinhibitory effect probably depended on CBD interaction with the peroxisome proliferator-activated receptor-γ. CBD could exert mild immunosuppressive properties on MSCs, while it most effectively acted anti-oxidatively and by restoring the differentiation capacity upon LPS treatment.

60 APPLIED LIFE SCIENCES↗

The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondrial stressor rotenone

The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial biogenesis and bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. -- Highlights: Black-Right-Pointing-Pointer NeuroD6 induces mitochondrial biogenesis in neuroprogenitor-like cells. Black-Right-Pointing-Pointer NeuroD6 augments the bioenergetic reserve of the neuronal PC12-NeuroD6 cells. Black-Right-Pointing-Pointer NeuroD6 increases the mitochondrial membrane potential and ATP levels. Black-Right-Pointing-Pointer NeuroD6 confers tolerance to rotenone via an adaptive mitochondrial response.

60 APPLIED LIFE SCIENCES↗