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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 433 records · Page 24
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Substrate stiffness modulates endothelial cell function via the YAP-Dll4-Notch1 pathway

Highlights: • Soft stiffness increases Dll4 expression in endothelial cells via YAP suppression. • Soft substrate-induced Dll4-Notch1 signaling is facilitated by VEGF stimulation. • Elevated Dll4-Notch1 signaling contributes to the regulation of VEGFRs expression. • Substrate stiffness modulates gene expression linked to endothelial cell function. Endothelial cells adapt their functions as a consequence of sensing extracellular substrate stiffness; these alterations allow them to maintain their vascular structure and function. Substrate stiffness-mediated yes-associated protein 1 (YAP) activation plays an important role in mechano-transduction and pro-angiogenic phenotype of endothelial cells, and Delta-like ligand 4 (Dll4)-Notch1 signaling is closely related to angiogenesis; however, the impact of substrate stiffness-mediated interrelation of these pathways on endothelial cell functions remains elusive. We confirmed that endothelial cells on softer substrates not only elongate cellular aspects but also attenuate YAP activation compared to cells on stiffer substrates. Endothelial cells on softer substrates also upregulate the vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2 mRNA expression that is enhanced by VEGF stimulation. We determined that endothelial cells on softer substrates increased Dll4 expression, but not Notch1 expression, via YAP signaling. Moreover, endothelial cells on soft substrates induced not only VEGFRs upregulation but also suppression of pro-inflammatory interleukin-6 and plasminogen activator inhibitor-1 mRNA expression and the facilitation of anti-coagulant thrombomodulin and pro-coagulant tissue factor mRNA expression. Our results suggest that endothelial cells activate the YAP-Dll4-Notch signaling pathway in response to substrate stiffness and dictate cellular function.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1996

Mechanisms of Bone Mineralization and Effects of Mechanical Loading

The data suggest that PTH and PKC inhibit nodule formation, and that alternative energy sources are utilized by osteoblasts in the process of mineralization. The conditions and techniques to grow, fix, photograph, and measure bone mineralization in vitro were defined. The results are presently in preliminary form and require further assessment as follows; quantitate the surface area of nodules + treatments via computer-aided image analysis; use PTH + inhibitors of signaling pathways to determine the mechanism of nodule formation; determine how protein kinase C is involved as a promotor of nodule formation; cell proliferation vs. cell death affected by modulation of signal transduction (i.e., PTH, enzyme inhibitors and activators); identify mRNA induced or decreased in response to PTH and signaling modulators that encode proteins that regulate cell morphology, proliferation, and nodule formation. Therefore, several follow-up studies between the laboratories at NASA-Ames Research Center and my laboratory at the University of Illinois have been initiated.

Babich, Michael↗
DOE OSTI2022

Triggering cell death in cancers using self-illuminating nanocomposites

Bioinspired photocatalysis has resulted in efficient solutions for many areas of science and technology spanning from solar cells to medicine. Here we show a new bioinspired semiconductor nanocomposite (nanoTiO 2 DOPA-luciferase, TiDoL) capable of converting light energy within cancerous tissues into chemical species that are highly disruptive to cell metabolism and lead to cell death. This localized activity of semiconductor nanocomposites is triggered by cancer-generated activators. Adenosine triphosphate (ATP) is produced in excess in cancer tissues only and activates nearby immobilized TiDoL composites, thereby eliminating its off-target toxicity. The interaction of TiDoL with cancerous cells was probed in situand in real-time to establish a detailed mechanism of nanoparticle activation, triggering of the apoptotic signaling cascade, and finally, cancer cell death. Activation of TiDoL with non-cancerous cells did not result in cell toxicity. Exploring the activation of antibody-targeted semiconductor conjugates using ATP is a step toward a universal approach to single-cell-targeted medical therapies with more precision, efficacy, and potentially fewer side effects.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2015

Cellular Response to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

Living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. Whether spaceflight factors, microgravity in particular, affects on the cellular response to DNA damage induced by exposures to radiation or other toxic chemicals will have an impact on the radiation risks for the astronauts, as well as on the mutation rate in microorganisms, is still an open question. Although the possible synergistic effects of space radiation and other spaceflight factors have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate the effects of spaceflight on the cellular response to DNA damages, human fibroblast cells flown to the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induces DNA damages including the double strand breaks (DSB) similar to the ionizing radiation. Damage in the DNA was measured by the phosphorylation of a histone protein H2AX (-H2AX), which showed slightly more foci in the cells on ISS than in the ground control. The expression of genes involved in the DNA damage response was also analyzed using the PCR array. Although a number of the genes, including CDKN1A and PCNA, were significantly altered in the cells after bleomycin treatment, no significant difference in the expression profile of DNA damage response genes was found between the flight and ground samples. At the time of the bleomycin treatment, the cells on the ISS were found to be proliferating faster than the ground control as measured by the percentage of cells containing positive Ti-67 signals. Our results suggested that the difference in -H2AX between flight and ground was due to the faster growth rate of the cells in space, but spaceflight did not affect the response of the DNA damage response genes to bleomycin treatment.

Lu, Tao↗
NASA NTRS2001

Ongoing cell death and immune influences on regeneration in the vestibular sensory organs

Hair cells in the vestibular organs of birds have a relatively short life span. Mature hair cells appear to die spontaneously and are then quickly replaced by new hair cells that arise from the division of epithelial supporting cells. A similar regenerative mechanism also results in hair cell replacement after ototoxic damage. The cellular basis of hair cell turnover in the avian ear is not understood. We are investigating the signaling pathways that lead to hair cell death and the relationship between ongoing cell death and cell production. In addition, work from our lab and others has demonstrated that the avian inner ear contains a resident population of macrophages and that enhanced numbers of macrophages are recruited to sites of hair cells lesions. Those observations suggest that macrophages and their secretory products (cytokines) may be involved in hair cell regeneration. Consistent with that suggestion, we have found that treatment with the anti-inflammatory drug dexamethasone reduces regenerative cell proliferation in the avian ear, and that certain macrophage-secreted cytokines can influence the proliferation of vestibular supporting cells and the survival of statoacoustic neurons. Those results suggest a role for the immune system in the process of sensory regeneration in the inner ear.

Non-NASA Center↗
DOE OSTI2021

The Role of Sugar Signaling in Regulating Plant Fatty Acid Synthesis

Photosynthates such as glucose, sucrose, and some of their derivatives play dual roles as metabolic intermediates and signaling molecules that influence plant cell metabolism. Such sugars provide substrates for de novo fatty acid (FA) biosynthesis. However, compared with the well-defined examples of sugar signaling in starch and anthocyanin synthesis, until recently relatively little was known about the role of signaling in regulating FA and lipid biosynthesis. Recent research progress shows that trehalose 6-phosphate and 2-oxoglutarate (2-OG) play direct signaling roles in the regulation of FA biosynthesis by modulating transcription factor stability and enzymatic activities involved in FA biosynthesis. Specifically, mechanistic links between sucrose non-fermenting−1–related protein kinase 1 (SnRK1)–mediated trehalose 6-phosphate (T6P) sensing and its regulation by phosphorylation of WRI1 stability, diacylglycerol acyltransferase 1 (DGAT1) enzyme activity, and of 2-OG–mediated relief of inhibition of acetyl-CoA carboxylase (ACCase) activity by protein PII are exemplified in detail in this review.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2000

Cell movement is guided by the rigidity of the substrate

Directional cell locomotion is critical in many physiological processes, including morphogenesis, the immune response, and wound healing. It is well known that in these processes cell movements can be guided by gradients of various chemical signals. In this study, we demonstrate that cell movement can also be guided by purely physical interactions at the cell-substrate interface. We cultured National Institutes of Health 3T3 fibroblasts on flexible polyacrylamide sheets coated with type I collagen. A transition in rigidity was introduced in the central region of the sheet by a discontinuity in the concentration of the bis-acrylamide cross-linker. Cells approaching the transition region from the soft side could easily migrate across the boundary, with a concurrent increase in spreading area and traction forces. In contrast, cells migrating from the stiff side turned around or retracted as they reached the boundary. We call this apparent preference for a stiff substrate "durotaxis." In addition to substrate rigidity, we discovered that cell movement could also be guided by manipulating the flexible substrate to produce mechanical strains in the front or rear of a polarized cell. We conclude that changes in tissue rigidity and strain could play an important controlling role in a number of normal and pathological processes involving cell locomotion.

NASA Discipline Cell Biology↗
NASA NTRS2009

Development of a GCR Event-based Risk Model

A goal at NASA is to develop event-based systems biology models of space radiation risks that will replace the current dose-based empirical models. Complex and varied biochemical signaling processes transmit the initial DNA and oxidative damage from space radiation into cellular and tissue responses. Mis-repaired damage or aberrant signals can lead to genomic instability, persistent oxidative stress or inflammation, which are causative of cancer and CNS risks. Protective signaling through adaptive responses or cell repopulation is also possible. We are developing a computational simulation approach to galactic cosmic ray (GCR) effects that is based on biological events rather than average quantities such as dose, fluence, or dose equivalent. The goal of the GCR Event-based Risk Model (GERMcode) is to provide a simulation tool to describe and integrate physical and biological events into stochastic models of space radiation risks. We used the quantum multiple scattering model of heavy ion fragmentation (QMSFRG) and well known energy loss processes to develop a stochastic Monte-Carlo based model of GCR transport in spacecraft shielding and tissue. We validated the accuracy of the model by comparing to physical data from the NASA Space Radiation Laboratory (NSRL). Our simulation approach allows us to time-tag each GCR proton or heavy ion interaction in tissue including correlated secondary ions often of high multiplicity. Conventional space radiation risk assessment employs average quantities, and assumes linearity and additivity of responses over the complete range of GCR charge and energies. To investigate possible deviations from these assumptions, we studied several biological response pathway models of varying induction and relaxation times including the ATM, TGF -Smad, and WNT signaling pathways. We then considered small volumes of interacting cells and the time-dependent biophysical events that the GCR would produce within these tissue volumes to estimate how GCR event rates mapped to biological signaling induction and relaxation times. We considered several hypotheses related to signaling and cancer risk, and then performed simulations for conditions where aberrant or adaptive signaling would occur on long-duration space mission. Our results do not support the conventional assumptions of dose, linearity and additivity. A discussion on how event-based systems biology models, which focus on biological signaling as the mechanism to propagate damage or adaptation, can be further developed for cancer and CNS space radiation risk projections is given.

Cucinotta, Francis A.↗
NASA NTRS1996

High-performance ultra-low power VLSI analog processor for data compression

An apparatus for data compression employing a parallel analog processor. The apparatus includes an array of processor cells with N columns and M rows wherein the processor cells have an input device, memory device, and processor device. The input device is used for inputting a series of input vectors. Each input vector is simultaneously input into each column of the array of processor cells in a pre-determined sequential order. An input vector is made up of M components, ones of which are input into ones of M processor cells making up a column of the array. The memory device is used for providing ones of M components of a codebook vector to ones of the processor cells making up a column of the array. A different codebook vector is provided to each of the N columns of the array. The processor device is used for simultaneously comparing the components of each input vector to corresponding components of each codebook vector, and for outputting a signal representative of the closeness between the compared vector components. A combination device is used to combine the signal output from each processor cell in each column of the array and to output a combined signal. A closeness determination device is then used for determining which codebook vector is closest to an input vector from the combined signals, and for outputting a codebook vector index indicating which of the N codebook vectors was the closest to each input vector input into the array.

Tawel, Raoul↗
DOE OSTI2025

Characterization of dangling bond defects at the crystalline Si/SiO x interface in a polycrystalline Si passivating contact solar cell at room temperature with electrically detected magnetic resonance spectroscopy

Monocrystalline silicon solar cells can achieve photoconversion efficiencies exceeding 26%; however, performance-limiting defects that trap carriers continue to be a challenge. In this work, we have characterized Si solar cells with tunneling SiO x /polycrystalline-Si (poly-Si) passivating contacts (TOPCon) on As-doped Czochralski Si wafers with electrically detected magnetic resonance (EDMR) spectroscopy. We fabricated 2 × 20 mm 2 TOPCon-like mini solar cells with edge passivation alongside larger 4 cm 2 sister cells and obtained similar device characteristics. We performed EDMR spectroscopy at 300 K on two minicells with different degrees of surface passivation based on the recombination parameter, J o , values of 40 and 310 fA/cm2. We optimized the resolution and the signal-to-noise ratio of the EDMR response of the minicells by varying the forward bias voltage and the magnetic field modulation amplitude. We detect two distinct signals with EDMR spectroscopy, an axial-like signal at g = 2.009, 2.0087, and 2.0015, and an isotropic signal at g = 2.0024, which we attribute to Si dangling bonds (P b0 and P b centers) and boron–oxygen related defects, respectively, at or near the c-Si/SiO x interface. The EDMR signals were lower for the cell with a lower value of J o , while the ratio of the two defect populations was very similar. The EDMR signal increases with forward bias but drops to zero at bias voltages >0.5 V, consistent with interface defects within or near the boron-doped emitter depletion region. Our study demonstrates a method to fabricate minicells that can be characterized with EDMR spectroscopy to detect industrially relevant defects in TOPCon cells.

14 SOLAR ENERGY↗
NASA NTRS2015

Cellular Response to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

Outside the protection of the geomagnetic field, astronauts and other living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. Whether spaceflight factors, microgravity in particular, have effects on cellular responses to DNA damage induced by exposure to radiation or cytotoxic chemicals is still unknown, as is their impact on the radiation risks for astronauts and on the mutation rate in microorganisms. Although possible synergistic effects of space radiation and other spaceflight factors have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on cellular responses to DNA damages, human fibroblast cells flown to the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induced DNA damages including double-strand breaks (DSB) similar to the ionizing radiation. Damages in the DNA were measured by the phosphorylation of a histone protein H2AX (g-H2AX), which showed slightly more foci in the cells on ISS than in the ground control. The expression of genes involved in DNA damage response was also analyzed using the PCR array. Although a number of the genes, including CDKN1A and PCNA, were significantly altered in the cells after bleomycin treatment, no significant difference in the expression profile of DNA damage response genes was found between the flight and ground samples. At the time of the bleomycin treatment, the cells on the ISS were found to be proliferating faster than the ground control as measured by the percentage of cells containing positive Ki-67 signals. Our results suggested that the difference in g-H2AX focus counts between flight and ground was due to the faster growth rate of the cells in space, but spaceflight did not affect initial transcriptional responses of the DNA damage response genes to bleomycin treatment.

Lu, Tao↗
NASA NTRS1979

Voltage-current-power meter for photovoltaic solar arrays

A meter is disclosed for measuring the voltage, current, and power (VIP) parameters of a photovoltaic solar array, or array module, under sunlight operating conditions utilizing a variable load connected across the array and controlled by a voltage regulator which responds to the difference between the output voltage of the array and a programmed test voltage from a source which generates a single ramp voltage for measuring and recording current as a function of voltage, repeated ramp voltages at a high rate for peak output measurements or a DC voltage for VIP measurements at selected points on the I-V characteristic curve of the array. The voltage signal from a current sensing element, such as a shunt resistor in series with the variable load, is compared with the output current of a reference solar cell to provide a normalizing signal to be added to the signal from the current-sensing element in order to provide a record of array current as a function of array voltage, i.e., for all load conditions from short circuit to open circuit. As the normalized current is thus measured, an analog multiplier multiplies the array voltage and normalized current to provide a measurement of power. Switches are provided to selectively connect the power, P, current, I, or voltage, V, to a meter, directly or through a peak detector. At the same time any one of the parameters V, I and P may be recorded as a function of any other parameter.

Ross, Ronald G.↗
NASA NTRS1989

Multi-port, optically addressed RAM

A random access memory addressing system utilizing optical links between memory and the read/write logic circuits comprises addressing circuits including a plurality of light signal sources, a plurality of optical gates including optical detectors associated with the memory cells, and a holographic optical element adapted to reflect and direct the light signals to the desired memory cell locations. More particularly, it is a multi-port, binary computer memory for interfacing with a plurality of computers. There are a plurality of storage cells for containing bits of binary information, the storage cells being disposed at the intersections of a plurality of row conductors and a plurality of column conductors. There is interfacing logic for receiving information from the computers directing access to ones of the storage cells. There are first light sources associated with the interfacing logic for transmitting a first light beam with the access information modulated thereon. First light detectors are associated with the storage cells for receiving the first light beam, for generating an electrical signal containing the access information, and for conducting the electrical signal to the one of the storage cells to which it is directed. There are holographic optical elements for reflecting the first light beam from the first light sources to the first light detectors.

Johnston, Alan R.↗
NASA NTRS2010

Growing B Lymphocytes in a Three-Dimensional Culture System

A three-dimensional (3D) culture system for growing long-lived B lymphocytes has been invented. The capabilities afforded by the system can be expected to expand the range of options for immunological research and related activities, including testing of immunogenicity of vaccine candidates in vitro, generation of human monoclonal antibodies, and immunotherapy. Mature lymphocytes, which are the effectors of adaptive immune responses in vertebrates, are extremely susceptible to apoptotic death, and depend on continuous reception of survival-inducing stimulation (in the forms of cytokines, cell-to-cell contacts, and antigen receptor signaling) from the microenvironment. For this reason, efforts to develop systems for long-term culture of functional, non-transformed and non-activated mature lymphocytes have been unsuccessful until now. The bone-marrow microenvironment supports the growth and differentiation of many hematopoietic lineages, in addition to B-lymphocytes. Primary bone-marrow cell cultures designed to promote the development of specific cell types in vitro are highly desirable experimental systems, amenable to manipulation under controlled conditions. However, the dynamic and complex network of stromal cells and insoluble matrix proteins is disrupted in prior plate- and flask-based culture systems, wherein the microenvironments have a predominantly two-dimensional (2D) character. In 2D bone-marrow cultures, normal B-lymphoid cells become progressively skewed toward precursor B-cell populations that do not retain a normal immunophenotype, and such mature B-lymphocytes as those harvested from the spleen or lymph nodes do not survive beyond several days ex vivo in the absence of mitogenic stimulation. The present 3D culture system is a bioreactor that contains highly porous artificial scaffolding that supports the long-term culture of bone marrow, spleen, and lymph-node samples. In this system, unlike in 2D culture systems, B-cell subpopulations developing within 3D cultures that have been modified to foster lymphopoiesis retain an immunophenotype that closely recapitulates cells in fresh bone marrow harvests. The 3D culture system has been found to be capable of supporting long-lived (8 weeks) populations of B and T lymphocytes from peripheral lymphoid organs, in the absence of activation signals, to an extent not achievable by conventional culture techniques. Interestingly, it has been found that 3D-culture B cells display a phenotype that has characteristics of both B1a and B2 cells. These promising preliminary observations suggest that the 3D culture system could be used with success in the study of peripheral-B-lymphocyte biology and in the development of biotechnological techniques and processes.

Wu, J. H. David↗
DOE OSTI2021

IL-10 Signaling Elicited by Nivolumab-Induced Activation of the $\mathrm{MAP}$ Kinase Pathway Does Not Fully Contribute to Nivolumab-Modulated Heterogeneous T Cell Responses

Immune checkpoint inhibitor (ICI) therapy has revolutionized anti-cancer treatment for many late-stage cancer patients. However, ICI therapy has thus far demonstrated limited efficacy for most patients, and it remains unclear why this is so. Interleukin 10 (IL-10) is a cytokine that has been recognized as a central player in cancer biology with its ability to inhibit anti-tumor T cell responses. Recent studies suggest that IL-10 might also exert some intrinsic anti-tumor T cell responses, and clinical studies using recombinant IL-10 alone or in combination with ICI are underway. This paradoxical effect of IL-10 and its underlying mechanisms impacting ICI-modulated T cell responses remain poorly understood. In this study, using an in vitro mixed lymphocyte reaction assay, we found that treatment with ICIs such as the anti-programmed cell death receptor-1 (PD-1) mAb nivolumab elicits a strong expression of IL-10. While neutralization of IL-10 signaling with an anti-IL-10 specific mAb significantly decreases the production of IFN-γ by T cells in a cohort of donor cells, the opposite effect was observed in other donor cells. Similarly, neutralization of IL-10 signaling significantly decreases the expression of T cell activation markers Ki67 and CD25, as well as the production of Granzyme B in a cohort of donor cells, whereas the opposite effect was observed in others. Furthermore, we found that nivolumab and IL-10 differentially modulate the signal transducer and activator of transcription 3 (STAT3) and AKT serine–threonine kinase pathways. Finally, we found that nivolumab activates the mitogen-activated protein kinase (MAPK) pathway, which in turn is responsible for the observed induction of IL-10 production by nivolumab. These findings provide new insights into the mechanisms underlying anti-PD-1-modulated T cell responses by IL-10, which could lead to the discovery of novel combination treatments that target IL-10 and immune checkpoint molecules.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling

Highlights: • INTS6 is upregulated in colorectal cancer and correlated with poor prognosis. • INTS6 promotes the growth of colorectal cancer cells in vitro and in vivo. • INTS6 affects the cell cycle distribution of colorectal cancer cells. • INTS6 activates the AKT and ERK signaling in colorectal cancer. INTS6 (integrator complex subunit 6) has been reported as a tumor suppressor in many cancers. However, the expression and biological function of INTS6 in colorectal cancer (CRC) has not been investigated yet. In this study, we found that INTS6 expression was significantly increased in CRC tissues when compared with normal tissues and was associated with poor prognosis. Downregulation of INTS6 induced G1/S-phase cell cycle arrest, and markedly suppressed the growth of CRC cells and the derived tumors, while overexpression of INTS6 showed opposite effect. Mechanism study revealed that INTS6 increased the levels of phosphorylated AKT (p-AKT) and ERK (p-ERK), and the growth-promoting effect of INTS6 was inhibited by AKT and ERK inhibitors. Besides, INTS6 also affected the expression of two targets of PI3K/AKT and MAPK signaling, c-Myc and CDK2, which contributed to cell cycle alteration. Altogether, the present study has revealed the oncogenic role of INTS6 in CRC, providing a novel therapeutic target for this malignant cancer.

60 APPLIED LIFE SCIENCES↗