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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 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Tailoring the Radionuclide Encapsulation and Surface Chemistry of La(223Ra)VO4 Nanoparticles for Targeted Alpha Therapy

The development of targeted alpha therapy (TAT) as a viable cancer treatment requires innovative solutions to challenges associated with radionuclide retention to enhance local tumor cytotoxicity and to minimize off-target effects. Nanoparticles (NPs) with high encapsulation and high retention of radionuclides have shown potential in overcoming these issues. This article shows the influence of pH on the structure of lanthanum vanadate (LaVO4) NPs and its impact on the radiochemical yield of 223Ra and subsequent retention of its decay daughters, 211Pb and 211Bi. An acidic pH (4.9) results in a high fraction of La(223Ra)VO4 NPs with tetragonal structure (44.6–66.1%) and a 223Ra radiochemical yield <40%. Adjusting the pH to 11 yields >80% of La(223Ra)VO4 NPs with monoclinic structure and increases the 223Ra radiochemical yield >85%. The leakage of decay daughters from La(223Ra)VO4 NPs (pH 11) was <5% and <0.5% when exposed to deionized water and phosphate-buffered saline, respectively. Altering the surface chemistry of La(223Ra)VO4 NPs with carboxylate and phosphate compounds resulted in a threefold decrease in hydrodynamic diameter and a 223Ra radiochemical yield between 74.7% and 99.6%. These results show the importance of tailoring the synthesis parameters and surface chemistry of LaVO4 NPs to obtain high encapsulation and retention of radionuclides.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A Mathematical Model of Breast Tumor Progression Based on Immune Infiltration

Breast cancer is the most prominent type of cancer among women. Understanding the microenvironment of breast cancer and the interactions between cells and cytokines will lead to better treatment approaches for patients. In this study, we developed a data-driven mathematical model to investigate the dynamics of key cells and cytokines involved in breast cancer development. We used gene expression profiles of tumors to estimate the relative abundance of each immune cell and group patients based on their immune patterns. Dynamical results show the complex interplay between cells and molecules, and sensitivity analysis emphasizes the direct effects of macrophages and adipocytes on cancer cell growth. In addition, we observed the dual effect of IFN-γ on cancer proliferation, either through direct inhibition of cancer cells or by increasing the cytotoxicity of CD8+ T-cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

A PDE Model of Breast Tumor Progression in MMTV-PyMT Mice

The evolution of breast tumors greatly depends on the interaction network among different cell types, including immune cells and cancer cells in the tumor. This study takes advantage of newly collected rich spatio-temporal mouse data to develop a data-driven mathematical model of breast tumors that considers cells’ location and key interactions in the tumor. The results show that cancer cells have a minor presence in the area with the most overall immune cells, and the number of activated immune cells in the tumor is depleted over time when there is no influx of immune cells. Interestingly, in the case of the influx of immune cells, the highest concentrations of both T cells and cancer cells are in the boundary of the tumor, as we use the Robin boundary condition to model the influx of immune cells. In other words, the influx of immune cells causes a dominant outward advection for cancer cells. We also investigate the effect of cells’ diffusion and immune cells’ influx rates in the dynamics of cells in the tumor micro-environment. Sensitivity analyses indicate that cancer cells and adipocytes’ diffusion rates are the most sensitive parameters, followed by influx and diffusion rates of cytotoxic T cells, implying that targeting them is a possible treatment strategy for breast cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Thiourea-Derived Chelating Ligands and Their Organometallic Compounds: Investigations into Their Anticancer Activity

Thiones have been investigated as ligands in metal complexes with catalytic and biological activity. We report the synthesis, characterization, and biological evaluation of a series of MII/III complexes of the general formulae [M II (cym)(L)Cl]X (cym = η 6 -p-cymene) or [M III (Cp*)(L)Cl]X (Cp* = η 5 -pentamethylcyclopentadienyl), where X = Cl - or PF 6 - , and L represents heterocyclic derivatives of thiourea. The thiones feature a benzyl-triazolyl pendant and they act as bidentate ligands via N,S-coordination to the metal centers. Several derivatives have been investigated by single-crystal X-ray diffraction analysis. NMR investigations showed a counterion-dependent shift of several protons due to the interaction with the counterions. These NMR investigations were complemented with X-ray diffraction analysis data and the effects of different counterions on the secondary coordination sphere were also investigated by DFT calculations. In biological studies, the Ir benzimidazole derivative was found to accumulate in the cytoplasm and it was the most cytotoxic derivative investigated.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Ultrathin Boron Growth onto Nanodiamond Surfaces via Electrophilic Boron Precursors

Diamond as a templating substrate is largely unexplored, and the unique properties of diamond, including its large bandgap, thermal conductance, and lack of cytotoxicity, makes it versatile in emergent technologies in medicine and quantum sensing. Surface termination of an inert diamond substrate and its chemical reactivity are key in generating new bonds for nucleation and growth of an overlayer material. Oxidized high-pressure high temperature (HPHT) nanodiamonds (NDs) are largely terminated by alcohols that act as nucleophiles to initiate covalent bond formation when an electrophilic reactant is available. In this work, we demonstrate a templated synthesis of ultrathin boron on ND surfaces using trigonal boron compounds. Boron trichloride (BCl 3 ), boron tribromide (BBr 3 ), and borane (BH 3 ) were found to react with ND substrates at room temperature in inert conditions. BBr 3 and BCl 3 were highly reactive with the diamond surface, and sheet-like structures were produced and verified with electron microscopy. Surface-sensitive spectroscopies were used to probe the molecular and atomic structure of the ND constructs’ surface, and quantification showed the boron shell was less than 1 nm thick after 1–24 h reactions. Observation of the reaction supports a self-terminating mechanism, similar to atomic layer deposition growth, and is likely due to the quenching of alcohols on the diamond surface. X-ray absorption spectroscopy revealed that boron-termination generated midgap electronic states that were originally predicted by density functional theory (DFT) several years ago. DFT also predicted a negative electron surface, which has yet to be confirmed experimentally here. The boron-diamond nanostructures were found to aggregate in dichloromethane and were dispersed in various solvents and characterized with dynamic light scattering for future cell imaging or cancer therapy applications using boron neutron capture therapy (BNCT). The unique templating mechanism based on nucleophilic alcohols and electrophilic trigonal precursors allows for covalent bond formation and will be of interest to researchers using diamond for quantum sensing, additive manufacturing, BNCT, and potentially as an electron emitter.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Enhanced Corneal Penetration of a Poorly Permeable Drug Using Bioadhesive Multiple Microemulsion Technology

Corneal penetration is a key rate limiting step in the bioavailability of topical ophthalmic formulations that incorporate poorly permeable drugs. Recent advances have greatly aided the ocular delivery of such drugs using colloidal drug delivery systems. Ribavirin, a poorly permeable BCS class-III drug, was incorporated in bioadhesive multiple W/O/W microemulsion (ME) to improve its corneal permeability. The drug-loaded ME was evaluated regarding its physical stability, droplet size, PDI, zeta potential, ultrastructure, viscosity, bioadhesion, in vitro release, transcorneal permeability, cytotoxicity, safety and ocular tolerance. Our ME possessed excellent physical stability, as it successfully passed several cycles of centrifugation and freeze–thaw tests. The formulation has a transparent appearance due to its tiny droplet size (10 nm). TEM confirmed ME droplet size and revealed its multilayered structure. In spite of the high aqueous solubility and the low permeability of ribavirin, this unique formulation was capable of sustaining its release for up to 24 h and improving its corneal permeability by 3-fold. The in vitro safety of our ME was proved by its high percentage cell viability, while its in vivo safety was confirmed by the absence of any sign of toxicity or irritation after either a single dose or 14 days of daily dosing. Our ME could serve as a vehicle for enhanced ocular delivery of drugs with different physicochemical properties, including those with low permeability.

Ibrahim, Mohamed Moustafa↗
DOE OSTI2023

One Health Approach to Tackle Microbial Contamination on Poultries—A Systematic Review

This study reports the search of available data published regarding microbial occupational exposure assessment in poultries, following the PRISMA methodology. Air collection through filtration was the most frequently used. The most commonly used passive sampling method was material collection such as dust, cages, soils, sediment, and wastewater. Regarding assays applied, the majority of studies comprised culture-based methods, but molecular tools were also frequently used. Screening for antimicrobial susceptibility was performed only for bacteria; cytotoxicity, virological and serological assays were also performed. Most of the selected studies focused on bacteria, although fungi, endotoxins, and β-glucans were also assessed. The only study concerning fungi and mycotoxins reported the carcinogenic mycotoxin AFB1. This study gives a comprehensive overview of microbial contamination in the poultry industry, emphasizing this setting as a potential reservoir of microbial pathogens threatening human, animal, and environmental health. Additionally, this research helps to provide a sampling and analysis protocol proposal to evaluate the microbiological contamination in these facilities. Few articles were found reporting fungal contamination in poultry farms worldwide. In addition, information concerning fungal resistance profile and mycotoxin contamination remain scarce. Overall, a One Health approach should be incorporated in exposure assessments and the knowledge gaps identified in this paper should be addressed in further research.

Gomes, Bianca (ORCID:0000000262646072)↗
DOE OSTI2021

Sequence-Defined Nanotubes Assembled from IR780-Conjugated Peptoids for Chemophototherapy of Malignant Glioma

Near-infrared (NIR) laser-induced phototherapy through NIR agents has demonstrated the great potential for cancer therapy. However, insufficient tumor killing due to the nonuniform heat or cytotoxic singlet oxygen ( 1 O 2 ) distribution over tumors from phototherapy results in tumor recurrence and inferior outcomes. To achieve high tumor killing efficacy, one of the solutions is to employ the combinational treatment of phototherapy with other modalities, especially with chemotherapeutic agents. In this paper, a simple and effective multimodal therapeutic system was designed via combining chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT) to achieve the polytherapy of malignant glioma which is one of the most aggressive tumors in the brain. IR-780 (IR780) dye-labeled tube-forming peptoids (PepIR) were synthesized and self-assembled into crystalline nanotubes (PepIR nanotubes). These PepIR nanotubes showed an excellent efficacy for PDT/PTT because the IR780 photosensitizers were effectively packed and separated from each other within crystalline nanotubes by tuning IR780 density; thus, a self-quenching of these IR780 molecules was significantly reduced. Moreover, the efficient DOX loading achieved due to the nanotube large surface area contributed to an efficient and synergistic chemotherapy against glioma cells. Given the unique properties of peptoids and peptoid nanotubes, we believe that the developed multimodal DOX-loaded PepIR nanotubes in this work offer great promises for future glioma therapy in clinic.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1985

Enhancing effects of gamma interferon on phagocytic cell association with and killing of Trypanosoma cruzi

Results are reported from a study of the influence gamma interferon (GIFN) and interleukin 2 (IL2) have on the capability of P388D1 cells and mouse resident peritoneal macrophages (MPM) to attach to the blood-resident parasites Trypanosoma cruzi and kill them. Cultures of trypomastigote forms of the Tulahuen strain of T. cruzi grown in bovine serum were introduced into peritoneal cells of mice, along with P388D1 cells incubated with GIFN, IL2 and both. Control cells were also maintained. Statistical analysis were then performed on data on counts of the number of dead T. Cruzi cells. The GIFN enhanced the interaction of MPM and P388D1 cells with the surface of T. Cruzi, provided the interaction was given over 12 hr to take place. A depression of the cytotoxicity of P388D1 cells was attributed to mediation by H2O2, an effect partially offset by incubation with the lymphokine GIFN.

Wirth, J. J.↗
NASA NTRS1988

Antibody enhancement of free-flow electrophoresis

Specific T cell clones and antibodies (ABs) were developed to study the efficiency of purifying closely associated T cells using Continuous Flow Electrophoresis System. Enhanced separation is accomplished by tagging cells first with ABs directed against the antigenic determinants on the cell surface and then with ABs against the Fc portion of the first AB. This second AB protrudes sufficiently beyond the cell membrane and glycocalyx to become the major overall cell surface potential determinant and thus causes a reduction of electrophoretic mobility. This project was divided into three phases. Phase one included development of specific T cell clones and separation of these specific clones. Phase two extends these principles to the separation of T cells from spleen cells and immunized lymph node cells. Phase three applies this double antibody technique to the separation of T cytotoxic cells from bone marrow.

Cohly, H. H. P.↗
NASA NTRS1991

Effects of microgravity on the immune system

Changes in resistance to bacterial and viral infections in Apollo crew members has stimulated interest in the study of immunity and space flight. Results of studies from several laboratories in both humans and rodents have indicated alterations after space flight that include the following immunological parameters: thymus size, lymphocyte blastogenesis, interferon and interleukin production, natural killer cell activity, cytotoxic T-cell activity, leukocyte subset population distribution, response of bone marrow cells to colony stimulating factors, and delayed hypersensitivity skin test reactivity. The interactions of the immune system with other physiological systems, including muscle, bone, and the nervous system, may play a major role in the development of these immunological parameters during and after flight. There may also be direct effects of space flight on immune responses.

Sonnenfeld, Gerald↗
NASA NTRS1992

Structure of a human monoclonal antibody Fab fragment against gp41 of human immunodeficiency virus type

The three-dimensional structure of a human monoclonal antibody (Fab), which binds specifically to a major epitope of the transmembrane protein gp41 of the human immunodeficiency virus type 1, has been determined by crystallographic methods to a resolution of 2.7 A. It has been previously determined that this antibody recognizes the epitope SGKLICTTAVPWNAS, belongs to the subclass IgG1 (kappa), and exhibits antibody-dependent cellular cytotoxicity. The quaternary structure of the Fab is in an extended conformation with an elbow bend angle between the constant and variable domains of 175 degrees. Structurally, four of the hypervariable loops can be classified according to previously recognized canonical structures. The third hypervariable loops of the heavy (H3) and light chain (L3) are structurally distinct. Hypervariable loop H3, residues 102H-109H, is unusually extended from the surface. The complementarity-determining region forms a hydrophobic binding pocket that is created primarily from hypervariable loops L3, H3, and H2.

He, X. M.↗
NASA NTRS1992

Structure of a human monoclonal antibody Fab fragment against gp41 of human immunodeficiency virus type 1

The three-dimensional structure of a human monoclonal antibody (Fab), which binds specifically to a major epitope of the transmembrane protein gp41 of the human immunodeficiency virus type 1, has been determined by crystallographic methods to a resolution of 2.7 A. It has been previously determined that this antibody recognizes the epitope SGKLICTTAVPWNAS, belongs to the subclass IgG1 (kappa), and exhibits antibody-dependent cellular cytotoxicity. The quaternary structure of the Fab is in an extended conformation with an elbow bend angle between the constant and variable domains of 175 deg. Structurally, four of the hypervariable loops can be classified according to previously recognized canonical structures. The third hypervariable loops of the heavy (H3) and light chain (L3) are structurally distinct. Hypervariable loop H3, residues 102H-109H, is unusually extended from the surface. The complementarity-determining region forms a hydrophobic binding pocket that is created primarily from hypervariable loops L3, H3, and H2.

He, Xiao M.↗
NASA NTRS1994

Microencapsulation of anti-tumor, antibiotic and thrombolytic drugs in microgravity

Encapsulation of cytotoxic or labile drugs enables targeted delivery and sustained release kinetics that are not available with intravenous injection. A new liquid-liquid diffusion process has been developed for forming unique microcapsules that contain both aqueous and hydrocarbon soluble drugs. Microgravity experiments, on sounding rockets (1989-92) and Shuttle missions STS-52 (1992) and STS-56 (1993) using an automated Materials Dispersion Apparatus, produced multi-lamellar microcapsules containing both Cis-platinum (anti-tumor drug) and iodinated poppy seed oil (a radiocontrast medium), surrounded by a polyglyceride skin. Microcapsules formed with amoxicillin (antibiotic) or urokinase (a clot dissolving enzyme), co-encapsulated with IPO, are still intact after two years. Microcapsules were formed with the drug so concentrated that crystals formed inside. Multi-layered microspheres, with both hydrophobic drug compartments, can enable diffusion of complementary drugs from the same microcapsule, e.g. antibiotics and immuno-stimulants to treat resistant infections or multiple fibrinolytic drugs to dissolve emboli. Co-encapsulation of enough radio-contrast medium enables oncologists to monitor the delivery of anti-tumor microcapsules to target tumors using computerized tomography and radiography that would track the distribution of microcapsules after release from the intra-arterial catheter. These microcapsules could have important applications in chemotheraphy of certain liver, kidney, brain and other tumors.

Morrison, Dennis R.↗
NASA NTRS1994

Cellular changes in microgravity and the design of space radiation experiments

Cell metabolism, secretion and cell-cell interactions can be altered during space flight. Early radiobiology experiments have demonstrated synergistic effects of radiation and microgravity as indicated by increased mutagenesis, increased chromosome aberrations, inhibited development, and retarded growth. Microgravity-induced changes in immune cell functions include reduced blastogenesis and cell-mediated, delayed-type hypersensitivity responses, increased cytokine secretions, but inhibited cytotoxic effects an macrophage differentiation. These effects are important because of the high radiosensitivity of immune cells. It is difficult to compare ground studies with space radiation biology experiments because of the complexity of the space radiation environment, types of radiation damage and repair mechanisms. Altered intracellular functions and molecular mechanisms must be considered in the design and interpretation of space radiation experiments. Critical steps in radiocarcinogenesis could be affected. New cell systems and hardware are needed to determine the biological effectiveness of the low dose rate, isotropic, multispectral space radiation and the potential usefulness of radioprotectants during space flight.

Morrison, D. R.↗
NASA NTRS1994

Production and action of cytokines in space

B6MP102 cells, a continuously cultured murine bone marrow macrophage cell line, were tested for secretion of tumor necrosis factor-alpha and Interleukin-1 during space flight. We found that B6MP102 cells secreted more tumor necrosis factor-alpha and interleukin-1 when stimulated in space with lipopolysaccharide than controls similarly stimulated on earth. This compared to increased secretion of interferon-beta and -gamma by lymphocytes that was measured on the same shuttle flights. Although space flight enhanced B6MP102 secretion of tumor necrosis factor-alpha, an experiment on a subsequent space flight (STS-50) found that cellular cytotoxicity, mediated by tumor necrosis factor-alpha, was inhibited.

Chapes, Stephen K.↗
NASA NTRS1994

Experiment K-7-23: Effect of Spaceflight on Level and Function of Immune Cells: Immunology Studies - Part 1

Two different experiments were carried out in this segment of the immunology protocol for samples received from rats flown on Cosmos 2044. Control groups included vivarium, synchronous and antiorthostatically suspended rats. In the first experiment, rat bone marrow cells were examined in Moscow for their response to recombinant murine colony stimulating factor-granulocyte / monocyte (CSF-GM). In the second experiment, rat spleen and bone marrow cells were stained in Moscow with a variety of antibodies directed against cell surface antigenic markers. These cells were preserved and shipped to the United States for analysis on a flow cytometer. The results of the studies indicated that bone marrow cells from flown and suspended rats showed a decreased response to CSF-GM as compared to bone marrow cells from control rats. Spleen cells from flown rats showed increased percentages of suppressor-cytotoxic-T and helper-T cells amongst the entire cell population. Bone marrow cells showed an increase in the percentage of helper-T cells in the myelogenous population and increased percentages of anti-asialo GM-1 bearing, interleukin-2 receptor bearing, pan-T and helper-T cells in the lymphocytic population. Cell populations from rats suspended antiorthostatically did not follow the same pattern of distribution of leukocytes as cell populations for flown rats. These results are similar, but not identical to, earlier results from Cosmos 1887, and confirm that space flight can have profound effects on immune system components and activities.

Sonnenfeld, G.↗