Fragmented Nuclei Research Articles

Evaluation of photodynamic therapy against Leishmania tropica promastigotes using different photosensitizers.

Photodynamic therapy is a two-step procedure, involving the use of photosensitizing agents followed by selective illumination of the target lesion with visible light. Photodynamic therapy has been described recently as a promising strategy for treatment of leishmaniasis. This study aims to evaluate the in vitro phototoxic, morphological, and apoptotic effect of methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy on the viability of Leishmania tropica promastigotes. Parasites were treated with methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a or/and methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy, and cell proliferation, morphological changes, and apoptosis were evaluated by XTT, giemsa staining, DAPI staining, and DNA fragmentation, respectively. Parasite viability was significantly different in between the groups treated with methylene blue, toluidine blue, and pheophorbide a, with or without irradiation. chloro-aluminum phthalocyanine treatment did not lead to any alterations in cell viability in Leishmania tropica promastigotes with or without irradiation. DAPI staining results indicated that apoptotic bodies and nucleus fragmentation started to be visible in methylene blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy groups. DNA ladder pattern which is used to define apoptosis was observed in irradiated methylene blue, chloro-aluminum phthalocyanine, and pheophorbide a groups. The results revealed that apoptosis-induced cell death was observed in Leishmania tropica promastigotes after the application of photosensitizers in combination with light irradiation.

Calculation of barrier potential height using fraction parameter

Nucleus deformation refers to a change in the nucleus surface shape. The expression of the radius of the nucleus can represent this deformation. Generally, these radii are expansions involving spherical harmonics. In addition, some divide the nucleus shape into three parts. The left and right ends are spherical, while the middle or neck uses the hyperbolic function. The deformation shape does not contain the fraction of the nucleus fragments. In fact, including all possible fraction values will provide all the probability that occurs. These probabilities can be accumulated to determine the value of the potential barrier height. Based on this reason, a technique was developed to include the fragment fraction as part of the input variable. This technique is intended to be able to use experimental data from fission products. Namely, as input to get a potential barrier height. By changing the function expression for the radius of the nucleus, the fragment fraction can insert into the function. For this purpose, the method is to form the three parts of the nuclear radius. The first part is the head in the form of spherical harmonics. The second part is the neck which has a shape like hyperbolic cosines. By applying the continuity condition between the neck and the head, the fraction parameter becomes the expansion coefficient of the spherical harmonics. This technique shows fairly good calculation results. The figure of the potential barrier height shows the results of these calculations. It is through comparisons between this work and several other works that two main conclusions are drawn. First, the insertion of fraction parameters at the nucleus radius was successfully carried out. Second, the fission yield data can be used as input for calculating the fission barrier height.

An Enhancement of Formation of Unstable 8Be Nucleus with the Growth of α-Particle Multiplicity in Fragmentation of Relativistic Nuclei

In this paper, the correlation between the formation of the unstable $^{8}$Be nucleus and accompanying $\alpha$ particles in the fragmentation of relativistic $^{16}$O, $^{22}$Ne, $^{28}$Si, and $^{197}$Au nuclei in a nuclear track emulsion is investigated. The $^{8}$Be decays are identified in a wide energy range by invariant masses calculated from 2$\alpha$-pair opening angles. The adopted approximations are verified by data on fragmentation of $^{16}$O nuclei in a hydrogen bubble chamber in a magnetic field. An increase in the $^{8}$Be contribution to the dissociation with the growth of $\alpha$-particle multiplicity is found.

Thermodynamically Consistent Description of One-Phonon States Fragmentation in Hot Nuclei

Thermodynamically Consistent Description of One-Phonon States Fragmentation in Hot Nuclei

Assessment of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy on Bone Metastases: An in Vitro Study.

Simple SummaryBone metastases are typically associated with a short-term prognosis. Photodynamic therapy (PDT) emerges as a promising alternative treatment for targeting metastatic lesions. In this study we investigated the effect of 5-aminolevulinic acid-mediated PDT treatment on both primary and human bone metastatic cancer cell lines. We found that human cell lines have different sensitivity to the same doses and exposure of 5-ALA PDT resulting in two different cell fates, apoptosis or senescence, depending on the extent of the cellular damage. As such, PDT has potential applicability in bone metastases of invasive ductal carcinoma.Bone is a frequent site of metastases, being typically associated with a short-term prognosis in affected patients. Photodynamic therapy (PDT) emerges as a promising alternative treatment for controlling malignant disease that can directly target interstitial metastatic lesions. The aim of this study was to assess the effect induced by PDT treatment on both primary (giant cell bone tumor) and human bone metastatic cancer cell lines (derived from a primary invasive ductal breast carcinoma and renal carcinoma). After 24 h post light delivery (blue light-wavelength 436 nm) with 5-aminolevulinic acid, the effect on cellular migration, viability, apoptosis, and senescence were assessed. Our results showed that bone metastasis derived from breast cancer reacted with an inhibition of cell migration coupled with reduced viability and signs of apoptosis such as nuclei fragmentation following PDT exposure. A limited effect in terms of cellular viability inhibition was observed for the cells of giant cell bone tumors. In contrast, bone metastasis derived from renal carcinoma followed a different fate—cells were characterized by senescent features, without a notable effect on cell migration or viability. Collectively, our study illustrates that PDT could act as a successful therapy concept for local tumor control in some entities of bone metastases.

Fission-fragment yields and prompt-neutron multiplicity for Coulomb-induced fission of U234,235 and Np237,238

Low-energy fission of U234,235 and Np237,238 radioactive beams, provided by the Fragment Separator (FRS) of the GSI Helmholtzzentrum für Schwerionenforschung facility (GSI), has been studied using the Reactions with Relativistic Radioactive Beams / Studies on Fission with Aladin (R3B/SOFIA) setup. The latter allows us, on an event-by-event basis, to simultaneously identify, in terms of their mass and atomic numbers, the fissioning nucleus in coincidence with both fission fragments after prompt-neutron emission. This article reports new results on elemental, isotonic, isobaric, and isotopic yields. Moreover, the high accuracy of our data allowed us to study in detail proton even-odd staggering, from elemental yields; neutron excess, from isotopic yields; and total prompt-neutron multiplicity, from the difference of masses of the fissioning nucleus and fission fragments. These results are then compared to previous experimental data in order to probe how these fission observables change as function of the excitation energy and atomic and neutron numbers of the compound nucleus.14 MoreReceived 23 June 2021Accepted 25 August 2021DOI:https://doi.org/10.1103/PhysRevC.104.044602©2021 American Physical SocietyPhysics Subject Headings (PhySH)Research AreasFissionModels & methods for nuclear reactionsPropertiesA ≥ 220Nuclear Physics

Effect of irradiation with heavy Xe22+ ions with energies of 165–230 MeV on change in optical characteristics of ZrO2 ceramic

The aim of this work is to study the effect of irradiation with heavy Xe22+ ions with energies of 165 MeV, 200 MeV, and 230 MeV on the change in the optical properties of ZrO2 ceramic. The choice of ion energies, as well as irradiation fluences of 1013-1014 ion/cm2, is primarily due to the possibility of simulating radiation damage in ceramics that occurs when overlapping damaged areas in the material, comparable to damage from fission fragments of uranium nuclei in an atomic reactor. Using UV–Vis spectroscopy methods, changes in the throughput of ceramics were evaluated depending on the irradiation fluence and the energy of incident ions. It was found that a change in the irradiation conditions leads to the formation of irradiation-induced defects with an energy of 2.4–2.45 eV in the structure, the concentration of which increases with the irradiation dose. Changes in the band gap and refractive index depending on irradiation fluence and incident ions energy indicate a change in the electronic and optical density of ceramics, as well as the formation of additional absorbing centers in the structure.

Piceatannol, a Structural Analog of Resveratrol, Is an Apoptosis Inducer and a Multidrug Resistance Modulator in HL-60 Human Acute Myeloid Leukemia Cells.

Acute myeloid leukemia is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Despite recent advances in the treatment of this disease, the prognosis and overall long-term survival for patients remain poor, which drives the search for new chemotherapeutics and treatment strategies. Piceatannol, a polyphenolic compound present in grapes and wine, appears to be a promising chemotherapeutic agent in the treatment of leukemia. The aim of the present study was to examine whether piceatannol induces autophagy and/or apoptosis in HL-60 human acute myeloid leukemia cells and whether HL-60 cells are able to acquire resistance to piceatannol toxicity. We found that piceatannol at the IC90 concentration of 14 µM did not induce autophagy in HL-60 cells. However, it induced caspase-dependent apoptosis characterized by phosphatidylserine externalization, disruption of the mitochondrial membrane potential, caspase-3 activation, internucleosomal DNA fragmentation, PARP1 cleavage, chromatin condensation, and fragmentation of cell nuclei. Our findings also imply that HL-60 cells are able to acquire resistance to piceatannol toxicity via mechanisms related to MRP1 activity. Our results suggest that the use of piceatannol as a potential chemotherapeutic agent may be associated with the risk of multidrug resistance, warranting its use in combination with other chemotherapeutic agents.

In vitro evaluation of cytotoxic and apoptotic activities of ethanolic extract of sweet apricot kernel on PANC-1 pancreatic cancer cells

PurposeThis study aimed to evaluate the cytotoxic/apoptotic effects of sweet apricot kernel ethanolic extract (SAEE) on human cancerous PANC-1 and 293/KDR normal cells.Design/methodology/approachThe extract was prepared by maceration, and its chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). The biological effects of SAEE on PANC-1 and 293/KDR cells were investigated using MTT (3–(4, 5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide) assay, DAPI (4',6-diamidino-2-phenylindole) and AnnexinV/propidium iodide (PI) staining. The expression of pro- and anti-apoptotic genes was evaluated by real-time quantitative polymerase chain reaction (real-time q-PCR) analysis.FindingsThe SAEE showed the selective growth inhibitory activity against PANC-1 cells with an IC50 (the 50% inhibitory concentration) value of about 1 mg/mL at 72 h. Further investigations by DAPI staining and flow cytometry revealed nucleus fragmentation and elevation of apoptotic cells, respectively. Also, a significant decrease in B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated x protein (Bax) ratio (0.41, p = 0.001) and the up-regulation of caspase-3 expression (1.5 fold, p = 0.002) indicated the induction of apoptosis in PANC-1 cells but not in 293/KDR non-cancerous cells. These results suggest that SAEE could induce apoptosis in cancer cells via a mitochondrial dependent pathway. Furthermore, GC-MS analysis showed that the SAEE is rich in γ-sitosterol and γ-tocopherol. Overall, the findings suggest that because of the selective impacts of SAEE on PANC-1 cells, it can be considered as a supportive care in adjuvant therapy for pancreatic cancer. However, the potent anticancer effects of main components of SAEE and its clinical value as an antitumor drug should be further investigated.Research limitations/implicationsConsiderable limitations of this study were that the related mechanisms of selective impacts of SAEE on cancerous and normal cells and potent cytotoxic/apoptotic effects of γ-sitosterol and γ-tocopherol as major components of SAEE were not investigated.Originality/valueRecently, a growing interest has been dedicated to plant-based natural products. Sweet apricot kernel exerts a number of pharmacological activities; however, the anticancer effect, related mechanisms and its active compounds were rarely investigated. In this study, the authors aimed to evaluate the cytotoxic/apoptotic effects of SAEE on human cancerous PANC-1 and 293/KDR normal cells.

Orchestration of Force Generation and Nuclear Collapse in Apoptotic Cells.

Apoptosis, or programmed cell death, is a form of cell suicide that is extremely important for ridding the body of cells that are no longer required, to protect the body against hazardous cells, such as cancerous ones, and to promote tissue morphogenesis during animal development. Upon reception of a death stimulus, the doomed cell activates biochemical pathways that eventually converge on the activation of dedicated enzymes, caspases. Numerous pieces of information on the biochemical control of the process have been gathered, from the successive events of caspase activation to the identification of their targets, such as lamins, which constitute the nuclear skeleton. Yet, evidence from multiple systems now shows that apoptosis is also a mechanical process, which may even ultimately impinge on the morphogenesis of the surrounding tissues. This mechanical role relies on dramatic actomyosin cytoskeleton remodelling, and on its coupling with the nucleus before nucleus fragmentation. Here, we provide an overview of apoptosis before describing how apoptotic forces could combine with selective caspase-dependent proteolysis to orchestrate nucleus destruction.

A novel derivative of picolinic acid induces endoplasmic reticulum stress-mediated apoptosis in human non-small cell lung cancer cells: synthesis, docking study, and anticancer activity

Thirteen new derivatives of picolinic acid (4–7) were designed and synthesized from the starting parent molecule, picolinic acid. The new compounds were characterized by ATR-FTIR, 1HNMR, and CHNS analysis. A molecular docking study was performed to evaluate the binding affinity of the synthesized compounds toward EGFR kinase domain that indicated occupation of the critical site of EGFR kinase pocket and excellent positioning of the compounds in the pocket. The cytotoxic activity of the compounds against two human cancer cell lines (A549 and MCF-7), the non-tumorigenic MCF10A cell line, and white blood cells (WBC) was evaluated using the MTT assay. Compound 5 showed anticancer activity against A549 lung cancer cells (IC50 = 99.93 µM) but not against MCF-7 breast cancer cells or normal cells. Compound 5 mediated cytotoxicity in A549 lung cancer cells by inducing apoptotic cell death, as suggested by fragmented nuclei after DAPI staining, and agarose gel electrophoresis. Moreover, compound 5 triggered the activation of caspases 3, 4 and 9. However, compound 5 treatment did not affect the release of cytochrome c from the mitochondria to the cytosol, as compared to the vehicle-treated control cells. Nevertheless, compound 5-treated cells reported greater release of smac/DIABLO to the cytosol. In the same context, both compound 5 and thapsigargin (specific inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA)) enhanced eIF2 phosphorylation, reflecting the activation of the atypical ER stress pathway and the potential applicability of compound 5 in lung cancer treatment.

Sulindac and vitamin D3 synergically inhibit proliferation of MCF-7 breast cancer cell through AMPK/Akt/β-catenin axis in vitro.

Breast cancer is associated with a high rate of recurrence, resistance therapy and mortality worldwide. We aimed at investigating the inhibitory effects of Sulindac and vitamin D3 (VD) on MCF-7 human breast cancer cells. MCF-7 cells were cultured with different concentrations of Sulindac and VD over a period of 24, 48 and 72 hours for cell viability and IC50 experiments. Hochst staining was used to evaluate apoptosis, whereas quantitative PCR (qPCR) was performed to measure mRNA levels of BCL-2 and BAX genes. Immunofluorescence staining was used to monitor intracellular β-catenin expression. The protein levels of AKT, AMPK and P65 were measured by western blotting. The result showed that cell viability decreased in treated cells dose/time dependently (P < .05). Hochst staining showed an increase in fragmented nuclei in treated cells. The expression of BCL-2 and BAX genes decreased and increased in treated cells, respectively (P < .05). Immunofluorescence staining indicated that the expression of β-catenin significantly reduced in treated cells. The AKT-1/p-Akt-1 and AMPK/p-AMPK ratio increased in treated cells (P < .05), but the P65/p-P65 ratio did not change significantly (P > .05). Our results indicated that the combination of Sulindac and VD has a growth-inhibiting effect on MCF-7 cells through AMPK/Akt/β-catenin axis.

Forward Hodoscopes of Charged Nuclei Fragments for the BM @ N Experiment

Forward Hodoscopes of Charged Nuclei Fragments for the BM @ N Experiment

Multi-Organ Histopathological Changes in a Mouse Hepatitis Virus Model of COVID-19

Infection with SARS-CoV-2, the virus responsible for the global COVID-19 pandemic, causes a respiratory illness that can severely impact other organ systems and is possibly precipitated by cytokine storm, septic shock, thrombosis, and oxidative stress. SARS-CoV-2 infected individuals may be asymptomatic or may experience mild, moderate, or severe symptoms with or without pneumonia. The mechanisms by which SARS-CoV-2 infects humans are largely unknown. Mouse hepatitis virus 1 (MHV-1)-induced infection was used as a highly relevant surrogate animal model for this study. We further characterized this animal model and compared it with SARS-CoV-2 infection in humans. MHV-1 inoculated mice displayed death as well as weight loss, as reported earlier. We showed that MHV-1-infected mice at days 7–8 exhibit severe lung inflammation, peribronchiolar interstitial infiltration, bronchiolar epithelial cell necrosis and intra-alveolar necrotic debris, alveolar exudation (surrounding alveolar walls have capillaries that are dilated and filled with red blood cells), mononuclear cell infiltration, hyaline membrane formation, the presence of hemosiderin-laden macrophages, and interstitial edema. When compared to uninfected mice, the infected mice showed severe liver vascular congestion, luminal thrombosis of portal and sinusoidal vessels, hepatocyte degeneration, cell necrosis, and hemorrhagic changes. Proximal and distal tubular necrosis, hemorrhage in interstitial tissue, and the vacuolation of renal tubules were observed. The heart showed severe interstitial edema, vascular congestion, and dilation, as well as red blood cell extravasation into the interstitium. Upon examination of the MHV-1 infected mice brain, we observed congested blood vessels, perivascular cavitation, cortical pericellular halos, vacuolation of neuropils, darkly stained nuclei, pyknotic nuclei, and associated vacuolation of the neuropil in the cortex, as well as acute eosinophilic necrosis and necrotic neurons with fragmented nuclei and vacuolation in the hippocampus. Our findings suggest that the widespread thrombotic events observed in the surrogate animal model for SARS-CoV-2 mimic the reported findings in SARS-CoV-2 infected humans, representing a highly relevant and safe animal model for the study of the pathophysiologic mechanisms of SARS-CoV-2 for potential therapeutic interventions.

Single-cell measurement of higher-order 3D genome organization with scSPRITE.

Although three-dimensional (3D) genome organization is central to many aspects of nuclear function, it has been difficult to measure at the single-cell level. To address this, we developed 'single-cell split-pool recognition of interactions by tag extension' (scSPRITE). scSPRITE uses split-and-pool barcoding to tag DNA fragments in the same nucleus and their 3D spatial arrangement. Because scSPRITE measures multiway DNA contacts, it generates higher-resolution maps within an individual cell than can be achieved by proximity ligation. We applied scSPRITE to thousands of mouse embryonic stem cells and detected known genome structures, including chromosome territories, active and inactive compartments, and topologically associating domains (TADs) as well as long-range inter-chromosomal structures organized around various nuclear bodies. We observe that these structures exhibit different levels of heterogeneity across the population, with TADs representing dynamic units of genome organization across cells. We expect that scSPRITE will be a critical tool for studying genome structure within heterogeneous populations.

Pseudoalteromonas piscicida X-8 causes bleaching disease in farmed Saccharina japonica

Saccharina japonica is a commercially farmed seaweed of global importance. However, disease occurrence during different stages of cultivation can result in substantial economic losses. Identification of the causative agents of disease remains a significant bottleneck to the large scale cultivation of S. japonica. In this study, an aerobic heterotrophic, flagellated, rod-shaped Gram-negative bacterial strain X-8 was isolated from the bleaching diseased S. japonica sporelings. Pathogenecity of strain X-8 was tested by re-infection assay. The ultrastructural changes of infected S. japonica cells by strain X-8 indicated that chloroplasts were the first organelle responding to X-8 infection with deformed structure and later followed by fragmented nucleus. However, the ultra-structure of mitochondria and cell wall remained intact during the re-infection. Based on 16S rRNA gene sequence, morphological and biochemical characteristics, strain X-8 was designated as Pseudoalteromonas piscicida X-8. The pathogenicity of P. piscicida X-8 was identified by Koch's Postulate under laboratory conditions. Our results will not only help to establish a stable experimental model between the pathogenic bacteria and the host S. japonica to further elucidate the virulence mechanisms, but will also provide information for disease management to effectively prevent and mitigate the occurrence of bleaching disease of S. japonica at nursery stage.

Phenethyl Isothiocyanate Induces Apoptosis Through ROS Generation and Caspase-3 Activation in Cervical Cancer Cells.

The latest research shows that current chemotherapeutics are ineffective because of the development of resistance in cervical cancer cells, and hence, their scope of use is limited. The main concern of researchers at the moment is the discovery of safe and effective antiproliferative plant chemicals that can aid in the battle against cervical cancer. Previous studies have shown the possible anticancer potential of phenethyl isothiocyanate obtained from cruciferous plants for many cancers, which targets various signaling pathways to exercise chemopreventive and therapeutic effects. This provides the basis for studying phenethyl isothiocyanate's therapeutic potential against cervical cancer. In the present study, cervical cancer cells were treated with various doses of phenethyl isothiocyanate, alone and in combination with cisplatin. Phenethyl isothiocyanate alone was sufficient to cause nucleus condensation and fragmentation and induce apoptosis in cervical cancer cells, but evident synergistic effects were observed in combination with cisplatin. In addition, phenethyl isothiocyanate treatment increased the production of intracellular ROS in a dose-dependent manner in cervical cancer cells. Furthermore, investigation of phenethyl isothiocyanate induced mitochondrial reactive oxygen species production, and activation of caspases showed that phenethyl isothiocyanate significantly activated caspase-3.

Comparison of emulsifying properties of fibrils formed from whey protein concentrate following induction by nuclei and nuclei fragments

The structural and emulsification properties of amyloid fibrils in whey protein concentrate (WPC) with certain ratios of added nuclei or nuclei fragments, generated using ultrasound, high-speed shear treatment and enzymatic hydrolysis methods, were compared. The emulsifying properties of nuclei fragments produced by high-speed shear treatment were effectively improved, but those of nuclei hydrolysed by alkaline protease decreased, since the determinant structures were destroyed. However, the emulsifying activity index and emulsifying stability index of fibrils subsequently formed by nuclei fragment induction (enzymatic hydrolysis method) were higher than those of fibrils formed by the heat-induced method and nuclei induction method in all pH environments. The fibril size induced by nuclei fragment induction was smaller, and the fibril level was higher, and thus the ability to improve the emulsifying properties of WPC was stronger.

Morphological, biochemical and molecular hallmarks of programmed cell death in stigmatic papillae of Brassica oleracea L.

The aim of this study is to determine the programmed cell death hallmarks in the stigmatic papillae of Brassica oleracea L. The flower development was divided in two main stages; pre-anthesis and post-anthesis. Programmed cell death hallmarks were examined in parallel to these stages. At pre-anthesis, the stigmatic papillae were ovoid and their dense cytoplasm were rich in insoluble polysaccharide and protein. At post-anthesis, vacuolization and enlargement were quite evident in papillae. Besides, the protein content decreased, but reactive oxygen species increased in comparison to the pre-anthesis stage. Although no significant change in superoxide dismutase activity was detected, catalase activity decreased and hydrogen peroxide content increased at post-anthesis. DAPI stained nuclei appeared rounded and smooth appearance at pre-anthesis, however, some invaginations and fragmentation in nuclei were observed at post-anthesis. Although, TUNEL staining was negative at pre-anthesis, while TUNEL positive reaction was significant in the nuclei of papillae at post-anthesis. In comparison to the pre-anthesis, the number of fragmented nuclei monitored by DAPI and TUNEL staining increased at post-anthesis.

Space radiation electrostatic shielding scaling laws: Beam-like and isotropic angular distributions

Passive radiation shielding alone cannot provide adequate protection for astronauts on long-term, deep-space missions. High atomic number and energy (HZE) ions, and/or their secondaries, can penetrate any realistic mass shielding for long-term deep-space missions and cause damage to cells via direct energy deposition and/or through the production of secondary particles and fragmented nuclei. Active shielding, or the use of electromagnetic fields to deflect or stop incoming ions before reaching the spacecraft, has gained substantial attention over the last decade as a way to augment passive shielding. Recently, a mathematical relationship between a dimensionless scaling parameter characterizing the active shield and the incoming ion and a protected area formed on a downstream detector due to the deflection of HZE ions by the applied field was validated in Earth-based laboratory conditions. In the present work, the mathematical formulation is extended to relate electrostatic shielding efficacy with the ability to deflect positively charged ions with parameters relevant to space applications. Additionally, a modified scaling parameter is formulated to characterize the shielding efficacy of a “family” of electrostatic active shielding configurations for reducing flux density for a space-relevant isotropic source of energetic protons. The results of this study demonstrate a strong correlation among dimensionless scaling parameters and shielding efficacy metrics for space radiation-relevant HZE ions in beam and isotropic angular distributions. Furthermore, it establishes a framework for optimizing design of three-dimensional electrostatic shielding configurations to improve space radiation protection for astronauts on exploration-class missions.