The significance of multipole interactions for the stability of regular structures composed from charged particles.

Identifying the forces responsible for stabilising binary particle lattices is key to the controlled fabrication of many new materials. Experiments have shown that the presence of charge can be integral to the formation of ordered arrays; however, a complete analysis of the forces responsible has not included many of the significant lattice types that may form during fabrication. A theory of many-body electrostatic interactions has been applied to six lattice stoichiometries, AB, AB2, AB3, AB4, AB5 and AB6, to show that induced multipole interactions can make a very significant (>80 %) contribution to the total lattice energy of arrays of charged particles. Particle radii ratios which favour global minima in electrostatic energy are found to be the same or a close match to those observed by experiment. Although certain lattice types exhibit local energy minima, the calculations show that many-body rather than two-body interactions are ultimately responsible for the structures observed by experiment. For a lattice isostructural with CFe4, a particle size ratio not previously observed is found to be particularly stable due to many-body effects.

Study of photonuclear reactions with the alpha particles' emission on zirconium, niobium, and molybdenum.

Photonuclear reactions with the emission of protons and alpha particles have been little studied experimentally since their cross-sections are much smaller than those of the (γ, n) channel due to the Coulomb barrier. However, the study of such reactions is of great applied interest to producing medical isotopes. Besides, experimental data on photonuclear reactions with the emission of charged particles for nuclei with Z = 40, 41, 42 open up great opportunities for learning the role of magic numbers. In the presented article, we obtained the weighted average yields of (γ, αn)-reactions for natural zirconium, niobium, and molybdenum at bremsstrahlung γ-quanta of 20 MeV boundary energy for the first time. A significant effect of a closed N = 50 shell was established on the reaction yield with the emission of alpha particles. Our research shows that the semi-direct mechanism for (γ, αn) reactions dominates in the energy range below the Coulomb barrier. As a result, we can note the prospects of applying (γ, αn)-reaction on 94Mo to produce the 89Zr promise medical radionuclide isotope using electron accelerators.

Pattern Formation in Two-Component Monolayers of Particles with Competing Interactions.

Competing interactions between charged inclusions in membranes of living organisms or charged nanoparticles in near-critical mixtures can lead to self-assembly into various patterns. Motivated by these systems, we developed a simple triangular lattice model for binary mixtures of oppositely charged particles with additional short-range attraction or repulsion between like or different particles, respectively. We determined the ground state for the system in contact with a reservoir of the particles for the whole chemical potentials plane, and the structure of self-assembled conglomerates for fixed numbers of particles. Stability of the low-temperature ordered patterns was verified by Monte Carlo simulations. In addition, we performed molecular dynamics simulations for a continuous model with interactions having similar features, but a larger range and lower strength than in the lattice model. Interactions with and without symmetry between different components were assumed. We investigated both the conglomerate formed in the center of a thin slit with repulsive walls, and the structure of a monolayer adsorbed at an attractive substrate. Both models give the same patterns for large chemical potentials or densities. For low densities, more patterns occur in the lattice model. Different phases coexist with dilute gas on the lattice and in the continuum, leading to different patterns in self-assembled conglomerates ('rafts').

Compact portable sources of high-LET radiation: Validation and potential application for galactic cosmic radiation countermeasure discovery.

Implementation of a systematic program for galactic cosmic radiation (GCR) countermeasure discovery will require convenient access to ground-based space radiation analogs. The current gold standard approach for GCR simulation is to use a particle accelerator for sequential irradiation with ion beams representing different GCR components. This has limitations, particularly for studies of non-acute responses, strategies that require robotic instrumentation, or implementation of complex in vitro models that are emerging as alternatives to animal experimentation. Here we explore theoretical and practical issues relating to a different approach to provide a high-LET radiation field for space radiation countermeasure discovery, based on use of compact portable sources to generate neutron-induced charged particles. We present modeling studies showing that DD and DT neutron generators, as well as an AmBe radionuclide-based source, generate charged particles with a linear energy transfer (LET) distribution that, within a range of biological interest extending from about 10 to 200 keV/µm, resembles the LET distribution of reference GCR radiation fields experienced in a spacecraft or on the lunar surface. We also demonstrate the feasibility of using DD neutrons to induce 53BP1 DNA double-strand break repair foci in the HBEC3-KT line of human bronchial epithelial cells, which are widely used for studies of lung carcinogenesis. The neutron-induced foci are larger and more persistent than X ray-induced foci, consistent with the induction of complex, difficult-to-repair DNA damage characteristic of exposure to high-LET (>10 keV/µm) radiation. We discuss limitations of the neutron approach, including low fluence in the low LET range (<10 keV/µm) and the absence of certain long-range features of high charge and energy particle tracks. We present a concept for integration of a compact portable source with a multiplex microfluidic in vitro culture system, and we discuss a pathway for further validation of the use of compact portable sources for countermeasure discovery.

Motion-Encoded Electric Charged Particles Optimization for Moving Target Search Using Unmanned Aerial Vehicles.

In this paper, a new optimization algorithm called motion-encoded electric charged particles optimization (ECPO-ME) is developed to find moving targets using unmanned aerial vehicles (UAV). The algorithm is based on the combination of the ECPO (i.e., the base algorithm) with the ME mechanism. This study is directly applicable to a real-world scenario, for instance the movement of a misplaced animal can be detected and subsequently its location can be transmitted to its caretaker. Using Bayesian theory, finding the location of a moving target is formulated as an optimization problem wherein the objective function is to maximize the probability of detecting the target. In the proposed ECPO-ME algorithm, the search trajectory is encoded as a series of UAV motion paths. These paths evolve in each iteration of the ECPO-ME algorithm. The performance of the algorithm is tested for six different scenarios with different characteristics. A statistical analysis is carried out to compare the results obtained from ECPO-ME with other well-known metaheuristics, widely used for benchmarking studies. The results found show that the ECPO-ME has great potential in finding moving targets, since it outperforms the base algorithm (i.e., ECPO) by as much as 2.16%, 5.26%, 7.17%, 14.72%, 0.79% and 3.38% for the investigated scenarios, respectively.

A simple software for swift computation of photon and charged particle interaction parameters: PAGEX.

PAGEX is a compact and user-friendly cross-platform software developed for swift computation of photon (X-ray and γ-ray) and charged particle interaction parameters for various applications. It is designed based on well-established theoretical formulations and computational techniques integrating various Python packages to effectively calculate parameters such as partial/total photon interaction cross-sections and mass attenuation coefficients, charged particle mass stopping powers and cross-sections, effective atomic number and electron density, mass-energy absorption coefficient, KERMA and build-up factors over a wide energy range. This tool is capable of generating both tabular and graphical outputs which can be saved in any user desired format. PAGEX has been verified against other widely employed software and databases, demonstrating good agreement. This software which facilitates robust computation is freely available from the authors.

Adsorption in Mixtures with Competing Interactions.

A binary mixture of oppositely charged particles with additional short-range attraction between like particles and short-range repulsion between different ones in the neighborhood of a substrate preferentially adsorbing the first component is studied by molecular dynamics simulations. The studied thermodynamic states correspond to an approach to the gas-crystal coexistence. Dependence of the near-surface structure, adsorption and selective adsorption on the strength of the wall-particle interactions and the gas density is determined. We find that alternating layers or bilayers of particles of the two components are formed, but the number of the adsorbed layers, their orientation and the ordered patterns formed inside these layers could be quite different for different substrates and gas density. Different structures are associated with different numbers of adsorbed layers, and for strong attraction the thickness of the adsorbed film can be as large as seven particle diameters. In all cases, similar amount of particles of the two components is adsorbed, because of the long-range attraction between different particles.

Monitoring Carbon Ion Beams Transverse Position Detecting Charged Secondary Fragments: Results From Patient Treatment Performed at CNAO.

Particle therapy in which deep seated tumours are treated using 12C ions (Carbon Ions RadioTherapy or CIRT) exploits the high conformity in the dose release, the high relative biological effectiveness and low oxygen enhancement ratio of such projectiles. The advantages of CIRT are driving a rapid increase in the number of centres that are trying to implement such technique. To fully profit from the ballistic precision achievable in delivering the dose to the target volume an online range verification system would be needed, but currently missing. The 12C ions beams range could only be monitored by looking at the secondary radiation emitted by the primary beam interaction with the patient tissues and no technical solution capable of the needed precision has been adopted in the clinical centres yet. The detection of charged secondary fragments, mainly protons, emitted by the patient is a promising approach, and is currently being explored in clinical trials at CNAO. Charged particles are easy to detect and can be back-tracked to the emission point with high efficiency in an almost background-free environment. These fragments are the product of projectiles fragmentation, and are hence mainly produced along the beam path inside the patient. This experimental signature can be used to monitor the beam position in the plane orthogonal to its flight direction, providing an online feedback to the beam transverse position monitor chambers used in the clinical centres. This information could be used to cross-check, validate and calibrate, whenever needed, the information provided by the ion chambers already implemented in most clinical centres as beam control detectors. In this paper we study the feasibility of such strategy in the clinical routine, analysing the data collected during the clinical trial performed at the CNAO facility on patients treated using 12C ions and monitored using the Dose Profiler (DP) detector developed within the INSIDE project. On the basis of the data collected monitoring three patients, the technique potential and limitations will be discussed.

Cold Atmospheric Pressure Plasma-Activated Medium Induces Selective Cell Death in Human Hepatocellular Carcinoma Cells Independently of Singlet Oxygen, Hydrogen Peroxide, Nitric Oxide and Nitrite/Nitrate.

Cold atmospheric pressure plasma (CAP) and plasma-activated medium (PAM) induce cell death in diverse cancer cells and may function as powerful anti-cancer agents. The main components responsible for the selective anti-cancer effects of CAP and PAM remain elusive. CAP or PAM induces selective cell death in hepatocellular carcinoma cell lines Hep3B and Huh7 containing populations with cancer stem cell markers. Here, we investigated the major component(s) of CAP and PAM for mediating the selective anti-proliferative effect on Hep3B and Huh7 cells. The anti-proliferative effect of CAP was mediated through the medium; however, the reactive oxygen species scavenger N-acetyl cysteine did not suppress PAM-induced cell death. Neither high concentrations of nitrite or nitrite/nitrate nor a low concentration of H2O2 present in the PAM containing sodium pyruvate affected the viability of Hep3B and Huh7 cells. Inhibitors of singlet oxygen, superoxide anions, and nitric oxide retained the capacity of PAM to induce anti-cancer effects. The anti-cancer effect was largely blocked in the PAM prepared by placing an aluminum metal mesh, but not a dielectric PVC mesh, between the plasma source and the medium. Hence, singlet oxygen, hydrogen peroxide, nitric oxide, and nitrite/nitrate are not the main factors responsible for PAM-mediated selective death in Hep3B and Huh7 cells. Other factors, such as charged particles including various ions in CAP and PAM, may induce selective anti-cancer effects in certain cancer cells.

Chronic Low Dose Neutron Exposure Results in Altered Neurotransmission Properties of the Hippocampus-Prefrontal Cortex Axis in Both Mice and Rats.

The proposed deep space exploration to the moon and later to Mars will result in astronauts receiving significant chronic exposures to space radiation (SR). SR exposure results in multiple neurocognitive impairments. Recently, our cross-species (mouse/rat) studies reported impaired associative memory formation in both species following a chronic 6-month low dose exposure to a mixed field of neutrons (1 mGy/day for a total dose pf 18 cGy). In the present study, we report neutron exposure induced synaptic plasticity in the medial prefrontal cortex, accompanied by microglial activation and significant synaptic loss in the hippocampus. In a parallel study, neutron exposure was also found to alter fluorescence assisted single synaptosome LTP (FASS-LTP) in the hippocampus of rats, that may be related to a reduced ability to insert AMPAR into the post-synaptic membrane, which may arise from increased phosphorylation of the serine 845 residue of the GluA1 subunit. Thus, we demonstrate for the first time, that low dose chronic neutron irradiation impacts homeostatic synaptic plasticity in the hippocampal-cortical circuit in two rodent species, and that the ability to successfully encode associative recognition memory is a dynamic, multicircuit process, possibly involving compensatory changes in AMPAR density on the synaptic surface.

Genomic Instability and Carcinogenesis of Heavy Charged Particles Radiation: Clinical and Environmental Implications.

One of the uses of ionizing radiation is in cancer treatment. The use of heavy charged particles for treatment has been introduced in recent decades because of their priority for deposition of radiation energy in the tumor, via the Bragg peak phenomenon. In addition to medical implications, exposure to heavy charged particles is a crucial issue for environmental and space radiobiology. Ionizing radiation is one of the most powerful clastogenic and carcinogenic agents. Studies have shown that although both low and high linear energy transfer (LET) radiations are carcinogenic, their risks are different. Molecular studies have also shown that although heavy charged particles mainly induce DNA damage directly, they may be more potent inducer of endogenous generation of free radicals compared to the low LET gamma or X-rays. It seems that the severity of genotoxicity for non-irradiated bystander cells is potentiated as the quality of radiation increases. However, this is not true in all situations. Evidence suggests the involvement of some mechanisms such as upregulation of pro-oxidant enzymes and change in the methylation of DNA in the development of genomic instability and carcinogenesis. This review aimed to report important issues for genotoxicity of carcinogenic effects of heavy charged particles. Furthermore, we tried to explain some mechanisms that may be involved in cancer development following exposure to heavy charged particles.

Clinical applications of proton and carbon ion therapy.

Treatment of cancer patients with charged particles like proton and carbon ions landmarks a new era in high-precision medicine. This review aims to summarize the physical and biological advantages of charged particle beams over conventional photon irradiation, presents some highlights in the treatment of selected tumor entities, and gives an update on previous and ongoing clinical trials.

Towards the production of natural rubber-calcium phosphate hybrid for applications as bioactive coatings.

This paper assesses the morphological, structural and bio-physicochemical stability of natural rubber (NR) Hevea brasiliensis coatings incorporated with microparticles of calcium phosphate-based (CaP) bioactive ceramics. Optical and electronic spectroscopic imaging techniques were employed to successfully evaluate the NR encapsulation capability and the stability of the coating in a biologically relevant media for bio-related application, i.e., simulated body fluid (SBF). The chemical structure of the natural polymer, the microchemical environment at the NR-CaP interface and the morphology of the CaP clusters were fully characterized. Further, the response of the hybrid coating to SBF was evaluated by incubating the samples for 30 days. The hybrid coating formed on Si surface (inert substrate) exhibited both stability and biodegradability in different levels (time dependence), thus opening horizons for applications as coatings for both biomaterials and drug delivery systems.

Developing Predictive or Prognostic Biomarkers for Charged Particle Radiotherapy.

The response to radiotherapy can vary greatly among individuals, even though advances in technology allow for the highly localized placement of therapeutic doses of radiation to a tumor. This variability in patient response to radiation is biologically driven, but the individuality of tumor and healthy tissue biology are not used to create individual treatment plans. Biomarkers of radiosensitivity, whether intrinsic or from hypoxia, would move radiation oncology from precision medicine to precise, personalized medicine. Charged particle radiotherapy allows for even greater dose conformity, but the biological advantages of charged particle radiotherapy have not yet been cultivated. The development of biomarkers that would drive biologically based clinical trials, identify patients for whom charged particles are most appropriate, or aid in particle-selection strategies could be envisioned with appropriate biomarkers. Initially, biomarkers for low-linear energy transfer (LET) radiation responses should be tested against charged particles. Biomarkers of tumor radioresistance to low-LET radiations could be used to identify patients for whom the enhanced relative biological effectiveness (RBE) of charged particles would be more effective compared with low-LET radiations and those for whom specific DNA-repair inhibitors, in combination with charged particles, may also be appropriate. Furthermore, heavy charged particles can overcome the radioresistance of hypoxic tumors when used at the appropriate LET. Biomarkers for hypoxia could identify hypoxic tumors and, in combination with imaging, define hypoxic regions of a tumor for specific ion selection. Moreover, because of the enhanced RBE for charged particles, the risk for adverse healthy tissue effects may be greater, even though charged particles have greater tumor conformality. There are many validated healthy-tissue biomarkers available to test against charged particle exposures. Lastly, newer biological techniques, as well as newer bioinformatic and computational methods, are rapidly changing the landscape for biomarker identification, validation, and clinical trial design.

Radiogenomics.

PURPOSE: Radiogenomics is the study of genomic changes that underlie the radioresponse of normal and tumor tissues. And while this is generally regarded as a whole genome approach, one must keep in mind the impact of single gene biology on radioresponse, (ataxia telangiectasia, Nijmegen breakage syndrome). METHODS: This review begins with the association of single nucleotide polymorphisms in the DNA with adverse normal tissue events to the prediction of therapeutic outcome after radiotherapy. From there it covers transcriptome (protein coding RNA transcripts) analysis, which is where the greatest understanding of the molecular signaling responsible for the radioresponse of tumors and normal tissues is known. Non-protein coding RNA transcripts (miRNA, lncRNA), transcribed from what was once thought of as junk DNA, are now known to be negative regulators of the transcription of mRNA by multiple mechanisms. miRNA can act as tumor suppressors or oncogenes regulating a diverse range of cellular processes that drive radioresponse and biosignatures that predict outcome after radiotherapy are described. RESULTS: Biological signatures that explain differences in radioresponse based upon cell type, biological signatures that predict surviving fraction at 2 Gy and signatures that identify hypoxia have been described. The omics analysis of the response of mammalian cells to charged particle, predominantly proton and carbon ions, is less mature than that seen with low LET radiation exposures. However, there appear to be responses after charged particle exposure that parallel the responses seem with low LET exposures. This commonality of response is centered around the downstream signaling of p53. There are also novel omics responses to charged particles that help explain the response of tumors to charged particle exposures. For instance, signaling pathways associated with angiogenesis, vasculogenesis, migration and invasion appear to be downregulated in a number of cell types when exposed to charged particles. This response supports both in vitro and in vivo data suggesting that tumors exposed to charged particles are less invasive, unlike the response of tumors to low LET exposures. Profoundly lacking for low LET and charged particle exposures are predictive or prognostic signatures of radioresponse or tumor physiology affecting radioresponse that have been validated in prospective clinical trials. For example, the identification of low LET tumor radioresistance could be used as a marker of patient eligibility for carbon therapy. Tissue specific signatures, or accurate imaging of hypoxic regions, could be used for charged particle selection to overcome hypoxia per se, or could be used to prescribe a high LET therapeutic boost to a hypoxic region of a tumor. CONCLUSIONS: Integrating radiogenomics into radiation oncology has the potential to personalize an already precise form of cancer therapy.

Damaging Intermolecular Energy and Proton Transfer Processes in Alpha-Particle-Irradiated Hydrogen-Bonded Systems.

Although the biological hazard of alpha-particle radiation is well-recognized, the molecular mechanisms of biodamage are still far from being understood. Irreparable lesions in biomolecules may not only have mechanical origin but also appear due to various electronic and nuclear relaxation processes of ionized states produced by an alpha-particle impact. Two such processes were identified in the present study by considering an acetylene dimer, a biologically relevant system possessing an intermolecular hydrogen bond. The first process is the already well-established intermolecular Coulombic decay of inner-valence-ionized states. The other is a novel relaxation mechanism of dicationic states involving intermolecular proton transfer. Both processes are very fast and trigger Coulomb explosion of the dimer due to creation of charge-separated states. These processes are general and predicted to occur also in alpha-particle-irradiated nucleobase pairs in DNA molecules.

Alterations in synaptic density and myelination in response to exposure to high-energy charged particles.

High-energy charged particles are considered particularly hazardous components of the space radiation environment. Such particles include fully ionized energetic nuclei of helium, silicon, and oxygen, among others. Exposure to charged particles causes reactive oxygen species production, which has been shown to result in neuronal dysfunction and myelin degeneration. Here we demonstrate that mice exposed to high-energy charged particles exhibited alterations in dendritic spine density in the hippocampus, with a significant decrease of thin spines in mice exposed to helium, oxygen, and silicon, compared to sham-irradiated controls. Electron microscopy confirmed these findings and revealed a significant decrease in overall synapse density and in nonperforated synapse density, with helium and silicon exhibiting more detrimental effects than oxygen. Degeneration of myelin was also evident in exposed mice with significant changes in the percentage of myelinated axons and g-ratios. Our data demonstrate that exposure to all types of high-energy charged particles have a detrimental effect, with helium and silicon having more synaptotoxic effects than oxygen. These results have important implications for the integrity of the central nervous system and the cognitive health of astronauts after prolonged periods of space exploration.

Carbon ion radiotherapy for inoperable pediatric osteosarcoma.

BACKGROUND: Unresectable pediatric osteosarcoma has poor outcomes with conventional treatments. RESULTS: Twenty-six patients aged 11-20 years (median 16) had inoperable osteosarcoma of the trunk (24 pelvic, 1 mediastinal and 1 paravertebral) without any other lesion at initial examination. There were 22 primary, 1 locally recurrent and 3 metastatic cases. Median CIRT dose was 70.4 Gy RBE (relative biological effectiveness) delivered in 16 fractions. Median follow-up was 32.7 months. Overall survival was 50.0% and 41.7% at 3 and 5 years, respectively. Ten patients survived for more than 5 years (range 5-20.7 years). Local control was 69.9% and 62.9% at 3 and 5 years, respectively and progression-free survival was 34.6% at 3 and 5 years. Only largest tumor diameter correlated with 5-year overall survival and local control. There were 4 grade 3-4 CIRT-related late toxicities, 1 case of bone fracture and no treatment-related mortalities. All patients (except 1) were able to ambulate after CIRT. CONCLUSIONS: CIRT was safe and efficacious in the treatment of inoperable pediatric osteosarcoma with improved local control and overall survival compared to conventional treatments. METHODS: We retrospectively reviewed the records of pediatric and adolescent patients who received carbon ion radiotherapy (CIRT) for inoperable osteosarcoma between 1996 and 2014.

Ti:Pt:Au:Ni thin-film CVD diamond sensor ability for charged particle detection.

This work demonstrates the development of diamond sensors with reliable contacts using a new metallization formula, which can operate under high-pressure gas environment. The metallization was created using thin film layers of titanium, platinum, gold and nickel deposited on a single crystal electronic grade CVD diamond chip. The contacts were 2 mm in diameter with thickness of 50/5/20/150 nm of Ti:Pt:Au:Ni. The optimum operating voltage of the sensor was determined from the current-voltage measurements. The sensor was calibrated with 239Pu and 241Am alpha radiation sources at 300 V. The energy resolution of the Ti:Pt:Au:Ni diamond sensor was determined to be 7.6% at 5.2 MeV of 239Pu and 2.2% at 5.48 MeV of 241Am. The high-pressure gas loading environment under which this sensor was used is discussed. Specifically, experimental observations are described using hydrogen loading of nickel as a means of initiating low energy nuclear reactions. No neutrons, electrons, ions or other ionizing radiations were observed in these experiments.

Spontaneous Charge Separation and Sublimation Processes are Ubiquitous in Nature and in Ionization Processes in Mass Spectrometry.

Ionization processes have been discovered by which small and large as well as volatile and nonvolatile compounds are converted to gas-phase ions when associated with a matrix and exposed to sub-atmospheric pressure. Here, we discuss experiments further defining these simple and unexpected processes. Charge separation is found to be a common process for small molecule chemicals, solids and liquids, passed through an inlet tube from a higher to a lower pressure region, with and without heat applied. This charge separation process produces positively- and negatively-charged particles with widely different efficiencies depending on the compound and its physical state. Circumstantial evidence is presented suggesting that in the new ionization process, charged particles carry analyte into the gas phase, and desolvation of these particles produce the bare ions similar to electrospray ionization, except that solid particles appear likely to be involved. This mechanistic proposition is in agreement with previous theoretical work related to ion emission from ice. Graphical Abstract ᅟ.