Canadian Nuclear Laboratories

The duocarmycin family is a group of potent cytotoxic agents originally isolated from the bacterium Streptomyces. This discovery has spurred significant interest due to duocarmycins' unique chemical structures and powerful mechanism of action. This review comprehensively details the history of the duocarmycin family, the current understanding of their therapeutic potential, and the major clinical trials that have been conducted. Chemically, the duocarmycin family is characterized by a DNA-binding unit that confers specificity, a subunit-linking amide that positions the molecule within the DNA helix, and an alkylating unit that interacts with the DNA. This configuration allows them to bind selectively to the minor groove of DNA and alkylate adenine bases, a notable deviation from the more common guanine targeting performed by other alkylating agents. Duocarmycin's mechanism of action involves the formation of covalent adducts with DNA, leading to the disruption of the DNA architecture and subsequent inhibition of replication and transcription. Recent advancements in drug delivery systems, such as antibody-drug conjugates (ADCs), have further elevated the therapeutic prospects of duocarmycin analogs by providing a promising mechanism for enhancing intracellular concentrations and selective tumor delivery. Preclinical studies have highlighted the efficacy of duocarmycin derivatives in various in vitro models, providing a strong foundation for translational research. However, further biological research is required to fully understand the toxicology of duocarmycin family members before it can be clinically relevant. The major focus of this review is to cache the major biologically relevant findings of different duocarmycin analogs as well as their biological shortcomings to propose next steps in the field of cancer therapy with these potent therapeutics.

The energy sector is transitioning to a low-carbon era requiring the wide use of renewable energy sources, mainly wind and solar. In this context, aluminum could serve as a sustainable energy carrier as it stores energy in a safe and compact way. It could be used to help decarbonize remote communities and industries, trade energy on a global scale, or provide seasonal energy storage. The Hall–Héroult process, reducing aluminum oxides to aluminum, is already a technology deployed at an industrial scale. The maturity of this industry could therefore be leveraged to store electricity. To convert aluminum back to power, it can be fully oxidized with high-temperature liquid water. The hydrogen and high-temperature heat produced can then be converted to power using a combination of heat engines and/or fuel cells. For this concept to be viable, the oxides produced must be collected and reduced in a sustainable way. In this work, aluminum recharging costs were evaluated by reviewing the current reduction process and the literature available on the development of inert anodes, a technology enabling carbon-free smelting. Results show that aluminum can be cost-competitive on a chemical energy basis with most common hydrogen carriers discussed in the literature. To contextualize the findings, a remote mine case study integrates transportation, storage and power generation costs for aluminum, compared to liquefied hydrogen and ammonia. The analysis reveals that aluminum is comparable to other carbon-free solutions, although they all currently remain more expensive than diesel fuel at an input electricity price of $30/MWhe. Aluminum emerges as marginally more expensive than the direct use of ammonia, while avoiding concerns related to toxicity and NOx emissions. This study thus positions aluminum as a promising energy carrier that merits further consideration in various other applications.

Cross sections for production of the medical isotope 225Ac by the 226Ra(p,2n) reaction have not previously been measured in fine steps over the relevant energy region, and no measurements are presently available in the literature for the actinium contaminant isotopes created by the adjacent 226Ra(p,n)226Ac and 226Ra(p,3n)224Ac reactions. We report thin-target cross-section measurements for production of 224Ac and 225Ac by protons of 15.1 to 16.8 MeV incident on radium. An upper limit for the 226Ac cross section is also reported.

This study demonstrates that the reaction of Li2BeF4 (FLiBe) with graphite both in the liquid phase and the gas phase of the molten salt leads to the formation of covalent and semi-ionic carbon–fluorine bonds at the graphite surface and is accompanied by surface microstructural changes, removal of C–O groups, and deposition of metallic beryllium, based on XPS, Raman, and glow discharge mass spectroscopy characterization. At 700 °C, the observed surface density of C–F is higher after 240 h than after 12 h of exposure to molten FLiBe salt; the kinetics of covalent C–F formation is slower than that of semi-ionic C–F formation, and the relative amount of semi-ionic C–F content increases with depth. The graphite sample exposed to the cover gas exhibits less surface fluorination than the salt-exposed sample, with predominantly semi-ionic C–F. Based on these observations and the observed LiF/BeF2 ratio by surface XPS, the hypotheses that fluorination of the salt-exposed graphite occurs via a gas-phase mechanism or that it requires salt intrusion are refuted; future studies are warranted on the transport of C–F semi-ionic and covalent species in graphite at high temperatures.

Molten salts could play an important role in energy storage, in the form of liquid batteries, and heat storage for solar and nuclear power. However, their widespread application is hindered by a limited understanding of the mechanisms by which they corrode metallic containers. This knowledge gap necessitates atomic-scale studies on salt-metal interactions. Molecular dynamics simulations are well suited for such research but require interatomic potential capable of accurately modeling both ionic and neutral states of salt and metal elements. Herein, we developed a moment tensor potential (MTP) with this capability, employing a small-cell training approach. The proposed MTP is compact: It is described by 449 parameters fitted on 609 configurations; 30% of these are one- or two-atom configurations. Extensive testing of our MTP points to a high-fidelity description of the structural and transport properties of solid/liquid Na, gaseous Cl, and crystalline/molten NaCl. Furthermore, we applied this MTP to calculate the standard reduction potential and solubility limit of Na in molten NaCl, achieving results that closely align with experimental and ab initio simulation data. This approach offers a robust framework for exploring the electrochemical and physical properties of molten salts across various compositions and solutes.

Cerium dioxide (CeO 2 ) finds extensive utility in electro ceramics applications, including solid oxide fuel cells, oxygen sensors, and catalysts. However, Spark Plasma Sintering (SPS) of CeO 2 presents challenges due to the heightened mobility of O ²⁻ ions in the presence of an electric field, as well as its reactivity with graphite tooling. Traditionally, CeO 2 is sintered in an oxidative environment to prevent it from reducing to CeO 2−δ or Ce 2 O 3 . Nevertheless, oxidative atmospheres are detrimental to the graphite and steel tooling used in SPS processing. In this study, we investigated CeO 2 SPS in a CO 2 atmosphere and observed substantial enhancement in the relative density (RD) of the as-sintered samples in comparison to those sintered in an Ar atmosphere. The improved densification is attributed to reduced formation of oxygen vacancies in the CO 2 atmosphere. Furthermore, the reaction between CeO 2 and graphite generates CO x gases, and that reaction can be reversed in a CO 2 atmosphere. In summary, CeO 2 SPS in a CO 2 environment demonstrates superior densification, effectively mitigating the challenges associated with ionic mobility and graphite reactivity.

Abstract After considering epidemiological studies on the induction of cataracts in individuals exposed to radiation, the International Commission on Radiological Protection recommended, in 2012, a reduction in the annual eye-dose limit of occupationally exposed workers. This imposed higher performance demands on existing dosimetry systems and the development of new dosimetry technologies. The operational quantity to be measured is Hp(3), the personal dose equivalent at a depth of 3 mm in an ICRU 4-element tissue cylinder 20 cm in height and 20 cm in diameter. The conversion coefficients per unit incident fluence, Hp(3)/Φ, were calculated using Monte Carlo simulation codes. In the case of incident electrons, the literature shows that the resulting coefficients depend on the electron transport options selected for the Monte Carlo simulations as well as the tally zone thickness. In this study, electron operational eye-lens dose coefficients were calculated using MCNP6.2 in its default settings and by invoking the single-event feature. The results were compared to those from PENELOPE, a well-known code for its enhanced accuracy in handling low-energy electron transport. The results are in agreement for the entire energy range for these two series of simulations, but differences are found with previously published dose coefficients in the literature. This impacts the calibration of dosimeters for electrons and may require a change in the commonly accepted dose coefficients.

In this paper, the suitability of digital image correlation (DIC) technology in evaluating the flexural behaviour of as-built and carbon-fiber-reinforced polymer (CFRP) strengthened reinforced concrete beams was verified by conducting a four-point bending test on four large-size beams. The DIC data obtained during the tests were compared to the results measured using traditional techniques such as displacement sensors and electrical strain gauges, as well as the findings derived from finite element (FE) numerical simulations. A good agreement was achieved between the local displacement and strain measurements and the data from DIC as a function of the applied load. Moreover, the crack patterns generated by the FE modelling were validated by the corresponding patterns derived from DIC. This suitability study is expected to contribute to the future field implementation of DIC technology to monitor the CFRP-strengthened members of critical structures such as bridges.

Background: Nuclear medicine has made enormous progress in the past decades. However, there are still significant inequalities in patient access among different countries, which could be mitigated by improving access to and availability of radiopharmaceuticals. Main body: This paper summarises major considerations for a suitable pharmaceutical regulatory framework to facilitate patient access to radiopharmaceuticals. These include the distinct characteristics of radiopharmaceuticals which require dedicated regulations, the impact of the variable complexity of radiopharmaceutical preparation, personnel requirements, manufacturing practices and quality assurance, regulatory authority interfaces, communication and training, as well as marketing authorisation procedures to ensure availability of radiopharmaceuticals. Finally, domestic and regional supply to ensure patient access via alternative regulatory pathways, including in-house production of radiopharmaceuticals, is described, and an outlook on regulatory challenges faced by new developments, such as the use of alpha emitters, is provided. Conclusions: All these considerations are an outcome of a dedicated Technical Meeting organised by the IAEA in 2023 and represent the views and opinions of experts in the field, not those of any regulatory authorities.

The small modular reactor (SMR) is considered to be an enabling technology for providing economical and clean energy in remote areas in Canada. To ensure the SMR technology is developed within a robust framework that addresses environmental and waste management concerns, data are required on radionuclide inventory and characteristics of SMR depleted fuel at the end of reactor service life and at various times thereafter. These data provide essential inputs to assessment of fuel recycle analysis, understanding of environmental impact, and strategy development for waste disposal and management. In this paper, radionuclide inventories of depleted fuel in a small fluoride molten salt reactor (sm-FMSR) and a micro-sized high-temperature gas-cooled reactor (m-HTGR) are calculated using the Monte Carlo neutron transport code Serpent and the point neutron activation and decay code SCALE/ORIGEN. The inventory calculation methods for two selected small modular reactors are described, and radionuclide inventory results from Serpent and ORIGEN are compared. Overall, ORIGEN produces more conservative results than Serpent for both sm-FMSR and m-HTGR. The major characteristics of the radionuclide inventories are discussed for both SMRs.

Purpose: The growing concern over potential unintended nuclear accidents or malicious activities involving nuclear/radiological devices cannot be overstated. Exposure to whole-body doses of radiation can result in acute radiation syndrome (ARS), colloquially known as "radiation sickness," which can severely damage various organ systems. Long-term health consequences, such as cancer and cardiovascular disease, can develop many years post-exposure. Identifying effective medical countermeasures and devising a strategic medical plan represents an urgent, unmet need. Various clinical studies have investigated the therapeutic use of umbilical cord blood (UCB) for a range of illnesses, including ARS. The objective of this review is to thoroughly discuss ARS and its sub-syndromes, and to highlight recent findings regarding the use of UCB for radiation injury. UCB, a rich source of stem cells, boasts numerous advantages over other stem cell sources, like bone marrow, owing to its ease of collection and relatively low risk of severe graft-versus-host disease. Preclinical studies suggest that treatment with UCB, and often UCB-derived mesenchymal stromal cells (MSCs), results in improved survival, accelerated hematopoietic recovery, reduced gastrointestinal tract damage, and mitigation of radiation-induced pneumonitis and pulmonary fibrosis. Interestingly, recent evidence suggests that UCB-derived exosomes and their microRNAs (miRNAs) might assist in treating radiation-induced damage, largely by inhibiting fibrotic pathways. Conclusion: UCB holds substantial potential as a radiation countermeasure, and future research should focus on establishing treatment parameters for ARS victims.

A new sensitive method to determine polonium-210 (210Po) and lead-210 (210Pb) in a diversity of environmental samples was developed. For fresh and marine waters, Po was pre-concentrated using a titanium (III) hydroxide (Ti(OH)3) co-precipitation. Solid environmental samples were digested with nitric acid (HNO3) and hydrogen peroxide (H2O2). The alpha thin layer source was prepared using CuS micro-precipitation and 210Po was measured by alpha spectrometry. Lead-210 was left to decay for up to a year and indirectly measured via its progeny, 210Po. The chemical recoveries for 210Po and 210Pb were high, 90% and 97%, respectively, for a large variety of samples and a very low minimum detectable activity (MDA) was obtained. The method was validated using standardized solutions and certified reference materials.