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ABSTRACT This is a single–case longitudinal study in which we monitored antibody responses and plasma proteome dynamics over a 310–day period in a single individual who underwent COVID–19 vaccination and SARS–CoV–2 infection. To evaluate COVID–19 antibody responses, human plasma samples collected over 310 days (August 18, 2021, to June 22, 2022) were analyzed by DIA–LC–MS/MS proteomics. This led to the acquisition of a quantitative protein profile and allowed validation of the temporal behavior of expressed proteins within the samples. A total of 1,502 proteins were identified from the plasma samples. Before vaccination, after the first dose, after the second dose, and during the period after contracting the novel coronavirus, protein quantification values during each event interval were compared. Despite minimal changes before and after COVID–19 vaccination, notable proteins exhibiting distinct high–expression and low–expression patterns were identified after SARS–CoV–2 infection.

This study investigates the flow dynamics and local scour around a Reef Cube® artificial reef deployed in Torbay, UK, using computational fluid dynamics. The flow is modelled using Reynolds-Averaged Navier–Stokes (RANS) equations with a k-ω SST turbulence model. A novel hydro-morphodynamic model employing the generalized internal boundary method in HELYX (OpenFOAM-based) is used to simulate scour development. Model performance was validated against experimental data for flow fields, bed shear stress, and local scour. Flow simulations across various scenarios demonstrated that parameters such as the orientation angle and arrangement of Reef Cubes significantly influence flow patterns, bed shear stress, and habitat suitability. The hydro-morphodynamic model was used to simulate scouring around a reef cube in the Torbay marine environment. Results indicate that typical tidal flow velocity flow in the region is barely sufficient to initiate sediment motion, whereas extreme flow events, represented by doubling the mean flow velocity, significantly accelerate scour development, producing holes up to ten times deeper. These findings underscore the importance of considering extreme flow conditions in scour analyses due to their potential impact on the stability and failure risk of AR projects.

The importance of behavioral health challenges in current and future human space flight are likely to increase, along with the resulting needs for new mitigation and prevention strategies in astronautics. Mindfulness training is now seen as one of these potential countermeasures, holding transdiagnostic and transtherapeutic qualities in clinical and non-clinical applied research in real-life contexts. To discuss its potential functions mindfulness and psychological flexibility are described from an experiential perspective to showcase how they work and contribute to human behavior: mindfulness can foster contextually functional adaptation, or the opposite, contextually dysfunctional and maladaptive behaviors. This spectrum of adaptivity is commonly referred to as behavioral health. Building on this framework in contextual behavioral science and contemplative science, this paper introduces the existing efforts of mindfulness training in human space exploration. The existing research is scarce, but contains theoretical, survey-based descriptive, and experimental studies too. Results are consistent with research from other applied areas of mindfulness, for example sports and other performance scenarios, as well as military and defense, and indicate that it may be effective to increase behavioral health (resilient coping strategies, mental health, team cohesion, and performance). The utility of mindfulness training in space exploration has promising potential in BHP, and its benefits may extend beyond behavioral health and performance to potential uses in space tourism: mindfulness has the potential to facilitate and strengthen the insights gained from the overview effect. Furthermore, mindfulness training may have neuropsychological protective potential against the adverse effects of space flight. Finally, a number of important recommendations are placed to consider when implanting mindfulness training in space exploration: (1) treat mindfulness training as a process-based approach (for example Acceptance and Commitment Therapy); (2) to maximize benefits and facilitate contextually functional adaptive behaviors; (3); apply an organizational perspective, where not just astronauts, but all mission critical personnel are trained in mindfulness and psychological flexibility; (4) apply an intensive longitudinal design, and collect various kinds of data from self-reported subjective measures to objective digital and biomedical data, as well as qualitative experiential accounts too. The author stresses the potential benefits of mindfulness and psychological flexibility to be explored in more robust controlled experiments in human space flight and seeks for the means to collaborate with researchers and professional bodies and the space agencies.

This study explores the investigation of security concerns surrounding online banking, the prevailing fraud factors that affect banks and customers and discusses effective measures towards preventing fraudulent activities using combination of authentication and verification methods. Employing a qualitative research approach, data was collected through online interviews during the pandemic lockdown and restrictions. Findings reveal that while online banking has transformed financial transactions by offering unprecedented convenience and efficiency, it has simultaneously exposed both banks and customers to significant fraud risks. The study discusses user perceptions of online security, the impact of fraud on reputation and customer trust and recommends integrated fraud detection, prevention, and resolution measures. These insights provide a critical contribution to the ongoing development of robust online banking security protocols. The study further discusses preventative measures that aid fraud mitigation and prevention in online banking.

Abstract The rapid development of the Graphics Processing Units (GPU) enables affordable Large Eddy Simulations (LES) for gas turbine combustion. This work evaluates the accuracy and the computational efficiency of a newly-developed native GPU solver on single and multiple GPUs, develops the optimal GPU numerical formulations for LES, and analyzes the solver’s capability to resolve large meshes and complex physics for a gas turbine combustor, which substantially reduces the computational costs whilst ensuring sufficient solution convergence and accuracy. The combustor investigated is the swirl-stabilized, partially-premixed methane/air PRECCINSTA burner, using LES with the WALE sub-grid scale model for turbulence, and the species transport-based Finite Rate model for combustion, combining with the Stiff Chemistry solver. Rich experimental data are available for this combustor, ideal for GPU validation purposes. To optimize the GPU calculations, the Rapid Octree meshing technique has also been utilized in this work, generating high-quality octree cells for the combustor mesh. A detailed mesh sensitivity analysis has been performed to identify the optimal mesh for the present combustor with the GPU solver. This study then compares two different LES numerical settings on their solution accuracy for the same GPU solver, finding that the GPU-dedicated, Optimized LES Numerics offer slightly more accurate results. The GPU solutions have also been validated against the available experimental data. Finally, the speed-up and the scalability performance of the GPU solver have been discussed. In summary, the best practice settings and workflows developed in this work may be helpful to the deployment of this new GPU solver to more complicated industrial gas turbine combustor simulations.

Urban heat stress is a growing public health concern, particularly for soft mobility users such as cyclists and pedestrians. Understanding how urban and green infrastructure design, together with local micrometeorology, influences cycling behavior, is essential for developing effective heat mitigation strategies and promote sustainable urban mobility.Using the Brussels Capital Region (BCR) as a case study, this research utilizes data collected by Brussels Mobility, which deployed 18 monitoring stations to continuously record bicycle count and speed at 15-minute intervals. For the year 2023, the data was aggregated into hourly intervals, and Mean Radiant Temperature (Tmrt), Universal Thermal Climate Index (UTCI), and Physiologically Equivalent Temperature (PET) were computed for a 25 m × 25 m area surrounding each monitoring station. Additionally, the stations were classified as either green or non-green (26°C UTCI; >23°C PET). In warmer months, greenness also influenced cycling behavior, with a higher count ratio, especially on weekends and in the mornings. However, this effect was not observed when PET exceeded 35°C.Overall, thermal comfort, greenness and time of day have shown to affect cycling behavior. These findings highlight the need for further research to examine the role of greenery in cycling behavior, particularly given the limited route options available to cyclists.

Abstract KRAS mutations are present in 30% of cancer patients, underscoring the importance of KRAS as a critical target for drug development. Despite the advancements in small molecule inhibitors targeting specific KRAS mutations, such as G12C and G12D, significant challenges persist in addressing other prevalent mutations such as G12V. Furthermore, small molecule inhibitors predominantly target the GDP-bound form of KRAS due to accessibility of the SWITCH II pocket, even though most mutant KRAS proteins in cancer cells are in the activated GTP-bound form. Peptide drugs have emerged as promising alternatives due to their exceptional binding affinity and specificity, along with their reduced dependency on the presence of a well-defined binding pocket. Utilizing Syneron’s innovative technology, we have successfully developed cyclic peptides capable of cell penetration and oral bioavailability, to overcome some of the limitations associated with small molecule KRAS therapeutics. SYNB021225 is a potent pan-KRAS inhibitor effective against multiple KRAS mutations, including G12V. With sub-nanomolar potency in both binding and in vitro cell killing, SYNB021225 induces tumor regression at oral doses of 10-20 mpk administered once daily. Besides expanding the treatable patient population, its broad targeting profile can also potentially address tumor heterogeneity and mitigate resistance. SYNB021225 inhibits both KRAS-ON and KRAS-OFF forms, directly disrupting the interaction between GTP-bound KRAS and RAF. Given that most mutant KRAS proteins in cancer cells are in the activated GTP-bound form, comparing to small molecules that mainly target the GDP-bound KRAS, this dual action offers potential advantage in enhancing efficacy as well as overcoming resistance from activated Receptor Tyrosine Kinases like EGFR. Indeed, in the in vitro proliferation assay, the potency of SYNB021225 remained unaffected when treated with EGF. Furthermore, SYNB021225 demonstrates efficacy against KRAS wild-type amplified tumors, which are resistant to KRAS-ON only molecular glue inhibitors. Current small molecule inhibitors often fail to maintain sustained p-ERK inhibition, impacting overall survival. In preclinical studies, SYNB021225 has shown prolonged tumor retention and p-ERK suppression lasting up to 72 hours, that may translate to improved clinical efficacy. Unlike small molecules, peptides such as SYNB021225 are metabolized by proteases and excreted via the kidneys, minimizing liver toxicity. This profile makes SYNB021225 more suitable for combination therapies, such as with anti-PD1 agents, without exacerbating the liver inflammation as seen in the clinic with small molecule inhibitors. Currently, SYNB021225 is being prepared for clinical development. Citation Format: Michael Poss, Caihong Zhou, Cheng Lu, Ruochi Zhang, Yu Wang, Yuanpeng Xiong, Xin Gao, Xiao Zhang, Yan Degenhardt. SYNB021225: a potent oral pan-KRAS peptide inhibitor that can address unmet needs of small molecule inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4384.

IL-12 mediates innate and adaptive immune responses and has demonstrated therapeutic antitumor activity, but clinical development has been hindered by a narrow therapeutic window. We generated a novel IL-12-anchored drug conjugate by physiochemical linking of murine IL-12 to aluminum hydroxide (alum). The complex was designed to utilize alum as a scaffolding for durable retention of IL-12 within the tumor microenvironment as a strategy to increase the therapeutic window. To better define the systemic pharmacokinetic (PK) profile of the anchored IL-12 (mANK-101), a model-based assessment tool was developed to describe the systemic PK profile and downstream signaling factors following intratumoral injection of mANK-101. When compared with nonanchored IL-12, mANK-101 exhibited a distinct PK profile. Specifically, mANK-101 treatment was associated with a significant ninefold increase in the systemic terminal volume of distribution (Vd). Furthermore, linear mixed-effects models provided evidence that CD8+ T-cell infiltration and increased serum IFN-γ levels were correlated with tumor regression after a single dose of mANK-101. In addition, PK/pharmacodynamic modeling confirmed a link between systemic IL-12 and serum IFN-γ. The model also suggests that the anchored IL-12 drug conjugate is expected to prolong the absorption half-life (115 hours vs. 8 hours for the unanchored drug) with durable local retention and limited systemic absorption. In addition, serum IFN-γ may be a surrogate marker for drug activity. The PK modeling predictions may also contribute to determining the optimal clinical dose and schedule of mANK-101 and other anchored drug conjugates in patients with solid tumors.