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Abstract As spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated “spaceflight secretome profiles,” which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight. Moreover, these proteomic alterations correlated better with peripheral blood mononuclear cells than whole blood, suggesting that immune cells contribute more DAPs than erythrocytes. Finally, to discern possible mechanisms leading to brain-enriched protein detection and blood-brain barrier (BBB) disruption, we examined protein changes in dissected brains of spaceflight mice, which showed increases in PECAM-1, a marker of BBB integrity. These data highlight how even short-duration spaceflight can disrupt human and murine physiology and identify spaceflight biomarkers that can guide countermeasure development.

Abstract It is now widely recognised that the environment in space activates a diverse set of genes involved in regulating fundamental cellular pathways. This includes the activation of genes associated with blood homeostasis and erythropoiesis, with a particular emphasis on those involved in globin chain production. Haemoglobin biology provides an intriguing model for studying space omics, as it has been extensively explored at multiple -omic levels, spanning DNA, RNA, and protein analyses, in both experimental and clinical contexts. In this study, we examined the developmental expression of haemoglobin over time and space using a unique suite of multi-omic datasets available on NASA GeneLab, from the NASA Twins Study, the JAXA CFE study, and the Inspiration4 mission. Our findings reveal significant variations in globin gene expression corresponding to the distinct spatiotemporal characteristics of the collected samples. This study sheds light on the dynamic nature of globin gene regulation in response to the space environment and provides valuable insights into the broader implications of space omics research.

This review aims to provide an overview and update of current literature on the use of intranasal (IN) drug delivery in pediatric emergency medicine (PEM), in terms of the anatomy, physiology, pharmacokinetics, limitations, drug delivery methods, necessary training, safety, contraindications, effectiveness, current indications and trends, and implications for clinical practice and future developments in IN drug administration. We evaluate how IN medication use in PEM has recently evolved, what recent research has revealed about the utility of IN drug delivery in PEM, and what the future of IN drug delivery might look like.

Pain arising from trigeminal systems such as headache is common, debilitating, and current treatments (e.g., sumatriptan) are limited. New treatments that target novel mechanisms of action may be required to innovate both short- and long-term pain therapy. Fatty acid amide hydrolase and soluble epoxide hydrolase are two pain-related enzymes that regulate pain and inflammation via independent pathways. We have previously demonstrated that simultaneous inhibition of these enzymes using a novel dual inhibitor alleviates acute inflammatory pain in the hindpaw and does not depress wheel running in rats. Here, we expanded on these findings and performed structure-activity relationships of our lead compound, the 4-phenyl-thiazole-based dual inhibitor SW-17, to generate 18 analogs and tested them for their inhibition at both enzymes. Conversion of the sulfonamide group to a tertiary amine led to a general decrease in the potency for the sEH enzyme, while this change was well-tolerated at the FAAH enzyme yielding several strong inhibitors. Six selected inhibitors were evaluated in mouse and rat sEH inhibition assays and results showed a species difference, i.e. 4-phenyl-thiazole-based analogs are significantly less or not active in mouse sEH compared to human and rat enzymes. The most potent inhibitor, SW-17, was evaluated in a plasma stability assay in human and rat plasma and showed moderate stability. However, SW-17 did not alleviate orofacial inflammatory pain in female rats compared to the traditional anti-migraine agent sumatriptan. Although modification of 4-phenyl-thiazole-based dual inhibitor SW-17 changes potencies at both FAAH and sEH, these approaches may not produce antinociception against trigeminal pain. Key Words: polypharmacology, formalin, inflammation, enzyme inhibition, structure-activity relationship studies

E-commerce has become very important in our daily lives. Many business transactions are made easier on this platform. Sellers and consumers are the two main parties that gain a lot of benefits from it. Although many sellers are attracted to set up their businesses on this online platform, it also causes challenges such as a highly competitive business environment and unpredictable sales. Thus, we propose a data analytics approach for short-term sales forecasts using limited information in the e-commerce marketplace. Product details are scraped from the e-commerce marketplace using a content scraping tool. Since the information in the e-commerce marketplace is limited and essential, scraped product details are pre-processed and constructed into meaningful data. These data are used in the computation of the forecasting methods. Three types of quantitative forecasting methods are computed and compared. These are simple moving average, dynamic linear regression and exponential smoothing. Three different evaluation metrics, namely mean absolute deviation, mean absolute percentage error and mean squared error, are used for the performance evaluation in order to determine the most suitable forecasting method. In our experiment, we found that the simple moving average has the best forecasting accuracy among other forecasting methods. Therefore, the application of the simple moving average forecasting method is suitable and can be used in the e-commerce marketplace for sales forecasting.

The demand for advanced air mobility (AAM) operations is expected to be at a much larger scale than conventional aviation. Additionally, AAM flight operators are likely to compete in providing a range of on-demand services in congested airspaces, with varying operational costs. These characteristics motivate the need for the development of new traffic management algorithms for advanced air mobility. In this paper, we explore the use of traffic management protocols (“rules-of-the-road” for airspace access) to enable efficient and fair operations. First, we show that it is possible to avoid gridlock and improve efficiency by leveraging the concepts of cycle detection and backpressure. We then develop a cost-aware traffic management protocol based on the second-price auction. Using simulations of representative advanced air mobility scenarios, we demonstrate that our traffic management protocols can help balance efficiency and fairness, in both the operational and the economic contexts.

Sulforaphane (SFN) is a compound [1-isothiocyanato-4-(methylsulfinyl)-butane] found in broccoli and other cruciferous vegetables that is currently of interest because of its potential as a chemopreventive and a chemotherapeutic drug. Recent studies in a diverse range of cellular and animal models have shown that SFN is involved in multiple intracellular pathways that regulate xenobiotic metabolism, inflammation, cell death, cell cycle progression, and epigenetic regulation. In order to better understand the mechanisms of action behind SFN-induced cell death, we undertook an unbiased genome wide screen with the yeast knockout (YKO) library to identify SFN sensitive (SFNS) mutants. The mutants were enriched with knockouts in genes linked to vacuolar function suggesting a link between this organelle and SFN’s mechanism of action in yeast. Our subsequent work revealed that SFN increases the vacuolar pH of yeast cells and that varying the vacuolar pH can alter the sensitivity of yeast cells to the drug. In fact, several mutations that lower the vacuolar pH in yeast actually made the cells resistant to SFN (SFNR). Finally, we show that human lung cancer cells with more acidic compartments are also SFNR suggesting that SFN’s mechanism of action identified in yeast may carry over to higher eukaryotic cells.

This paper presents a numerical study on the hydrodynamic coefficients of the DARPA SUBOFF hull when deeply submerged and near the seabed. The CFD-based model was validated with experimental data, namely experiments involving the SUBOFF and BB2 undergoing straight-ahead motion near the free surface and the SUBOFF only when deeply submerged at drift angles without the influence of either the free surface or the seabed. The validated model was used to investigate the effects of the seabed's effect on the hydrodynamic behaviour of the SUBOFF across a range of speeds, drift angles, and submergence depths. The results were then compared to operations near the free surface. The results show that the seabed has a smaller influence on the hydrodynamic coefficients compared to the free surface. Also, the hydrodynamic coefficients do not vary with Froude number when near the seabed but do vary with Froude number when near the free surface.

This investigation focuses on the modelling of a floating oscillating water column (FOWC) wave energy converter with a numerical code (ANSYS AQWA) based on potential flow theory. Free-floating motions predicted by the numerical model were validated against experimental data extrapolated from a 1:36 scale model device in regular and irregular sea states. Upon validation, an assessment of the device’s motions when dynamically coupled with a four-line catenary mooring arrangement was conducted at different incident wave angles and sea states ranging from operational to survivable conditions, including the simulation of the failure of a single mooring line. The lack of viscosity in the numerical modelling led to overpredicted motions in the vicinity of the resonant frequencies; however, the addition of an external linear damping coefficient was shown to be an acceptable method of mitigating these discrepancies. The incident wave angle was found to have a limited influence on the magnitudes of heave, pitch, and surge motions. Furthermore, the obtained results indicated that the mooring restoring force is controlled by the forward mooring lines under the tested conditions.

This paper considers the feasibility of using augmented reality (AR) as a tool for enhancing visualization in maritime operations to avoid collision in different environmental conditions. According to the International Maritime Organization (IMO 2010), 90% of maritime accidents due to collisions at sea are caused in part by human error. This study investigates the new technology (AR) used to superimpose holographic images onto the real world; now reaching a state of readiness for commercial application. This paper demonstrates the competence of AR technology to serve as a maritime navigational aid. The research explores the viability of improving navigational safety in low visibility by projecting holograms of real-world objects in the same geo-location as the real object to make them “visible”. The paper presents the logical deconstruction of the technical problems and identified solutions, together with results of experiments used to validate the concept and technology readiness for real word maritime application. The paper presents a verified demonstrator; a proposed holographic bridge interface with an innovative way of presenting information using AR technology. Furthermore, it identifies that new technologies offer the opportunity for enhanced operator performances, with the expectation being that this should lead to reduce risk to persons, property, and the environment.

Glioblastoma Multiforme (GBM) is the most common malignant primary brain tumor. Despite aggressive multimodality treatment it remains one of the most challenging and intractable cancers (1]. While current standard of care treatment for GBM is maximal safe surgical resection, systemic chemotherapy with Temozolimide (TMZ), and radiation therapy, the current prognosis of GBM patients remains poor, with a median overall survival of 12–15 months (2, 3). Therefore, other treatments are needed to provide better outcomes for GBM patients. Immunotherapy is one of the most promising new cancer treatment approaches. Immunotherapy drugs have obtained regulatory approval in a variety of cancers including melanoma (4), Hodgkin lymphoma (5), and non-small cell lung cancer (6). The basis of immunotherapy in cancer treatment is linked to stimulating the immune system to recognize cancer cells as foreign, thereby leading to the eventual elimination of the tumor. One form of immunotherapy utilizes vaccines that target tumor antigens (7), while other approaches utilize T-cells in patients to stimulate them to attack tumor cells (8). Despite intensive efforts all approaches have not been overtly successful (9), suggesting that we need to better understand the underlying biology of tumor cells and their environment as they respond to immunotherapy. Recent studies have elucidated epigenetic pathway regulation of GBM tumor expansion (10), suggesting that combined epigenetic pathway inhibition with immunotherapy may be feasible. In this review, we discuss current GBM clinical trials and how immune system interactions with epigenetic pathways and signaling nodes can be delineated to uncover potential combination therapies for this incurable disease.

Foldable containers have the potential to enhance the cost efficiency of the logistics industry and improve the problem of space allocation at seaports. Using primary and secondary data sources the pros and cons of using foldable containers as compared to standard containers are identified, and it is shown that a port can gain cost efficiencies by using foldable containers. A simulation for the Port of Melbourne (Australia) demonstrates that using foldable containers would reduce the projected total number of containers handled by the port in 2035 from 7.057 million to 5.817 million, with an 80% decrease in the number of empty containers. Foldable containers can therefore have a significant impact on the reformation of the transport and logistics systems.

Caspofungin was the first member of a new class of antifungals called echinocandins to be approved by a drug regulatory authority. Like the other echinocandins, caspofungin blocks the synthesis of β(1,3)-D-glucan of the fungal cell wall by inhibiting the enzyme, β(1,3)-D-glucan synthase. Loss of β(1,3)-D-glucan leads to osmotic instability and cell death. However, the precise mechanism of cell death associated with the cytotoxicity of caspofungin was unclear. We now provide evidence that Saccharomyces cerevisiae cells cultured in media containing caspofungin manifest the classical hallmarks of programmed cell death (PCD) in yeast, including the generation of reactive oxygen species (ROS), the fragmentation of mitochondria, and the production of DNA strand breaks. Our data also suggests that deleting AIF1 but not YCA1/MCA1 protects S. cerevisiae and Candida albicans from caspofungin-induced cell death. This is not only the first time that AIF1 has been specifically tied to cell death in Candida but also the first time that caspofungin resistance has been linked to the cell death machinery in yeast.

The increasing adoption of solar photovoltaic systems has brought attention to performance degradation factors, such as soiling, that hinder their efficiency. This study investigates the impact of dust particle thermophysical properties on solar cell temperature and energy losses, using transient thermal analysis and computational fluid dynamics simulations to analyse the complex interactions between dust and solar panels specifically focusing on solar cell temperature. By analyzing dust particle thermophysical characteristics and their interaction with solar collectors, this study provides a comprehensive understanding of performance degradation in solar energy systems. Simulation results reveal that velocity distributions around the solar panel, particularly in low-pressure zones and regions of high turbulence, significantly affect dust dispersion and deposition. Thermal emissions from the panel further influence dust accumulation through thermophoresis. Response surface methodology and contour analysis identified dust particle size as the most critical factor affecting cell temperature, followed by density and specific heat capacity. Thermal conductivity exhibited an inverse relationship with cell temperature, acting as an insulator at lower values. The developed response surface model demonstrated high accuracy (R2 = 0.9964) and statistical significance (p-value = 0.0001), predicting temperature variations based on different dust thermophysical parameters. Energy computations, extrapolated from the computational fluid dynamics and thermal simulations for a 50 kW grid-tied solar system over six months, indicated an overall energy loss of 18.93 %, due to transmittance loss (14.89 %), normal cell temperature rise (3.31 %), and temperature rise due to soiling (0.73 %). The study further revealed an overall revenue loss of 4.3 %, with 0.83 % attributed to thermal losses due to soiling. By understanding the influence of dust particle characteristics on solar cell temperature and performance, the findings can inform better maintenance practices and improve long-term energy yield predictions for solar installations.