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The complex hydroenvironmental computer models are used for predicting flow, water quality and sediment transport processes in coastal, estuarine and inland waters. The limitations and restrictions of both physical and numerical hydraulic models used in the planning and management of aquatic basins along the South Wales coast are discussed.

The Severn Estuary is an ideal site for tidal renewable energy projects and the probability of coastal flood risk in the estuary will increase accordingly due to climate change. Therefore, it is significant to predict the future status of coastal flooding in this estuary using various scenarios with the effects of climate change and potential barrage construction. An existing two-dimensional hydrodynamic model is outlined first. Three scenarios at the open seaward boundary are then presented. Finally, the model was used to simulate the hydrodynamic processes in the estuary using three boundary scenarios. Simulated results show that (i) without the barrage, the maximum levels along the estuary could rise by 1.0-1.2 m due to sea-level rise, and the effect of extreme sea levels on the distribution of maximum water levels would be noticeable only in the outer estuary reach; (ii) with the barrage, the maximum water levels could reduce by 0.5-1.2 m upstream of the barrage even if a sea-level rise of 1.0 m would occur by 2100, and extreme sea levels could not influence the distribution of maximum water levels upstream of the barrage; and (iii) the future flood risk in a small coastal floodplain would increase and the potential losses could reach £6.5 M/year due to sea-level rise without the barrage, and it could be avoided completely if the barrage were to be constructed as proposed. [ABSTRACT FROM AUTHOR]

Poly(lactic acid) (PLA) is characterized by unique features, e.g., it is environmentally friendly, biocompatible, has good thermomechanical properties, and is readily available and biodegradable. Due to the increasing pollution of the environment, PLA is a promising alternative that can potentially replace petroleum-derived polymers. Different biodegradable polymers have numerous biomedical applications and are used as packaging materials. Because the pure form of PLA is delicate, brittle, and is characterized by a slow degradation rate and a low thermal resistance and crystallization rate, these disadvantages limit the range of applications of this polymer. However, the properties of PLA can be improved by chemical or physical modification, e.g., with biomolecules. The subject of this review is the modification of PLA properties with three classes of biomolecules: polysaccharides, proteins, and nucleic acids. A quite extensive description of the most promising strategies leading to improvement of the bioactivity of PLA, through modification with these biomolecules, is presented in this review. Thus, this article deals mainly with a presentation of the major developments and research results concerning PLA-based materials modified with different biomolecules (described in the world literature during the last decades), with a focus on such methods as blending, copolymerization, or composites fabrication. The biomedical and unique biological applications of PLA-based materials, especially modified with polysaccharides and proteins, are reviewed, taking into account the growing interest and great practical potential of these new biodegradable biomaterials. [ABSTRACT FROM AUTHOR]

A numerical model is presented for solving the dam–reservoir interaction (DRI) problem in the time domain. The primary aim of this paper is to introduce a coupling method that could be simply implemented in a monolithic DRI model, yields a symmetrical system of equations, and maintains accuracy comparable to existing studies. The finite element method is employed to solve the equation of motion for the structure, and the finite volume method is for the Navier–Stokes equations in the fluid domain. These two solvers are coupled using an innovative approach to generate a pressure-based symmetric system of equations, which is resolved implicitly. Moreover, unlike most previous DRI studies, free surface waves are considered in the modeling procedure, and their effects are investigated. Comparison of the results with benchmark test cases from the literature demonstrates that the proposed numerical method is both straightforward and precise. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review, we introduce and summarize the canonical roles of Ataxia Telangiectasia and Rad3-related protein (ATR) in the DNA damage response (DDR) pathway. More importantly, we also summarize the most recent discoveries of ATR's non-canonical roles in regulating nuclear membrane integrity, mechanical force, chromosome segregation, and its role in PML bodies and discuss how they are relevant to the current progress of ATR inhibitors in clinical trials. Ataxia Telangiectasia and Rad3-related protein (ATR) is an apical kinase of the DNA Damage Response (DDR) pathway responsible for detecting and resolving damaged DNA. Because cancer cells depend heavily on the DNA damage checkpoint for their unchecked proliferation and propagation, ATR has gained enormous popularity as a cancer therapy target in recent decades. Yet, ATR inhibitors have not been the silver bullets as anticipated, with clinical trials demonstrating toxicity and mixed efficacy. To investigate whether the toxicity and mixed efficacy of ATR inhibitors arise from their off-target effects related to ATR's multiple roles within and outside the DDR pathway, we have analyzed recently published studies on ATR's non-canonical roles. Recent studies have elucidated that ATR plays a wide role throughout the cell cycle that is separate from its function in the DDR. This includes maintaining nuclear membrane integrity, detecting mechanical forces, and promoting faithful chromosome segregation during mitosis. In this review, we summarize the canonical, DDR-related roles of ATR and also focus on the non-canonical, multifaceted roles of ATR throughout the cell cycle and their clinical relevance. Through this summary, we also address the need for re-assessing clinical strategies targeting ATR as a cancer therapy based on these newly discovered roles for ATR. [ABSTRACT FROM AUTHOR]

Hydrokinetic tidal energy is one of the few marine renewable energy resources with sufficiently mature technology for commercial exploitation. However, several parameters affect its exploitability, such as the minimum speed threshold, ambient turbulence levels, or tidal asymmetry, to name but a few. These parameters are particularly important in regions with lower mean speeds than those in first-generation sites, such as the North Sea. The Gulf of California is one of those regions. In this paper, a Delft3D Flexible Mesh Suite (Delft3D FM) model in barotropic configuration is set up over the Gulf of California using a flexible mesh with resolution varying from O (500 m) in the deep regions to O (10 m) in the coastal regions. A simulation is run over the year of 2020, with a tidal forcing of 75 components. The model is validated at four tidal gauge locations and four Acoustic Doppler Current profiler (ADCP) locations. The speed, U, and tidal power density ( T P D ) indicators used for the validation were the annual means, the annual means for speeds above the 0.5 m s−1 threshold, the annual means of the spring tide maxima, and the annual maxima. The contour maps of the annual means, that is, the annual means for speeds above the 0.5 m s−1 threshold, allow us to identify tidal energy hot spots throughout the Gulf of California, particularly in the Great Island region (GIR). In this region, these hot spots have higher U and T P D values, in agreement with previous studies. The patterns of circulation around Tiburón Island and San Esteban Island on the East, and Ángel de la Guarda Island and San Lorenzo Island on the West, the four islands in the region with the highest tidal energy potential, are also discussed while recognizing that Tiburón Channel, between Tiburón Island and San Esteban Island, has proved to be the best siting location, based on the technical results obtained so far. The hot spots sites are further characterized by computing the tidal asymmetry in these small regions, showing the locations of the sites with smallest asymmetry, which would be the best for tidal energy exploitation. The hot spots around San Esteban Island are particularly important because they have the largest T P D in the GIR, with the model predicting a T P D on the order of 500–1000 W m−2. Here, complementary field measurements obtained with two ADCPs, close to San Esteban Island, one at 15 m depth, SEs (shallow region), and the other at 60 m depth, SEd (deep region), produced T P D s of 1200 W m−2 and 400 W m−2, respectively. The analysis of the vertical profiles and the tidal asymmetry over the vertical shows the importance of developing 3D models in future investigations. [ABSTRACT FROM AUTHOR]

Lung cancer is a major threat to human health and a leading cause of death. Accurate localization of tumors in vivo is crucial for subsequent treatment. In recent years, fluorescent imaging technology has become a focal point in tumor diagnosis and treatment due to its high sensitivity, strong selectivity, non-invasiveness, and multifunctionality. Molecular probes-based fluorescent imaging not only enables real-time in vivo imaging through fluorescence signals but also integrates therapeutic functions, drug screening, and efficacy monitoring to facilitate comprehensive diagnosis and treatment. Among them, near-infrared (NIR) fluorescence imaging is particularly prominent due to its improved in vivo imaging effect. This trend toward multifunctionality is a significant aspect of the future advancement of fluorescent imaging technology. In the past years, great progress has been made in the field of NIR fluorescence imaging for lung cancer management, as well as the emergence of new problems and challenges. This paper generally summarizes the application of NIR fluorescence imaging technology in these areas in the past five years, including the design, detection principles, and clinical applications, with the aim of advancing more efficient NIR fluorescence imaging technologies to enhance the accuracy of tumor diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Meningiomas are predominantly benign tumors, but there are also malignant forms that are associated with a poor prognosis. Like almost all tumors, meningiomas metabolize glucose as part of aerobic glycolysis (Warburg effect) for energy supply, so there are attempts to influence the prognosis of tumor diseases using a glucose-reduced diet. This altered metabolism leads to so called hallmarks of cancer, such as glycation and glycosylation. In this study, we investigated the influence of low (3 mM), normal (5.5 mM) and high glucose (15 mM) on a malignant meningioma cell line (IOMM-Lee, WHO grade 3). In addition, the influence of methylglyoxal, a by-product of glycolysis and a precursor for glycation, was investigated. Impedance-based methods (ECIS and RTCA) were used to study migration and invasion, and immunoblotting was used to analyze the expression of proteins relevant to these processes, such as focal adhesion kinase (FAK), merlin or integrin ß1. We were able to show that low glucose reduced the invasive potential of the cells, which was associated with a reduced amount of sialic acid. Under high glucose, barrier function was impaired and adhesion decreased, which correlated with a decreased expression of FAK. [ABSTRACT FROM AUTHOR]

The charge-reversal nano-drug delivery system (CRNDDS) is a promising system for delivering chemotherapy drugs and has gained widespread application in cancer treatment. In this review, we summarize the recent advancements in CRNDDSs in terms of cancer treatment. We also delve into the charge-reversal mechanism of the CRNDDSs, focusing on the acid-responsive, redox-responsive, and enzyme-responsive mechanisms. This study elucidates how these systems undergo charge transitions in response to specific microenvironmental stimuli commonly found in tumor tissues. Furthermore, this review explores the pivotal role of CRNDDSs in tumor diagnosis and treatment, and their potential limitations. By leveraging the unique physiological characteristics of tumors, such as the acidic pH, specific redox potential, and specific enzyme activity, these systems demonstrate enhanced accumulation and penetration at tumor sites, resulting in improved therapeutic efficacy and diagnostic accuracy. The implications of this review highlight the potential of charge-reversal drug delivery systems as a novel and targeted strategy for cancer therapy and diagnosis. [ABSTRACT FROM AUTHOR]