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The European Food Safety Authority (EFSA) has a goal to efficiently conduct aggregate exposure assessments (AEAs) for chemicals using both exposure models and human biomonitoring (HBM) data by 2030. To achieve EFSA's vision, a roadmap for action for advancing aggregate exposure (AE) in the EU was developed. This roadmap was created by performing a series of engagement and data collection activities to map the currently available methods, data, and tools for assessing AE of chemicals, against the needs and priorities of EFSA. This allowed for the creation of a AEA framework, identification of data and knowledge gaps in our current capabilities, and identification of the challenges and blockers that would hinder efforts to fill the gaps. The roadmap identifies interdependent working areas (WAs) where additional research and development are required to achieve EFSA's goal. It also proposes future collaboration opportunities and recommends several project proposals to meet EFSA's goals. Eight proposal projects supported by SWOT analysis are presented for EFSA's consideration. The project proposals inform high‐level recommendations for multi‐annual and multi‐partner projects. Recommendations to improve stakeholder engagement and communication of EFSA's work on AEA were gathered by surveying stakeholders on specific actions to improve EFSA's communication on AE, including webinars, virtual training, social media channels, and newsletters. [ABSTRACT FROM AUTHOR]

Copyright of Dokuz Eylul University Muhendislik Faculty of Engineering Journal of Science & Engineering / Dokuz Eylül Üniversitesi Mühendislik Fakültesi Fen ve Mühendislik Dergisi is the property of Dokuz Eylul Universitesi Muhendislik Fakultesi Fen ve Muhendislik Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Muscles undergo developmental transitions in gene expression and alternative splicing that are necessary to refine sarcomere structure and contractility. CUG-BP and ETR-3-like (CELF) family RNA-binding proteins are important regulators of RNA processing during myogenesis that are misregulated in diseases such as Myotonic Dystrophy Type I (DM1). Here, we report a conserved function for Bruno 1 (Bru1, Arrest), a CELF1/2 family homolog in Drosophila, during early muscle myogenesis. Loss of Bru1 in flight muscles results in disorganization of the actin cytoskeleton leading to aberrant myofiber compaction and defects in pre-myofibril formation. Temporally restricted rescue and RNAi knockdown demonstrate that early cytoskeletal defects interfere with subsequent steps in sarcomere growth and maturation. Early defects are distinct from a later requirement for bru1 to regulate sarcomere assembly dynamics during myofiber maturation. We identify an imbalance in growth in sarcomere length and width during later stages of development as the mechanism driving abnormal radial growth, myofibril fusion, and the formation of hollow myofibrils in bru1 mutant muscle. Molecularly, we characterize a genome-wide transition from immature to mature sarcomere gene isoform expression in flight muscle development that is blocked in bru1 mutants. We further demonstrate that temporally restricted Bru1 rescue can partially alleviate hypercontraction in late pupal and adult stages, but it cannot restore myofiber function or correct structural deficits. Our results reveal the conserved nature of CELF function in regulating cytoskeletal dynamics in muscle development and demonstrate that defective RNA processing due to misexpression of CELF proteins causes wide-reaching structural defects and progressive malfunction of affected muscles that cannot be rescued by late-stage gene replacement. The CELF family of RNA binding proteins are important regulators of RNA processing during myogenesis. This study shows that the Drosophila homolog Bruno1 promotes a transition to mature spliceD isoforms, which is necessary for myofibrillogenesis and balanced growth in sarcomere length and width in flight muscles. [ABSTRACT FROM AUTHOR]

Murray and Gordon argue against mass upzonings that are unaccompanied by value capture tools based on the grounds that (a) cities are giving away valuable public air rights to private property owners when undertaking mass upzoning and thus (b) cities should employ value-capture policies to avoid complete privatization of public air rights. I first add a cautionary note that development of value capture strategies must be grounded in country-specific political, cultural, and legal contexts. To spark further scholarly and policy debates, I develop two propositions in response to the article. First, I contend that mass rezoning may be justifiable in the United States even if this means valuable public air rights are privatized. Second, I posit that mass rezoning is not only justifiable but also one of the most cost-effective and least risky policy solutions for tackling housing affordability and supply challenges in the United States. I conclude by suggesting directions for future research on upzoning and value capture. [ABSTRACT FROM AUTHOR]

Repetitive, long-term inhalation of radioactive radon gas is one of the leading causes of lung cancer, with exposure differences being a function of geographic location, built environment, personal demographics, activity patterns, and decision-making. Here, we examine radon exposure disparities across the urban-to-rural landscape, based on 42,051 Canadian residential properties in 2034 distinct communities. People living in rural, lower population density communities experience as much as 31.2% greater average residential radon levels relative to urban equivalents, equating to an additional 26.7 Bq/m3 excess in geometric mean indoor air radon, and an additional 1 mSv/year in excess alpha radiation exposure dose rate to the lungs for occupants. Pairwise and multivariate analyses indicate that community-based radon exposure disparities are, in part, explained by increased prevalence of larger floorplan bungalows in rural areas, but that a majority of the effect is attributed to proximity to, but not water use from, drilled groundwater wells. We propose that unintended radon gas migration in the annulus of drilled groundwater wells provides radon migration pathways from the deeper subsurface into near-surface materials. Our findings highlight a previously under-appreciated determinant of radon-induced lung cancer risk, and support a need for targeted radon testing and reduction in rural communities. [ABSTRACT FROM AUTHOR]

Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress-related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome-related genes revealed that the expression of the mucolipin 1 gene (Mcoln1; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte-specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive-like behaviors by inhibiting lysosomal exocytosis-mediated adenosine 5'-triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive-like behaviors induced by astrocyte-specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress-sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

A reference Geological Disposal System (GDS) for high level long lived heat emitting radioactive waste with dimension 20–10–6.25 m has been evaluated for time dependent heat field distribution, stress build up and possibility of micro-fracturing. The GDS comprises of three cylindrical heat sources (0.30 m diameter and 2 m length) mimicking radioactive waste loaded canisters emplaced within Jalore granite (JG) with barrier layers of Barmer bentonite (BB) clays, from Rajasthan. The methodology adopted in the study includes thermo- mechanical characterization of the granites and clays, followed by finite difference method (FDM) based numerical analysis for time dependent buildup of thermal and mechanical stresses, evolution of temperature field and micro fracturing phenomena within the studied GDS. The study reveals that three heat sources (waste filled SS canisters) of 500 watt intensity with spacing of 2.5 m and clay granite (CG) ratio of 60:40 and 70:30 produces maximum temperature of 92.42 and 94.69 °C and total stress (thermal and mechanical) of 24.77 and 24.97 MPa respectively within the system. 3.32 and 3.31 mm maximum displacement observed in the GDS for 60:40 and 70:30 CG ratio respectively which is within design limit. Analysis further establishes that clay admixture having bentonite clay and granite ratio in the range of 70:30 and 60:40 is capable of smooth dissipation of heat thorough them with resultant maximum temperature of < 100 °C throughout the entire duration of the time periods analysed. Based on these results it is concluded that JG and BB clay in 60:40 and 70:30 ratio with waste canister spacing of 2.5 m have appropriate characteristics suitable for hosting geological disposal system for heat emitting high level waste canisters. The study marks first analysis of multi-canister geological disposal system in Indian context. [ABSTRACT FROM AUTHOR]

Clay-based barrier wall has been diffusely employed as vertical barriers. Nevertheless, there were few project practices of these walls in China. And few research have been performed to study the impact on the permeability of the addition of domestic bentonites. To solve this problem, the influences of bentonite level on hydraulic conductivity, porosity and clay-bound water of soil-bentonite admixtures have been assessed employing a flexible-wall test and water centrifugal dewatering experiment with various bentonites. The outcomes revealed that as barrier walls are constructed by blending bentonite and Fujian standard sandy soil, there is a critical bentonite level of the smallest porosity. If the bentonite level is less than the critical bentonite content, hydraulic conductivity is reduced quickly, while if the bentonite level is greater than the critical bentonite content, hydraulic conductivity is reduced gently. Additionally, as the bentonite level grew, the clay-bound water centage of the admixtures continually improved. Supposing that the clay-bound water enclosed the clay grains, a near computation approach of the effective porosity is put forward and showed that the effective porosity decreased with bentonite content. Additionally, an exponential relationship was found between the effective porosity and the permeability. [ABSTRACT FROM AUTHOR]

Several countries are planning to safely contain and isolate used nuclear fuel in a deep geologic repository. Similar to other countries, Canada's Nuclear Waste Management Organization (NWMO) proposes to place used fuel in corrosion-resistant containers deep underground as part of a multiple barrier approach. Key components of the sealing systems are bentonite-based and must maintain low hydraulic conductivity and an ability to swell when in contact with free groundwater. Swelling pressure (Ps) and hydraulic conductivity (k) data for the specific bentonite product known as MX80 bentonite under low (<15 g/L) through high (>325 g/L) total dissolved solids' (TDS) pore fluids that simulate groundwaters that could be encountered in sedimentary and crystalline rock geospheres are reviewed, and information from ongoing NWMO studies of behaviour is presented. These data are statistically evaluated to establish the best-fit and prediction limit relationships between compacted dry density and Ps and k as they are influenced by porefluid composition. They also allow identification of dry density and(or) TDS (salinity) conditions where Ps and k may not meet defined performance. From these analyses, it is expected that bentonite can be placed such that on achieving fluid saturation and density equilibration, it meets the requirements set for placement room fill. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis caused by the intracellular parasite Leishmania major, exhibits significant public health challenge worldwide. With limited treatment options available, the identification of novel therapeutic targets is of paramount importance. Present study manifested the crucial role of ATG8 protein as a potential target in combating L. major infection. Using machine learning algorithms, we identified non-conserved motifs within the ATG8 in L. major. Subsequently, a peptide library was generated based on these motifs, and three peptides were selected for further investigation through molecular docking and molecular dynamics simulations. Surface Plasmon Resonance (SPR) experiments confirmed the direct interaction between ATG8 and the identified peptides. Remarkably, these peptides demonstrated the ability to cross the parasite membrane and exert profound effects on L. major. Peptide treatment significantly impacted parasite survival, inducing alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, indicating their involvement in autophagy regulation within L. major. In vitro studies revealed that the selected peptides effectively decreased the parasite load within the infected host cells. Encouragingly, in vivo experiments corroborated these findings, demonstrating a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II, a known autophagy marker within the host cells. Collectively, our findings highlight the efficacy of these novel peptides in targeting L. major ATG8 and disrupting parasite survival, wherein P2 is showing prominent effect on L. major as compared to P1. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis., (© 2024 Wiley‐VCH GmbH.)

The exact determination of settlement and the time required to complete that settlement is very important from the safety point of view. There are several methods available to find the rate of consolidation that is highly dependent on the settlement versus time curve. Here, it has been attempted to identify the suitable method for the determination of the rate of consolidation of coal ash. After analyzing the value of the coefficient of consolidation (Cv) estimated from various methods, the rectangular hyperbola method (RH method) is found to be in best linear correlation between the measured Cv and calculated Cv. The coal ash shows an increment in Cv with the increase in effective pressure. The Cv obtained from the RH method is higher than the Cv obtained from Taylor's and Casagrande method that helps in close approximation with field Cv. The precise determination of Cv helps in better prediction of the time required for the consolidation settlement that will increase the performance of the structure. [ABSTRACT FROM AUTHOR]

Chronic inflammation represents a major threat to human health since long‐term systemic inflammation is known to affect distinct tissues and organs. Recently, solid evidence demonstrated that chronic inflammation affects hematopoiesis; however, how chronic inflammation affects hematopoietic stem cells (HSCs) on the mechanistic level is poorly understood. Here, we employ a mouse model of chronic multifocal osteomyelitis (CMO) to assess the effects of a spontaneously developed inflammatory condition on HSCs. We demonstrate that hematopoietic and nonhematopoietic compartments in CMO BM contribute to HSC expansion and impair their function. Remarkably, our results suggest that the typical features of murine multifocal osteomyelitis and the HSC phenotype are mechanistically decoupled. We show that the CMO environment imprints a myeloid gene signature and imposes a pro‐inflammatory profile on HSCs. We identify IL‐6 and the Jak/Stat3 signaling pathway as critical mediators. However, while IL‐6 and Stat3 blockage reduce HSC numbers in CMO mice, only inhibition of Stat3 activity significantly rescues their fitness. Our data emphasize the detrimental effects of chronic inflammation on stem cell function, opening new venues for treatment. Synopsis: Chronic inflammation induces HSC expansion and reduces HSC fitness by hyperactivating the IL‐6/Jak/Stat3 signaling pathway. These effects of chronic inflammation on HSCs are mitigated upon inhibition of Stat3. CMO mice, suffering from sterile chronic inflammation, exhibit an expansion of the HSC pool and a reduction of HSC fitness.The CMO environment imprints a myeloid gene signature and imposes a pro‐inflammatory profile in HSCs.Inactivation of the IL‐1β/MyD88 pathway in CMO mice is not sufficient to prevent defects in the HSC compartment.IL‐6 and Jak/Stat3 signaling mediate HSC alterations in CMO mice and inhibition of Stat3 activity rescues HSC function. [ABSTRACT FROM AUTHOR]

In this study, the drying-induced microstructure evolution of compacted silt with different salinities is investigated using mercury intrusion porosimetry and environmental scanning electron microscope. The pore size distribution (PSD) of specimens compacted near optimum (w = 17%) exhibited bimodal characteristics. Upon drying (w = 8%), the PSD changed to a trimodal pattern with the appearance of a new nano-pore population. This suggested the development of nano-fissures, which could occur in the clay fraction and at the interface between clay particles and silt/sand grains due to the clay shrinkage. With further drying (w = 3%), the nano-pores disappeared and the PSD recovered to bimodal characteristics, suggesting that the nano-fissures created were enlarged until they became micro-fissures. The salinity seemed to decrease the frequency of the drying-induced micro-pores due to the enhanced mechanical strength of salted soil by the soil aggregation resulting from the compression of the diffuse double layer and a possible cementation effect produced by precipitated salt. However, the salinity effect was relatively low, owing to: (a) the low clay fraction (15·7%) and the low-activity clay minerals (illite, chlorite and kaolinite); (b) the low specific surface area (24 m2/g), which limited the salinity effect on the diffuse double layer. [ABSTRACT FROM AUTHOR]

Copyright of Revista Portuguesa de Enfermagem de Reabilitação is the property of Associacao Portuguesa dos Enfermeiros de Reabilitacao (APER) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A variety of chemicals are used in various stages of oil exploitation to ensure the normal progress of exploitation and improve the efficiency of oil recovery. However, most of the conventional petroleum-based chemicals are non-biodegradable, which will remain as wastes after applying, leading to serious environmental menace. In recent years, cellulose nanomaterials have attracted extensive interest due to their renewable and biodegradable features, as well as excellent chemical, mechanical, and rheological properties. This review comprehensively summarizes recent advances in exploring cellulose nanomaterials for oil exploration applications. Firstly, the preparation and properties of cellulose nanomaterials are briefly introduced. Then, the applications of cellulose nanomaterials in different petroleum exploitation processes, including drilling, cementing, and enhancing oil recovery are systematically discussed. Finally, the perspectives and challenges of cellulose nanomaterials for oil exploration applications are provided. It is expected that cellulose nanomaterials will be developed as promising oilfield chemicals for large scale application. The review comprehensively summarizes recent advances in exploring cellulose nanomaterials for oil exploration applications, specifically focuses on their applications in different petroleum exploitation processes, including drilling, cementing, and enhancing oil recovery. [ABSTRACT FROM AUTHOR]

Impermeable layers consist of compacted clay mixtures, synthetic membranes or combinations of clay mixtures and synthetic membranes. When compacted clay liners are employed, they are required to have low hydraulic conductivity, high swelling characteristics, good radionuclide adsorption capacity and good self-sealing capacity. Investigation of the factors affecting the swelling behavior of zeolite-bentonite mixtures (ZBMs) is of great importance for controlling the stability and permeability of landfill sites. In this study, the effect of bentonite content in ZBMs on swelling behavior of compacted high plasticity clays were investigated. For this aim, two types of ZBMs containing 20% and 30% bentonite were prepared. 100% bentonite (pure bentonite) specimens were also tested. Compaction tests were performed on specimens of the ZBMs and pure bentonite, and compaction values were determined. Swelling tests were conducted at optimum water contents of the specimens of ZBMs and pure bentonite. The specimens of ZBMs were loaded under effective vertical stress levels of 1, 2.5, 5, 12.5, 25, and 50 kPa. Pure bentonite specimens were additionally subjected to 100 kPa effective vertical stress. Swelling was observed on ZBM specimens under all effective stress levels. Pure bentonite specimens exhibited limited swelling at 100 kPa effective vertical stress. Swelling of ZBMs increases with increasing bentonite content. The swelling behavior of compacted high plasticity clays was interpreted in terms of bentonite content and final void ratio. [ABSTRACT FROM AUTHOR]

To investigate the effect of the changes in the soil suction on volume changes, expansion index, swelling pressure, shear strength and the coefficient of permeability, small-scale experiments were conducted on pure bentonite and bentonite mixed with sand with proportions of 30, 40 and 50% at different initial water contents and dry unit weights that were chosen from the compaction curves. In addition, large-scale model of soil with dimensions (700 × 700 × 650) mm was used to prepare the soil samples at the same initial water content and dry unit weight to show the effect of water content changes in different relations (swelling with time, swelling pressure with time, shear strength and soil suction). The results showed that the swelling potential decreases with increase in sand content from 14 to 2.4% by adding 50% sand to pure bentonite. The swelling percent found from the large-scale model is higher than that obtained from the oedometer swelling test for the same soil. This result applies well on BS5 (50:50, bentonites: sand) soil sample for which the swelling potential from large scale model is 8.3% and from the conventional swelling test is 3.6% only. The measured swelling pressure from the swelling test at small soil samples is much higher than that measured from the large-scale model. For soil sample BS3 (60:40, bentonite: sand), the swelling pressure decreases from 50 kPa in the swelling test to 23.2 kPa in the large-scale model. [ABSTRACT FROM AUTHOR]

An experimental program was employed to evaluate the effects of curing time and temperature on the shear behavior of a sand-bentonite mixture. The specimens were treated at temperatures of 40°C, 60°C, and 80°C on Days 1, 3, and 5 under 100 kPa, 500 kPa, and 1000 kPa confinements. The results of the consolidated undrained triaxial shear tests indicated that an increase in the temperature from 40° C to 80° C on Days 1, 3, and 5 of curing intensified the shear strength by 25%, 24%, and 23%, respectively. In addition, an increase in the curing time from 1 to 3 and from 1 to 5 days at 80° C increased the shear strength of samples up to 12% and 24%, respectively. The failure of pre-cured samples was observed in lower strains as a result of greater induced brittleness. Moreover, the secant modulus and size of yield loci as well as slope of the critical state line increased by pre-curing. Application of thermal cycles resulted in increasing the shear strength and experiencing a negative pore water pressure that exhibited a transition towards the quasistructured behavior. The results of Scanning Electron Microscopy (SEM) studies confirmed an increase in the void ratio during thermal curing. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Central South University is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

mRNA display is a powerful biological display platform for the directed evolution of proteins and peptides. mRNA display libraries covalently link the displayed peptide or protein (phenotype) with the encoding genetic information (genotype) through the biochemical activity of the small molecule puromycin. Selection for peptide/protein function is followed by amplification of the linked genetic material and generation of a library enriched in functional sequences. Iterative selection cycles are then performed until the desired level of function is achieved, at which time the identity of candidate peptides can be obtained by sequencing the genetic material. The purpose of this review is to discuss the development of mRNA display technology since its inception in 1997 and to comprehensively review its use in the selection of novel peptides and proteins. We begin with an overview of the biochemical mechanism of mRNA display and its variants with a particular focus on its advantages and disadvantages relative to other biological display technologies. We then discuss the importance of scaffold choice in mRNA display selections and review the results of selection experiments with biological (e.g., fibronectin) and linear peptide library architectures. We then explore recent progress in the development of "drug-like" peptides by mRNA display through the post-translational covalent macrocyclization and incorporation of non-proteogenic functionalities. We conclude with an examination of enabling technologies that increase the speed of selection experiments, enhance the information obtained in post-selection sequence analysis, and facilitate high-throughput characterization of lead compounds. We hope to provide the reader with a comprehensive view of current state and future trajectory of mRNA display and its broad utility as a peptide and protein design tool. [ABSTRACT FROM AUTHOR]

The impact of time-dependent unsaturated behaviour of virgin and the impact of cation self-diffusion on the time-dependent unsaturated behaviour of exhumed geosynthetic clay liner (GCL) specimens were investigated using a chilled mirror hygrometer. Total suction values (after 7 weeks' water homogenisation) are reported for ten virgin (six different bentonites) and one GCL exhumed after exposure to the thermo-hydro-mechanical (THM) conditions in Antarctica. The time-dependent unsaturated responses of four different virgin GCLs 1 day and 1 week after hydration are compared with the results at homogenisation and the implications discussed. For the suction (0.1–300 MPa) and water content range (5–140%) examined, the post-water homogenisation water retention behaviour of the GCLs is affected by bentonite characteristics. At a given gravimetric water content, the total suction of GCLs increased with increasing smectite content and total soluble salt content and decreased with increasing total bound cation content in the bentonite. Cation self-diffusion also increased the total suction in the GCL exhumed after exposure to Antarctic THM conditions. It is concluded that the impact of cation self-diffusion on the unsaturated behaviour of a GCL during its time in service before exposure to pollutants needs to be considered in designing hydraulic and gas barriers. [ABSTRACT FROM AUTHOR]