Search Results (1,390,771)

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by the insufficient production of the AAT protein. Due to availability limitations, not all AATD patients receive protein therapy treatment. In this study, the technoeconomic analysis of different processes (conventional and intensified) producing 200 kg/year of PEGylated recombinant AAT (PEG-AAT) using a Chinese hamster ovary cell line was investigated. All bioprocesses consist of upstream, downstream, and PEGylation sections. A base-case model (process A) of the conventional fed-batch production bioreactor was developed using SuperPro Designer software (Version 13) to evaluate the economic feasibility of the process. The cost of goods (COG) was estimated to be approximately USD 387.6/g. Furthermore, an intensified process (B) was modeled and evaluated to reduce the COG. Process intensification was implemented in the process (N-1 perfusion bioreactor). The specific operating COG for process B was found to be 10% less than that of process A. Scenario analysis was performed to assess the impact of process capacity (100–1000 kg/year) and cell-specific productivity (30–90 pg/cell/day). With an increase in process capacity, the specific operating COG was reduced for all processes. Increasing cell-specific productivity decreases the specific operating COG at different rates for each process, depending on the titer level. Future investigations into the PEGylation section are required since it has the highest COG of all the sections. Full article

Epigenetic alterations that lead to differential expression of microRNAs (miRNAs/miR) are known to regulate tumour cell states, epithelial–mesenchymal transition (EMT) and the progression to metastasis in breast cancer. This study explores the key contribution of miRNA-18a in mediating a hybrid E/M cell state that is pivotal to the malignant transformation and tumour progression in the aggressive ER-negative subtype of breast cancer. The expression status and associated effects of miR-18a were evaluated in patient-derived breast tumour samples in combination with gene expression data from public datasets, and further validated in in vitro and in vivo breast cancer model systems. The clinical relevance of the study findings was corroborated against human breast tumour specimens (n = 446 patients). The down-regulated expression of miR-18a observed in ER-negative tumours was found to drive the enrichment of hybrid epithelial/mesenchymal (E/M) cells with luminal attributes, enhanced traits of migration, stemness, drug-resistance and immunosuppression. Further analysis of the miR-18a targets highlighted possible hypoxia-inducible factor 1-alpha (HIF-1α)-mediated signalling in these tumours. This is a foremost report that validates the dual role of miR-18a in breast cancer that is subtype-specific based on hormone receptor expression. The study also features a novel association of low miR-18a levels and subsequent enrichment of hybrid E/M cells, increased migration and stemness in a subgroup of ER-negative tumours that may be attributed to HIF-1α mediated signalling. The results highlight the possibility of stratifying the ER-negative disease into clinically relevant groups by analysing miRNA signatures. Full article

Ceramic matrix composites (CMCs) are a significant advancement in materials science and engineering because they combine the remarkable characteristics of ceramics with the strength and toughness of fibers. With their unique properties, which offer better performance and endurance in severe settings, these advanced composites have attracted significant attention in various industries. At the same time, lightweight ceramic matrix composites (LCMCs) provide an appealing alternative for a wide range of industries that require materials with excellent qualities such as high-temperature stability, low density, corrosion resistance, and excellent mechanical performance. CMC uses will expand as production techniques and material research improve, revolutionizing aerospace, automotive, and other industries. The effectiveness of CMCs primarily relies on the composition of their constituent elements and the methods employed in their manufacturing. Therefore, it is crucial to explore the functional properties of various global ceramic matrix reinforcements, their classifications, and the manufacturing techniques used in CMC fabrication. This study aims to overview a diverse range of CMCs reinforced with primary fibers, including their classifications, manufacturing techniques, functional properties, significant applications, and global market size. Full article

Classical Hodgkin Lymphoma (cHL) is a highly curable disease, but around 20% of patients experience progression or relapse after standard frontline chemotherapy regimens. Salvage regimens followed by autologous stem cell transplants represent the historical treatment approach for these cases. In the last decade, with the increasing understanding of cHL biology and tumor microenvironment role in disease course, novel molecules have been introduced in clinical practice, improving outcomes in the relapsed/refractory setting. The anti-CD30 antibody-drug conjugated brentuximab vedotin and PD-1/PD-L1 checkpoint inhibitors represent nowadays curative options for chemorefractory patients, and randomized trials recently demonstrated their efficacy in frontline immune-chemo-combined modalities. Several drugs able to modulate the patients’ T-lymphocytes and NK cell activity are under development, as well as many anti-CD30 chimeric antigen receptor T-cell products. Multiple tumor aberrant epigenetic mechanisms are being investigated as targets for antineoplastic compounds such as histone deacetylase inhibitors and hypomethylating agents. Moreover, JAK2 inhibition combined with anti-PD1 blockade revealed a potential complementary therapeutic pathway in cHL. In this review, we will summarize recent findings on cHL biology and novel treatment options clinically available, as well as promising future perspectives in the field. Full article

Experimental validation of computational simulations is important because it provides empirical evidence to verify the accuracy and reliability of the simulated results. This validation ensures that the simulation accurately represents real-world phenomena, increasing confidence in the model’s predictive capabilities and its applicability to practical scenarios. The use of musculoskeletal models in orthopedic surgery allows for objective prediction of postoperative function and optimization of results for each patient. To ensure that simulations are trustworthy and can be used for predictive purposes, comparing simulation results with experimental data is crucial. Although progress has been made in obtaining 3D bone geometry and estimating contact forces, validation of these predictions has been limited due to the lack of direct in vivo measurements and the economic and ethical constraints associated with available alternatives. In this study, an existing commercial surgical training station was transformed into a sensorized test bench to replicate a knee subject to a total knee replacement. The original knee inserts of the training station were replaced with personalized 3D-printed bones incorporating their corresponding implants, and multiple sensors with their respective supports were added. The recorded movement of the patella was used in combination with the forces recorded by the pressure sensor and the load cells, to validate the results obtained from the simulation, which was performed by means of a multibody dynamics formulation implemented in a custom-developed library. The utilization of 3D-printed models and sensors facilitated cost-effective and replicable experimental validation of computational simulations, thereby advancing orthopedic surgery while circumventing ethical concerns. Full article

Toxoplasma gondii is a zoonotic pathogen and the ingestion of tissue cysts by consumption of lamb or mutton has been identified as a possible cause of infection in humans. Many serological surveys in sheep have been performed, showing relevant serological rates; however, while the detection of antibodies indicates an exposure to T. gondii, this does not necessarily imply the presence of tissue cysts in edible tissue. The current study aims to provide further understanding on the occurrence of T. gondii in sheep muscles and the strength of correlation between serological positivity and presence of the parasite in sheep. From 349 sheep, samples (i.e., blood, heart and diaphragm) were collected and subjected to ELISA tests, real-time PCR and histological tests. Despite the high seroprevalence, T. gondii DNA was detected in the heart and/or the diaphragm from 13 out of the 349 tested sheep (3.7%); all were adults (13/191). Furthermore, the histological tests did not reveal the presence of T. gondii tissue cysts in any of the examined portions of interventricular septum. It should be considered that the likelihood of detecting genetic material of the parasite is probably influenced by the uneven distribution of the tissue cysts in the carcass as well as the methodology applied. The findings of this study support the importance of describing the uncertainty associated with the data used for risk assessment to reduce inaccurate estimation or risk overestimation. Full article

French Guiana is a French territory in South America. The exposome of persons living there is quite different from that in mainland France and the ethnic make-up of the population is also quite different. Poverty is also widespread with difficulties in accessing care magnified by the low medical-professional density. In this singular context, we aimed to measure the incidence of pediatric cancers and to compare it with other continents. We used French Guiana’s certified cancer registry to study this between 2003 and 2017. Incidences were standardized using the world population with three strata: 0–4 years, 5–9 years, and 10–14 years. There were 164 solid tumors or hematologic malignancies diagnosed in children under the age of 15 (92 in boys and 72 in girls). Over the study period, the standardized incidence rate was 14.1 per 100,000 among children aged under 15 years. There was no significant trend during the study period. The three most common causes of cancer were leukemias—mostly lymphoblastic—CNS tumors, and sarcoma. The standardized incidence of pediatric cancers in French Guiana was similar to those in Western Europe and North America. As others have discovered, we found that males tended to be more likely to develop cancer, notably leukemia, CNS tumors, sarcoma, and retinoblastoma. As elsewhere, the predominant cancer types changed with age. Our initial assumption was that given the singular context of French Guiana, there may have been differences in pediatric cancer incidences. Here we showed that overall, contrary to our assumption and to trends in tropical countries, the incidence of pediatric cancers was in a range between Western Europe and North America with some apparent but non-significant differences in the main types of cancers observed in global statistics. Quality cancer registry data in this tropical region confirm the suspicion that lower incidences in tropical low- and middle-income countries are likely to result from incomplete diagnosis and data collection. Full article

With the rapid development of electric vehicles (EVs) in Chinese cities, accurately forecasting the number of EVs used by urban residents in the next five years and more long term is beneficial for the government to adjust industrial policies of EVs, guide the rational planning of urban charging facilities and supporting distribution network, and achieve the rational and orderly development of the EV industry. The paper considers the advantages of using the grey GM(1,1) prediction model to predict the short-term ownership of EVs by urban residents. Then, by forecasting the number of EV users in a certain city in the future and predicting the number of private vehicles in the future, the boundary conditions for long-term year ownership of EVs by residents are determined. Combined with historical data and short-term forecast data generated by the grey prediction model, the model parameters that include the innovation coefficient and imitation coefficient of the Bass model are trained using a genetic algorithm. Finally, the Bass model is used for medium- to long-term ownership forecasting from 2023 to 2040. The prediction error for the target year is provided. The simulation results indicate that the ownership of resident EVs in this city will experience rapid growth in the next five years. Full article

We present the use of interconnected optical mesh networks for early earthquake detection and localization, exploiting the existing terrestrial fiber infrastructure. Employing a waveplate model, we integrate real ground displacement data from seven earthquakes with magnitudes ranging from four to six to simulate the strains within fiber cables and collect a large set of light polarization evolution data. These simulations help to enhance a machine learning model that is trained and validated to detect primary wave arrivals that precede earthquakes’ destructive surface waves. The validation results show that the model achieves over 95% accuracy. The machine learning model is then tested against an M4.3 earthquake, exploiting three interconnected mesh networks as a smart sensing grid. Each network is equipped with a sensing fiber placed to correspond with three distinct seismic stations. The objective is to confirm earthquake detection across the interconnected networks, localize the epicenter coordinates via a triangulation method and calculate the fiber-to-epicenter distance. This setup allows early warning generation for municipalities close to the epicenter location, progressing to those further away. The model testing shows a 98% accuracy in detecting primary waves and a one second detection time, affording nearby areas 21 s to take countermeasures, which extends to 57 s in more distant areas. Full article

The inhalation of gasoline vapors (GV) is associated with developing various pathologies. Particularly, oil refinery and gas station workers are at a greater risk of developing lung cancer, kidney cancer, bladder cancer, and hematological disorders, including acute myeloid leukemia. Therefore, preventing the harmful effects of GV and alleviating their consequences appear to be important and timely issues. In this study, we investigated the potential of vitamin D₃, turmeric powder, and their combination to ameliorate the toxicity of gasoline fumes in rats. Separate groups of animals fed with a standard rodent diet, with or without the supplementation of vitamin D₃ (750 IU/kg body weight) and/or turmeric powder (0.5%, w/w, in food), were untreated or treated with GV (11.5 ± 1.3 cm³/h/m³/day) for 30, 60, or 90 days. Changes in the body weight were monitored weekly. Histological, biochemical, and hematological parameters were determined at the end of each treatment period. While the exposure of rats to GV resulted in a time-dependent reduction in body weight, supplementation with vitamin D₃, but not with turmeric root powder or their combination, partially prevented weight loss. Macroscopical and histological analyses showed pronounced time-dependent changes in the organs and tissues of GV-treated rats. These included alveolar wall collapse in the lungs, the destruction of the lobular structure and hepatocytolysis in the liver, the shrinkage and fragmentation of glomeruli in the kidneys, and the disorganization of the lymphoid follicles in the spleen. However, co-treatment with the nutritional supplements tested, especially vitamin D₃, noticeably alleviated the above conditions. This was accompanied by a significant improvement in the blood chemistry and hematological parameters. Collectively, our results demonstrate that the harmful effects of environmental exposure to GV can be reduced upon supplementation of vitamin D₃. The fact that the protective activity of vitamin D₃ alone was higher than that of turmeric root powder or the combined treatment suggests that combinations of these supplements may not always be more beneficial than each agent applied separately. Full article

This paper presents the results of the influence of variation of the synthesis conditions of CuBi/CuBi₂O₄ films with a change in the applied potential difference, as well as a change in electrolyte solutions (in the case of adding cobalt or nickel sulfates to the electrolyte solution) on changes in the phase composition, structural parameters and strength characteristics of films obtained using the electrochemical deposition method. During the experiments, it was found that, in the case of the addition of cobalt or nickel to the electrolyte solutions, the formation of films with a spinel-type tetragonal CuBi₂O₄ phase is observed. In this case, a growth in the applied potential difference leads to the substitution of copper with cobalt (nickel), which in turn leads to an increase in the structural ordering degree. It should be noted that, during the formation of CuBi/CuBi₂O₄ films from solution–electrolyte №1, the formation of the CuBi₂O₄ phase is observed only with an applied potential difference of 4.0 V, while the addition of cobalt or nickel sulfates to the electrolyte solution results in the formation of the tetragonal CuBi₂O₄ phase over the entire range of the applied potential difference (from 2.0 to 4.0 V). Studies have been carried out on the strength and tribological characteristics of synthesized films depending on the conditions of their production. It has been established that the addition of cobalt or nickel sulfates to electrolyte solutions leads to an increase in the strength of the resulting films from 20 to 80%, depending on the production conditions (with variations in the applied potential difference). During the studies, it was established that substitution of copper with cobalt or nickel in the composition of CuBi₂O₄ films results in a rise in the shielding efficiency of low-energy gamma radiation by 3.0–4.0 times in comparison with copper films, and 1.5–2.0 times for high-energy gamma rays, in which case the decrease in efficiency is due to differences in the mechanisms of interaction of gamma quanta, as well as the occurrence of secondary radiation as a result of the formation of electron–positron pairs and the Compton effect. Full article

The unmanned surface vessel (USV) is an emerging marine tool with its advantages of automation and intelligence in recent years; the good trajectory tracking performance is an important capability. This paper proposes a novel prescribed performance fixed-time fault-tolerant control scheme for a USV with model parameter uncertainties, unknown external disturbances, and actuator faults, based on an improved fixed-time disturbances observer. Firstly, the proposed observer can not only accurately and quickly estimate and compensate the lumped nonlinearity, including actuator faults, but also reduce the chattering phenomenon by introducing the hyperbolic tangent function. Then, under the framework of prescribed performance control, a prescribed performance fault-tolerant controller is designed based on a nonsingular fixed-time sliding mode surface, which guarantees the transient and steady-state performance of a USV under actuator faults and meets the prescribed tracking performance requirements. In addition, it is proved that the closed-loop control system has fixed-time stability according to Lyapunov’s theory. Finally, upon conducting numerical simulations and comparing the proposed control scheme with the SMC and the finite-time NFTSMC scheme, it is evident that the absolute error tracking performance index of the proposed control scheme is significantly lower, thus indicating its superior accuracy. Full article

Constructed from a dataset capturing the seasonal and annual water body distribution of the lower Qarqan River in the Taitma Lake area from 2017 to 2022, and combined with the meteorological and hydraulic engineering data, the spatial and temporal change patterns of the Taitma Lake watershed area were determined. Analyses were conducted using Planetscope (PS) satellite images and a deep learning model. The results revealed the following: ① Deep learning-based water body extraction provides significantly greater accuracy than the conventional water body index approach. With an impressive accuracy of up to 96.0%, UPerNet was found to provide the most effective extraction results among the three convolutional neural networks (U-Net, DeeplabV3+, and UPerNet) used for semantic segmentation; ② Between 2017 and 2022, Taitma Lake’s water area experienced a rapid decrease, with the distribution of water predominantly shifting towards the east–west direction more than the north–south. The shifts between 2017 and 2020 and between 2020 and 2022 were clearly discernible, with the latter stage (2020–2022) being more significant than the former (2017–2020); ③ According to observations, Taitma Lake’s changing water area has been primarily influenced by human activity over the last six years. Based on the research findings of this paper, it was observed that this study provides a valuable scientific basis for water resource allocation aiming to balance the development of water resources in the middle and upper reaches of the Tarim and Qarqan Rivers, as well as for the ecological protection of the downstream Taitma Lake. Full article

This paper considers the scattering of a probe laser pulse by an intense light spring in a QED vacuum. This new scattering configuration can be seen as the vacuum equivalent to the process originally associated with the scattering of light by a rotating black hole, which is usually called Penrose superradiance. Here, the rotating object is an intense laser beam containing two different components of orbital angular momentum. Due to these two components having slightly different frequencies, the energy profile of the intense laser beam rotates with an angular velocity that depends on the frequency difference. The nonlinear properties of a quantum vacuum are described by a first-order Euler–Heisenberg Lagrangian. It is shown that in such a configuration, nonlinear photon–photon coupling leads to scattered radiation with frequency shift and angular dispersion. These two distinct properties, of frequency and propagation direction, could eventually be favorable for possible experimental observations. In principle, this new scattering configuration can also be reproduced in a nonlinear optical medium. Full article

The precipitation-hardenable nickel-based superalloy Rene 41 exhibits remarkable mechanical characteristics and high corrosion resistance at high temperatures, properties that allow it to be used in high-end applications. This research paper presents findings on the influence of thermal shocks on its microstructure, hardness, and thermal diffusivity at temperatures between 700 and 1000 °C. Solar energy was used for cyclic thermal shock tests. The samples were characterized using microhardness measurements, optical microscopic analysis, scanning electron microscopy coupled with EDS elemental chemical analysis, X-ray diffraction, and flash thermal diffusivity measurements. Structural transformations and the variation of properties were observed with an increase in the number of shocks applied at the same temperature and with temperature variation for the same number of thermal shocks. Full article