Search Results (1,286)

Eliciting DNA damage in tumor cells continues to be one of the most successful strategies against cancer. This is the case for classical chemotherapy drugs and radiotherapy. In the modern era of personalized medicine, this strategy tries to identify specific vulnerabilities found in each patient’s tumor, to inflict DNA damage in certain cell contexts that end up in massive cancer cell death. Cells rely on multiple DNA repair pathways to fix DNA damage, but cancer cells frequently exhibit defects in these pathways, many times being tolerant to the damage. Key vulnerabilities, such as BRCA1/BRCA2 mutations, have been exploited with PARP inhibitors, leveraging synthetic lethality to selectively kill tumor cells and improving patients’ survival. In the DNA damage response (DDR) network, kinases ATM, ATR, Chk1, and Chk2 coordinate DNA repair, cell cycle arrest, and apoptosis. Inhibiting these proteins enhances tumor sensitivity to DNA-damaging therapies, especially in DDR-deficient cancers. Several small-molecule inhibitors targeting ATM/Chk2 or ATR/Chk1 are currently being tested in preclinical and/or clinical settings, showing promise in cancer models and patients. Additionally, pharmacological blockade of ATM/Chk2 and ATR/Chk1 axes enhances the effects of immunotherapy by increasing tumor immunogenicity, promoting T-cell infiltration and activating immune responses. Combining ATM/Chk2- or ATR/Chk1-targeting drugs with conventional chemotherapy, radiotherapy or immune checkpoint inhibitors offers a compelling strategy to improve treatment efficacy, overcome resistance, and enhance patients’ survival in modern oncology. Full article

Electromagnetic hyper-sensitivity (EHS) and its causal link with radio-frequencies raise a major question of public health. In the frame of the clinical study DEMETER, 26 adult volunteers self-diagnosed as EHS-positive agreed to reply to a self-assessment questionnaire and to provide a skin biopsy sampling to establish a primary fibroblast cell line. The questionnaire and the biological data revealed, independently, 2 subsets of donors associated each with a low background, highly responsive (LBHR) and a high background, lowly responsive (HBLR) phenotype. A couple of subsets based on questionnaire data and based on the yield of spontaneous DNA double-strand breaks were found to be composed of the same donors at 64% identity. After exposure to X-rays, and application of anti-γH2AX, pATM, and MRE11 immunofluorescence, all the DEMETER fibroblasts (26/26) elicited a delayed radiation-induced ATM nucleoshuttling (RIANS). The use of RIANS biomarkers showed that the 2 phenotypes described above corresponded to DEMETER donors with a high risk of cancer (LBHR) or high risk of accelerated aging (HBLR). By exposing DEMETER cells to H₂O₂ followed by an antioxidative agent, we confirmed that EHS may be related to the management of DNA strand breaks. A preliminary molecular model of EHS inspired by the RIANS model was proposed. Full article

In an integrated gasification combined cycle (IGCC), a gasification process produces a gas stream from a solid fuel, such as coal or biomass. This gas (syngas or synthesis gas) resulting from the gasification process contains carbon monoxide, molecular hydrogen, and carbon dioxide (other gaseous components may also be present depending on the gasified solid fuel and the gasifying agent). Separating hydrogen from this syngas stream has advantages. One of the methods to separate hydrogen from syngas is selective permeation through a palladium-based metal membrane. This separation process is complicated as it depends nonlinearly on various variables. Thus, it is desirable to develop a simplified reduced-order model (ROM) that can rapidly estimate the separation performance under various operational conditions, as a preliminary stage of computer-aided engineering (CAE) in chemical processes and sustainable industrial operations. To fill this gap, we present here a proposed reduced-order model (ROM) procedure for a one-dimensional steady plug-flow reactor (PFR) and use it to investigate the performance of a membrane reactor (MR), for hydrogen separation from syngas that may be produced in an integrated gasification combined cycle (IGCC). In the proposed model, syngas (a feed stream) enters the membrane reactor from one side into a retentate zone, while nitrogen (a sweep stream) enters the membrane reactor from the opposite side into a neighbor permeate zone. The two zones are separated by permeable palladium membrane surfaces that are selectively permeable to hydrogen. After analyzing the hydrogen permeation profile in a base case (300 °C uniform temperature, 40 atm absolute retentate pressure, and 20 atm absolute permeate pressure), the temperature of the module, the retentate-side pressure, and the permeate-side pressure are varied individually and their influence on the permeation performance is investigated. In all the simulation cases, fixed targets of 95% hydrogen recovery and 40% mole-fraction of hydrogen at the permeate exit are demanded. The module length is allowed to change in order to satisfy these targets. Other dependent permeation-performance variables that are investigated include the logarithmic mean pressure-square-root difference, the hydrogen apparent permeance, and the efficiency factor of the hydrogen permeation. The contributions of our study are linked to the fields of membrane applications, hydrogen production, gasification, analytical modeling, and numerical analysis. In addition to the proposed reduced-order model for hydrogen separation, we present various linear and nonlinear regression models derived from the obtained results. This work gives general insights into hydrogen permeation via palladium membranes in a hydrogen membrane reactor (MR). For example, the temperature is the most effective factor to improve the permeation performance. Increasing the absolute retentate pressure from the base value of 40 atm to 120 atm results in a proportional gain in the permeated hydrogen mass flux, with about 0.05 kg/m².h gained per 1 atm increase in the retentate pressure, while decreasing the absolute permeate pressure from the base value of 20 bar to 0.2 bar causes the hydrogen mass flux to increase exponentially from 1.15 kg/m².h. to 5.11 kg/m².h. This study is linked with the United Nations Sustainable Development Goal (SDG) numbers 7, 9, 11, and 13. Full article

This study investigates the heterogeneous impact of bank automation on institutional performance, emphasizing the role of mechatronic systems like automated teller machines (ATMs) and artificial intelligence-based tools such as chatbots and robo-advisors. Using Method of Moments Quantile Regression (MMQR), the analysis examines how these technologies influence key performance indicators, including return on equity (ROE), in the European Union (EU) banking sector from 2017 to 2022. The MMQR method allows for the differentiation of the effects of automation technologies by distinguishing between hardware-based mechatronic systems and software-driven AI solutions, providing a nuanced perspective on the digital transformation within the banking sector. The results highlight the heterogeneous effects of economic, financial, and institutional factors on banking performance in the EU. They emphasize the need for differentiated policy interventions to reduce performance gaps between EU economies and ensure that banks across all member states can leverage financial and technological advancements to enhance profitability. The findings underline the importance of strategic interventions to address digitalization disparities, promote financial inclusion, and establish a regulatory framework that fosters transparency, cybersecurity, and equitable access to AI-driven financial services. Full article

C1QBP (Complement Component 1 Q Subcomponent-Binding Protein) plays a critical role in maintaining cellular metabolism, but its function in radiation-induced damage remains unclear. In this study, we generated C1QBP-deficient Huh-7 hepatocellular carcinoma (HCC) cells using CRISPR/Cas9 technology and observed that C1QBP deficiency significantly enhanced radiation-induced damage, as indicated by reduced cell proliferation, impaired colony formation, and increased γ-H2AX foci, a marker of DNA double-strand breaks. Additionally, C1QBP deficiency resulted in elevated phosphorylation of key DNA damage response (DDR) molecules, ATM and CHK2, and caused pronounced S phase cell cycle arrest. Mechanistic investigations revealed that C1QBP modulates NF-κB nuclear activity via the AMPK signaling pathway. The loss of C1QBP reduced NF-κB nuclear translocation, further exacerbating radiation-induced damage. Reintroducing C1QBP alleviated DNA damage, enhanced cell proliferation, and improved survival following radiation exposure. These findings highlight the critical role of C1QBP in modulating HCC cells radiosensitivity and underscore its potential as a therapeutic target to enhance radiotherapy outcomes. Full article

Leaching represents a significant challenge for the mining industry due to its slow and incomplete kinetics under ambient conditions (20 °C, 1 atm) and its increased prevalence in global ore deposits. In this context, the use of hydrogen peroxide (H₂O₂) has proved to be a promising oxidizing agent for improving process efficiency. This article reviews the most recent breakthroughs in the use of H₂O₂ for chalcopyrite leaching, analyzing the experimental conditions that maximize copper extraction, including combinations with novel leachants such as organic systems, inorganic salts, and amino acids. In addition, the main challenges associated with the use of H₂O₂, such as its catalytic decomposition and thermal stability, are highlighted, along with strategies to overcome these limitations. Perspectives and challenges for its application are presented, emphasizing the need for hybrid and optimized approaches to integrate this oxidizing agent in sustainable hydrometallurgical processes. The objective of this paper is to make an exhaustive review of what has been published on chalcopyrite leaching in order to find ways to leach it in large quantities and in a simple way. Full article

Multi-stage axial compressors play a crucial role in aerospace propulsion systems, as their exit flow field characteristics directly impact engine performance and stability. This study conducted numerical simulations on the first 3.5 stages of the NASA 74A transonic multi-stage axial compressor to analyze the exit flow field characteristics under different typical operating conditions. The research primarily investigated airflow deflection angle, radial velocity distribution, and their variation patterns. Additionally, the effects of inlet airflow angle and pressure variations on the exit flow field under non-uniform inlet conditions were examined in detail. The results indicate that at 68% rotational speed, the exit flow field of the NASA 74A compressor deteriorates significantly, with noticeable changes in distribution patterns. For the other four operating conditions, as the rotational speed decreases, both velocity and airflow angle exhibit a positive correlation with rotational speed. Compared to the design condition, peak velocity decreases by 2%, 3.7%, and 7%, while airflow deflection angle changes remain within 3°. Under non-uniform inlet conditions, when the inlet airflow angle decreases from 90° to 70°, variations in peak and average exit velocities remain within 2%, and the changes in peak and average airflow deflection angles are within 1%. However, when the inlet airflow angle decreases from 90° to 70°, the curve of the airflow deflection angle exhibits a leftward shift, with a deviation of 2.6%. Meanwhile, changes in inlet pressure under non-uniform conditions have a relatively minor impact on the overall flow field but significantly affect local distributions. When the inlet pressure increases from 1 atm to 1.05 atm, peak velocity increases by 0.98%, and average velocity rises by 3%. The maximum velocity difference reaches 6%, while the average airflow deflection angle differs by 0.7%, with a maximum deviation of 1.9°. Overall, the compressor exit flow field undergoes significant variations under different operating conditions, with increased flow instability at lower rotational speeds leading to flow separation, low-energy fluid accumulation, and non-uniform pressure distribution. In contrast, non-uniform inlet conditions have a relatively minor effect on the overall flow field but induce noticeable local changes, providing theoretical insights for compressor design optimization and performance evaluation. Full article

This study presents the development of a kinetic model for the gasification of biochar with carbon dioxide and compares the results obtained using a thermogravimetric analyzer (TGA) and a fluidized bed reactor (FBR). The kinetic experiments investigated the effects of the CO₂ partial pressure (0.33–1 atm), temperature (800–1000 °C), and CO₂/C ratio (3.5–10.5). Three structural models, the shrinking core model (SCM), volumetric model (VM), and power-law model (PLM), were evaluated for their ability to predict experimental results. The results demonstrated that increasing the temperature, CO₂ partial pressure, and CO₂/C ratio enhanced the gasification rate, reducing the time required for complete biochar conversion. The apparent activation energy for both reactors was similar (156–159 MJ/kmol), with reaction orders of 0.4–0.49. However, the kinetic models varied significantly between setups. In the TGA, the PLM provided the best fit to experimental data, with standard deviations of 2.6–9%, while in the FBR, the SCM was most accurate, yielding an average deviation of 1.5%. The SCM effectively described the layer-by-layer char consumption, where gasification slowed at high conversion levels. Conversely, the PLM for the TGA revealed a unique mathematical function not aligned with traditional models, indicating localized reaction behaviors. This study highlights the inability to directly extrapolate TGA-derived kinetic models to FBR systems, underscoring the distinct mechanisms governing char consumption in each reactor type. These findings provide critical insights for optimizing biochar gasification across diverse reactor configurations. Full article

Hydrogen and some of its derivatives (such as e-methanol, e-methane, and e-ammonia) are promising energy carriers that have the potential to replace conventional fuels, thereby eliminating their harmful environmental impacts. An innovative use of hydrogen as a zero-emission fuel is forming weakly ionized plasma by seeding the combustion products of hydrogen with a small amount of an alkali metal vapor (cesium or potassium). This formed plasma can be used as a working fluid in supersonic open-cycle magnetohydrodynamic (OCMHD) power generators. In these OCMHD generators, direct-current (DC) electricity is generated straightforwardly without rotary turbogenerators. In the current study, we quantitatively and qualitatively explore the levels of electric conductivity and the resultant volumetric electric output power density in a typical OCMHD supersonic channel, where thermal equilibrium plasma is accelerated at a Mach number of two (Mach 2) while being subject to a strong applied magnetic field (applied magnetic-field flux density) of five teslas (5 T), and a temperature of 2300 K (2026.85 °C). We varied the total pressure of the pre-ionization seeded gas mixture between 1/16 atm and 16 atm. We also varied the seed level between 0.0625% and 16% (pre-ionization mole fraction). We also varied the seed type between cesium and potassium. We also varied the oxidizer type between air (oxygen–nitrogen mixture, 21–79% by mole) and pure oxygen. Our results suggest that the ideal power density can reach exceptional levels beyond 1000 MW/m³ (or 1 kW/cm³) provided that the total absolute pressure can be reduced to about 0.1 atm only and cesium is used for seeding rather than potassium. Under atmospheric air–hydrogen combustion (1 atm total absolute pressure) and 1% mole fraction of seed alkali metal vapor, the theoretical volumetric power density is 410.828 MW/m³ in the case of cesium and 104.486 MW/m³ in the case of potassium. The power density can be enhanced using any of the following techniques: (1) reducing the total pressure, (2) using cesium instead of potassium for seeding, and (3) using air instead of oxygen as an oxidizer (if the temperature is unchanged). A seed level between 1% and 4% (pre-ionization mole fraction) is recommended. Much lower or much higher seed levels may harm the OCMHD performance. The seed level that maximizes the electric power is not necessarily the same seed level that maximizes the electric conductivity, and this is due to additional thermochemical changes caused by the additive seed. For example, in the case of potassium seeding and air combustion, the electric conductivity is maximized with about 6% seed mole fraction, while the output power is maximized at a lower potassium level of about 5%. We also present a comprehensive set of computed thermochemical properties of the seeded combustion gases, such as the molecular weight and the speed of sound. Full article

This study quantified the effects of seven proposed traffic management strategies (MS) to leverage the synergy between Active Traffic Management (ATM) and connected and automated vehicles (CAV) to mitigate congestion, reduce queue lengths, and improve travel time after incident occurrence. First, three proposed MS are discussed: (a) controlling speed limit but not restricting lane changes, (b) directing CAV to change lanes earlier, and (c) restricting CAV in open lanes from lane changes near incidents. Then, combinations of these strategies are presented. At 10% CAV MP, MS1 that focuses on longitudinal control reduced travel time by 11.6% compared to 1.9% with no MS. Similarly, MS2, which directs CAV to change lanes earlier, were most effective when applied at 1-mile upstream of the incident site, achieving a notable 6.0% travel time reduction compared to 1.9% with no MS. The beneficial impact of MS3, which restricts CAV in open lanes from making lane changes near incident sites, became more pronounced with increasing CAV MP. Among the combined strategies (MS4 to MS7), some strategies proved more effective than others. Findings from Vissim simulation runs showed the importance of combining CAV and MS. Full article

Aviation operations are increasingly impacted by clear-air turbulence (CAT) encounters, a growing concern in both media and academic circles. Research into CAT focuses on the generation, prediction, detection, and monitoring of the occurring events (thanks to weather-related methodologies and instruments) along with technologies and operational aspects to mitigate their effects, from the perspective of both the flight segment (aircraft and pilot and related onboard systems) and the ground segment (ATM and ATC and related tools). Climate changes have led to more frequent and severe CAT events, highlighting the need for sustainable aviation solutions, aiming to achieve improved theoretical knowledge and technological and operational management advancements. This paper addresses the CAT topic under two main perspectives: the scientific understanding of the phenomena, and the technological management of such occurrence in aviation operations. With reference to the first addressed domain, the paper provides a comprehensive review of the currently used and perspective proposed methodologies and tools for understanding, detecting, and predicting CAT phenomena. With reference to the second addressed domain, then, this paper aimed to analyze the state of the art and trends in the technological and operational management and mitigation of the CAT occurrences at a tactical level (i.e., while in flight) by the aviation, covering the technologies and procedures implemented onboard and in the ground segment. Overall, therefore, this paper assesses the state of the art and identifies the most promising innovations that promote safer, more sustainable future aviation operations, by bridging weather and climate science with aviation engineering, in the presence of CAT events. Full article

The link between financial inclusion and financial stability is a central concern in public economic policymaking, particularly in emerging countries where access to financial services remains limited. While financial inclusion is widely regarded as a key driver of economic development, its impact on financial stability remains debated. Some studies highlight the stabilizing effect of financial inclusion, whereas others, like emphasize its potential risks. This study empirically investigates the relationship between financial inclusion and financial stability across the years 2011, 2014, 2017, and 2021 in 26 African and MENA countries. The hierarchical multiple regression (HMR) method is employed to assess the independent effect of financial inclusion, controlling for macroeconomic variables. The findings reveal that financial inclusion positively contributes to financial stability through channels such as digital payments and the number of bank branches. Conversely, savings, the number of ATMs, and the money supply exhibit a negative effect on financial stability. These results underscore the need for a regulatory framework that balances financial inclusion with financial stability. In particular, cybersecurity measures must be implemented to support the expansion of digital payments, and supervisory mechanisms should be reinforced to mitigate liquidity risks. Full article

Metastatic prostate cancer (mPCa) remains a significant cause of cancer-related mortality in men. Advances in molecular profiling have demonstrated that the androgen receptor (AR) axis, DNA damage repair pathways, and the PI3K/AKT/mTOR pathway are critical drivers of disease progression and therapeutic resistance. Despite the established benefits of hormone therapy, chemotherapy, and bone-targeting agents, mPCa commonly becomes treatment-resistant. Recent breakthroughs have highlighted the importance of identifying actionable genetic alterations, such as BRCA2 or ATM defects, that render tumors sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Parallel efforts have refined imaging—particularly prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography—to detect and localize metastatic lesions with high sensitivity, thereby guiding patient selection for PSMA-targeted radioligand therapies. Multi-omics innovations, including liquid biopsy technologies, enable the real-time tracking of emergent AR splice variants or reversion mutations, supporting adaptive therapy paradigms. Nonetheless, the complexity of mPCa necessitates combination strategies, such as pairing AR inhibition with PI3K/AKT blockade or PARP inhibitors, to inhibit tumor plasticity. Immuno-oncological approaches remain challenging for unselected patients; however, subsets with mismatch repair deficiency or neuroendocrine phenotypes may benefit from immune checkpoint blockade or targeted epigenetic interventions. We present these pivotal advances, and discuss how biomarker-guided integrative treatments can improve mPCa management. Full article

Purpose: To determine if the risk of clonal hematopoiesis (CH) would be higher among those with germline alterations in homologous recombination repair genes (gHRR) in the four BRCA-associated cancers (breast, ovarian, prostate, pancreas) compared to those without inherited predisposition (the sporadic group). Methods: We retrospectively analyzed deidentified data from 24,849 patient samples from the Tempus database with a primary diagnosis of breast, ovarian, prostate, and pancreatic cancers. Germline pathogenic or likely pathogenic variants in BRCA1, BRCA2, ATM, PALB2, and CHEK2 were identified across all four cancer types. CH was determined based on the presence of pathogenic or likely pathogenic alterations in any one of 52 CH-associated genes with a variant allele fraction of at least 2% found in the normal match. Age-adjusted odds ratios were calculated for risk of CH across cancer types. Results: CH was identified in 14% of patients with BRCA-associated cancers. DNMT3A, PPM1D, and TET2 were the most common CH gene alterations. After adjusting for age at time of biopsy, having any germline alteration in the breast cancer cohort was associated with a 41% increased likelihood of CH (OR 1.41; 95% CI 1.07–1.84, p = 0.014). An increase in CH prevalence was not seen in the three other cancer types. Conclusions: When accounting for age at time of testing, pathogenic germline alterations in DNA repair genes were associated with an increased risk of CH only among patients with breast cancer, but not in those with ovarian, pancreatic, or prostate cancers. Full article

Background/Objectives: Compared to single gene testing (SGT), multigene panel testing (MGPT) improves pathogenic variants (PVs) detection. However, MGPT yields complex results, including secondary findings, heterozygous PVs in recessive genes, low-penetrance PVs, and variants of uncertain significance. We reported our mono-institutional experience of germline testing in breast cancer (BC), comparing SGT and MGPT. Methods: We retrospectively analyzed clinical and molecular data from 1084 BC patients: 308 underwent SGT (BRCA1/BRCA2) and 776 MGPT (for 28 cancer-related genes). We compared these approaches regarding the genetic classification of the findings (positive, uncertain, uninformative) and their impact on clinical management (primary findings (PFs); complex and inconclusive results). Additionally, we described clinical features supporting one approach over the other and focused on copy number variation (CNV) frequency in non-BRCA genes. Results: We found ≥1 PV in 165 patients (165/1084 = 15.2%), including 91 in BRCA1/BRCA2 (91/1084 = 8.4%), with 42 identified by SGT (42/308 = 13.6%) and 49 by MGPT (49/776 = 6.3%). MGPT detected PVs in non-BRCA genes in 74 patients (74/776 = 9.5%), including 40 PFs. Overall, MGPT identified 89 PFs (89/776 = 11.5%). We observed complex results in 21 patients (21/308 = 6.8%) with SGT and in 300 (300/776 = 38.7%) with MGPT. Compared to MGPT, SGT detected a similar percentage of PFs (13.6% vs. 11.5%) but a significantly reduced percentage of complex results (6.8% vs. 38.7%) (p < 0.001). Triple-negative BCs prevailed in BRCA1 carriers, while ER-positive BCs were more prevalent in ATM/CHEK2 carriers. Concerning non-BRCA genes, MGPT detected CNVs in PALB2, representing 20% of PVs in this gene. Conclusions: Although MGPT increases hereditary BC detection, its complexity requires clear guidelines for optimal clinical management and strategies for merging the benefits of SGT and MGPT. Full article