It has been more than three decades since the discovery of multifunctional factors, Non-POU Domain-Containing Octamer-Binding Protein, NonO and Splicing Factor, Proline-and Glutamine-Rich, SFPQ. Some of their functions, including their participations in transcriptional and posttranscriptional regulation as well as their contribution to paraspeckle subnuclear body organization have been well-documented. In this review, we focus on the roles of NonO and SFPQ in cell cycle with particular attention to their participation in nonhomologous end joining (NHEJ) and homologous recombination (HR) of DNA damage responses induced by irradiation. In these contexts, absence or malfunction of either or both lead to genome instability and ultimately to apoptosis, cellular senescence, and tumor development. This review also will shed light on NonO and SFPQ function in DNA/RNA/protein binding and their association with Ku heterodimer of the NHEJ pathway required for repair of DNA double-strand breaks (DSBs).

The investigation on the issue of damage diagnosis based on strain modal parameters is conducted in this paper using simply supported wooden Beams as the study's object. First, ABAQUS is utilized to create finite element models of intact wooden beams as well as wooden beams with varying degrees of damage and perform modal analyses on them. Next, damage identification studies are conducted on the wooden beam structure using various strain modal parameters (strain mode strain modal difference, strain modal curvature difference), the timber beam damage identification test then yields the modal parameters of timber beams under various damage situations, and the test findings are contrasted with those of the numerical simulation. The outcomes demonstrate that the damage identification of the test data using the three types of damage identification indexes is consistent with the results of the numerical simulation; the three types of damage identification indexes can locate the damage to timber beams, but the identification effect of the indexes is different, the best-recognized metric is the strain mode curvature difference; the next best is the strain mode difference, and the worst is the strain modes. The study's findings can serve as a guide for future damage detection on wood beams.

With more and more transportation tunnels have been and will be constructed in loess areas in Northwest China with high earthquake potential, the overall stability of portal section under earthquakes actions and the related aseismic countermeasures attracted the attentions from both the scholars and engineers, especially the tunnels in the upper slope connecting the high bridges crossing rivers or valleys. In order to study the dynamic response characteristics and damage evolution of steep loess slope with a tunnel under the earthquake actions, a large-scale shaking table tests were performed on steep loess slope with a tunnel. Wenchuan-tangyu (WT) wave and El Centro (El) wave records were applied on the model to investigate the displacement response and acceleration response of loess slope with a tunnel under the horizontal (X) and the combined action of horizontal and vertical (X-Z) seismic loads, respectively. In particular, three-dimensional non-contact optical measurement techniques were used to obtain the slope surface displacements. The results showed that the main deformation pattern of the slope was horizontal movement and settlement when the seismic wave input was in the X and X-Z directions, respectively. However, the X direction seismic wave had a greater impact on the deformation of the slope, and the tunnel portal slope was destroyed under the action of a large horizontal seismic acceleration finally. Slope failure ahead of a tunnel could be divided into four stages, i.e. elastic deformation stage, plastic deformation accumulation stage, local failure stage, and overall failure stage. The peak ground displacement of X direction (PGDX) and peak ground displacement of Z direction (PGDZ) of the slope surface increased with the increasing of the input peak ground acceleration (PGA) when the input wave was same waveform and same direction. The existence of the tunnel had a great influence on the PGA and the PGA amplification factor (PGAAF) of the soil mass surrounding it. This was because the seismic waves encounter a tunnel surface with clear differences in the physical properties of the medium during their propagation in the slope, thereby forming a strong reflection and refraction effect, and the amplitude changed significantly. Numerical simulation results were basically consistent with the experimental results.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is considered one of the leading causes of mortality. Multiple immunological pathways are involved in the pathogenesis of SLE, which makes it imperative to deepen our knowledge about this disease's immunopathological complexity and explore new therapeutic targets. Since an altered redox state contributes to immune system dysregulation, this document briefly addresses the role of oxidative stress (OS), oxidative DNA damage, antioxidant enzymes, mitochondrial function, and mitophagy in SLE and LN. Although adaptive immunity's participation in the development of autoimmunity is undeniable, increasing data emphasize the importance of innate immunity elements, particularly the Toll-like receptors (TLRs) that recognize nucleic acid ligands, in inflammatory and autoimmune diseases. Here, we discuss the intriguing role of TLR7 and TLR9 in developing SLE and LN. Also included are the essential characteristics of conventional treatments and some other novel and little-explored alternatives that offer options to improve renal function in LN.

Enhanced oil recovery using nanoparticles is a promising method. However, when injected into a reservoir, nanoparticles can block pores and cause permeability damage. Therefore, enhancing their performance to lower the permeability damage effect is crucial. This study investigated the effect of pH alteration through carbon dioxide (CO2) injection on the permeability damage of limestone caused by the aluminum oxide (α-Al2O3) nanofluid. The methodology involved nanofluid alternating CO2 core flooding experiments by using nanofluids with pH of 4.5 and 2.8. After core flooding, permeability damage was calculated as a percentage of the reduction of the original permeability. The results revealed that the permeability damage in the case of nanofluid alternating CO2 injection was 23.23%. In only nanofluid with a pH of 4.5 injection case, permeability damage was 47.53%. In the 2.8 pH nanofluid injection case, permeability damage was 31.01%. The retention of nanoparticles was confirmed through scanning electron microscopy and energy dispersive X-ray analysis. Permeability damage could be attributed to a large nanoparticles’ agglomeration size, roughness of pore surfaces, and nanoparticle sedimentation. The results of the study revealed that altering pH through the α-Al2O3 nanofluid alternating CO2 injection can effectively reduce the permeability damage of limestone.

In this paper, we present the investigation results of radiation-induced effects in metal-oxide-semiconductor (MOS) doped with moderate amounts of Zinc Oxide (ZnO) as a potential candidate for space-borne application. The samples were fabricated via the sputtering method at a working pressure of 3mTorr and a deposition temperature of 300oC. The ZnO samples were exposed to 1.25-MeV gamma-ray utilizing Co60 source, and their electronic response was measured at ionizing doses ranging from 10 kGy to 300 kGy. A comparative work was performed through finite element method to simulate the electronic response of the PN junction diode due to ionizing radiation. The results indicate that the ideality factor of the MOS diode increases as the ionizing dose increases, rendering it unsuitable for use as a diode. The degradation of the electrical parameters was also simulated, showing the increase in hole concentration. These findings suggest that the ejection of electrons occurred, which agrees with the gamma radiation effects trend. Furthermore, as the intensity of radiation increases, the spatial charge that arises from the separation of hole-electron pairs results in a substantial reduction of the electric field in the central portion of the n-type region. These findings provide insights into the degradation of electrical parameters in MOS devices under gamma radiation and have implications for their use in space-borne applications.

Urban trees are often more sun- and wind-exposed than their forest-grown counterparts. These environmental differences can impact how many species grow – impacting trunk taper, crown spread, branch architecture, and other aspects of tree form. Given these differences, windthrow models derived from traditional forest production data sources may not be appropriate for urban forest management. Additionally, visual abnormalities historically labeled as “defects” in timber production may not have a significant impact on tree failure potential. In this study, we look at urban tree failures associated with Hurricane Irma in Tampa, Florida, USA. We used spatial analysis to determine if patterns of failure existed among our inventoried trees. We also looked at risk assessment data to determine which visual defects were the most common and the most likely to be associated with branch or whole-tree failure. Results indicate that there was no spatial pattern associated with the observed tree failures – trees failed or withstood the storm as individuals. While some defects like decay and dead wood were associated with increased tree failure, other defects like weak branch unions and poor branch architecture were less problematic.

Damage detection based on modal parameter changes becomes popular in the last decades. Nowadays are available robust and reliable mathematical relations to predict the natural frequency changes if damage parameters are known. Using these relations, it is possible to create databases containing a large variety of damage scenarios. Damage can be thus assessed by applying an inverse method. The problem is the complexity of the database, especially for structures with more cracks. In this paper, we propose two machine learning methods, namely the random forest (RF) and the artificial neural network (ANN) as search tools. The databases we developed contain damage scenarios for a prismatic cantilever beam with one crack and ideal and non-ideal boundary conditions. The crack assessment is made in two steps. First, a coarse damage location is found from the networks trained for scenarios comprising the whole beam. Afterward, the assessment is made involving a particular network trained for the segment of the beam on which the crack is previously found. Using the two machine learning methods, we succeed to estimate the crack location and severity with high accuracy for both simulation and laboratory experiments. Regarding the location of the crack, which is the main goal of the practitioners, the errors are less than 0.6%. Based on these achievements, we concluded that the damage assessment we propose, in conjunction with the machine learning methods, is robust and reliable.

The paper presents the identification and classification of steel cord failures in the conveyor belt core based on an analysis of a two-dimensional image of magnetic field changes recorded using the Diagbelt system around scanned failures in the test belt. The obtained set of identified changes in images obtained for numerous devices parameters settings were the base for statistical analysis. It makes it possible to determine the Pearson’s linear correlation coefficient between the parameters being changed and the image of the failures. In the second stage of the research, artificial intelligence methods were applied to construct a multilayer neural network (MLP) and to teach its appropriate identification of damage. In both methods were used the same data sets, which made it possible to compare methods.

Fatigue in any material is a result of continuous irreversible degradation process. Traditionally, fatigue life is predicted by extrapolating experimentally curve fitted empirical models. In the current study, unified mechanics theory is used to predict fatigue life of Ti-6Al-4V under monotonic tensile, compressive and cyclic load conditions. The unified mechanics theory is used to derive constitutive model for fatigue life prediction using a three-dimensional computational model. The proposed analytical and computational models have been used to predict the low cycle fatigue life of Ti-6Al-4V alloys. It is shown that the unified mechanics theory can be used to predict fatigue life of Ti-6Al-4V alloys by using simple predictive models that are based on fundamental equation of the material, which is based on thermodynamics associated with degradation of materials.

This study aimed to assess the ecotoxicological effects of the interaction of fullerene (C₆₀) and benzo[a]pyrene (B[a]P) on the marine mussel, Mytilus galloprovincialis. The uptake of nC₆₀, B[a]P and mixtures of nC₆₀ and B[a]P into tissues was confirmed by GC-MS, LC-HRMS and ICP-MS. Biomarkers of DNA damage as well as proteomics analysis were applied to unravel the toxic effect of B[a]P and C₆₀. Antagonistic responses were observed at the genotoxic and proteomic level. Differentially expressed proteins (DEPs) were only identified in the B[a]P single exposure and the B[a]P mixture exposure groups containing 1 mg/L of C₆₀, the majority of which were down-regulated (~52%). No DEPs were identified at any of the concentrations of nC₆₀ (p < 0.05, 1% FDR). Using DEPs identified at a threshold of (p < 0.05; B[a]P and B[a]P mixture with nC₆₀), gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis indicated that these proteins were enriched with a broad spectrum of biological processes and pathways, including those broadly associated with protein processing, cellular processes and environmental information processing. Among those significantly enriched pathways, the ribosome was consistently the top enriched term irrespective of treatment or concentration and plays an important role as the site of biological protein synthesis and translation. Our results demonstrate the complex multi-modal response to environmental stressors in M. galloprovincialis.

Background: Increased DNA damage and the propension to cancer development, depend on the modulation of the mechanisms to control and maintain genomic integrity. Poly(ADP-Ribose)Polymerase activation and automodification are early responses to genotoxic stress. Upon binding to DNA strand breaks, the enzyme, a molecular DNA nick sensor, is hyperactivated: this is the first step in a series of events leading to either DNA repair or apoptosis. Enzyme hyperactivation and automodification can be easily measured and are widely used to look at DNA damage extent in the cell. We investigated whether these two markers (increased catalytic activity and auto modification), could help to monitor DNA damage in lymphocytes of flower growers from Southern Italy, occupationally exposed to pesticides. Methods: Peripheral lymphocyte lysates were analysed for Poly(ADP-Ribose) Polymerase activity, and by SDS-PAGE and anti-Poly(ADP-Ribose)Polymerase 1-antibody to measure automodified anti-Poly(ADP-Ribose) Polymerase levels by densitometry. Results: Poly(ADP-Ribose)Polymerase activity levels were consistent with those of enzyme auto-modification. Growers daily exposed to pesticides, showed both biomarkers very high, either in the presence or in the absence of pathologies. Conclusions: PARP activity and auto-modification in peripheral blood lymphocytes are possible,non-invasive, and routinar tools to monitor the healthy conditions of floricoltorists.

Insects, nematodes, and aquatic animals face several biotic and abiotic stressors that can significantly affect their fitness – specifically damaging their cellular proteins' competent functional nature. In response, they have evolved sophisticated stress-responsive mechanisms. Certain endogenous proteins, known as small heat shock proteins (sHSPs), serve to maintain the stability and function of proteins under stress. Since the identification of the first sHSPs, an increasing number of sHSPs, mainly due to the new robust sequencing tools, continue to be identified and reported to play a critical role in the organism’s response to stress. This review explores and summarizes the contributions of the sHSPs implicated in stress response. Understanding their function is crucial for advancing our knowledge in agricultural pest management, climate change adaptation, and biotechnology.

As a long lifeline system of buried structures, Utility tunnel (UT) is vulnerable to earthquake invading. For utility tunnels with inverted siphon arrangement crossing the river, the seismic response is more complex due to the basin effect of acceleration in the topography and the influence of fluctuating hydrodynamic pressure. Based on a UT project in Haikou, this paper studied seismic response of cast-in-place UT considering the coupled model of water-soil-tunnel structure on ABAQUS software. Herein, the dynamic fluctuation of hydrodynamic pressure is simulated using acoustic-solid interaction model. A viscoelastic artificial boundary was used to simulate the soil boundary effect, and seismic loads were equivalent to nodal forces. Considering seismic invading direction and varying water elevation, the paper investigates the dynamic response characteristics and damage mechanisms of river-crossing utility tunnels. The study shows that basin effects cause the different acceleration amplifying of the soil around the UT in different sections, and the greater damage to the tunnels in bidirectional seismic excitation, which the damage concentrated at the junction of the transition between the horizontal section and the vertical section; Bending moments and axial forces are the dominant mechanical behaviors along the axial direction; and the river water level change influences the internal distribution of the tunnels, showing a certain amount of energy dissipation and seismic damping effects. For the aseismic design of cross-river cast-in-place utility tunnels, bidirectional seismic calculations should be performed, and the influence of river hydrodynamic pressure should not be neglected.

To achieve rapid post-earthquake repair of self-centering ribbed floor flat beam frame structures, a ductile hybrid joint consisting of dog bone weakened energy dissipating steel bars connected to the upper and lower column sections through high-strength threads based on the damage control design concept is proposed. By moving the ductile energy dissipating zone out to the locally weakened section of the energy dissipating steel bars and the locally unbonded prestressed steel bars in the core area, the residual deformation was limited and the seismic performance was improved. Based on the working principle of hybrid joints, low cycle loading tests were conducted on two joint specimens to analyze the influence of lateral prestress on the seismic performance of the hybrid joints. Numerical modeling methods were used to compare the position of the energy-consuming steel bars in the composite layer and the friction performance of joints. The research results indicated that the hybrid joint had stable load-bearing, deformation, and energy dissipation capabilities, with damage primarily concentrated on the energy-consuming steel bars. Even at an inter-story displacement angle of 5.5%, the upper and lower column segments remained elastic. After unloading, the connection seam at the joint was closed, and the self-centering performance was good. When the inter-story displacement angle reached 5.5%, the lateral prestress increased from 150 kN to 250 kN, the ultimate bearing capacity of the joint increased by 16.3%, and the cumulative energy consumption increased by 30.0%. The influence of the friction coefficient of the joint surface on the structural performance was set at a threshold of 0.7. When it was less than the threshold, the ultimate bearing capacity and initial stiffness of the joint increased with an increase in the friction coefficient. After reaching the threshold, the increase in the ultimate bearing capacity of the joint slowed down, and the rate of stiffness degradation gradually accelerated. This joint had excellent seismic performance and can also achieve post-earthquake repair of structures.

Background: One of the most astounding discoveries of recent times is the recognition that cancer embodies a transition from a higher level of metazoan cell organization to a more foundational pre-metazoic state. This shift is steered by genes housed within the ancestral genome compartment, pervasive across all metazoan genomes, encompassing humans, and governed by a pre-metazoic gene regulatory mechanism (aGRN). This work aims to highlight the emerging field of evolutionary cancer cell biology (ECCB), which points to the deep homology between cancer and protist life cycles tracing back to the common ancestor of amoebozoans, metazoans, and fungi (AMF). The ECCB analysis reveals the essence of the non-gametogenic germline of the AMF ancestor, which serves as a blueprint for all metazoan germlines and stem cell lineages and controls the life cycle of cancer. Every germ and stem cell lineage of humans and metazoans traces its lineage back to this Urgermline, transmitting crucial processes such as asymmetric cell cycling, differentiation, stemness, and phenomena like GST and SGT (aka EMT and MET) to their subsequent evolutionary descendants. Oxygen-sensitive germline and stem cells suffer DNA-DSB due to stress and oxygen ranges reminiscent of ancestral hyperoxia, leading to cell senescence. Cells that can overcome senescence can proliferate as DSCD cells with defective symmetric cell division, paving the way for malignancy and PGCC cancers. Conclusions: Understanding cancer from its evolutionary origins may help break some of the logjams in cancer prevention and open up new therapeutic pathways.

Thermoplastic composites are continuously replacing thermosetting composites in lightweight structures. However, the accomplished work on the fatigue behavior of thermoplastics is quite limited. In the present work, we propose a numerical modeling approach for simulating fatigue delamination growth and predicting the residual tensile strength of quasi-isotropic TC 1225 LM PAEK thermoplastic coupons. The approach is supported and validated by tension and fatigue (non-interrupted and interrupted) tests. Fatigue delamination growth is simulated using a mixed-mode fatigue crack growth model, which is based on the cohesive zone modeling method. All interfaces between the thermoplastic plies were modelled using cohesive elements. Quasi-static tension analyses on pristine and fatigued coupons were performed using a progressive damage model implementing a set of Hashin-type strain-based failure criteria and a damage mechanics-based material property degradation module. Using the fatigue model, delamination growth was predicted as a function of number of cycles at all interfaces. The results agree well with C-scan images taken on fatigued coupons during interruptions of fatigue tests. An unequal and unsymmetric delamination growth was predicted due to the quasi-isotropic lay-up. Moreover, the combined models capture the decrease in the residual tensile strength of the coupons. In the quasi-static tension analysis of the fatigued coupons, the driving failure mechanisms are the fast propagation of the pre-existing delamination and the severe matrix cracking.

The appropriate maintenance of highway roads is critical for the safe operation of road networks and conserves maintenance costs. Multiple methods have been developed to investigate the surface of roads for various types of cracks and potholes, among other damage. Like road surface damage, the condition of expansion joints in concrete pavement is important to avoid unexpected hazardous situations. Thus, in this study, a new system is proposed for autonomous expansion joint monitoring using a vision-based system. The system consists of the following three key parts: (1) a camera-mounted vehicle, (2) indication marks on the expansion joints, and (3) a deep learning-based automatic evaluation algorithm. With paired marks indicating the expansion joints in a concrete pavement, they can be automatically detected. An inspection vehicle is equipped with an action camera that acquires images of the expansion joints in the road. You Only Look Once (YOLO) automatically detects the expansion joints with indication marks, which has a performance accuracy of 95%. The width of the detected expansion joint is calculated using an image processing algorithm. Based on the calculated width, the expansion joint is classified into the following two types: normal and dangerous. The obtained results demonstrate that the proposed system is very efficient in terms of speed and accuracy.

Coastal flooding exacerbated by climate change is recognised as a major global threat which is expected to impact more than a quarter of people currently residing in Pacific Islands countries. While most research in the last decade has focused on understanding the dynamics and impacts of future coastal flooding from extreme sea levels, relative sea level rise (RSLR) effects on tsunami hazards are not well understood. Far-field or distant-sourced tsunamis tend to have relatively lower impacts in Pacific Island states compared with locally sourced events, but there is limited understanding on how the impact of far-field tsunamis changes over time due to RSLR. Using the hydrodynamics software BG-Flood, we modelled the Tōhoku tsunami from propagation to inundation in Samoa under incremental SLR to examine the effects that RSLR has on changing the exposure of the built environment (e.g., buildings) to a far-field tsunami. Outputs of maximum tsunami inundation and flow depth intensities which incorporate incremental SLR were then combined with digital representations of buildings and depth-damage functions in the RiskScape multi-hazard risk modelling software to assess the changes in building exposure over time. Results indicate that present day buildings exposure in Samoa to a Tōhoku-oki type far-field tsunami will increase by approx. 600% with 1 m RSLR by 2080–2130, and approx. 2,350% with 2 m RSLR by 2130–2140. These findings provide a useful baseline for tsunami hazard risk assessment under changing sea level conditions in analogous island environments.

Background: The hypothesis is that a hypoxic-hyperoxic preconditioning (HHP) is associated with a protective effect on myocardial function by reducing endothelial damage and a beneficial effect on postoperative outcome in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: Patients (n=120) were randomly assigned to an HHP and a control group. A safe inhaled oxygen fraction for the hypoxic preconditioning phase (10-14% oxygen for 10 minutes) was determined by measuring the anaerobic threshold. At hyperoxic phase, 75-80% oxygen fraction was used during 30 minutes. Results: The cumulative frequency of postoperative complications was 14 (23.3%) in the HHP vs 23 (41.1%), p=0.041. The nitrate decreased after surgery by up to 20% in the HHP group and up to 38% in the control group. Endothelin-1 and nitric oxide metabolites were stable in HHP but remained low more than 24 h in control group. The endothelial damage markers appeared to be predictors of postoperative complications. Conclusion: The HHP with individual parameters based on the anaerobic threshold is a safe procedure, it can reduce the frequency of postoperative complications. The endothelial damage markers appeared to be predictors of postoperative complications.

Damage in concrete structures initiates as the growth of diffuse microcracks that is followed by damage localisation and eventually leads to structural failure. Weak changes such as diffuse microcracking processes are failure precursors. Identification and characterisation of these failure precursors at an early stage of concrete degradation and application of suitable precautionary measures will considerably reduce the costs of repair and maintenance. To this end, a reduced order multiscale model for simulating microcracking-induced damage in concrete at the mesoscale levelis proposed. The model simulates the propagation of microcracks in concrete using a two-scale computational methodology. First, a realistic concrete specimen that explicitly resolves the coarse aggregates in a mortar matrix was generated at the mesoscale. Microcrack growth in the mortar matrix is modelled using a synthesis of continuum micromechanics and fracture mechanics. Model order reduction of the two-scale model is achieved using clustering technique. Model predictions are calibrated and validated using uniaxial compression tests performed in the laboratory.

In recent years in Bangladesh, there has been regular cyclonic event, flooding and erratic pre-monsoons precipitation that has hampered production greatly and forced Bangladesh to import salt from abroad to manage market deficiency. There is much uncertainty about the effects of climate change on the frequency and intensity of small-scale, sudden onset weather phenomena such as heavy rainfall and subsequent loss and damage (L&D). But, several studies indicate that an obvious strong relationship exists between irregular rainfall and associated L&D. Nowadays, severe changing rainfall patterns are observed in Bangladesh, which is rapid-onset in nature, but low exposed in terms of response. The current study explored a ‘double-exposed’ burden combined of both climatic (e.g., uneven rainfall) and non-climatic governance factors (e.g., imperfect trade policy, the absence of risk transfer mechanisms) which are hindering salt production and pushing the country from the aspiration of salt exporting to the net buyer. This chapter mainly assesses the impacts of L&D due to climatic events that are causing overwhelming effects on the well-being of marginal salt farmers at Kutubdia Upazila of Bangladesh. Data were mainly collected through Participatory Vulnerability Analysis (PVA), Key informant interviews (KII), and Sample Surveys (SS). This study would provide insights for improved disaster management policy and an appropriate adaptive measure to address such extreme events as well as to initiate a further study for understanding the nexus of ‘nature and market’ in building resilience among the marginal salt farmers.

The horse chestnut leaf miner Cameraria ohridella (Lepidoptera: Gracillariidae) is an invasive pest of horse chestnut and has spread through Europe since 1985. The horse chestnut leaf blotch Guignardia aesculi (Botryosphaeriales: Botryosphaeriaceae) is a fungal disease that also seriously damages horse chestnut trees in Europe. The interaction between the leaf miner and the fungus has not yet been sufficiently described. Therefore, the aim of the present study was to assess leaf damage inflicted to horse chestnut by both C. ohridella and G. aesculi during the vegetation season and to model their interaction. The damage to leaf area was measured monthly from May to September 2013 in České Budějovice, the Czech Republic. A simple phenomenological model describing the expected dynamics of the two species was developed. The study revealed a significant effect of sampling site and sampling period on the damage caused by both the pest and the fungus. The mathematical model indicates that infestation by C. ohridella is more affected by G. aesculi than vice versa. The possible mechanisms affecting the relationship between G. aesculi and C. ohridella are discussed.

We analyze damage propagation modeling of turbo-engines in a data-driven approach. We investigate subspace tracking assuming a low dimensional manifold structure and a static behavior during the healthy state of the machines. Our damage propagation model is based on the deviation of the data from the static behavior and uses the notion of health index as a measure of the condition. Hence, we incorporate condition-based maintenance and estimate the remaining useful life based on the current and previous health indexes. This paper proposes an algorithm that adapts well to the dynamics of the data and underlying system, and reduces the computational complexity by utilizing the low dimensional manifold structure of the data. A significant performance improvement is demonstrated over existing methods by using the proposed algorithm on CMAPSS Turbo-engine datasets.

Timely detection of surface damages on wind turbine blades is imperative for minimising downtime and avoiding possible catastrophic structural failures. With recent advances in drone technology, a large number of high-resolution images of wind turbines are routinely acquired and subsequently analysed by experts to identify imminent damages. Automated analysis of these inspection images with the help of machine learning algorithms can reduce the inspection cost, thereby reducing the overall maintenance cost arising from the manual labour involved. In this work, we develop a deep learning based automated damage suggestion system for subsequent analysis of drone inspection images. Experimental results demonstrate that the proposed approach could achieve almost human level precision in terms of suggested damage location and types on wind turbine blades. We further demonstrate that for relatively small training sets advanced data augmentation during deep learning training can better generalise the trained model providing a significant gain in precision.

DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer. Eukaryotes have evolved two major pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ) to repair DSBs. Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated. This review summarizes recent discoveries on the identification of non-coding RNAs and RNA-mediated regulation of DSB repair

Damage to crops from wildlife interference is a common threat to food security among rural communities in or near Game Management Areas (GMAs) in Zambia. This study uses a two-stage econometric model and cross-sectional data from a survey of 2,769 households to determine the impact of land use planning on the probability and extent of wildlife-inflicted crop damage. The results show that crop damage is higher in GMAs as compared to non-GMAs, and that land use planning could be an effective tool to significantly reduce the likelihood of such damage. These findings suggest that there is merit in the current drive to develop and implement land use plans as means to minimize human-wildlife conflict such as crop damage. This is especially critical as Zambian conservation policies do not have an explicit provision for compensation in the event of damage from wildlife.

Detection of early stage corrosion on slender steel members is crucial for preventing buckling failures of steel structures. An active photoacoustic fiber optic sensors (FOS) system has been reported for early stage steel corrosion detection of steel plates and rebars using surface ultrasonic waves. The objective of this paper is to investigate the surface corrosion/rust detection problem on steel rods using numerically simulated surface ultrasonic waves. The finite element method (FEM) is applied in simulating the propagation of ultrasonic waves on steel rod models. Transmission mode of damage detection is adopted, in which one source (transmitter) and one sensor (receiver) are considered. In this research, radial displacements at the receiver were simulated and analyzed by short-time Fourier transform (STFT) for detecting, locating, and quantifying a surface rust located between the transmitter and the receiver. From our time domain and frequency domain analyses, it is found that the presence, location, and dimensions (length, width, and depth) of surface rust can be estimated by ultrasonic waves propagating through the surface rust.

Prostate cancer (PCa) is the most prevalent malignancy and the second leading cause of can-cer-related death in men. Although current therapies can effectively manage the primary tumor, most patients with late-stage disease manifest with metastasis in different organs. From surgery to treatment intensification (TI), several combinations of therapies are administered to improve prognosis of patients with metastatic PCa. Due to the high frequency of mutation during the metastatic phase, the Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genetic engineering tool can accelerate the effects of TI by enhancing targeted gene therapy or immunotherapy. This review describes the genetic backgrounds of metastatic PCa and how CRISPR/Cas9 technology can contribute to the field of PCa treatment development. It also dis-cusses current limitations of conventional PCa therapy and the potential of CRISPR-based-PCa therapy.

Background/Objective: In this study, for the first time, we examined and compared the sensitivity of four patient-derived cutaneous melanoma cell lines to alpha radiation in vitro and analyzed it in view of cell nucleus area and the formation of double strand breaks (DSB). Melanoma cells sensitivity to alpha radiation was compared to photon radiation effects. Furthermore, we compared the sensitivity of the melanoma cells to squamous cell carcinoma. Methods: Human melanoma cell lines YDFR.C, DP.C, M12.C and M16.C, and the squamous cell carcinoma cell line, CAL 27, were irradiated in-vitro using Americium-241 as alpha-particle source. Cells were irradiated with doses of 0 to 2.8 gray (Gy). Cell viability, DNA DSB and nuclear size were measured. Results: 1. Alpha radiation caused death and proliferation arrest of all four melanoma cell lines, but inter-tumor heterogeneity was observed. 2. The most sensitive cell line (DP.C) had a significantly larger nucleus area (408 mM²) and the highest mean number of DSB per cell (9.61) compared to more resistant cells. 3. The most resistant cell, M16.C, had a much lower nucleus area (236.99 mM²) and DSB per cell (6.9). 4. Alpha radiation was more lethal than photon radiation for all melanoma cells. 5. The SCC cell, CAL 27, was more sensitive to alpha radiation than all melanoma cells, yet, had a similar number of DSB (6.67) and nucleus size (175.49 mM²) as the more resistant cells. 6. The cytotoxic effect of alpha radiation was not affected by proliferation arrest after serum starvation. 7. Killing of cells by alpha radiation was marginally elevated by ATR or topoisomerase 1 inhibition. Conclusions: This study demonstrates that various human melanoma cells can be killed by alpha radiation but exhibit variance in sensitivity to alpha radiation. Alpha radiation applied using Intra-tumoral Diffusing alpha-emitters Radiation Therapy (Alpha DaRT) methodology may serve as an efficient treatment for human melanoma.

Kiwifruit (Actinidia chinensis) cultivation is expanding worldwide being China, New Zealand and Italy the major producing countries. Halyomorpha halys, the brown marmorated stink bug, has been raising serious concerns to kiwifruit cultivation both in China and Italy. This study aimed at improving the chemical control efficacy against this pest by comparing two insecticide spray techniques (a conventional ray atomizer and a trumpet-modified atomizer adapted for localized spray application in kiwifruit). In fact, kiwifruit is often grown with a ‘pergola’ training system, which may reduce the effectiveness of insecticide penetration into the canopy. Experiments have been performed in naturally infested orchards of both Actinidia chinensis var. chinensis ‘Jintao’ and A. chinensis var. deliciosa ‘Hayward’ during two consecutive seasons. Furthermore, mesh cages, each containing three H. halys adults, were deployed in the orchards to assess the insects’ mortality at 1, 3, 7 and 10 days after the insecticide application with the two spray techniques. In the cultivar 'Jintao', the two systems performed similarly, while in the cultivar 'Hayward', an overall significantly higher insect mortality was recorded with the trumpet atomizer. The crop damage was also evaluated on both cultivars, simulating the grower insecticide applications with the two spray techniques. At harvest, no difference emerged between the spray techniques, which provided a significantly better protection compared to the untreated control. Further investigations in this direction are needed also considering the restriction of insecticidal active substances ongoing in European Union and the need to maximize the efficacy of the available tools.

The DNA damage response (DDR) system is a complicated network of signaling pathways that detects and repairs DNA damage or induces apoptosis. Critical regulators of the DDR network include the DNA damage kinases ataxia telangiectasia mutated Rad3-related kinase (ATR) and ataxia-telangiectasia mutated (ATM). The ATR pathway coordinates processes such as replication stress response, stabilization of replication forks, cell cycle arrest, and DNA repair. ATR inhibition disrupts these functions, causing reduction of DNA repair, accumulation of DNA damage, replication fork collapse, inappropriate mitotic entry and mitotic catastrophe. Recent data have shown that the inhibition of ATR can lead to synthetic lethality in ATM-deficient malignancies. In addition, ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Taken together, we review stimulating data showing that ATR kinase inhibition can alter the DDR network, the immune system and their interplay and therefore potentially provide a novel strategy to improve the efficacy of antitumor therapy, using ATR inhibitors as monotherapy or in combination with genotoxic drugs and/or immunomodulators.

Forest damage has become more frequent in Europe in the last decades, and remote sensing offers a powerful tool for monitoring them rapidly and cost-effectively. A novel approach was developed to utilize high-resolution ESA Sentinel-2 satellite imagery and Google Earth Engine cloud computing. The processing, analysing, and visualization of vegetation and water index (NDVI, NDVIch, Z NDVI, EVI, NDWI) maps and charts derived from satellite images took place in the cloud to ensure the detection of forest disturbances in the Hungarian study site for the period 2017-2020. The index maps were classified to reveal forest disturbances, and the cloud-based method successfully showed drought and frost damage in the oak-dominated Nagyerdő forest of Debrecen. Differences in the reaction to damage between tree species were visible in the index values, therefore a Random Forest Machine Learning classifier was applied to show the spatial distribution of dominant species. Accuracy assessment was accomplished with confusion matrices that compared classified index maps to field-surveyed data, demonstrating 71% Total Accuracy for forest damage and 76% for tree species. Based on the results of this study and the resilience of Google Earth Engine, the presented method has the potential to be extended to monitor the entire Hungary.

Windthrow (i.e., trees broken and uprooted by wind) is a major natural disturbance in the Amazon. Images from medium-resolution optical satellites (mostly Landsat) combined with extensive field data have allowed researchers to assess patterns of tree mortality and monitor forest recovery over decades of subsequent succession in different regions. Although satellites with high spatial-resolution have become available for the Amazon in the last decade, they have not yet been employed for the mapping and quantification of windthrow tree-mortality. Here, we address how increasing the spatial resolution of satellites affects plot-to-landscape estimates of windthrow tree-mortality. We combined forest inventory data with Landsat 8 (30 m pixel), Sentinel 2 (10 m), and WorldView 2 (2 m) imagery over an old-growth forest in the Central Amazon that was disturbed by a single windthrow event in November/2015. Remote sensing estimates of tree mortality were produced with Spectral Mixture Analysis and analyzed together with forest inventory data using Generalized Linear Models. Windthrow tree-mortality measured in 3 transects (30 subplots) crossing the entire disturbance gradient was 26.9 ± 11.1% (mean ± 95% CI). Based on this ground truth, the three satellites produced reliable and statistically similar estimates (from 26.5% to 30.3% windthrow tree-mortality, p&lt;0.001). The mean-associated uncertainties decreased systematically with increasing spatial resolution (i.e., from Landsat 8 to Sentinel 2 and WorldView 2). However, the overall quality of fit of models showed the opposite pattern, which may reflect the influence of crown damage not accounted for in our field study, and fast-growing regeneration of leaf area. Among the satellites studied, Landsat 8 most accurately captured field observations of variations in tree mortality across the disturbance gradient (i.e., lower under- and/or overestimation from undisturbed to extremely damaged forest). Although satellites with high spatial-resolution can refine estimates of windthrow severity by allowing the quantification of individual tree damage and mortality, our results validate the reliability of Landsat imagery for assessing patterns of windthrow tree-mortality in dense and heterogeneous tropical forests. Although high-resolution imagery may improve estimates of tree damage and mortality, these should be validated using field data at compatible scales.

This research is aimed to develop the method for damage degree evaluation in metals and alloys during their deformation and destruction based on acoustic emission (AE) technique. Experimental studies were carried out on tensile specimens of high-strength steel with simultaneous registration of AE signals in tested material. It was shown that the time-dependent AE primary parameters, such as the AE signal maximum amplitudes and AE activity, do not have a clear relationship with the material damage degree. This fact makes it difficult to use standard methods for assessing the damage degree of acoustic signal sources, including defects. It was proposed to use the Kolmogorov-Smirnov criterion to differ the processes of metal plastic deformation and crack propagation during the rupture. The possibility of estimating the material damage degree by high-energy AE hits share was shown. Besides, a particular expression was obtained for evaluating the damage degree for the material under study.

The angle of seismic excitation is a significant factor of the seismic response of RC buildings. The procedure required for the calculation of the angle for which the potential seismic damage is maximized (critical angle) contains multiple nonlinear time history analyses using in each one of them different angles of incidence. Moreover, the seismic codes recommend the application of more than one accelerograms for the evaluation of seismic response. Thus, the whole procedure becomes time consuming. Herein, a method to reduce the time required for the estimation of the critical angle based on Multilayered Feedforward Perceptron Neural Networks is proposed. The basic idea is the detection of cases in which the critical angle increases the class of seismic damage compared to the class which arises from the application of the seismic motion along the buildings’ structural axes. To this end, the problem is expressed and solved as Pattern Recognition problem. As inputs of networks the ratios of seismic parameters’ values along the two horizontal seismic records' components, as well as appropriately chosen structural parameters, were used. The results of analyses show that the neural networks can reliably detect the cases in which the calculation of the critical angle is essential.

Keywords: underground engineering; numerical simulation; excavation length effect, major principal stress; displacement; damage initiation; CPU time

Ultrasonic measurements are used in civil engineering for structural health monitoring of concrete infrastructures. The late portion of the ultrasonic wavefield, the coda, is sensitive to small changes in the elastic moduli of the material. Coda Wave Interferometry (CWI) correlates these small changes in the coda with the wavefield recorded in intact, or unperturbed, concrete specimen to reveal the amount of velocity change that occurred. CWI has the potential to detect localised damages and global velocity reductions alike. In this study, the sensitivity of CWI to different types of concrete mesostructures and their damage levels is investigated numerically. Realistic numerical concrete models of concrete specimen are generated and damage evolution is simulated using the discrete element method. In the virtual concrete lab, the simulated ultrasonic wavefield is propagated from one transducer using a realistic source signal and recorded at a second transducer. Different damage scenarios reveal a different slope in the decorrelation of waveforms with the observed reduction in velocities in the material. Finally, the impact and possible generalizations of the findings are discussed and recommendations are given for a potential application of CWI in concrete at structural scale.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

From the wide range of engineering materials traditional Stellite 6 alloy exhibits excellent cavitation erosion (CE) resistance. In this work, the effect of nitrogen ion implantation of HIPed Stellite 6 on the improvement of CE resistance and both cobalt-rich matrix phase transformation due to nitrogen implantation and CE were stated. The CE resistance of stellites ion-implanted by 120 keV N+ ions two fluences: 5x1016 cm-2 and 1x1017 cm-2 were comparatively analysed with the unimplanted stellite and AISI 304 stainless steel. CE tests were conducted according to ASTM G32 with stationary specimen method. Erosion rate curves and mean depth of erosion confirm that the nitrogen implanted HIPed Stellite 6 two times exceeds the resistance to CE than unimplanted stellite, and has almost 10 times higher CE reference than stainless steel. The X-ray diffraction (XRD) confirms that HIPed Stellite 6 nitrogen ion implantation favours transformation of the ɛ(hcp) to γ(fcc) structure. Unimplanted stellite ɛ-rich matirx is less prone to plastic deformation than γ and consequently, increase of γ phase effectively holds carbides in cobalt matrix and prevents Cr7C3 debonding. This phenomenon elongates three times the CE incubation stage, slows erosion rate and mitigates the material loss. Metastable γ structure formed by ion implantation consumes the cavitation load for work-hardening and γ → ɛ martensitic transformation. In further CE stages, phases transform as for unimplanted alloy namely, the cavitation-inducted recovery process, removal of strain, dislocations resulting in increase of fcc phase. The CE mechanism was investigated using a surface profilometer, atomic force microscopy, SEM-EDS and XRD. HIPed Stellite 6 wear behaviour relies on the plastic deformation of cobalt matrix, starting at Cr7C3/matrix interfaces. Once the Cr7C3 losing their restrain, are debonding and removed. Carbides detachment creates cavitation pits which initiate cracks propagation through cobalt matrix, the loss of matrix phase and CE proceeds with a detachment of massive chunk of materials.

Rapid Visual Screening (RVS) is a procedure that estimates structural scores for buildings and prioritize their retrofit and upgrade requirements. Despite the speed and simplicity of RVS, many of the collected parameters are non-commensurable and include subjectivity due to visual observations. It might cause uncertainties in the evaluation, which emphasizes the use of a fuzzy-based method. This study aims to propose a novel RVS methodology based on the interval type-2 fuzzy logic system (IT2FLS) to set the priority of vulnerable building to undergo detailed assessment while covering uncertainties and minimizing their effects during evaluation. The proposed method estimates the vulnerability of a building, in terms of Visual Damage Index, considering the number of stories, age of building, plan irregularity, vertical irregularity, building quality, and peak ground velocity, as inputs with a single output variable. Applicability of the proposed method has been investigated using a post-earthquake damage database of 28 reinforced concrete buildings from the Bingöl earthquake in Turkey.

Cardiac ischemia-reperfusion injury (IRI) occurs when blood flow is restored to the myocardium after a period of ischemia, leading to oxidative stress and subsequent myocardial cell damage, primarily due to the accumulation of reactive oxygen species (ROS). In our previous research, we identified that miR-25 is significantly overexpressed in pressure overload-induced heart failure, and its inhibition improves cardiac function by restoring the expression of SERCA2a, a key protein involved in calcium regulation. In this study, we aimed to investigate the role of miR-25 in the context of ischemia-reperfusion injury. We found that miR-25 was markedly upregulated under hypoxic conditions in both in vitro and in vivo models. Through in silico analysis, we identified Sestrin3 (SESN3), an antioxidant protein known for its protective effects against oxidative stress, as a novel target of miR-25. Based on these findings, we hypothesized that inhibiting miR-25 would restore Sestrin3 expression, thereby reducing ROS-induced myocardial cell damage and improving cardiac function. To test this hypothesis, we employed two model systems: a hypoxia/reoxygenation (H/R) stress model using H9c2 myoblasts and a surgically induced ischemia-reperfusion injury mouse model. Our results demonstrated that the use of miR-25 inhibitors significantly improved cardiac function and reduced myocardial damage in both models through the restoration of SESN3 expression. In conclusion, our findings suggest that targeting miR-25 may serve as a novel therapeutic modality to alleviate oxidative damage in the heart.

A tritium resistant coating on the surface of materials is one of the main methods to reduce tritium permeability. In actual operating processes, mechanical damage such as spalling and scratches will occur on the surface of tritium resistant coatings. These mechanical damages will affect the hydrogen permeability resistance of the coatings. It is an important engineering problem that evaluate the effect of these damage on the tritium resistance of the coating. In this experiment, the mechanical damage of FeAl/Al2O3 tritium resistant coating on 316L stainless steel was simulated by scratching, debonding and thermal shock, and the gas hydrogen isotope permeation (GDP) test was carried out. The influence of mechanical damage degree on the tritium permeation behaviour of the coating was evaluated and discussed.

Carbon fiber-reinforced polymer (CFRP), noted for its outstanding properties including high specific strength and superior fatigue resistance, is increasingly employed in aerospace and other demanding applications. This study investigates the interactions between CFRP composites and high-energy lasers (HEL), with continuous wave laser powers reaching up to 120 kW. A novel automated sample exchange system, operated by a robotic arm, minimizes human exposure while enabling a sequence of targeted laser tests. High-speed imaging captures the rapid expansion of a plume consisting of hot gases and dust particles during the experiment. The research significantly advances empirical models by systematically examining the relationship between laser power, perforation times, and ablation rates. It demonstrates scalable predictions for the effects of high-energy laser radiation. Detailed examination of the damaged samples, both visually and via micro-focused computed X-ray tomography, offers insights into heat distribution and ablation dynamics, highlighting the anisotropic thermal properties of CFRP. Compression-after-impact (CAI) tests further assess the residual strength of the irradiated samples, enhancing the understanding of CFRP’s structural integrity post-irradiation. Collectively, these tests improve the knowledge of the thermal and mechanical behavior of CFRP under extreme irradiation conditions. The findings not only contribute to predictive modeling of CFRP's response to laser irradiation but also enhance the scalability of these models to higher laser powers, providing robust tools for predicting material behavior in high-performance settings.

The effectiveness of a hybrid technique for identifying seismic damage in planar, multistory, steel X or V-braced frames is demonstrated here through an example of a six-story frame. This proposed technique, referred to as “M and P”, combines the instrumental Monitoring (M) with Pushover analysis (P). According to the methodology, the diagram of stepping eigenfrequencies of the frame in the inelastic region is initially plotted against seismic roof displacement. The fundamental natural frequency detected via the monitoring process is then utilized in this key diagram to reveal the inelastic roof displacement that corresponds to the damage state of the steel braced frame. This displacement is subsequently used as the target in the pushover analysis, facilitating the identification of seismic damage in the existing steel braced frame. Finally, the damage image is correlated with the damage stiffness matrix of the frame at the same inelastic roof displacement. The investigation results indicate that combining instrumental monitoring with pushover analysis enables accurate identification of seismic damage potential in existing steel braced frames.

Obesity and environmental toxins are risk factors for breast cancer, however there is limited knowledge on how these risk factors interact to promote breast cancer. Acrylamide, a probable carcinogen and obesogen, is a biproduct in foods prevalent in the obesity-inducing Western diet. Acrylamide is metabolized by cytochrome P450 2E1 (CYP2E1) to the genotoxic epoxide, glycidamide, and is associated with increased risk for breast cancer. To investigate how acrylamide and obesity interact to increase breast cancer risk, female mice were fed a low-fat (LFD) or high-fat diet (HFD) and 0.7mM acrylamide-supplemented water or control water. While HFD significantly enhanced weight gain in mice, the addition of acrylamide did not significantly alter body weights compared to respective controls. Mammary epithelial cells from obese, acrylamide-treated mice had increased DNA strand breaks and oxidative DNA damage compared to all other groups. In vitro, glycidamide-treated COMMA-D cells showed significantly increased DNA strand breaks while acrylamide-treated cells demonstrated significantly higher levels of intracellular reactive oxygen species. Knockdown of CYP2E1 rescued the acrylamide-induced oxidative stress. These studies suggest that long-term acrylamide exposure through foods common in the Western diet may enhance DNA damage and CYP2E1-induced generation of oxidative stress in mammary epithelial cells, potentially enhancing obesity-induced breast cancer risk.

The initiation reactions of DNA synthesis are central processes during human chromosomal DNA replication. They are separated into two main processes: the initiation events at replication origins, the start of the leading strand synthesis for each replicon, and the numerous initiation events taking place during lagging strand DNA synthesis. In addition, a third mechanism is the re-initiation of DNA synthesis after replication fork stalling, which takes place when DNA lesions hinder the progression of DNA synthesis. The initiation of leading strand synthesis at replication origin is regulated at multiple levels, from the origin recognition to the assembly and activation of replicative helicase, the Cdc45-MCM2-7-GINS (CMG) complex. In addition, the multiple interactions of the CMG complex with the eukaryotic replicative DNA polymerases such as DNA polymerase α-primase (Pol α), DNA polymerase δ and ε at replication forks play pivotal roles in the mechanism of initiation reactions including the initiation of signalling unperturbed and stalled replication forks, ‘replication stress’ events, via ATR (ATM-Rad 3-related protein kinase). All these processes are essential for the accurate transfer of the cells’ genetic information to their daughters. Failures and dysfunctions in these processes gives rise to genome instability followed by genetic diseases including cancer. Thus, in their review ‘Hallmarks of Cancer: New Dimensions‘ Hanahan and Weinberg (2022) called genome instability a fundamental function in the development process of cancer cells. In recent years, the understanding of the initiation processes and mechanisms of human DNA replication has made substantial progress at all levels which will be discussed in the review.

Replication protein A (RPA) is a heterotrimeric protein complex and the main single-stranded DNA (ssDNA) binding protein in eukaryotes. RPA has key functions in most of the DNA-associated metabolic pathways and DNA damage signalling. Its high affinity for ssDNA helps to stabilise ssDNA structures and prevents the DNA sequence from nuclease attacks. RPA consists of multiple DNA-binding domains which are oligonucleotide/oligosaccharide-binding (OB)-folds, responsible for DNA binding, and interactions with proteins. These RPA-ssDNA and RPA-protein interactions are crucial for DNA replication, DNA repair, DNA damage signalling, and the conversation of the genetic information of cells. Proteins such as ATR use RPA to locate to regions of DNA damage for DNA damage signalling. Recruitment of nucleases and DNA exchange factors to sites of double strand breaks are also an important RPA function to ensure effective DNA recombination to correct these DNA lesions. Due to its high affinity to ssDNA, RPA’s removal from ssDNA is of central importance to allow these metabolic pathway to proceed and processes to exchange RPA against downstream factors are established in all eukaryotes. These facetted and multi-layered functions of RPA will be discussed in detail in the review. RPA is also a major player in a variety of human diseases, which will be discussed.

The tension cable-supported power transmission structure (TC-PTS) is a new type of power transmission structure suitable for mountainous terrain, which is sensitive to wind load. In this regard, a nonlinear finite element analysis model of wind-induced vibration is proposed for the TC-PTS, and the wind-induced vibration response of the structure is analyzed. Firstly, the tangent stiffness matrix of the three-dimensional truss element for the supporting suspension cable and transmission line, considering the geometric nonlinearity of structures, is derived through the relationship between the element elastic energy and its displacement. Subsequently, the element mass matrix and damping matrix of the supporting suspension cable and transmission line, as well as the element nodal load vector obtained from wind load equivalence are given. Then, based on the nonlinear finite element theory, the nonlinear dynamic equation of wind-induced vibration is established for the TC-PTS and solved by Newmark-β method combined with Newton-Raphson iterative method. Furthermore, the rain-flow counting method and Miner's linear fatigue cumulative damage theory were used for wind induced fatigue damage assessment. Finally, a two-span TC-PTS is selected as an example, and the wind-induced nonlinear vibration and fatigue damage assessment are analyzed through the proposed model. The results show that the proposed model has high computational accuracy and efficiency. With the increase of wind speed and wind direction angle, the maximum lateral displacement and tension of the supporting suspension cable and transmission line increase, and their degree of increase shows a nonlinear trend. In terms of the wind-induced fatigue analysis results of TC-PTS, the fatigue damage at the end of the supporting-conductor suspension cable is greater than the fatigue damage at its midpoint. Compared to the fatigue damage at the midpoint of the conductor, the fatigue damage at the end of the conductor is less affected by wind direction angle, and both are more significantly affected by the wind speed.

Alzheimer’s disease (AD) and vascular dementia (VaD) together contribute to almost 90% of all dementia cases leading to major health challenges of our time with a substantial global socioeconomic burden. While in Alzheimer’s disease, the improved understanding of Amyloid beta (Aß) mismetabolism and tau hyperphosphorylation as pathophysiological hallmarks has led to significant clinical breakthroughs, similar advances in VaD are lacking. We thus highlight here the importance of shared pathomechanisms found in AD and VaD: Endothelial damage, blood brain barrier (BBB) breakdown and hypoperfusion inducing oxidative stress, inflammation and demyelination and thus trophic uncoupling in the neurovascular unit. A dysfunctional endothelium and BBB lead to the accumulation of neurotoxic molecules and Aß through impaired clearance, which in turn leads to neurodegeneration. In this context we discuss possible neuropathological parameters, which might serve as biomarkers and thus improve diagnostic accuracy or reveal targets for novel therapeutic strategies for both forms of dementia.

Ultrasonic-guided lamb wave approach is an effective non-destructive testing (NDT) method used for detecting localized mechanical damage, corrosion, and welding defects experienced in metallic pipelines. Signal processing of the guided waves is often challenged due to the complexity of operational conditions and environments in the pipelines. Machine learning approaches in recent years, including convolutional neural networks (CNN) and long short-term memory (LSTM), have exhibited their advantages to overcome these challenges for signal process and data classification of complex systems, thus great potential for damage detection of critical oil/gas pipeline structures. In this study, a CNN-LSTM hybrid model is utilized for decoding ultrasonic guided waves for damage detection of metallic pipelines, and twenty-nine features are extracted as input to classify different types of defects from metallic pipes. The prediction capacity of the CNN-LSTM model is assessed by comparing it to the CNN and LSTM. The results demonstrate that the CNN-LSTM hybrid model exhibits much higher accuracy, with 94.8%, as compared to those of CNN and LSTM. Interestingly, the results also reveal that predetermined features, including time-, frequency-, and time-frequency domains, could significantly improve the robustness of the deep learning approaches, even though the deep learning approaches are often believed they include automated feature extraction, without the hand-crafted steps as the shallow learning do. Furthermore, the CNN-LSTM model displays higher performance when the noise level is relatively low (e.g., SNR=9 or higher), as compared to the other two models, but its prediction drops gradually with the increase of the noise.

To study the strengthening effect on recycled concrete columns by carbon fiber composite materials (CFRP) under different levels of seismic damage, four column specimens were designed for pseudo-static tests. The four specimens were respectively non-destructive without strengthening (prototype), non-destructive strengthening, medium seismic damage strengthening and severe seismic damage strengthening, according to the replacement rate of recycled aggregates and the level of seismic damage. The characteristics of the deformation damage and seismic performance indicators of each specimen were compared and analyzed. A decrease was observed in the initial stiffness of the seismically damaged recycled concrete column specimens strengthened with CFRP, while the ductility, peak bearing capacity and energy dissipation capacity of the specimens were improved. On the other hand, with the reduction of seismic damage and the increase of recycled aggregate replacement rate, the ductility and energy dissipation capacity of the reinforced seismic damaged recycled concrete column specimens were enhanced to different levels. In particular, the cumulative energy consumption of the strengthened specimens under medium seismic damage increased most significantly by 32.5%. In general, the hysteretic curves of the strengthened specimens were full, and the average ductility coefficients were 4.1–6.8. CFRP strengthening was more effective in restoring and enhancing the performance of the recycled concrete column specimens with medium and lower seismic damage levels (displacement ratio ≤ 3%).

The dynamic response of structural elements subjected to blast loading is a problem of growing interest in the field of defense and security. In this work, a novel computational tool for the rapid evaluation of the effects of explosions, hereafter referred as SimEx, is presented and discussed. The classical correlations for the reference chemical (1 kg of TNT) and nuclear (106 kg of TNT) explosions, both spherical and hemispherical, are used together with the blast wave scaling laws and the International Standard Atmosphere (ISA) model to compute the dynamic response of Single-Degree-of-Freedom (SDOF) systems subject to blast loading. The underlying simplifications in the analysis of the structural response follow the directives established by UFC 3-340-02 and the Protective Design Center Technical Reports of the US Army Corps of Engineers, which offer useful estimates with a low computational cost, enabling in particular the computation of damage diagrams in the Charge Weight-Standoff distance (CW-S) space for the rapid screening of component (or building) damage levels. SimEx is a computer application based on Matlab and developed by the Fluid Mechanics Research Group at University Carlos III of Madrid (UC3M), which has been successfully used for both teaching and research purposes in the Degree in Security Engineering, taught to the future Guardia Civil officers at the Spanish University Center of the Civil Guard (CUGC). This dual use has allowed the development of the application well beyond its initially objective, testing on one hand the implemented capacities by undergraduate cadets with end-user profile, and implementing new functionalities and utilities by Masters and PhD students. With this experience, the application has been continuously growing since its initial inception in 2014 both at a visual and a functional level, including new effects in the propagation of the blast waves, such as clearing and confinement, and incorporating new calculation assistants, such as those for the thermochemical analysis of explosive mixtures; crater formation; fragment mass distributions, ejection speeds and ballistic trajectories; and the statistical evaluation of damage to people due to overpressure, body projection, and fragment injuries.

Epithelial-mesenchymal transition (EMT) networks are essential in acquiring the drug resistance and cancer malignant features in cancer stem cells (CSCs). In this regard, gene expression profiles in diffuse- and intestinal-type gastric cancer (GC) have been analyzed to reveal the network pathways in EMT and CSCs, since the diffuse-type GC has much more mesenchymal features than intestinal-type GC that has the intestinal features. The study results revealed that the activation state of several canonical pathways related to cell cycle regulation was altered. The canonical pathway on Cell cycle: G1/S checkpoint regulation was activated in diffuse-type GC, and canonical pathways on Cell cycle control of chromosomal replication and Cyclins and cell cycle regulation were activated in intestinal-type GC. Canonical pathway related to Role of BRCA1 in DNA damage response was activated in intestinal-type GC, where BRCA1, which is related to G1/S phase transition was up-regulated in intestinal-type GC. Several microRNAs (miRNAs), including mir-10, mir-17, mir-19, mir-194, mir-224, mir-25, mir-34, mir-451, and mir-605, were identified to have direct relationships of RNA-RNA interaction in Cell cycle: G1/S checkpoint regulation pathway. Additionally, cell cycle regulation may be altered in EMT conditions. The alterations in activation states of the pathways related to cell cycle regulation in diffuse- and intestinal-type GC would indicate the significance of cell cycle regulation in EMT.

Recent technological improvements have made abundant changes in construction industry. In specific, some technical applications, such as Building Information Modeling (BIM) opens up many possibilities. Some studies have articulated the use of BIM and its advantages in construction, but most of them are theoretical, not practical. This study is to provide an insight to such obstacles in BIM research. By investigating a real project that could utilize BIM in planning and construction phases, the authors try to investigate a possible outline of advantages in BIM implementation. The study area was set to a railway construction site in South Korea. The site covers a multiple railway tracks, stations, telecommunication facilities, infrastructure facilities, railway structures, and so numerous. In the site, the authors have identified 12 errors in 7 projects that could be prevented if BIM was utilized before the construction. The total upfront costs required to provide a BIM for 7 projects were $116,348. On the other hand, the total costs required to fix the errors in 7 projects were $166,486. This can be regarded as the benefits of using BIM because if BIM was implemented then the associated errors are easily replaced. Therefore, the benefit-cost ratio can be estimated as 1.32 for one-month delay and 1.36 for a three-month delay.

The Siret River crosses NE Romania from the north to the south and it discharges into the Danube, near the city of Galati. During the period, 17^th June - 10^th July 2010, significant amounts of precipitations in the mountainous basin of Siret were recorded. The floods comprised two periods with four bimodal cycles and they were counted among the strongest on the Romanian territory. The exceptional floods occurred in the rivers of Siret, Suceava, Moldova, Bistrita, Trotus and so on. The most important compound flood wave was determined by the precipitations which fell within the period, 29^th June to 1^st July 2010, when significant amounts of rain were recorded, sometimes, exceeding 80 mm. The high discharges on the Bistrita River – downstream from the Bicaz Reservoir – were controlled by complex hydro technical works. The maximum discharge for the year 2010 summer floods was recorded at Dragesti hydrometric station: 2,884 m³/s (historic discharge) compared to the preceding historic discharge of the year 2008 (2,850 m³/s). The effects of floods were strongest in the counties of Suceava, Neamt, and Bacau. The floods on the main course of the Siret River were analyzed in correlation with the tributaries within the mountainous sector.

In order to study the effect of explosion load on the flexural performance of RC beams, two RC beams of the same size were carried out explosion test and bearing capacity test successively. Piezoelectric intelligent aggregate was embedded in the beams in advance to monitor the damage state of the beams, which realized the whole process of damage monitoring of the concrete inside the structure from explosion damage to compression damage.Based on wavelet packet analysis and residual bearing capacity damage evaluation criteria, the beam damage was quantitatively evaluated, and the bending bearing capacity of RC beam after explosion damage was compared and analyzed.The results show that the change of concrete strain gauge signal, the phenomenon of crack development and the increase of internal crack development index indicate that the RC beam is damaged by explosion load.After explosion damage, the damage index of the beam increases and the residual bending capacity decreases, which proves that the piezoelectric intelligent aggregate sensor can effectively monitor the bending capacity change of the component after explosion damage.

The catastrophic twin earthquakes that struck southern Turkey and northern Syria on February 6 2023, caused massive casualties and extensive damage to infrastructure, with the province of Hatay bearing the brunt of the impact. To investigate the potential of nighttime light (NTL) data for earthquake disaster assessment, we performed an analysis of pre- and post-earthquake NPP-VIIRS and SDGSAT-1 NTL data. The NTL change ratio (NCR) was employed to identify the extent of damage in Hatay Province following the earthquake to assess the impact on affected buildings and populations. NPP-VIIRS daily NTL Time-series data was used to establish an economic recovery framework for earthquake disasters in Hatay Province, assessing regional economic recovery after earthquake. The results revealed a strong correlation between the total reduced NTLs of NPP-VIIRS and SDGSAT-1 and the presence of severely and moderately damaged buildings. Conversely, the correlation with slightly damaged buildings was relatively weaker. Furthermore, the reduced NTLs of NPP-VIIRS provide a more precise identification of all earthquake damage compared to the SDGSAT-1 data, achieving an overall accuracy of 86.21% in earthquake damage identification and a Kappa coefficient of 0.72. In accordance with the earthquake economic recovery framework, as of the end of March 2024, neither the provincial economy nor any of its districts have fully restored to their pre-earthquake levels. The findings offered new and valuable insights into earthquake disaster assessment, assisting decision-makers in accurately assessing the level of disaster risk following an earthquake and efficiently allocating post-earthquake relief funds.

The DNA Damage Response (DDR) network and the mitogen-activated protein kinase (MAPK) signaling pathway are crucial mechanisms for the survival of all living beings. An accumulating body of evidence suggests that there is a crosstalk between these two systems, thus favoring the appropriate functioning of multi-cellular organisms. On the other hand, aberrations within these mechanisms are thought to play a vital role in the onset and progression of several diseases, including cancer, as well as in the emergence of drug resistance. Here, we provide an overview of the current knowledge regarding alterations in the DDR machinery and the MAPK signaling pathway, as well as abnormalities in the DDR-MAPK functional crosstalk in multiple myeloma, the second most common hematologic malignancy. We also present the latest advances in the development of anti-myeloma drugs targeting crucial DDR- and MAPK-associated molecular components. These data could potentially be exploited to discover new therapeutic targets and effective biomarkers, as well as for the design of novel clinical trials. Interestingly, they might provide a new approach to increase the efficacy of anti-myeloma therapy by combining drugs targeting the DDR network and the MAPK signaling pathway.

In the process of use and manufacture, carbon fiber foam sandwich structures were often damaged by low-energy impact, resulting in performance degradation. Therefore, it was necessary to study the damage caused by low-speed impact of composite sandwich structures. In this paper, based on Hashin failure criterion, an equivalent finite element model of carbon fiber foam sandwich panel under low velocity impact was established. The model was used to simulate the damage of foam sandwich panel with [±45°/±45°/ (core) /±45°/±45°] ply structure under the impact energy of 10.58J, 21.17J, 31.75J and 42.34J. The simulation results of impact damage depth were compared with the experimental results. The error was less than 10%, which proved the rationality of the impact equivalent model. The model was used to predict and analyze the damage of foam sandwich panels with [±45°/ (core) /±45°], [±45°/ (0°, 90°) / (core) /±45°] and [±45°/ (0°, 90°) (core) / (0°, 90°) /±45°] ply structures under 21.17J impact energy. By comparing and analyzing the damage situation, impact force response time and impact velocity response time, the low energy impact resistance was analyzed. The results showed that increasing the number of ply structure of [±45°] can reduce the impact damage degree and improve the bearing capacity of sandwich panels.

Hepatitis D virus (HDV) infection represents the most severe form of chronic viral hepatitis. We have shown that the delivery of HDV replication-competent genomes to the hepatocytes using adenoassociated virus (AAV-HDV) as gene delivery vehicles offers a unique platform to investi-gate the molecular aspects of HDV and associated liver damage. Here, we generated HDV ge-nomes modified by site directed mutagenesis aimed to: i) prevent some post-translational modi-fications of HDV antigens (HDAgs) such as Large-HDAg (L-HDAg) isoprenylation or Short-HDAg (S-HDAg) phosphorylation ii) alter the localization of HDAgs within the subcellular compartments and iii) inhibit the right conformation of the delta ribozyme. First, the different HDV mutants were tested in vitro using plasmid-transfected Huh-7 cells and then in vivo in C57BL/6 mice using AAV vectors. We found that Ser 177 phosphorylation and the ribozymal ac-tivity are essential for HDV replication and HDAg expression. Mutation of the isoprenylation domain prevent the formation of infectious particles and increase cellular toxicity and liver dam-age. Finally, altering the intracellular localization od HDAg have a profound on viral replication in vivo but liver toxicity is maintained. Mutation in the nuclear export signal impair the for-mation of infectious viral particles. These findings contribute valuable insights into the intricate mechanisms of HDV biology and have implications for therapeutic considerations

Premature failure and degradation of layers are the main problems for transportation infrastruc-ture. Addressing these issues necessitates implementing structural health monitoring (SHM) for transportation layers. This strategic approach is instrumental in mitigating maintenance expenses, prolonging the operational lifespan, and preventing accidents resulting from abrupt layer col-lapse. To this end, this research investigated the stress/strain and damage detection capabilities of a self-sensing cementitious composite developed for potential utilization in the construction of an intelligent subgrade layer. The prepared self-sensing cementitious composite consisted of 10% cement and hybrid conductive fillers, including multiwalled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) in sand. Initial findings reveal that the electrical resistivity of the composite is significantly affected by the concentration of MWCNTs/GNPs, with a minimum concentration of more than 0.5% needed to achieve a responsive cementitious composite. More-over, the piezoresistive analysis indicates that an increase in the concentration of MWCNTs/GNPs and stress levels leads to an improvement in the stress/strain sensing perfor-mance. When the self-sensing cementitious composite is subjected to equivalent stress levels, variations in the FCR exhibit an increasing trend with decreasing resilient modulus, stemming from a decrease in stiffness due to the increased concentration of MWCNTs/GNPs. Additionally, the EIS analysis demonstrates a contraction for the Nyquist curves under compressive ramp loading prior to failure, followed by the expansion of these curves postfailure. Scanning electron microscopy (SEM) images visually showcase the bridging effects of MWCNTs and the filling ef-fects of GNPs within the composite structure.

Nonlinear properties of zinc germanium diphosphide (ZGP) crystals enable their ap-plications in powerful mid-IR optical parametric oscillators and second-harmonic generators. This paper summarizes mechanisms of the laser induced damage (LID) in high-purity ZGP crystals under periodically pulsed nanosecond irradiation by a Ho3+:YAG laser at 2.1 μm. The ZGP samples were manufactured by “LOC” Ent., Tomsk, Russia, or Harbin Institute of Technology, China. The impact of processing techniques and the post-growing methods for polishing and anti-reflection coating on the LID threshold are discussed. The importance of the defect structure of the crystal lattice and the parameters of transparent coatings for increasing the LID threshold is discussed. The impact of the test laser parameters on the LID threshold is analyzed. The transient area near the LID threshold obtained using digital holography is ana-lyzed. Influence of the pre-damage processes on the optical parametric oscillations is reported. Prospects for improving ZGP crystals to further increase the LID threshold are discussed.

Pathological aseptic calcification is the most common form of structural valvular degeneration (SVD), leading to premature failure of heart valve bioprostheses (BHVs). The processing methods used to obtain GA-fixed pericardium-based biomaterials determine the hemodynamic characteristics and durability of BHVs. This article presents a comparative study of the effects of several processing methods on the degree of damage to the ECM of GA-fixed pericardium-based biomaterials as well as on their biostability, biocompatibility, and resistance to calcification. Based on the assumption that preservation of the native ECM structure will enable the creation of calcinosis-resistant materials, this study provides a soft biomimetic approach for the manufacture of GA-fixed biomaterials using gentle decellularization and washing methods. It has been shown that the use of soft methods for preimplantation processing of materials, ensuring maximum preservation of the intactness of the pericardial ECM, radically increases the resistance of biomaterials to calcification. The data obtained are of interest for the development of new calcinosis-resistant biomaterials for the manufacture of BHVs.

The fatty acid elongase ELOngation of Very-Long-chain fatty acids protein 2 (ELOVL2) controls the elongation of polyunsaturated fatty acids (PUFA) producing precursors for omega-3, do-cosahexaenoic acid (DHA), and omega-6, docosapentaenoic acid (DPAn6) in-vivo. Expectedly, Elovl2-ablation drastically reduced the DHA and DPAn6 in liver mitochondrial membranes. Unexpectedly, however, total PUFAs levels decreased further than could be explained by Elovl2 ablation. The lipid peroxidation process was not involved in PUFAs reduction since malondial-dehyde-lysine (MDAL) and other oxidative stress biomarkers were not enhanced. The content of mitochondrial respiratory chain proteins remained unchanged. Still, membrane remodeling was associated with high voltage-dependent anion channel (VDAC) and adenine nucleotide trans-locase 2 (ANT2), a possible reflection of the increased demand on phospholipid transport to the mitochondria. Mitochondrial function was impaired despite preserved content of the respiratory chain proteins and the absence of oxidative damage. Oligomycin-insensitive oxygen consumption increased, and coefficients of respiratory control were reduced by 50%. The mitochondria became very sensitive to fatty acid-induced uncoupling and permeabilization, where ANT2 is involved. Mitochondrial volume and number of peroxisomes increased as revealed by transmission elec-tron microscopy. In conclusion, the results imply that endogenous DHA production is vital for the normal function of mouse liver mitochondria and could be relevant not only for mice but also for human metabolism.

This paper focuses on parametric model order reduction (PMOR) of guided ultrasonic wave propagation and its interaction with damage in a fiber metal laminate (FML). Structural health monitoring in FML seeks to detect, localize and characterize the damage with high accuracy and minimal use of sensors. This can be achieved by the inverse problem analysis approach which employs the signal measurement data recorded by the embedded sensors in the structure. The inverse analysis requires to solve the forward simulation of the underlying system several thousand times. These simulations are often exorbitantly expensive and triggered the need for improving their computational efficiency. A PMOR approach hinged on the proper orthogonal decomposition method is presented in this paper. An adaptive parameter sampling technique is established with the aid of a surrogate model to efficiently update the reduced-order basis in a greedy fashion. A numerical experiment is conducted to illustrate the parametric training of the reduced-order model. The results show that the reduced-order solution based on the PMOR approach is accurately complying with that of the high fidelity solution.

Climate change causes weather extremes to rise in frequency and severity, which could have detrimental effects on human life, property and livelihood activity. There is significant uncertainty about the influences of anthropogenic climate change on the occurrence and severity of small-scale, sudden onset weather phenomena such as hailstorms and subsequent loss and damage. Yet, several studies indicate that there is an apparent stable connection between hailstorm activity and hailstorm damage. Severe hailstorm events are observed in Bangladesh in recent years, which are, in fact, rapid-onset disasters but low exposure in terms of giving government response and media consideration. Hence this study examines potential impacts and management strategies for loss and damage resulting from hailstorm events among smallholder farmers in Kurigram District's Phulbari Upazila of Bangladesh. Firstly, the direct and long term economic and non-economic loss and damage caused by the hailstorm on human well-beings and livelihoods were assessed. Then, the study evaluated the current adaptation, coping, management and response strategies at the institutional and community level in the context of such extreme events. Finally, a regulatory framework and implementation approaches had suggested achieving the country's resilience against disaster and climate change-induced loss and damage. Participatory Vulnerability Analysis, Key Informant Interviews and Sample Surveys accumulated the primary data for the study. In addition, secondary data were collected through analysis of literature, published and unpublished scientific articles and media reports, etc. This research outcome will help countries develop a guideline to address climate change and disaster-related loss and damage.

Imbalance in the oxidative status in neurons, along with mitochondrial damage, are common characteristics in some neurodegenerative diseases. The maintenance in energy production is crucial to face and recover from the oxidative damage and the coexistence of different sources of energy production, such as mitochondrial and glycolytic ATP, allows faster adaptative mechanisms to situations of high energy demand and may help in the maintenance of neuronal function in stress situations. Fingolimod phosphate is a drug with neuroprotective and antioxidant actions, used in the treatment of Multiple Sclerosis. This work has been performed in a model of oxidative damage on neuronal cell cultures exposed to menadione, in presence or absence of fingolimod phosphate. We have studied the mitochondrial function and several pathways related with glucose metabolism, including oxidative, glycolytic and pentose phosphate in neuronal cells cultures. Our results showed a beneficial effect on neuronal survival probably based in the recovery of all, oxidative balance, glycolysis and pentose phosphate, promoted by fingolimod phosphate. These effects are mediated, at least in part by the interaction with its specific receptor. These actions would make this drug a potential tool to the treatment of neurodegenerative processes, either to slow progression or alleviate symptoms.

Mitochondrial dysfunction is relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the heart of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n=8) or placebo (n=8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and abundance of mtDNA4834 deletion), and mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. TFAM binding to mtDNA regions involved in replication and deletion generation was increased following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling was found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.

Unavoidable exposure to radiosensitive normal tissues around cancerous tumor during the radiotherapy can cause side effects such as self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. Nevertheless, clinical use of currently available radiation protective agents is limited because of their generic cytotoxicity. A study on radiation protective effect of delphinidin was conducted with proton-beam-exposed human colon cells (CCD-18Co). The measurement in changes of survival fractions of CCD-18Co with/without delphinidin administration at different radiation doses were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The changes in expression of reactive oxygen species (ROS) and in activities of antioxidant enzymes were measured by colorimetric assays using pertinent assay kits. The measurement of pro-apoptosis/pro-survival protein expressions using Western blot assay and the measurement of DNA damage using comet assay were also fulfilled to evaluate the molecular level of radiation damages in CCD-18Co cells. The experimental results revealed that the pre-administration of delphinidin regulated antioxidant enzymes, reduced ROS, decreased DNA damage, regulated pro-apoptosis/pro-survival proteins, and eventually reduced apoptosis of CCD-18Co cells. In conclusion, it is claimed that delphinidin is nontoxic natural radiation protective compound, and thus delphinidin can be used to protect normal colon tissues during the proton beam therapy.

The Two Photon Absorption - Transient Current Technique (TPA-TCT) is a device characterisation technique that enables three-dimensional spatial resolution. Laser light in the quadratic absorption regime is employed to generate excess charge carriers only in a small volume around the focal spot. The drift of the excess charge carriers is studied to obtain information about the device under test. Neutron, proton, and gamma irradiated p-type pad silicon detectors up to equivalent fluences of about 7e15 neq/cm2 and a dose of 186 Mrad are investigated to study irradiation induce effects on the TPA-TCT. Neutron and proton irradiation lead to additional linear absorption, which does not occur in gamma irradiated detectors. The additional absorption is related to cluster damage and the absorption scales according to the non-ionising energy loss. The influence of irradiation on the two photon absorption coefficient is investigated, as well as potential laser beam depletion by the irradiation induced linear absorption. Further, the electric field in neutron and proton irradiated pad detectors at an equivalent fluence of about 7e15 neq/cm2 is investigated, where the space charge of the proton irradiated devices appears inverted compared to the neutron irradiated device.

Medulloblastoma (MB) is one of the most common malignant pediatric brain tumors. Current therapy results in poor prognosis for high-risk SHH/p53-mutated MB, emphasizing the importance of more effective therapeutic strategies. Here, we investigated potential radiosensitizing effects of checkpoint kinase inhibitors (Chk-i) prexasertib (Chk1/2) and SAR-020106 (Chk1) in human SHH/p53-mutated MB in vitro and in vivo. UW228 and DAOY cells were treated with Chk-i and irradiation (RT). Metabolic activity, proliferation, and apoptosis was determined at d3, long-term clonogenicity at d14. DNA damage was assessed after 1, 24, and 72 h. Patient-derived SHH/p53-mutated, luciferase-transfected MB cells were implanted orthotopically into NSG mice (d0). Fractionated therapy (daily, d7-11) was applied. Body weight (BW) was documented daily, tumor growth weekly, and proliferation at d42. In vitro, Chk-i exhibited dose-dependent reduction of metabolic activity, proliferation, and clonogenicity, and enhancement of apoptosis. Combination with RT showed additive antitumor effects and enhanced residual DNA damage. In vivo, tumor growth was delayed by Chk-i alone. Low-dose prexasertib enhanced RT-induced tumor growth inhibition (37-fold) and reduced proliferating cells, high-dose prexasertib and SAR-020106 showed opposite effects (n=3, n.s.). BW assessments revealed that the treatment was well tolerated. Our data indicate a benefit of Chk-i in combination with RT in SHH/p53-mutated MB. However, high-dose Chk-i may compromise the RT effect, possibly by its anti-proliferative activity. Furthermore, we demonstrate for the first time the antitumor activity of the Chk1-specific inhibitor SAR-020106 in the murine brain.

Aluminium alloys are used for fabrication of fuel clad of research grade nuclear reactors as well as of several types of core components of high flux research reactors. In order to carry out design and safety analysis of these components, their mechanical and fracture properties are required by the designer. In this work, experiments have been conducted on tensile specimens machined from an aluminium alloy block to evaluate the material stress-strain curve. For evaluation of fracture properties, experiments have been conducted on disc shaped compact tension specimens in order to determine the fracture toughness of aluminium alloy. From crystal plasticity based finite element analysis and experimental data, a material damage parameter for prediction of crack initiation has been evaluated. The variation of the parameter for various values of initial a/W ratios of the disc-shaped CT specimens have been studied. It was observed that the damage parameter is independent of crack geometry and hence, it qualifies as transferable material property which can be used to predict crack initiation in a component of this material subjected to different kinds of loading conditions. In addition, the JR curves of the disc-shaped CT specimens have also been evaluated from experiments. The material damage parameter has also been used to study the crack initiation in single crystal fracture specimens with two different orientations. It was observed that the [111] orientation is more susceptible to crack initiation and propagation compared to the [100] orientation as the damage parameter is high in the ligament of the specimen ahead of the crack-tip for the same level of load. The results of the experiments and the material damage parameter shall be helpful for integrity analysis of fuel clad of research reactors as well as components of high flux research reactors.

Clinical and analytical differences between adult patients monoinfected with Borrelia burgdorferi sensu lato (s.l.) and patients infected with B. burgdorferi s.l. who also had IgG antibodies against Babesia divergens have not been reported so far. Both Lyme disease caused by B. burgdorferi and babesiosis caused by B. divergens, endemic in Asturias, Northwestern Spain, are transmitted by Ixodes tick bites. Clinical, laboratory and other diagnostic tests characteristics (imaging, electro-cardiographic-ECG) of 120 residents of Asturias with confirmed B. burgdorferi s.l. infection, di-agnosed during 2015-2017, of whom 47 (39.2%) had B. divergens IgG antibodies, were retrospec-tively compared. Cardiorespiratory symptoms were reported in 9/47 (19.2%) patients with Lyme disease and B. divergens IgG antibodies compared to 4/73 (5.5%) patients with B. burgdorferi s.l. monoinfection (P=0.02). Dyspnea was recorded in 4/47 (8.5%) patients with Lyme disease and B. divergens IgG antibodies compared to 1/73 (1.4%) monoinfected (P=0.07). In addition ECG atri-oventricular (AV) block, mostly 1st degree, was detected in 5/47 (15.6%) patients with Lyme dis-ease and B. divergens IgG antibodies compared to 1/73 (2.6%) B. burgdorferi s.l. monoinfected (P=0.09). No other clinical, laboratory or other tests differences were observed between B. burgdorferi and B. divergens IgG antibodies carriers and B. burgdorferi monoinfected. We con-cluded that patients with Lyme disease and B. divergens IgG antibodies had more frequent car-diorespiratory symptoms, mainly dyspnea, compared to B. burgdorferi monoinfected patients. These symptoms were unrelated to anemia. ECG AV block, perhaps induced by summative myo-cardial damage due to either infections or B. divergens induced lung microcirculation slow-ing-down, might play a role in the cardiorespiratory dysfunction.

Beyond factors such as smoking and obesity, the risk of getting gastrointestinal cancer is passed down from parents to offspring, inherited by a gene mutation, predisposing them to develop cancer in their lifetime. Here we describe the clinical history of family members affected by gastrointestinal pathologies often leading to cancer. In the epidemiological study, the cohort of members of this family shared a high risk of developing gastrointestinal diseases. The subjects were monitored from May 2006 to December 2017 by collecting periodically clinical and endoscopic data, and determining both auto-modification of lymphocyte Poly(ADP-ribose)Polymerase as early signal of DNA damage, and erythrocyte membrane lipid composition (Fat Profile). Both biomarkers were demonstrated to be non invasive and easy tools, to monitor over time family members, first the oldest members (nine siblings), and thereafter their offspring, whose cell status evolved from physiological even to cancerous one. All subjects developed gastrointestinal pathologies of different kind and seriousness. Some diseases evolved to cancer, sometimes as a sudden and lethal event. The results of the two molecular approaches, agreed and even predicted the clinical and imaging paths. This cohort study supported the hypothesis that both noninvasive molecular analyses can predict altered cell states and support clinical and imaging tests.

The seismic damage in reinforced concrete bridges is identified in this study using the "M and P" hybrid technique initially developed for planar frames. The proposed methodology involves a series of pushover and instantaneous modal analyses with a progressively increasing target deck displacement along the longitudinal direction of the bridge. From the results of these analyses, the diagram of the instantaneous eigenfrequency of the bridge, ranging from the health state to near collapse, is plotted against the inelastic seismic deck displacement. By pre-determining the eigen-frequency of an existing bridge along its longitudinal direction through "monitoring and frequency identification", the target deck displacement corresponding to the damage state can directly be found from this diagram. Subsequently, the damage can be identified by examining the results of the pushover analysis at the step where the target deck displacement is indicated. The effectiveness of this proposed technique is evaluated in the context of multiple span bridges with unequal pier heights, illustrated through an example of a four-span bridge. The findings demonstrate that the damage potential in bridge piers can be successfully identified by combining the results of a monitoring process and pushover analysis.

It remains unclear in the literature what is the cause of the so-called alkali-carbonate reaction (ACR) damage to concrete yet, a consensus is reached when considering dedolimitization as non-expansive. However, expansion and cracks as distress features are often attributed to alkali-silica reaction (ASR) when evidence of a reactive mineral is found in the aggregate. Evidently, different types of aggregates may produce different types and degrees of damage. Therefore, this work aims to assess the damage to concrete generated and propagated by the so-called ACR susceptible reactive Kingston coarse aggregate through mechanical testing (i.e., direct shear test), microscopy (the damage rating index – DRI), and other techniques. Distinct induced expansion levels (i.e., 0%, 0.05%, 0.12%, and 0.20%) were selected to compare the distress caused by ACR to concrete affected by ASR. Result show that the behaviour of ACR, namely as captured through the DRI, is inconsistent with that of ASR thus attesting to ACR being a distinct distress mechanism.

Astronauts in space are subject to a continuous bombardment of ionizing radiation. The Earth's magnetic field and the ISS shield some biologically damaging particles traveling through. Still, travel beyond low-Earth orbit and extravehicular activities are exceedingly more dangerous and there is a concern for the acute and late-occurring adverse health effects befalling astronauts. So, it is vital to consider the current tools and models used to describe and study the organic consequences of ionizing radiation exposure. It is equally important to see where these models may improve. This article reviews the historical development and current state of knowledge of radiation effects impacting astronauts in orbit. We explain the space radiation environment, cellular microenvironment, and how these may be incorporated in radiobiological models to aid in our understanding of the influence space travel may have on astronaut health. The topics discussed in this paper include a review of DNA damage and repair mechanisms and the numerical models that aim to explain the biological effects resulting from ionizing radiation damage. Historically, radiobiological models focused on how radiation damages nuclear DNA, built upon the hypotheses of Crowther and Lea in the 1940s and 1960s, and neglected other sub-cellular targets outside of nuclear DNA.

The average age of in-service bridges has increased in recent years in the United States. To address this issue, structural health monitoring and damage identification approaches can be employed to prioritize maintenance/replacement of aging bridges. Among the damage identification and operational health monitoring approaches, finite element (FE) model updating methods can offer a solution to evaluate the mechanics-based characteristics of bridges. However, in a real-world setting, unidentifiability and mutual dependency between model parameters, modeling errors, especially due to boundary conditions, as well as ill-conditioning of updating algorithms can pose challenges to the application of FE model updating methods. To address these challenges, this study presents a two-step FE model updating approach. In the first step, modal-based model updating is used to estimate linear model parameters mainly related to the stiffness of boundary conditions and material properties. In the second step, in order to refine parameter estimation accounting for nonlinear response behavior of the bridge, a time-domain model updating is carried out. In this step, boundary conditions are fixed at their final estimates using modal-based model updating. To prevent the convergence of updating algorithm to local solutions, the initial estimates for nonlinear material properties are selected based on their corresponding final estimates in the modal-based model updating. To validate the applicability of the two-step FE model updating approach, a series of forced-vibration experiments are designed and carried out on a pair of decommissioned and deteriorated prestressed bridge I-girders. After carrying out the two-step FE model updating, the final estimates of concrete compressive strength are shown to provide reasonable assessment of the damage extent in the girders.

The genetic pool of valuable old ornamental cultivars and their in situ maintenance may be threated by climate change. Meanwhile, the ornamental plants like roses make up an important share of both gardens and urban green spaces, where they are particularly vulnerable to multistress growth conditions. The aim of this research was to evaluate the effect of changing climatic conditions on growth and flowering of 11 historic climber roses through long-term studies (2000-2017) conducted in Central Europe. The evaluation of plants consisted of assessment of frost damage and the timing of early phenological stages (starting of bud break, leaf unfolding) as well as gathering data on beginning, fullness and end of flowering and its abundance. Frost damage was not recorded in any year only in ‘Mme Plantier’, and did not occur for any cultivar after the winter in the years 2007, 2008, and 2014. Only a little damage to one-year shoots was recorded after the winter in the years 2015-2017. Frost damage to ‘Alberic Barbier’, ‘Albertine’, ‘Chaplin's Pink Climber’, ‘Orange Triumph clg’ and ‘Venusta Pendula’ led to pruning to ground level in every year excluding those listed above. Frost damage of once blooming roses limited their flowering; however, the many-year data-sets showed a trend for decreased frost damage and improved abundance of flowering, and these results can be interpreted as a response to the increase of average air temperature. The timing of bud breaking and leaf development in all climber roses was strictly correlated with average air temperature in the dormancy period. The reactions of climber roses to weather conditions confirmed the influence of climatic changes on ornamental crop plants in Central Europe, introducing the potential possibility for the wider application of climber roses, but without certainty of flowering every year.

Underwater natural gas pipelines constitute critical infrastructure for energy transportation. Any damage or leakage in these pipelines poses serious security risks, directly threatening marine and lake ecosystems and potentially causing operational issues and economic losses in the energy supply chain. Due to the difficulty in detecting deterioration over time and regularly inspecting these submerged pipelines by divers, the use of unmanned underwater vehicles (UUVs) becomes crucial in this field. In this study, an underwater pipeline tracking experiment was carried out by providing autonomous features to a remote-controlled unmanned underwater vehicle. During the tracking of the underwater pipeline, damages were identified, and the locations of these damages were determined. The navigation information of the underwater vehicle, including orientation in the x, y, z axes (roll, pitch, yaw) from a gyroscope integrated with magnetic compass, speed and position information in the three axes from an accelerometer, and the distance to the water surface from a pressure sensor, was integrated into the vehicle. Pre-tests determined the necessary pulse width modulation values for the thrusters of the vehicle, enabling autonomous operation by providing these values as input to the thruster motors. In this study, the vehicle moves in 3D was achived by the vertical thruster of the vehicle was activated to maintain a specific depth, and applying equal force to the vehicle’s right and left thrusters forward movement, while differential force induced deviation angles. In pool experiments, the unmanned underwater vehicle autonomously tracked the pipeline as intended, identifying damages on the pipeline using images captured by the vehicle's camera. The images for damage assessment were processed using a convolution neural network (CNN) algorithm, which is a deep learning method. The position of the damage relative to the vehicle was estimated from the pixel dimensions of the identified damage. The location of the damage relative to its starting point was obtained by combining these two positional pieces of information from the vehicle's navigation system. The all study was performed within the Python environment.

In order to study the collapse failure of shaft wall of high depth inclined ore-pass under ore impact wear behavior, 25 ore-passes in a deep mine in Yunnan, China were investigated. Considering the ore-pass structural characteristics and the impact wear effect of ore on shaft wall, the shaft wall damage model of high depth inclined ore-pass is constructed based on the contact mechanics theory. Furthermore, No. 1#, 2#, 3# and 9# ore-passes of the mine are taken as examples for analysis, and the three results of theoretical analysis, numerical simulation and engineering case are used for comparison and verification. The shaft wall damage degree is predicted, and the damage mechanism between total shaft wall damage volume Qtol and ore-pass depth H, ore-pass dip angle θ, inclined angle of chute α, shaft diameter D and ore block size P is quantitatively investigated. The results show that the rationality of the proposed model is verified by numerical analysis and field engineering situations. Moreover, the deeper ore-pass depth H, the more shaft wall damage volume Qtol with the increase of collision frequency. Qtol increases exponentially with P and increases gradually with D. With the increase of θ or α, Qtol increases generally first and then decreases. Therefore, Qtol can be effectively reduced by selecting the appropriate structure parameters of ore-pass and adopting the technology of drilling straight ore-pass. This work provides technical support for long period safe operation of high depth inclined ore-pass.

Base excision repair (BER) is a cellular process that removes damaged bases arising from exogenous and endogenous sources including reactive oxygen species, alkylation agents, and ionizing radiation. BER is mediated by the actions of multiple proteins that work in a highly concerted manner to resolve DNA damage efficiently to prevent toxic repair intermediates. During the initiation of BER, the damaged base is removed by one of 11 mammalian DNA glycosylases resulting in abasic sites. Many DNA glycosylases are product inhibited by binding to the abasic site more avidly than the damaged base. Traditionally apurinic/apyrimidinic endonuclease, APE1, was believed to help turnover the glycosylases to undergo multiple rounds of damaged base removal. However, in a series of papers from our laboratory we have demonstrated that UV-damaged DNA binding protein (UV-DDB) stimulates the glycosylase activities of human 8-oxoguanine glycosylase (OGG1), MUTY DNA glycosylase (MUTYH), alkyladenine glycosylase/N-methylpurine DNA glycosylase (AAG/MPG), and single-strand selective monofunctional glycosylase (SMUG1), between three-to-five-fold. Moreover, we have shown UV-DDB can assist chromatin decompaction facilitating access of OGG1 to 8-oxoguanine damage in telomeres. This review summarizes the biochemistry, single-molecule, and cell biology approaches that our group used to directly demonstrate the essential role of UV-DDB in BER.

This study investigates the interpretability of machine learning (ML) models applied to cumulative damage prediction during a sequence of earthquakes, emphasizing the use of techniques such as SHapley Additive exPlanations (SHAP), Partial Dependence Plots (PDPs), Local Interpretable Model-agnostic Explanations (LIME), Accumulated Local Effects (ALE), Permutation and Impurity-based technique. The research explores the cumulative damage during seismic sequences, aiming to identify critical predictors and assess their influence on the cumulative damage. Moreover, the predictors contribution in respect with the range of final damage is evaluated. Nonlinear time history analyses are applied to extract the seismic response of an eight-story Reinforced Concrete (RC) frame. The regression problem’s input variables are divided into two distinct physical classes: pre-existing damage from the initial seismic event and seismic parameters representing the intensity of the subsequent earthquake, expressed by Park and Ang damage index (DIPA) and Intensity Measures (IMs), respectively. The study offers a comprehensive review of cutting-edge ML methods, hyperparameter tuning, and ML method comparisons. A LightGBM model emerges as the most efficient, among 15 different ML methods examined, with critical predictors for final damage being the initial damage caused by the first shock and the IMs of the subsequent shock: IFVF and SIH. The importance of these predictors is supported by feature importance analysis and local/global explanation methods, enhancing the interpretability and practical utility of the developed model.

In this paper, we investigate the effects of mean stress, multiaxial loading, and residual stresses on the fatigue life of springs. We study the fatigue life of a homogeneously stressed material subjected to cyclic loading with nonzero mean stress. Traditional methods for estimating fatigue life are based on Goodman and HAIGH diagrams. The formal analytical descriptions, namely "stress-life" and "strain-life" approaches, are found to be more suitable for the numerical methods. The fatigue analysis method described above, which describes crack growth per cycle, is extended. The extensions allow consideration of the mean stress of a load cycle. Closed-form expressions for crack length versus number of cycles are derived. The complementary effects on the fatigue life of springs, which ultimately have a significant influence on the fatigue life of springs, are summarized. For the proposed unified fatigue life functions, the ranges for the stress loading factor are extended by introducing the effective stress intensity. The solution leads to the factor range for the effective stress intensity, the effective mean value of the stress intensity factor and the effective stress ratio. The developed method assumes the homogeneous stress state in the whole spring element. For the non-homogeneously loaded structural elements, the weak-link concept is applied to account for fatigue.

Abstract Eye health is crucial and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation of patients with natural antioxidants and nutraceuticals. In particular, evidence has been accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin, in particular, has been found to protect foto-receptors thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. On the other hand, CoQ10 has been demonstrated to produce consistent effect in reducing ocular pressure thereby leding to protection in patients undergoing glaucoma. Finally, both grape seed extract rich in anthocyanosides and polynsatured fatty acids (PUFAs) seem to contribute in the prevention of retinal disorders. Thus, combination of nutraceuticals and anti-oxidants may represent the right solution for a multiaction activity in eye protection to be associated to current drug therapies, and this will be of potential interest in early stages of eye disorders.

Wernicke-Korsakoff syndrome (WKS) is induced by thiamine deficiency (TD) and mainly related to alcohol consumption. Frontal cortex dysfunction has been associated to impulsivity and disinhibition in WKS patients. The pathophysiology involves oxidative stress, excitotoxicity and inflammatory responses leading to neuronal death, but the relative contributions of each factor (alcohol and TD, isolate or in interaction) to these phenomena are still poorly understood. A rat model was used by forced consumption of 20% (w/v) alcohol for 9 months (CA), TD hit (TD diet + pyrithiamine 0.25 mg/kg, i.p. daily injections the last 12 days of experimentation; TDD), and both combined treatments (CA+TDD). Motor and cognitive performance and cortical damage were examined. CA caused hyperlocomotion as a possible sensitization of ethanol-induced excitatory effects and recognition memory deficits. In addition, CA+TDD animals showed a disinhibited-like behavior, which appears to be dependent on TDD. Also, combined treatment led to more pronounced alterations in nitrosative stress, lipid peroxidation, apoptosis and cell damage markers. Correlations between injury signals and disinhibition suggest that CA+TDD disrupts behaviors dependent on the frontal cortex. Our study sheds light on the potential disease-specific mechanisms, reinforcing the need for neuroprotective therapeutic approaches along with preventive treatments for the nutritional deficiency in WKS.

Susceptibility to photoimmune suppression and photocarcinogenesis is greater in male than in female humans and mice and is exacerbated in female estrogen receptor-beta knockout (ER-β-/-) mice. We previously reported that the active vitamin D hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D) applied topically protects against ultraviolet radiation (UV)-induction of cutaneous cyclobutane pyrimidine dimers (CPDs) and suppression of contact hypersensitivity (CHS) in female mice. Here we compare these responses in female versus male Skh:hr1 mice, in ER-β-/- versus wild type C57BL/6 mice, and in female ER-blockaded Skh:hr1 mice. Induction of CPDs was significantly greater in male than female Skh:hr1 mice and was more effectively reduced by 1,25(OH)2D in female Skh:hr1 and C57BL/6 mice, than in male Skh:hr1 or ER-β-/- mice respectively. This correlated with reduced sunburn inflammation by 1,25(OH)2D in female but not male Skh:hr1 mice. Furthermore, although 1,25(OH)2D alone dose-dependently suppressed basal CHS responses in male Skh:hr1 and ER-β-/- mice, UV-induced immunosuppression was universally observed. In female Skh:hr1 and C57BL/6 mice, the immunosuppression was decreased by 1,25(OH)2D dose-dependently, but not in male Skh:hr1, ER-β-/- or ER-blockaded mice. These results reveal a sex bias in genetic, inflammatory and immune photoprotection by 1,25(OH)2D favoring female mice, that is dependent on the presence of ER-β.

In this paper, we investigated transducer placement strategies for detecting crack in primary aircraft structures using ultrasonic Structural Health Monitoring (SHM). The approach developed is for an expected damage location based on fracture mechanics, for example fatigue crack growth in a high stress location. To assess the performance of the developed approach, finite-element (FE) modelling of a damage tolerant aluminum fuselage has been performed by introducing an artificial crack at a rivet hole into the structural FE model and assessing its influence on the Lamb wave propagation, compared to a baseline measurement simulation. The efficient practical sensor position was determined from the largest change in area that is covered by reflected and missing wave scatter using an additive color model. Blob detection algorithms were employed in order to determine the boundaries of this area and to calculate the blob centroid. To demonstrate that the technique can be generalized, the results from different crack lengths and from tilted crack are also presented.

Changes in extreme weather patterns are expected under climate change. In this study, a risk assessment was conducted using 4 building damage history datasets and 33 weather datasets (precipitation, wind speed, snow, and temperature) from 230 regions in South Korea to quantitatively analyze and predict building damage caused by potential future natural disasters. Decision tree analysis was used to evaluate building damage risk in 230 regions. The decision tree model to determine the risk of flood, gale, and typhoon was generated, which excluded gales, with less damage. The weight (variable importance) and limit value (damage limit) of the weather variables ware derived using the decision tree model. Using these two factors, we assessed the building damage risk in 230 regions in South Korea until 2100. The number of regions at risk of flood damage increased by more than 30% in average. Conversely, regions at risk of snowfall damage decreased by more than 90%. The regions at risk of typhoons decreased by 57.5% on average, and the number of regions at high risk of typhoon damage increased by up to 62.5% in RCP 8.5. These results can be used as objective data to minimize future building damage throughout South Korea, representing the first step towards sustainable development in the region with respect to disaster response.

The rare abscopal effect during radiotherapy is thought to be caused by the release of immune-stimulated damage-associated molecular patterns, such as high mobility group box-1 protein (HMGB1), from cancer cells. Although external irradiation of cancer cells increases HMGB1 release, it is not clear if HMGB1 is released from cells after administering 131I-labeled m-iodobenzylguanidine (131I-MIBG) as an internal targeted radiotherapeutic agent. This study aimed to determine if HMGB1 is released from human-derived cancer and normal cells after administering 131I-MIBG. Methods: Extracellular lactate dehydrogenase (LDH) and HMGB1 released from H441 (human-derived lung adenocarcinoma cell line) and HaCaT (human keratinocyte cell line) 1 day after 2- and 10-Gy X-ray irradiation were measured. Accumulations of 131I-MIBG in SH-SY5Y (human-derived neuroblastoma cell line) and HaCaT were measured 60 min after administering 131I-MIBG (0.37, 1.85, 3.7 MBq/well). Extracellular LDH and HMGB1 released from SH-SY5Y and HaCaT 1 day after administering 131I-MIBG were also measured. Results: The extracellular LDH and HMGB1 released from H441 after 10-Gy X-ray irradiation were significantly increased. However, the extracellular LDH and HMGB1 released from HaCaT after 2-Gy and 10-Gy X-ray irradiation were not increased. After administering 1.85 MBq and 3.7 MBq 131I-MIBG, the extracellular LDH and HMGB1 released from SH-SY5Y were both significantly increased, but only the extracellular LDH released from HaCaT was significantly increased. Conclusions: HMGB1 was released from neuroblastomas but not from normal cells after 131I-MIBG administration, suggesting that a combination of 131I-MIBG and immunotherapy may be feasible.

Heat stress due to climate warming can significantly affect the synthesis of sex hormones in male adolescents, which can impair the ability of the hypothalamus to secrete gonadotropin-releasing hormone on the hypothalamic-pituitary-gonadal axis, which leads to a decrease in luteinizing hormone and follicle-stimulating hormone, which ultimately negatively affects spermatogenesis and testosterone synthesis. For optimal spermatogenesis, the testicular temperature should be 2–6°C lower than body temperature. Heat stress directly affects the testes, damaging them and re-ducing testosterone synthesis. Additionally, chronic heat stress abnormally increases the level of aromatase in Leydig cells, which increases estradiol synthesis while decreasing testosterone, lead-ing to an imbalance of sex hormones and spermatogenesis failure. Low levels of testosterone in male adolescents lead to delayed puberty and incomplete sexual maturation, negatively affect height growth and bone mineral density, and can lead to a decrease in lean body mass and an in-crease in fat mass. In order for male adolescents to acquire healthy reproductive capacity, it is recommended to provide sufficient nutrition and energy, avoid exposure to heat stress, and pro-vide foods and supplements to prevent or repair testosterone reduction, germ cell damage, and sperm count reduction caused by heat stress so that they can enter a healthy adulthood.

Background: Breast cancer incidence and mortality exhibit a rising trend globally among both premenopausal and postmenopausal women suggesting that there are serious errors in our preventive and therapeutic measures.Purpose: Providing a series of valuable, but misunderstood inventions highlighting the role of increasing estrogen signaling in prevention and therapy of breast cancer instead of its inhibition. Results: 1. Breast cells and breast cancer cells with germline BRCA1/2 mutations similarly show defect in liganded estrogen receptor (ER) signaling demonstrating its role in genomic instability and cancer initiation. 2. In breast cancers, the increased expression of certain receptor family is an effort for self directed improvement of genomic defects, while the weakness or loss of receptors indicates a defect requiring medical repair. 3. ER overexpression in breast cancer cells is capable of strengthening estrogen signaling and DNA repair, while in ER negative tumors, HER2 overexpression tries to upregulate unliganded ER activation and genome stabilization. 4. ER positive breast cancers responsive to endocrine therapy may show a compensatory ER overexpression resulting in a transient tumor response. Breast tumors, non responsive to endocrine therapy, show HER2 overexpression for compensation the complete blockade of liganded ER activation. 5. In breast tumors, somatic mutations serve upregulation of liganded or unliganded activation of ERs helping genome stabilization and apoptotic death. 6. The dynamic communication between breast cancer and its microenvironment is a wonderful collaboration among molecular players fighting for genomic repair and apoptosis in the tumor. 7. In breast cancers, there is no resistance to genotoxic or immune blocker therapies, but rather the non responsive tumor cells exhausted all compensatory possibilities against therapeutic damages. Conclusion: Understanding the behavior and ambition of breast cancer cells may achieve a turn in therapy via applying a supportive care instead of genotoxic measures.

The accompanying mechanical behavior during the flow of ore-rock dispersion is an important factor leading to the instability and failure of the orepass in the ore storage section. It is of great significance to accurately understand the instability characteristics of the well wall in the ore section, during the ore drawing process by understanding the flow characteristics and internal mechanical transfer mechanism of ore-rock dispersion. Using the discrete element method to analyze the flow characteristics, contact compactness, stress distribution characteristics and contact force probability distribution of the ore-rock dispersion, it realizes the quantitative characterization of the damage degree of ore-rock flow, and reveals the damage mechanism of mine storage wall. The results show that: (1) The friction between ore-rock particles, between ore-rock and well wall is an important reason for the change of the macroscopic flow form of ore-rock from “one” to “V” type. (2) The compactness and stress concentration of ores are increasing with the increase of storage depth, which is shown that with the increase of storage depth, the greater the probability of well wall instability. (3) The probability distribution of contact force strength between particles decreases exponentially in the whole process of ore drawing, in which the strong chain plays a major role in the stability of the dispersion system. (4) The number of overpressure and the overpressure coefficient can be used to quantitatively characterize the wall damage degree under the action of ore-rock flow. The dynamic side pressure decreases periodically in the form of exponential fluctuations, and the dynamic load formed by the ore-rock flow mainly played a role in the lower area of the ore storage section.

Leukemia encompasses diverse blood cancers marked by the unchecked growth and developmental blockage of myeloid or lymphoid precursor cells within the bone marrow and the bloodstream. Treatment traditionally involves intensive chemotherapy or hematopoietic stem cell transplantation, albeit these approaches often yield severe side effects and encounter resistance from leukemia cells. Hence, the quest for novel therapies targeting leukemic cells selectively is paramount to enhancing leukemia outcomes. Exploring natural products is a promising avenue for pursuing effective chemotherapy and preventive measures against leukemia. These compounds serve as a crucial wellspring for drug development and offer a source of biologically active elements for potential therapeutic interventions in leukemia. The enzyme telomerase plays a vital role in stabilizing chromosomes by adding DNA sections to the end of chromosomes during the mitotic cycle. Notably, hTERT mRNA expression strongly correlates with telomerase activity, making it a potential target for therapeutic intervention without adverse systemic effects. Telomerase inhibition is a promising target in cancer therapy, especially in combination with natural ingredients, demonstrating less cytotoxicity than chemotherapies.

The past is an important lesson for facing the future with greater awareness. In this context, school plays a key role to spread knowledge on natural phenomena and to promote behavior change. Together with researchers, teachers can be strong allies to build more resilient future citizens. The Istituto Nazionale di Geofisica e Vulcanologia (INGV) school training activities provide tools to get ready for the next earthquake and/or tsunamis. About 5000 students from both Middle schools (ISCED 2) and High schools (ISCED 3) were involved in active learning activities based on a flipped-up approach during special online scientific events in the Pandemic. Online lab activities were conducted respectively during the European Researchers’ Night (“Earthquakes: history teaches us the future: researchers for a day with experimentation in didactics for ESL”) and during the World Water Day 2021 and the World Earth Day 2021 (“Tsunamis: history teaches us the future researchers for a day with experimentation in didactics for ESL”). These two Episodes of Situated Learning (ELS) experiences triggered students’ interest, favoring remote learning, developing life skills, focusing on historical seismic studies of both past earthquakes and tsunamis.

To understand lung damage caused by COVID-19, we deduced two-phase lung damage mechanisms. After the lungs are infected with SARS-CoV-2 virus, the affected lung tissue swells and surface properties of pulmonary capillaries change, resulting in an increased flow resistance of affected capillaries. If a sufficient number of capillaries are affected by the infection, the swelling and increased cell wall adhesion collectively raise pulmonary vascular resistance. The increased vascular resistance further increases the dwell times of WBCs in affected capillaries and nearly capillaries. When pulmonary pressure is sufficiently higher, WBCs are forced to squeeze into interstitial spaces or alveolar spaces when local pressures are higher than what the capillaries can withstand. When more and more WBCs are dynamically retained, the flow resistance of more capillaries rises, pulmonary vascular resistance rises, and pulmonary pressure rises. The rise in the pulmonary pressure in turn results in elevated capillary pressures. When capillary pressures around the alveoli are sufficiently high, they cause interstitial pressures to change from normally negative values to positive values. The positive pressures cause fluid leakage to the alveolar space and thus degrade lung function. Tissue swelling, and occupation of WBCs in interstitial spaces and alveolar spaces further reduce compressible volume, and thus cause further rise in the pulmonary vascular resistance and pulmonary pressure. When the pulmonary pressure has reached a critical point as in the second phase, the blood breaks capillary walls and squeezes through interstitial spaces to reach alveolar spaces, resulting in irreversible lung damages. The available free volume in the thorax cage, organ usable capacities, temperature and humid are expected to have great impacts on degree of lung damages. The free volume in the thorax cage, lung usable surplus capacity, and other organ usable capacities determine the arrival time of last-phase irreversible damage. The mechanisms imply that the top priority for protecting lungs is maintaining pulmonary micro-circulation and preserving organ functions in the entire disease course while controlling viral reproduction should be stressed in the earliest time possible. The mechanisms also explain leukecytes are recruited and migrated into inflamed tissues by increasing their dwell times caused by increased local flow resistance.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor with a 5-year survival of <1%. Up to 80% of DIPG tumors contain a specific K27M mutation in one of two genes encoding histone H3 (H3K27M). Furthermore, p53 mutations found in >70-80% of H3K27M DIPG, and mutant p53 status is associated with a decreased response to radiation treatment and worse overall prognosis. Recent evidence indicates that H3K27M mutation disrupts tri-methylation at H3K27 leading to aberrant gene expression. Jumonji family histone demethylases collaborates with H3K27 mutation in DIPG by erasing H3K27 trimethylation and thus contributing to derepression of genes involved in tumorigenesis. Since the first line treatment for pediatric DIPG is fractionated radiation, we investigated the effects of Jumonji demethylase inhibition with GSK-J4, and mutant p53 targeting/oxidative stress induction with APR-246, on radio-sensitization of human H3K27M DIPG cells. Both APR-246 and GSK-J4 displayed growth inhibitory effects as single agents in H3K27M DIPG cells. Furthermore, both of these agents elicited mild radiosensitizing effects in human DIPG cells (sensitizer enhancement ratios (SERs) of 1.12 and 1.35, respectively; p<0.05). Strikingly, a combination of APR-246 and GSK-J4 displayed a significant enhancement of radiosensitization, with SER of 1.50 (p<0.05) at sub-micro-molar concentrations of the drugs (0.5 μM). The molecular mechanism of the observed radiosensitization appears to involve DNA damage repair deficiency triggered by APR-246/GSK-J4, leading to the induction of apoptotic cell death. Thus, a therapeutic approach of combined targeting of mutant p53, oxidative stress induction, and Jumonji demethylase inhibition with radiation in DIPG warrants further investigation.

The evaluation of geometric defects is necessary in order to maintain the integrity of structures over time. These assessments are designed to detect damages of structures and ideally help inspectors to estimate the remaining life of structures. Current methodologies for monitoring structural systems, while providing useful information about the current state of a structure, are limited in the monitoring of defects over time and in linking them to predictive simulation. This paper presents a new approach to the predictive modeling of geometric defects. A combination of segmented from point clouds are parametrized using the convex hull algorithm to extract features from detected defects, and a stochastic dynamic model is then adapted to these features to model the evolution of the hull over time. Describing a defect in terms of its parameterized hull enables consistent temporal tracking for predictive purposes, while implicitly reducing data dimensionality and complexity as well. In this study, 2D point clouds analogous to information derived from point clouds were first generated over simulated life-cycles. The evolutions of point cloud hull parameterizations were modeled as stochastic dynamical processes via autoregressive integrated moving average (ARIMA) and vectorized autoregression (VAR) and compared against ground truth. The results indicate that this convex hull approach provides consistent and accurate representations of defect evolution across a range of defect topologies and is reasonably robust to noisy measurements, however assumptions regarding the underlying dynamical process play a significant the role in predictive accuracy. The results were then validated on experimental data from fatigue testing with high accuracy. Longer term, the results of this work will support finite element model updating for predictive analysis of structural capacity.