Background, Leucoptera coffeella (Guerin-Meneville, 1842) is a moth species (Lyonetiidae, Lepidoptera) pest that causes severe losses to coffee crops. Further information about its genomic data is required to allow molecular strategies for the development of sustainable pesticides and to gain in-depth knowledge on phylogenetics. However, the closest complete genome available is within the superfamily level (Yponomeutoidea). Here we report the generation of the first long-read genome, transcriptome and proteome results of L. coffeella and the in silico analysis performed in these molecular levels to investigate genes involved in the siRNA processing. Results, PACBio and paired-end Illumina combined DNA sequencing from pupae samples resulted in more than 436 Gb subreads and 31Mb reads with N50 read length of 15,512 nt, mean read length 13.8 Kb and max read length 420.7 Kb. Additionally, 20Gb data of short DNA sequencing was combined to produce 1,984 contigs comprising 397 Mb in total. The longest and shortest scaffold sizes are 10,809,567 nt and 15,247 nt, respectively (mean size 200,178 nt). The N50 scaffold was 275,598 nt and the GC content was 36.10%. Predicted coding DNA sequences counted 39.930 gene models. Searching of 5286 BUSCO groups revealed 91.7 percent of completeness (single and duplicated genes combined) compared to lepidoptera genomes (lepidoptera_odb10). Flow cytometry showed the 1C DNA content is approximately 295 Mb. RNA-Seq from seven development stages resulted in 28294 identified transcripts. Additionally, proteomics from immature stages resulted in 2045 proteins matching the gene models. Conclusions, This first nuclear genome of the Lyonetiidae family brings valuable molecular resources to study Lepidoptera genomes. Genome, transcriptome and proteome sequencing to raise genome annotation precision may resolve uncovered taxonomic issues. In addition, these combined approaches provide insights into plant-insect interaction players, as horizontally transferred genes (HGT) and endosymbionts. Put together, the generated data enables the development of molecular tools towards sustainable biotechnology solutions for lepidopteran pest control.

This study describes the development of an image-based insect trap diverging from the plug-in camera insect trap paradigm. In short, a) it does not require manual annotation of images to learn how to count targeted pests and, b) it self-disposes the captured insects, and therefore is suitable for long-term deployment. The device consists of an imaging sensor integrated with Raspberry Pi microcontroller units with embedded deep learning algorithms that count agricultural pests inside a pheromone-based funnel trap. The device also receives commands from the server which configures its operation while an embedded servomotor can automatically rotate the detached bottom of the bucket to dispose of hydrated insects as they begin to pile up. Therefore, it completely overcomes a major limitation of camera-based insect traps: the inevitable overlap and occlusion caused by the decay and layering of insects during long-term operation, thus extending the autonomous operational capability. We study cases that are underrepresented in literature such as counting in situations of congestion and significant debris using crowd counting algorithms encountered in human surveillance. Finally, we perform comparative analysis of the results from different deep-learning approaches (YOLO7/8, crowd counting, deep learning regression) and we open-source the code and a large database of Lepidopteran plant pests.

Dengue virus infections are a serious public health problem worldwide. Aedes aegypti is the primary vector of dengue in Cuba. Since there is no vaccine or specific treatment, the control efforts are directed to reduce mosquito populations. The indiscriminate use of pesticides can lead to increase insecticide resistance as well as adverse effects on human health. The sterile insect technique is a species-specific and environmental friendly method of insect control based on the release of large numbers of sterile males. The success of this technique in sustainable control of agricultural pests has encouraged its evaluation for mosquito control. Here, we describe an open field trial to evaluate the effect of the release of irradiated males on a wild population of Aedes aegypti. The case-control study was performed in a suburb of Havana, and compared the mosquito population before and after the intervention, in both control and treated areas. The wild population was monitored by an ovitrap network, recording frequency and density of eggs as well as their hatch rate. A significant induced sterility was observed in the field population, compared to the control. The ovitrap index and the mean eggs/ trap declined dramatically after an expected lag period of twelve and five weeks, respectively. For the last three weeks, no egg was collected in the treated area, evidencing a significant suppression of the wild population. We conclude that the sterile males released competed successfully, and induced enough sterility to suppress the local Aedes aegypti population.

Samarinda City is one of the most attractive cities in Borneo Island (Indonesia) and also as a capital city of EastBorneo Province. The expansion of urban areas becomes essential due to rapid population and housing demand. Base on the statistical report, the annual population growth rate is 0.018% from the year 2016-2017 with a total population of 843446 inhabitants. Many natural disasters occur in some areas in this city, especially flooding. This natural disaster occurs almost every year, many people suffered and forced to evacuate. In 2018 there is 3 flood event with 28311 people was suffered and evacuated, and 5170 houses were flooded [1]. During the flood event, it was very possible to gain damages to their property and make traffic stuck. One common way to reducing the damages is using Early Warning Systems (EWS). Early warning is a major element for disaster risk reduction, including damages. To prevent and mitigate the impact of a disaster, many countries had taken action to build various methods of a public warning system. An effective early warning system focused on people-centered and comprises the following element, such as risk knowledge, technical monitoring and service, communication and dissemination of warnings, and community response capability [2]. Related to the existing condition which Samarinda is a Muslim-dominated city and obviously has a lot of a number of mosques. This is a good potency to develop an early warning system because every mosque has a loudspeaker for echoing Adzan (Muslim prayer-calling). With this existing condition, the loudspeaker can be utilized as a flood outdoor-voice warning announcer. The aim of this study is to briefly introduce the strategy of dissemination early warning by utilizing mosques. The hope of early warning dissemination is giving enough time to the people to evacuate their property to reduce damages and possibly to giving information to avoiding traffic stuck (in a certain location)due to flooding. The results of this study can be used as input for decision-makers to develop effective flood management strategies and policies, especially in the case of an early warning system where not well-developed in Samarinda.

Background: Morphological alterations in intracranial pressure pulse waveform (ICPPW) secondary to intracranial hypertension (ICP >20 mmHg) and reduction in intracranial compliance (ICC) are well known indicators of neurological severity. To date, no studies have documented the ICPPW modifications after intracranial hypertension resolution with decompressive craniectomy (DC). The present study aimed to assess the morphological alterations in ICPPW among neurocritical care patients with and without DC, by comparing the variations of ICPPW features according to elevations in mean ICP values. Methods: Patients requiring ICP monitoring because of severe traumatic or spontaneous conditions were included. Mean ICP values were compared with ICPPW features (P2/P1 ratio, TTP and pulse amplitude). Elevation in ICP was produced by means of ultrasound-guided manual internal jugular veins compression. Results were distributed for three groups: intact skull (exclusive burr hole for ICP monitoring), craniotomy/large fractures (group 2) or DC (group 3). Results: 57 patients were analyzed. 21 (36%) presented no skull defects, whereas 15 (26%) had DC. ICP was not significantly different between groups: ±13.59 for intact and ±17.66 mmHg for DC, with ICP induced elevation also similar between groups (p= 0.56). Significant elevation was observed for P2/P1 ratio for groups 1 and 2, whereas reduction was observed in group 3 (elevation of ±0.09 for groups 1 and 2, whereas reduction of 0.03 for group 3, p=0.01). Conclusion: In the present study, intracranial pressure pulse waveform analysis indicated that intracranial compliance was significantly more impaired among decompressive craniectomy patients, although ICPPW indicated DC to be protective for further influences of ICP elevations over the brain. Analysis of ICPPW seems to be an alternative to real time ICC assessment.

This paper analyses the evolution of the internal damage in two types of steel that show different fracture behaviours, with one of them being the initial material used for manufacturing prestressing steel wires, which shows a flat fracture surface perpendicular to the loading direction, and the other one being a standard steel used in reinforced concrete structures, which shows the typical cup-cone surface. 3mm-diameter cylindrical specimens are tested with a tensile test carried out in several loading stages and, after each of them, unloaded and analysed with X-ray tomography, which allows detection of internal damage throughout the tensile test. In the steel used for reinforcement, damage is developed progressively in the whole specimen, as predicted by Gurson-type models, while in the steel used for manufacturing prestressing steel-wire damage is developed only in the very last part of the test. In addition to the experimental study, a numerical analysis is carried out by means of the finite element method by using a Gurson model to reproduce the material behaviour.

Single-stand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase revealing SMUG1 has a unique helical wedge which influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.

This paper constructs a model of climate-related damage for small island developing states (SIDS). We focus on the loss of private productive capital stocks through extreme climate events. In contrast to most economic analyses of climate impacts, which assume temperature-dependent damage functions, we draw on the engineering literature to allow for a greater or lesser degree of anticipation of climate change when designing capital stocks and balancing current adaptation expenditure against future loss & damage. We apply the model to tropical storm damage in the small island developing state of Barbados and show how anticipatory behavior changes the damage to infrastructure for the same degree of climate change. Thus, in the model, damage depends on behavior as well as climate variables.

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.

Unlike electron microscopy, which can achieve very high resolutions, but to date can only be used to study static structures, time-resolved X-ray diffraction from contracting muscles can, in principle, be used to follow the molecular movements involved in force generation on a millisecond timescale albeit at moderate resolution. However, previous X-ray diffraction studies of resting muscles have come up with structures for the head arrangements in resting myosin filaments that are different from the apparently ubiquitous interacting heads motif (IHM) found by single particle analysis of electron micrographs of isolated myosin filaments from a variety of muscle types. This head organization is supposed to represent the super-relaxed state of the myosin filaments where ATP usage is minimized. Here we have tested whether the interacting heads motif structures will satisfactorily explain the observed low-angle X-ray diffraction patterns from resting vertebrate (bony fish) and invertebrate (insect flight) muscles. We find that the interacting heads motif does not, in fact, explain what is observed. Previous X-ray models fit the observations much better. We conclude that the X-ray diffraction evidence has been well interpreted in the past and that there is more than one ordered myosin head state in resting muscle. There is, therefore, no reason to question some of the previous X-ray diffraction results on myosin filaments; time-resolved X-ray diffraction should be a reliable way to follow crossbridge action in active muscle and may be one of the few ways to follow molecular changes in myosin heads on a millisecond timescale as force is actually produced.

This article proposes a monitoring system that allows to track transitions between different stages in the berry harvesting process (berry picking, waiting for transport, transport, and arrival to the packing) solely using information from temperature and vibration sensors located in the basket. The monitoring system assumes a characterization of the process based on Hidden Markov Models and uses the Viterbi algorithm to perform inference and estimate the most likely state trajectory. The obtained state trajectory estimate is then used to compute a potential damage indicator in real-time. The proposed methodology does not require information about the weight of the basket to identify each of the different stages, which makes it effective and more efficient than other alternatives available in the industry.

Several herbivores feed on maize in field and storage setups making the development of multiple-insect resistance a critical breeding target. In this study, an association mapping panel of 341 tropical maize lines was evaluated in three field environments for resistance to FAW (fall armyworm) whilst bulked grains were subjected to MW (maize weevil) bioassay, genotyped with Diversity Array Technologies single nucleotide polymorphisms (SNPs) markers. A multi-locus genome-wide association study (GWAS) revealed 62 quantitative trait nucleotides (QTNs) associated with FAW and MW resistance traits on all 10 maize chromosomes, of which, 47 and 31 were discovered at stringent Bonferroni genome-wide significance level of 0.05 and 0.01, respectively, and located within or close to multiple-insect resistance genomic regions (MIRGRs) concerning FAW, SB, and MW. Sixteen QTNs influenced multiple-traits of which six were associated with resistance to both FAW and MW suggesting a pleiotropic genetic control. Functional prioritization of candidate genes (CGs) located within 10-30kb of the QTNs revealed 64 putative GWAS-based CGs (GbCGs) showing evidence of involvement in plant defense mechanisms. Only one GbCG was associated with each of five of the six combined-resistance QTNs, thus, reinforcing the pleiotropy hypothesis. In addition, through In-silico co-functional network inferences, an additional 107 Network-based CGs (NbCGs), biologically connected to the 64 GbCGs, differentially expressed under biotic or abiotic stress were revealed within MIRGRs. The provided multiple-insect resistance physical map should contribute to the development of combined-insect resistance in maize.

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.

Bacillus thuringiensis (Bt) is a spore-forming bacterium that produces insecticidal proteins and other virulence factors and is considered one of the most successful bioinsecticides available to control pests in agriculture. Bt strains have been reported as endophyte or rhizospheric bacteria, but little is known about the implications of this property of Bt in crop protection. Here, we review if Bt can establish as an endophyte/rhizobacterium and evaluate if Bt as an endophyte/rhizobacterium can simultaneously act against different phytopathogens (fungi, bacteria, insects and viruses) plus promote plant growth. The implications of the proposed review will broaden our understanding of Bt as a versatile entomopathogen by exhibiting differential behavior depending on context.

Abstract5′,8-Cyclo-2′-deoxyadenosine (cdA), in the 5′R and 5′Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the genome. Poly(ADP-ribose) polymerase1 (PARP1) acts as an early responder to DNA damage and plays a key role as a nick sensor in the maintenance of the integrity of the genome by recognizing nicked DNA. So far, it was unknown whether the diastereomeric cdA lesions could induce specific PARP1 binding. Here we provide the first evidence of PARP1 to selectively recognize the diastereomeric lesions 5′S-cdA and 5′R-cdA in vitro as compared to deoxyadenosine in model DNA substrates (23-mers) by using circular dichroism,fluorescence spectroscopy, immunoblotting analysis and gel mobility shift assay. Several features of the recognition of the damaged and undamaged oligonucleotides by PARP1were characterized. Remarkably, PARP1 efficiently binds to both cdA lesions in the double stranded (ds)-oligonucleotides. In particular, PARP1 proved to bind 5′S-cdAwith a higher affinity constant for the 5'S lesion in a model of ds DNA than 5′R-cdA, showing different recognition patterns, also compared with undamaged dA. This new finding highlights the ability of PARP1 to recognize and differentiate the distorted DNA backbone in a biomimetic system caused by different diastereomeric forms of a cdA lesion.

Epidemiology of Hymenopteran-related deaths in Europe due to bee, wasp and hornet stings (Cause Code of Death: X23) based on official registers from WHO Mortality Database is described. Over a 23-year period (1994-2016), a total of 1,691 fatalities were officially recorded, mostly occurring in Western (42.8%) and Eastern (31.9%) Europe. The victims tended to concentrate in: Germany (n=327; 1998-2015), France (n=211; 2000-2014) and Romania (n=149; 1999-2016). The majority of deaths occurred in males (78.1%), within the age group of 25-64 years (66.7%), and in an “unspecified place” (44.2%). The X23 gender ratio (X23GR) of mortality varied from a minimum of 1.4 for Norway to a maximum of 20 for Slovenia. The highest X23MR, expressed in terms of annual rates and per million inhabitants, were recorded in countries from Eastern Europe (0.35) followed by Western (0.28), Northern (0.23) and Southern Europe (0.2). The countries with the highest and lowest mean X23MR were Estonia (0.61), Austria (0.6) and Slovenia (0.55); and Ireland (0.05), United Kingdom (0.06) and the Netherlands (0.06), respectively. Country-by-country data show that the incidence of insect-sting mortality is statistically low, but not negligible.

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.

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis but little is known about the molecular mechanisms involved. The recently developed HDV mouse model based on the delivery of HDV replication-competent genomes using adeno-associated vectors (AAV) develop a liver pathology very similar to the human disease, and allowed us to perform mechanistic studies. We have generated different AAV-HDV mutants to eliminate the expression HDV antigens (HDAgs), characterized them both in vitro and in vivo. We confirmed that S-HDAg is essential for HDV replication and cannot be replaced by L-HDAg or host cellular proteins, and the L-HDAg is essential for HDV infectious particle production. We have also found that the lack of L-HDAg resulted in the increase of of S-HDAg expression levels and the exacerbation of liver damage which is T cell independent but is associated with an increment in liver inflammation. Interestingly, early expression of L-HDAg significantly ameliorated the liver damage induced by the mutant expressing only the S-HDAg. In summary, the use of AAV-HDV represents a very attractive platform to interrogate in vivo the role of viral components in the HDV life cycle and to better understand the mechanism of HDV-induced liver pathology.

Fibre-reinforced composite structures under complex loads exhibit gradual damage behaviour with a degradation of effective mechanical properties and change of their structural dynamic behaviour. Damage manifests itself as spatial increase of inter-fibre failure and delamination-growth, resulting in local changes of stiffness. These changes affect not only the residual strengths but more importantly the structural dynamic behaviour. In case of composite rotors, this can lead to catastrophic failure if an eigenfrequency coincides with the rotational speed. The description and analysis of the gradual damage behaviour of composite rotors therefore provides the fundamentals for a better understanding of unpredicted structural phenomena. The gradual damage behaviour on the example of composite rotors and the resulting damage-dependent dynamic behaviour is experimentally investigated under propagating damage for combined out-of-plane and in-plane loads. A novel observation is reported, where monotonic increase of damage results in non-monotonic frequency shift of significant amount of eigenfrequencies.

Xylella fastidiosa (Xf) is classified as a quarantine pest due to its consequences on economically significant crops. Its main form of transmission in Europe is through the insect Philaenus spumarius. Due to climate change, populations of insect vectors became more extensive, resulting in the dissemination of the bacteria through longer periods, but destruction of these insects raises issues, due to their role in nature. Upon infection, Xf causes the occlusion of xylem vessels by bacterial aggregates, and tylosis production by the plant as a response to infection. Although symptomatic manifestations of Xf are often linked to water stress, a variety of plant species have been found to carry the pathogen without symptoms, making it all too easy to evade detection when relying on visual inspections. Beyond water stress, other conditions (individual plant resistance/tolerance, bacterial concentrations, transpiration rates, and interactions between subspecies) may be implicated in symptom development. A thorough understanding of how this disease develops, especially its capacity to spread from the initial focus and establish a systemic infection, is imperative. This review focuses on the Xf infection process, the development of symptoms, its spread within Portugal, and the actions that have been taken to counter it.

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.

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.

In intermediary metabolism, enzymes are mainly for the specific provision of one small molecule from another, B from A, for its further use. But there are also decades of work relating to another evolved purpose, which is to prevent untoward effects of odd compounds of various origins, and of ordinary intermediates, whose improper concentrations may be avoided by hydrolases and other activities of metabolic correction.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.

Rapid post-earthquake damage diagnosis of bridges can guide decision-making for emergency response management and recovery. This can be facilitated using digital technologies to remove the barriers of manual post-event inspections. Prior mechanics-based Finite Element (FE) models can be used for post-event response simulation using the measured ground motions at nearby stations; however, the damage assessment outcomes would suffer from uncertainties in structural and soil material properties, input excitations, etc. For instrumented bridges, these uncertainties can be reduced by integrating sensory data with prior models through a model updating approach. This study presents a sequential Bayesian model updating technique, through which a linear/nonlinear FE model, including soil-structure interaction effects, and the foundation input motions are jointly identified from measured acceleration responses. The efficacy of the presented model updating technique is first examined through a numerical verification study. Then, seismic data recorded from the San Rogue Canyon Bridge in California are used for a real-world case study. Comparison between the free-field and the foundation input motions reveals valuable information regarding the soil-structure interaction effects at the bridge site. Moreover, the reasonable agreement between the recorded and estimated bridge responses shows the potentials of the presented model updating technique for real-world applications. The updated FE model is considered as the digital twin of the bridge and can be used to analyze the bridge and monitor the structural response at element, section, and fiber levels to diagnose the location and severity of any potential damage mechanism.

A facile solid-phase synthetic method for incorporating the imidazoline ring motif, a surrogate for a trans peptide bond, into bioactive peptides is reported. The example described is the synthesis of an imidazoline peptidomimetic analog of an insect pyrokinin neuropeptide via a cyclization reaction of an iminium salt generated from the preceding amino acid and 2,4-diaminopropanoic acid (Dap).

Recently on the November 4, 2022 at 03:00 PM, a M_ww 5.6 earthquake struck Cianjur district of West Java province, Indonesia. To our best knowledge, an earthquake will cause a massive damage to the manmade infrastructure and this responsible for a massive casualty. A building damage is affected by various determinant factors. One of important factors is the geological bedrock variations. Here this research aiming to elaborate the associations of geological bedrocks in Cianjur district with residential building damages caused by recent earthquakes. The results confirm that majority of building damages account for 54.67% of the total building was associated with quaternary volcanic bedrocks. The second massive building damages were observed for Andesitic Dacitic volcanic rocks accounted for 32.07%. To conclude, elaborations of geological bedrock-building damage will contribute to the better planning in the future that can reduce the damages in the urban settings.

Critical infrastructures are those that are essential. For this type of infrastructure, it is necessary to implement analytical methodologies that will allow us to quickly obtain the susceptibility or resilience and possible damage generated in extreme precipitation episodes, through a holistic perspective in which the factors linked to hydrological risk intervene. In particular, urban hydraulic infrastructures are analyzed considering the degree of criticality, defined as the number of interactions on the different activities of the population. For this purpose, a hydrological risk analysis methodology is required. This methodology is focused on an integral approach of the system indicators to be analyzed and linked to the hydrological threat. This work proposes to delimit and analyze those factors that involve risk using an analytical expression. This model will estimate the damage to these infrastructures breaking down the factors involved in the risk equation and analyzing their variability according to the intrinsic characteristics linked to them as well as the interaction with external factors.

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.

Neuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress, and mitochondrial dysfunction are considered key risk factors. Microglia are considered immune sentinels of the central nervous system capable of initiating an innate and adaptive immune response. Nevertheless, the pathological mechanisms underlying the initiation and spread of inflammation in the brain are still poorly described. Recently, a new mechanism of intercellular signalling mediated by small extracellular vesicles (EVs) has been identified. EVs are nanosized particles (30-150 nm) with a bilipid membrane that carries cell-specific bioactive cargos that participate in physiological or pathological processes. Damage-associated molecular patterns (DAMPs) are cellular components recognized by the immune receptors of microglia, inducing or aggravating neuroinflammation in neurodegenerative disorders. Diverse evidence links mitochondrial dysfunction and inflammation mediated by mitochondrial-DAMPs (mtDAMPs) such as mitochondrial DNA, TFAM and cardiolipin, among others. Mitochondrial-derived vesicles (MDVs) are a subtype of EVs produced after mild damage to mitochondria and, upon fusion with multivesicular bodies (MVBs), are released as EVs to the extracellular space. MDVs are particularly enriched in mtDAMPs which can induce an immune response and the release of pro-inflammatory cytokines. Importantly, growing evidence supports the association between mitochondrial dysfunction, EVs release and inflammation. Here, we describe the role of extracellular vesicles-associated mtDAMPS in physiological conditions and as neuroinflammation activators contributing to neurodegenerative disorders.

In this paper, the methodology using Insect Intelligent Building (I^2B) technology for establishing energy consumption monitoring system of public buildings is prevailed. The computing process node and distributed algorithm are utilized to implement the energy consumption collection and data transmission and data pre-processing. Taking a commercial building as a case study, CPNs are applied to set up the building energy consumption monitoring system, with the Spanning Tree Algorithm for generating network topology，and BPNN method for solving abnormal data and recovering missing data. The research results demonstrate the proposed method can effectively improve the performance of plug-and-play and self-identified and self-configuration of energy consumption monitoring system.

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.

High temperature (HT) significantly affects the crop physiological traits and reduces the 12 productivity in plants. To increase yields as well as survival of crops under HT, developing heat13 tolerant plants is one of the main targets in crop breeding programs. The present study attempted 14 to investigate the linkage of the heat tolerance between the seedling and the reproductive growth 15 stages of tomato cultivars ’Dafnis‘ and ’Minichal’. This research was undertaken to evaluate heat 16 tolerance under two experimental designs such as screening at seedling stage and screening from 17 reproductive traits in greenhouses. Survival rate and physiological responses in seedlings of 18 tomatoes with 4-5 true leaf were estimated under HT (40 °C, RH 70%, day/night, respectively) and 19 under two control and HT greenhouse conditions (day time 28 °C and 40 °C, respectively). Heat 20 stress significantly affected physiological-chemical (photosynthesis, electrolyte conductivity, 21 proline) and vegetative parameters (plant height, shoot fresh weight, root fresh weight) in all 22 tomatoes seedlings. The finding revealed that regardless of tomato cultivars the photosynthesis, 23 chlorophyll, total proline and electrical conductivity parameters were varied in seedlings during the 24 heat stress period. The heat tolerance rate of tomatoes in the seedling stage might not be associated 25 always with reproductive parameters. HT reduced the fruit parameters likeas fruit weight (31.9%), 26 fruit length (14.1%), fruit diameter (19.1%) and fruit hardness (9.1%) in compared to NT under HT 27 in heat susceptible tomato cultivar ‘Dafnis’, while in heat tolerant cultivar ‘Minichal’ fruit length 28 (7.1%) and fruit diameter (12.1%) was decreased by the affect of HT but on the contrary fruit weight 29 (3.6%) and fruit hardness (8.3%) were increased. In conclusion, screening and selection for tomatoes 30 should be evaluated at the vegetative and reproductive stages with consideration of reproductive 31 parameters.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Abstract: Aedes aegypti were exposed to water treated with mosquitocidal chips containing the insecticide pyriproxyfen in a polymer formulation. Chips were tested under different conditions; different water volumes, in containers made of different material, and in water with different levels of organic matter. Treated chips caused 100% mortality of Ae. aegypti during their pupal stage independent of conditions chips were exposed to in water. When tested for longevity, the chips containing 840 µg of pyriproxyfen killed 100% of Ae. aegypti for 4 sequential months of the chips being reused in water. Chips containing 8.4 µg of pyriproxyfen ceased to work after the first week of treatment. When mosquitocidal chips were used in > 25% of the oviposition containers within their cages, there was a significant control of the mosquito populations. Mosquitocidal chips worked in different environments, lasted for extended periods of time, caused significant mosquito population decreases, and were effective in controlling Ae. Aegypti.

Management approaches inspired by the variability of natural disturbances are expected to produce forests in the future that will be significantly more resilient and better adapted to local environmental conditions. Due to climate change, windstorms are becoming increasingly common resulting in the destruction not only of extensive forest areas but, quite often, of small-sized and scattered forest lands that can ultimately become home to insects and disease dissemination sites. In the present study, an attempt is made to identify and record areas in the northeastern forests of Greece covered by mixed stands of conifers and broadleaves that experienced massive windthrow following local storms. Based on tree-level data, local topographic features, forest characteristics and the mechanical properties of green wood, a reliable model, to be used for the prediction of similar disturbances in the future, has been created after a thorough comparative study of the most well-known intelligent machine learning algorithms.

Spodoptera frugiperda is a new invasive and highly polyphagous pest that attacks corn in Indonesia. The availability of abundant plant species allows pests to switch to other host plants to maintain their population. This research aims to examine the development, reproduction, nutritional indices, and life table of S. frugiperda in several plant species. The plants tested were corn, rice, broccoli, oil palm, and baby corn as controls. Ten individual insects were used and repeated five times for each plant species. The test results show that different types of plant feed affect the development time, imago life span, fecundity, and fertility of S. frugiperda. The types of plant feed, that were baby corn fruit and broccoli had higher net reproduction value (R0), intrinsic growth rate (r), gross reproduction rate (GRR), shorter mean generation period (T), and population doubling time (DT) than in corn and rice leaves. On oil palm leaf feed no population parameters can be determined because no larvae developed into adults and had the lowest nutritional indices parameters, so that could not be exploited as a host plant. Also, the nutritional indices of several feed plant species tested provided information that broccoli could be a suitable host when there was no corn in the field.

The successive waves of the Covid-19 pandemic are driven by SARS-CoV-2 variants that reached critical detection levels in different parts of the world. But how evolved the Wuhan virus since its detection in December 2019 into the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529) variants of concern? This is a story of mice and men, of up to 1,000,000 infected cells in one person, where each cell produces between 10⁵ and 10⁶ viral RNAs, of immune-compromised patients, the digestive tract and viral recombination.

The effect of the strain rate on damage in carbon black filled EPDM stretched during single and multiple uniaxial loading is investigated. This has been performed by analysing the stress-strain response, the evolution of damage by Digital Image Correlation (DIC), the associated dissipative heat source by InfraRed thermography (IR), and the chains network damage by swelling. The strain rates were selected to cover the transition from quasi-static to medium strain rate conditions. In single loading conditions, the increase of the strain rate yields in a preferential damage of the filler network while rubber network is preserved. Such damage is accompanied by a stress softening and an adiabatic heat source rise. Conversely, increasing the strain rate in cyclic loading conditions yields in a filler network accommodation and a high self-heating whose combined effect is proposed as a possible cause of the ability of filled EPDM to limit damage, by reducing cavities opening during loading and favoring cavities closing upon unloading.

Impact of Nitrogen Foamed Stimulation Fluids Stabilized by Nanoadditives on Reservoir Rocks of Hydrocarbon Deposits

Today, the most powerful approach to detect distant homologs of a protein is based on structure prediction and comparison. Yet this approach is still inapplicable to many viral proteins. Therefore, we developed a powerful sequence-based procedure to identify distant homologs of viral proteins. It relies on 3 main principles: 1) Traces of sequence similarity with a protein can persist beyond the significance cutoff of homology detection programs; 2) Candidate homologs can be identified among proteins with weak sequence similarity to the query, by using "contextual" information, e.g. taxonomy or type of host infected; 3) These candidate homologs can be validated using highly sensitive profile-profile comparison.As a test case, we applied our approach to a protein without known homologs, ORF4 of Lake Sinai virus (which infects bees). We discovered that ORF4 is composed of a domain that has homologs in proteins from >20 taxa of viruses infecting arthropods. We called it “Widespread, Intriguing, Versatile” (WIV) domain because it is found in proteins with a wide variety of domain organizations and functions. For example, WIV is encoded by the NSs protein of tospoviruses, a global threat to food security, which infect plants through arthropod vectors; by the protein encoded by RNA2 ORF1 of chronic bee paralysis virus, a widespread virus of bees; and by various proteins of cypoviruses, which infect the silkworm bombyx mori. WIV has a previously unknown structural fold, according to Alphafold predictions. In some viral species, WIV facilitates infection of arthropods, according to bibliographical evidence

The study assessed the changes in the quality and physical and chemical parameters of apples of four cultivars (‘Gala’, ‘Idared’, ‘Topaz’, ‘Red Prince’) subjected to mechanical vibrations during transport under model conditions and after storage (shelf-life). Quality changes in apples were evaluated based on skin and flesh colour, total soluble solids, dry matter, firmness, titratable acidity, pH value, total polyphenol content and antioxidant capacity. The applied vibrations at a frequency of 28 Hz caused changes in the above parameters, which were visible also after storage and depended on cultivar, but did not show any clear trend or direction. Skin colour varied whereas flesh colour remained stable. Vibrations resulted in a decrease in firmness. The greatest stability of quality parameters, the highest content of bioactive compounds and the highest antioxidant capacity were observed for ‘Red Prince’ and ‘Topaz’ apples – this refers to the control and treated samples before and after storage. However, total polyphenol content and antioxidant capacity increased in all studied cultivars as a result of vibrations and storage, which suggests that 28 Hz mechanical vibrations and short-term cold storage did not reduce the health promoting potential of the apples.

As a result of the growing demand for foods with reduced animal protein content, many new alternative diets are now emerging. Nevertheless, recent studies have shown that the Western population is unprepared for drastic changes and is disinclined to accept foods based on alternative proteins. However, hybrid products might become a good transitional offer. This study used a desirability-based mixture design to model hybrid spreadable cheese analogues (SCAs). The design combined the dairy protein (MPC), Tenebrio molitor (IF) and faba bean (FBP) flours. Nine SCAs with different MPC/FBP/IF ratios were formulated, representing 0, 50 and 100% MPC replacement (7.1% of the formula). Incorporating the IF negatively impacted the desirable texture properties. The FBP flour improved the texture (achieving increased firmness and stickiness and decreased spreadability), but only when combined with MPC. Changing the MPC/FBP/IF ratio affected the colour of SCAs. Sensory analysis showed that hybrid SCAs (≤ 50% MPC) had a more characteristic cheesy flavour than the commercial plant-based reference, and sample C2 had a texture profile similar to the dairy reference. Samples containing IF showed a better flavour profile than the products without IF. The SCAs had higher protein and lower saturated fat, starch and sugar con-tent than commercial analogues.This study demonstrates that the inclusion of alternative proteins can be effective as a strategy to reduce dairy protein content in hybrid product formulations.

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.

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

The formation of high-melting-point Cu₆Sn₅ interconnections is crucial to overcome the collapse of Sn-based micro-bumps and produce reliable intermetallic interconnections in three-dimensional (3D) package. However, because of the multiple reflows in 3D package manufacturing, Cu₆Sn₅ interconnections will experience the cyclic polymorphic transitions in the solid state. The repeated and abrupt change in the Cu₆Sn₅ lattice due to the cyclic polymorphic transitions can cause extreme strain oscillations, producing damages at the surface and in the interior of the Cu₆Sn₅ matrix. Moreover, because of the polymorphic-transition-induced grain splitting and superstructure phase formation, the reliability of Cu₆Sn₅ interconnections will thus face great challenges in 3D package. In addition, the Cu₆Sn₅ polymorphic transition is structure-dependent, and the η′↔η polymorphic transition will occur at the surface while the η′↔ηs↔η polymorphic transition will occur in the deep matrix. Our results can provide in-depth understandings of structural evolution and damage mechanism of Cu₆Sn₅ interconnections in real 3D package manufacturing.

Pv11, an insect cell line established from the midge Polypedilum vanderplanki, is capable of ametabolic desiccation tolerance, so-called anhydrobiosis. We previously discovered that heat shock factor 1 (HSF1) contributes to the acquisition of desiccation tolerance by Pv11 cells, but the mechanistic details have yet to be elucidated. Here, by analyzing the gene expression profiles of newly established HSF1-knockout and -rescue cell lines, we show that HSF1 has a genome-wide effect on gene regulation in Pv11. HSF1-knockout cells exhibit a reduced desiccation survival rate, but this is completely restored in HSF1-rescue cells. By comparing mRNA profiles of the two cell lines, we reveal that HSF1 induces anhydrobiosis-related genes, especially genes encoding late embryogenesis abundant proteins and thioredoxins, but represses a group of genes involved in basal cellular processes, thus promoting an ametabolic state in the cell. In addition, HSF1 binding motifs are enriched in the promoters of anhydrobiosis-related genes and we demonstrate binding of HSF1 to these promoters by ChIP-qPCR. Thus, HSF1 directly regulates the transcription of anhydrobiosis-related genes and consequently plays a pivotal role in the induction of anhydrobiotic ability in Pv11 cells.

Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras expressing or transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Oncogenes induce replication stress, re-sulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment cause toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overex-pressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but interestingly not by nucleoside supplementation. This suggest that cancer selectivity is unrelated oncogene-induced replication stress. We conclude that the molecular toxi-cological mechanisms how TH588 and TH1579 kill c-Myc overexpressing cells have several com-ponents and involves MTH1-independent proteosomal degradation of c-Myc itself, c-Myc driven transcription and CDK activation, and is likely unrelated to oncogene-induced replication stress.

Genes that affect adaptive traits have been identified, but our knowledge of the genetic basis of adaptation in a more general sense (across multiple traits) remains limited. We combined population-genomic analyses of evolve and resequence experiments, genome-wide association mapping of performance traits, and analyses of gene expression to fill this knowledge gap, and shed light on the genomics of adaptation to a marginal host (lentil) by the seed beetle Callosobruchus maculatus. Using population-genomic approaches, we detected modest parallelism in allele frequency change across replicate lines during adaptation to lentil. Mapping populations derived from each lentil-adapted line revealed a polygenic basis for two host-specific performance traits (weight and development time), which had low to modest heritabilities. We found less evidence of parallelism in genotype-phenotype associations across these lines than in allele frequency changes during the experiments. Differential gene expression caused by differences in recent evolutionary history exceeded that caused by immediate rearing host. Together, the three genomic data sets suggest that genes affecting traits other than weight and development time are likely to be the main causes of parallel evolution, and that detoxification genes (especially cytochrome P450s and beta-glucosidase) could be especially important for colonization of lentil by C. maculatus.

Current bridge inspection practices rely on paper-based data acquisition, digitization, and multiple conversions in between incompatible formats to facilitate data exchange. This practice is time-consuming, error-prone, cumbersome, and leads to information loss. One aim for future inspection procedures is to have a fully digitized workflow that achieves loss-free data exchange, which lowers costs and offers higher efficiency. On the one hand, existing studies proposed methods to automatize data acquisition and visualization for inspections. These studies lack an open standard to make the gathered data available for other processes. On the other hand, several studies discuss data structures for exchanging damage information through out different stakeholders. However, those studies do not cover the process of automatic data acquisition and transfer. This study focused on a framework that incorporates automatic damage data acquisition, transfer, and a damage information model for data exchange. This enables inspectors to use damage data for subsequent analyses and simulations. The proposed framework shows the potentials for a comprehensive damage information model and related (semi-)automatic data acquisition and processing.

Polyurethane (PU) is a polymer widely used by humans whose recycling is highly complex due his chemical structure, being limited to incineration or accumulation in landfills. Biodegradation by enzymes and microorganisms has been studied for decades as an effective method of biological decomposition. In this study, Tenebrio molitor larvae (T. molitor) were fed with polyurethane foams, which gut enzymes and microorganisms were capable of degrading the polymer by 35% in 17 days of treatment, producing a weight loss of 14% in the mealworm. Changes in T. molitor gut bacterial community and diversity were observed, which may be due to colonization of species associated with PU degradation. Physical and structural biodegradation in PU by T. molitor compared to virgin PU, was demonstrated by Fourier Transform InfraRed spectroscopy (FTIR), Thermal Gravimetric Analysis (TGA) and Scanning Electron Microphotography (SEM).

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.

Marine mortar was the goal material and its multi-scale physical-chemical-mechanical characteristics were the principal interest in this study. The on-line multi-scale damage detection experiments art was designed to quantify the characteristics mathematically and graphically. The normal cylinder specimen with 70-day age was produced and investigated by dynamically global MSHCT scan and local detection of EDS, SEM and XRD. The experiments results indicated that the marine mortar offered the appreciable strength at the early age at least, although some saline minerals were generated during the preparation. The micro-interfacial behavior and the parental foci controlled the damage development of the marine mortar the performance of which was still the adjustable one by the composition optimization.

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.

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.

Epoxy asphalt (EA) concrete is widely used in constructing long-span steel bridge pavements (SBDPs). This study aims to derive a fatigue damage evolution law, conducting an experimental investigation of SBDP. First, a general theoretical form of the fatigue damage evolution law of materials is established based on the thermal motion of atoms. Then, fatigue experiments demonstrate that this evolution law well represents the known damage–life relationships of SBDP. Taking into account the experimental relationships between damage and fatigue life under symmetrical cyclic loadings with different overload amplitudes and temperature variations, a detailed damage evolution law is deduced. Finally, the role of damage accumulation is discussed on the basis of the proposed damage evolution law for the extreme situation of heavy overload and severe environments. The results show that both heavy loading and falling temperatures increase the fatigue damage of SBDP considerably; therefore, SBDP should avoid heavy loading combined with winter temperatures. EA shows a fatigue life two to three times longer than that of modified matrix asphalt (SMA) or guss asphalt (GA). For the same thickness, EA pavement is demonstrated to be more suitable for an anti-fatigue design of large-span SBDP under high traffic flows and low temperatures.

Galangin(Gal) is a natural active flavonoid compound separated from the roots and rhizomes of Alpinia ofcinarum Hance. Modern pharmacological studies have shown that Gal has a variety of biological activities such as anti-tumor, anti-fungal, anti-bacterial, anti-inflammatory, anti-ischemic stroke, suppressing vitiligo and Alzheimer’s disease, etc. The purpose of this research was to prepare a galangin self-microemulsion drug delivery system (Gal-SMEDDS) and compare its anti-oxidant activity and pharmacokinetics with free Gal.The average particle size of the prepared Gal-SMEDDS was approximately 21.33 nm, the polydispersity index was 0.096, the zeta potential was -4.09 mV, and the entrapment efficiency was 96.74%. Compared with free Gal, the release of Gal-SMEDDS was improved in vitro release experiment. Cell experiments showed that Gal had obvious anti-oxidation effect, and the effect of Gal-SMEDDS was better than that of free Gal. In vivo pharmacokinetic experiments showed that the pharmacokinetic parameters of Gal-SMEDDS were better than that of free Gal, which indicated that the self-microemulsion drug delivery system(SMEDDS) effectively increases the oral bioavailability of Gal and alters its pharmacokinetic parameters, such that it may be effective in the treatment of anti-oxidant.

Translation is spatiotemporally regulated and ER-associated mRNAs are generally in efficient translation. It is unclear whether the ER-associated mRNAs are deadenylated or degraded on the ER surface in situ or in the cytosol. Here, we showed that ER possessed active deadenylases, particularly the poly(A)-specific ribonuclease (PARN), in common cell lines and mouse tissues. Consistently, purified recombinant PARN exhibited a strong ability to insert into the Langmuir monolayer and liposome. ER-anchored PARN was found to be able to reshape the poly(A) length profile of the ER-associated RNAs by suppressing long poly(A) tails without significantly influencing the cytosolic RNAs. The shortening of long poly(A) tails did not affect global translation efficiency, suggesting that the non-specific action of PARN towards long poly(A) tails was beyond the scope of translation regulation on the ER surface. Transcriptome sequencing analysis indicated that the ER-anchored PARN trigged the degradation of a small subset of ER-enriched transcripts. The ER-anchored PARN modulated the translation of its targets by redistributing ribosomes to heavy polysomes, suggesting that PARN may play a role in dynamic ribosome reallocation. During DNA damage response, MK2 phosphorylated PARN-Ser557 to modulate PARN translocation from the ER to cytosol. By promoting the decay of ER-associated MDM2 transcripts with low ribosome occupancy, the ER-anchored PARN modulated DNA damage response and thereby cell viability. These findings revealed that a highly regulated communication between mRNA degradation rate and translation efficiency is present on the ER surface in situ and that PARN may contribute to this communication by modulating the dynamic ribosome reallocation between transcripts with low and high ribosome occupancies.

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.

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.

Magnetorheological processing was applied to polish the working surfaces of the ZnGeP2 single crystal, in which a non-aqueous liquid with magnetic particles of carbonyl iron with the addition of nanodiamonds was used. Samples of a single crystal ZnGeP2 with an angstrom level of surface roughness were received. the use of MRP has allowed more accurately characterizing possible structural defects that have emerged on the surface of a single crystal and have a size of ~ 0.5-1.5 μm. the LIDT value at the indicated or-ders of magnitude of the surface roughness parameters is determined not by the quality of polishing, but by the number of point depressions caused by physical limitations of the structural configuration of the crystal volume. These results are in good agreement with the assumption made about a significant effect of the concentration of dislocations in a ZnGeP2 crystal on LIDT.

The lipid composition of biomembranes influence the properties of the lipid bilayer as well as that of the proteins. In this study, the lipidome and the lipid/protein ratio of membranes from High FiveTM insect cells overexpressing mouse P-glycoprotein was characterized. This provides a better understanding of the lipid environment in which P-glycoprotein is embedded, and thus of its functional and structural properties. The relative abundance of the distinct phospholipid classes and their acyl chain composition was characterized. A mass ratio of 0.57 +/- 0.11 phospholipids to protein was obtained. Phosphatidylethanolamines are the most abundant phospholipids, followed by phosphatidylcholines. Membranes are also enriched in negatively charged lipids (phosphatidylserines, phosphatidylinositols and phosphatidylglycerols), and contain small amounts of sphingomyelins, ceramides and monoglycosilatedceramides. The most abundant acyl chains are monounsaturated, with significant amounts of saturated chains. The characterization of the phospholipids by HPLC-MS allowed identification of the combination of acyl chains, with palmitoyl-oleoyl being the most representative for all major phospholipid classes except for phosphatidylserines, which are mostly saturated. A mixture of POPE:POPC:POPS in the ratio 45:35:20 is proposed for the preparation of simple representative model membranes. The adequacy of the model membranes was further evaluated by characterizing their surface potential and fluidity.

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.

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.

Fanconi anemia (FA) develops due to a mutation in one of the FANC genes that are involved in repair of interstrand crosslinks (ICLs). FANCG, a member of the FA core complex, is essential for ICL repair. Previous FANCG-deficient mouse models were generated with drug-based selection cassettes in mixed mice backgrounds, leading to a disparity in interpretation of genotype-related phenotype. To exclude these confounders, we created a Fancg-KO (KO) mouse model using CRISPR/Cas9. The entire Fancg locus was targeted and maintained on the immunological well-characterized C57BL/6J background. Intercrossing of heterozygous mice resulted in sub-Mendelian numbers of homozygous mice, suggesting loss of FANCG can be embryonic lethal. KO mice displayed infertility, hypogonadism but no other developmental problems. Bone marrow analysis revealed a defect in various hematopoietic stem and progenitor subsets with a bias towards myelopoiesis. Cell lines derived from Fancg-KO mice were hypersensitive to crosslinking agents-cisplatin and Mitomycin C, and Fancg-KO mouse embryonic fibroblasts (MEFs) displayed increased γ-H2AX upon cisplatin treatment. Reconstitution of these MEFs with Fancg cDNA corrected for the ICL hypersensitivity. Collectively, this project provides a new, genetically and immunologically well-defined Fancg-KO mouse model for further in vivo and in vitro studies on FANCG and ICL repair.

This work demonstrates the antimycotic activity and structural damage of stingless bee propolis against Malassezia pachydermatis,causative agent of canine otitis.Two propolis ethanolic extracts(EEP) derived from the stingless bees, Scaptotrigona mexicana and Tetragonisca angustula were tested against three clinical strains of Malassezia pachydermatis and one of reference (ATCC 14522). Each ethanolic extract of propolis was analyzed by Gas Chromatography – Mass Spectrometry(GC-MS). Antimycotic activity was evaluated by plate microdilution. To evaluate the induced changes in yeasts, by fluorescence microscopy, stains were performed with chalcofluor white and propidium iodide. For both propolis, sesquiterpenes were the main components determined by GC-MS. Minimum inhibitory concentration (MIC) of 32 mg/mL and a minimum fungicidal concentration of 64 mg/Ml were determined in both extracts. EPP of Scaptotrigona mexicana and Tetragonisca angustula caused significant damage to yeast morphology. Propidium iodide penetration was observed, indicating damage to the yeast and with calcofluor-white stain, only morphology deformation was observed..The antimycotic activity and structural damage of propolis from Scaptotrigona mexicana and Tetragonisca angustula against Malassezia pachydermtais was demonstrated .This probably being the first scientific report that demonstrates structural damage in Malassezia pachydermatis of Mexican stingless bee propolis

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.

Fixed offshore wind turbines continue to be developed for high latitude areas where not only wind and wave loads need to be considered, but also moving sea ice. Current rules and regulations for the design of fixed offshore structures in ice-covered waters do not adequately consider effects of ice loading and its stochastic nature on fatigue life of the structure. Ice crushing on such structures results in ice-induced vibrations, which can be represented by loading the structure using a variable-amplitude loading (VAL) sequence. Typical offshore load spectra are developed for wave and wind loading. Thus, a combined VAL spectrum is developed for wind, wave, and ice action. To this goal, numerical models are used to simulate the dynamic ice-, wind-, and wave-structure interaction. The stress time-history at an exemplarily selected critical point in an offshore wind energy monopile support structure is extracted from the model and translated into a VAL sequence, which can then be used as a loading sequence for the fatigue assessment or fatigue testing of welded joints of offshore wind turbine support structures. This study presents the approach to determine combined load spectra and standardized time series for wind, wave, and ice action.

The enterohemorrhagic Escherichia coli (EHEC) O157: H7 EspF is known to be a multifunctional effector that triggers several damage processes in the host cells. However, in the process of EHEC O157: H7 infection, the interactions between EspF, its N- or C-terminus, and host proteins are still unclear. In this work, we use co-immunoprecipitation combined with mass spectrometry (CoIP-MS) to screen the interactions between EspF/EspF-N/EspF-C terminus and host proteins. A total of 311 host proteins are analyzed. The N-terminus of EspF is found to interact with 192 proteins, whereas 205 proteins interact with the C-terminus. These proteins are mainly involved in RNA splicing, endoplasmic reticulum stress, and a variety of metabolic signaling pathways. Surprisingly, MS results reveal that EspF can also phosphorylate H2AX, suggesting that EspF may directly mediate DNA damage. Here, by western blot and immunofluorescence (IF), we verified that EspF can cause phosphorylation of H2AX and mediates cell multi-nuclearation and cell hypertrophy. Furthermore, we verify here for the first time that SMC1 interacts with EspF -C-terminus, and provide evidence that EspF increases p-SMC1 levels. p-SMC1 is known to influence S-phase cell cycle arrest and usually increases during periods of DNA damage. Our work revealed a novel interaction between EspF and the host protein SMC1 and lays a foundation for further research on EspF-mediated host DNA damage, apoptosis, and even colorectal carcinogenesis.

Wenchuan earthquake that occurred in China in 2008 caused severe damage to a large number of electric substations. In this paper, Kriging interpolation method was used to calculate the impact area of the instrumental seismic intensity in Wenchuan earthquake, and to compare the intensities based on strong motion observation against the instrumental seismic intensities at locations where the observation data is available. The instrumental seismic intensities were calculated for the Wenchuan Earthquake at substations in the national power grid with voltage of 110kV or higher in areas of Mianyang, Deyang, Guangyuan and Chengdu. The cumulative Gaussian distribution function was then used to fit the relationship of the curves of the damage probabilities of high-voltage electrical equipment such as transformers, voltage mutual inductors, current mutual inductors, circuit breakers, isolating switches and lightning arrester with their instrumental seismic intensities. The damage probability density distribution curve of high-voltage electrical equipment based on the instrumental seismic intensities was obtained. The results showed that: (1) In the lower seismic intensity region, the mean instrumental seismic intensity was in good agreement with the traditional seismic intensity, but there was noticeable dispersion; in regions of intensity IX and above, the instrumental intensity was lower than the seismic intensity, but there was a lower degree of dispersion. (2) Among high-voltage electrical equipment, the transformers were most vulnerable to damage and they had some damage even under lower instrumental intensity. More damage would be produced when the instrumental intensity reached VIII or above; the second most vulnerable equipment was the circuit breaker, and the damage was most likely to occur when the instrument intensity was IX or above . (3) The damage rate curves of lightning arresters, current mutual inductors, voltage mutual inductors and isolating switches were relatively close to each other and the damage probability was the highest when the instrumental intensity was about X.

This study proposes a machine-learning-based framework for detecting mechanical damage in pipelines, utilizing physics-informed datasets collected from simulations for mechanical damage. The framework provides an effective workflow from dataset generation to damage detection and identification for three types of pipeline events: welds, clamps, and corrosion defects. While the study initially focused on optimizing the CNN structure using various advanced optimizers, it also investigated the impact of sensing systems on data classification and the effect of noise on classification performance. The study's analysis highlights the importance of selecting the appropriate sensing system for the specific application. The authors also found that the proposed framework is robust to experimentally relevant levels of noise, suggesting its applicability in real-world scenarios where noise is present. Overall, this study contributes to the development of a more reliable and effective method for detecting mechanical damage in pipelines. The proposed framework provides an effective workflow for damage detection and identification, and the findings on the impact of sensing systems and noise on classification performance add to its robustness and reliability.

In this paper, the results of finite element analyses of a single-layer cylindrical latticed shell under severe earthquake is presented. A 3D Finite Element model using fiber beam elements were used to investigate the collapse mechanism of this type of shell. The failure criteria of structural members are simulated based on the theory of damage accumulation. Severe earthquake of peak ground acceleration (PGA) of 500 gal was applied to the shell. The stress and defeomation of the shell were studied in detail. A three-stages collapse mechanism “double-diagonal -members-failure-belt” of this type of structure was discovered. Based on the analysis results, the measures to mitigate collapse of this type of structure is recomanded.

DNA damage response (DDR) pathways in keto-enol genotoxicity have not been characterized, and few studies have reported genotoxic effects in non-target organisms. The present study shows that concentrations of 11.2, 22.4, 37.3 mg/L of Movento® 240SC and 12.3, 24.6, 41.1 mg/L of Envidor® 240SC for 72 h oral exposure induced DSBs by significantly increasing the percentage of γH2AV expression in regions 2b and 3 from the germarium of wildtype females of Drosophila melanogaster Oregon R, compared to the control group (0.0 mg/L of insecticides), by confocal immunofluorescence microscopy. The comparison between both insecticides’ revels that only the Envidor® 240SC induces concentration-dependent DNA damage, as well as structural changes in the germarium. We determined that the DDR induced by Movento® 240SC depends on the activation of the ATMtefu, Chk1grp and Chk2lok kinases by significantly increasing the percentage of expression of γH2AX in regions 2b and 3 of the germarium, and that ATRmei-29D and p53dp53 kinases only respond at the highest concentration of 37.3 mg/L of Movento® 240SC. With the Envidor® 240SC insecticide, we determined that the DDR depends on the activation of the ATRmei-29D/Chk1grp and ATMtefu/Chk2lok kinases, and p53dp53 by significantly increasing the percentage of expression of γH2AX in the germarium.

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).

Cellular aging has drawn the attention of researchers, scientists, and biotech businesses for the treatment of a number of medical conditions. Cellular aging is primarily defined by consistent cessation of proliferative development in response to internal and external stressors, including DNA damage, telomere shortening, mitochondrial dysfunction, and regulation of the senescence-associated secretory phenotype (SASP). Disturbances involving these factors may contribute to age-related disease development. Therefore, the current review aims to explore anti-aging factors targeting DNA damage response and SASP regulation and their detailed signaling networks. In addition, it provides an opportunity for researchers to identify not only anti-aging targets, but also anti-aging therapeutic strategies based on identified and non-identified targets.

Agricultural landscapes are more and more characterized by intensification and habitat losses. Landscape composition and configuration are known to mediate insect abundance and richness. In the context of global insect decline, and despite 75% of crops being under insect’s dependence, there is still a gap of knowledge about the link between pollinators and aromatic crops. Fennel (Foeniculum vulgare) is an aromatic plant cultivated in South of France, for its essential oil which is of great economic interest. Using pan-traps, we investigated the influence of the surrounding habitats at landscape scale (semi-natural habitat proportion and vicinity, landscape configuration) and local scale agricultural practices (insecticides and patch size) on fennel-flower-visitor abundance and richness and their subsequent impact on fennel essential oil yield. We found that fennel may to be a generalist plant species. We did not find any effect of intense local management practices on insect abundance and richness. Landscape configuration and the proximity to semi-natural habitat were the main drivers of flying insect’s family richness. This richness positively influenced fennel essential oil yield. Maintaining a complex configuration of patches at the landscape scale are important to sustain insect diversity and crop yield.

Brevibacillus laterosporus (Bl) is a Gram-positive and spore-forming bacterium belonging to the Brevibacillus brevis phylogenetic cluster. Globally, insect pathogenic strains of the bacterium have been isolated, characterised, and some activities patented. Two isolates, Bl 1821L and Bl 1951, exhibiting pathogenicity against the diamondback moth and mosquitoes, are under development as a biopesticide in New Zealand. However, due to the suspected activity of putative antibacterial proteins (ABPs), the endemic isolates often grow erratically. Various purification methods including size exclusion chromatography, sucrose density gradient centrifugation, polyethylene glycol precipitation, and ammonium sulphate precipitation employed in this study enabled the isolation of two putative antibacterial proteins of ~30 kD and ~48 kD from Bl 1821L and one putative antibacterial protein of ~30 kD from Bl 1951. Purification of the uninduced cultures of Bl 1821L and Bl 1951 also yielded the protein bands of ~30 kD and ~48 kD on SDS-PAGE which indicated their spontaneous induction. Disc diffusion assay was used to determine the antagonistic activities of the putative ABPs. Subsequent transmission electron microscope (TEM) examination of purified putative antibacterial protein-containing solution showed the presence of encapsulin (~30 kD) and polysheath (~48 kD) like structures. Although only the ~30 kD protein was purified from Bl 1951, both structures were seen in this strain under TEM. Furthermore, while assessing the antibacterial activity of some fractions of Bl 1951 against Bl 1821L in size exclusion chromatography method, population of Bl 1821L persister cells was noted. Overall, this work added a wealth of knowledge for the purification of the HMW proteins (bacteriocins) of the Gram-positive bacteria including Bl.

Formulating a novel concept about the origin of human aging has been constrained by the dominance of a “classic theory” that was proposed nearly 70 years ago. Despite concern over the validity of some of its assumptions, the theory remained basic to our understanding of aging’s relationship with natural selection (NS). However, the logic upon which it rests was tested and subsequently challenged. The present theory describes the single cause of human aging consistent with Darwin’s evolutionary requirement for selection of adaptive traits. It describes an emergent property of the developmental program (DP), that is expressed upon completion of ontogenesis. It involves redundant expression of regulatory processes from the last stage of the DP. That mechanism subsequently preserves a non-aging, stable interval of unchanging NS during which reproductive fitness is achieved. Thereafter, loss of DP regulatory redundancy due to reliability limits, stochastic mutation accumulation, reproductive and a specific type of DNA damage, initiates aging which causes an inexorable decline in strength of NS to begin. It starts approximately a decade later than proposed in the classic theory. Since reproduction and aging are inextricably linked by the same emergent property, selection of that regulatory mechanism makes both traits products of NS.

Identifying cracks in the incipient state is essential to prevent the failure of engineering structures. Detection methods relying on the analysis of the changes in modal parameters are widely used because of the advantages they present. In our previous research, we have found that eigenfrequencies were capable of indicating the position and depth of damage when sufficient vibration modes were considered. The damage indicator we developed was based on the relative frequency shifts (RFS). To calculate the RFSs for various positions and depths of a crack, we established a mathematical relation that involved the squared modal curvatures in the healthy state and the deflection of the healthy and damaged beam under dead mass, respectively. In this study, we propose to calculate the RFS for beams with several cracks by applying the superposition principle. We demonstrate that this is possible if the cracks are far enough from each other. In fact, if the cracks are close to each other, the superposition method does not work and we distinguish two cases: (i) when the cracks affect the same beam face, the frequency drop is less than the sum of the individual frequency drops, and (ii) on the contrary, cracks on opposite sides cause a decrease in frequency, which is greater than the sum of the frequency drop due to individual damage. When the RFS curves are known, crack assessment becomes an optimization problem, the cost function being the distance between the measured RFSs and all possible RFSs for several vibration modes. Thus, the RFS constitutes a benchmark that characterizes damage using only the eigenfrequencies. We can accurately locate multiple cracks and estimate their severity trough experiments and thus prove the reliability of the proposed method.

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.

The work is devoted to the study of the mechanisms of damage accumulation in a polymer composite material (PCM) during fatigue loading. Mechanical testing of a fiberglass sample was carried out by cyclic tension accompanied by registration of acoustic emission (AE). For the recorded AE signals, the Fourier spectra were calculated and used for clustering with Kohonen self-organizing map. Relations between clusters and types of damage in the PCM structure were established. The analysis of the peak frequencies of the Daubechies D14-wavelet components of AE signals was carried out. Obtained results has allows one to describe the processes of destruction in the PCM sample. It has been established that, on the base of local formation of microdamages in the matrix and the fracture of the fibers detected during recording of the AE data, it is possible to predict the destruction of the polymer composite material, while the beginning of a material destruction can be registered if the damage identified as an adhesion failure is observed. Perspectives of application of adaptive fiber-optic AE sensors for structural monitoring of PCMs on the base of preliminary experimental results are considered and discussed.

Selected glasses with 10 Na₂O + (90-x) P₂O₅ + x BCD where bypass cement dust (BCD) x value =10, 20, 30 in mol% were synthesized by recognizable melting annealing technique. Cooperative characterization of the prepared glasses were carried out through FTIR and SEM analysis before and after immersed in simulated body fluid (SBF) solution for 13 and 23 days at 37 ^oC. After immersion in SBF, apatite layer is produced on the glass surface after 13 day and increase after 23 day, showing good bioactivity after immersion in the SBF especially for bioglass sample with 30% BCD. A porous hydroxy apatite layer produced on the surface of SBF-glass composite and this layer became denser after more soaking time, periods were extended from 13 to 23 days. Atomic absorption spectroscopy explained the early period of soaking that cause release of both Si and Ca ions through the glass beside decreasing of phosphrous ions. Bioglass (BCD-30) is studied as shielding for gamma, protons and alphas by using Phy-X software, SRIM Monte Carlo simulation code and its subroutine TRIM. The gamma shielding parameters, mass stopping power (MSP), range for both proton (H- ions) and alpha (He- ions) in bioglass- BCD-30 and human bone tissue have estimated. Also, comparison between them is calculated in predicting the radiation damage and atomic displacements per atom (dpa).

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.

Genetic adaptation of Hermetia illucens (BSF) to suboptimal single sourced wastes can open new perspectives for insect production. Here, four replicate BSF lines were maintained on a single sourced, low-quality wheat bran diet (WB) or on a high-quality chicken feed diet (CF) for 13 generations. We continuously evaluated evolutionary responses in several performance traits to rearing at the two diets. Subsequently, we tested responses to interchanged diets, i.e. of larvae that had been adapted to low-quality feed and to high quality feed and vice versa to evaluate costs associated with diet adaptation. BSF were found to experience rapid adaptation to the diet composition. While performances on WB diet were always inferior to CF diet, the adaptive re-sponses were stronger to the former diet. This stronger response was likely due to stronger se-lection pressure experienced by BSF fed on the low-quality single sourced diet. The interchanged diet experiment found no costs associated with diet adaptation but confirmed diet adaptation for the larval biomass and insect frass traits for the WB diet treatment. Our results revealed that BSF can rapidly adapt to diet through evolutionary responses, which has potential to be utilized to produce lines tailored to specific diets.

Biocontrol strategies are gaining tremendous attention with the growing awareness of the irreparable harm caused by the continuous use of synthetic pesticides. This study examines the proteolytic and chitinolytic activities of Bacillus velezensis CE 100 and its termiticidal effect through cuticle degradation. The proteolytic and chitinolytic activities of B. velezensis CE 100 systematically increased with cell growth to the respective peak of 68.3, and 128.3 units/mL after seventh days of inoculation, corresponding with the highest cell growth of 16 x 107 colony forming units (CFU)/mL. The in vitro termiticidal assay showed that B. velezensis CE 100 caused a rapid and high rate of termite mortality with the median lethal time (LT50) of &gt; 1h, and the highest mortality rate of 91.1% and 92.2% recorded at 11h and 12h in the bacterial broth culture and crude enzyme fraction, respectively. In addition to broken setae and deformed sockets, termites treated with the bacterial broth culture exhibited degraded epicuticles, while the crude enzyme fraction caused severe disintegration of both the epicuticle and endocuticle. These results indicate a tremendously higher prospect of B. velezensis CE 100 in the biological control of subterranean termites compared to the previously used entomopathogenic bacteria.

The incidence of chronic enteropathies (CE), in particular food-responsive enteropathies (FRE) in dogs, is on the rise in veterinary practice. The symptoms of these digestive disorders cannot be alleviated with the use of commercial hypoallergenic feeds. The applicability of novel substrates in hypoallergenic dog feeds is limited, and edible insects could pose a viable alternative. Insects have a high nutritional value, and their potential can be harnessed to design personalized nutrition strategies. However, the use of insects in animal feeds should be rigorously tested. The aim of this study was to analyze the applicability of edible insects as a source of dietary protein for companion animals, including the current and future prospects. Canine food formulas should be evaluated in a clinical setting. The role edible insects in pet diets and the efficacy of this substrate in animal nutrition should be examined in advanced clinical trials in gastroenterology, histology, immunology, and microbiology. These efforts are required to guarantee the safety and efficacy of innovative insect-based feeds and to increase their popularity among veterinary practitioners, pet food producers, and animal owners.

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.

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.

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.

Replication stress (RS) is a characteristic state of cancer cells as they tend to exchange precision of replication for fast proliferation and increased genomic instability. To overcome the consequences of improper replication control malignant cells frequently inactivate parts of their DNA damage response (DDR) pathways (the ATM-CHK2-p53 pathway), while relying on other pathways which help to maintain replication fork stability (ATR-CHK1). This creates a dependency on the remaining DDR pathways, vulnerability to further destabilization of replication and synthetic lethality of DDR inhibitors with common oncogenic alterations such as mutations of TP53, RB1, ATM, amplifications of MYC, CCNE1 and others. The response to RS is normally limited by coordination of cell cycle, transcription and replication. Inhibition of WEE1 and PKMYT1 kinases, which prevent unscheduled mitosis entry, leads to fragility of under-replicated sites. Recent evi-dence also shows that inhibition of Cyclin-dependent kinases (CDKs), such as CDK4/6, CDK2, CDK8/19 and CDK12/13 can contribute to RS through disruption of DNA repair and replication control. Here, we review the main causes of RS in cancers as well as main therapeutic targets – ATR, CHK1, PARP and their inhibitors.

As a medical student (Granada University Medical School, Spain), interested in Pediatrics, expended countless hours at the hospital pediatric facilities and got to know many of the children and their medical problems. A particular case, still vivid on my mind, awaken my scientific curiosity. One day, walking and talking with a seven years old child he unexpectedly felt down unconscious with multiple, incontrollable and erratic muscular contractions involving face, body and extremities and salivating. I was overwhelmed thinking it was the child’ last hour. At the time, my knowledge of epilepsy was nil. Following the seizures, the child was up, talking and walking with me as if nothing has happened and without any knowledge of the event. What could have caused the brain motor cortex to suddenly discharge that amount of altered activity causing generalized and erratic muscular contractions remains inexplicable. I migrated to USA, become a Pediatric (Developmental) Pathologist and Director of the Pediatrics Autopsy Service (1962-1999) at the Dartmouth-Hitchcock Medical Center, New Hampshire. I carried out countless postmortem studied of children brains, normal (unaltered) as well as those altered by hemorrhagic, hypoxic-ischemic and/or traumatic damage. With an NIH Fellowship, I spend one year (1967-68) at the Cajal Institute (Madrid, Spain) studying Cajal’ old Golgi preparations and learning about the method. Some of my Golgi studies of children’ brains have been published: The Human Brain. Prenatal Development and Structure, Springer, Heidelberg, Germany, 2012. The present monograph explores the developmental neuropathology of selected perinatal cortical injuries through their acute, subacute and chronic stages. Including: a) how an altered neuronal activity evolves in a damaged cortical region; b) how it moves through the cortex (epileptic auras); and c) how it reaches the motor cortex to be discharged as erratic and incontrollable muscular contractions. Understanding these processes should provide insights into the pathogenesis of epilepsy secondary to perinatal brain damage.

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.

High costs for the repair of concrete structures can be prevented if damage at an early stage of degradation is detected and precautionary maintenance measures are applied. To this end, we use numerical wave propagation simulations to identify simulated damage in concrete using convolutional neural networks (CNN). Damage in concrete subjected to compression is modeled at the mesoscale using the discrete element method. Ultrasonic wave propagation simulation on the damaged concrete specimens are performed using the rotated staggered finite-difference grid method. The simulated ultrasonic signals are used to train a CNN based classifier capable of classifying three different damage stages (microcrack initiation, microcrack growth and microcrack coalescence leading to macrocracks). The performance of the classifier is improved by refining the dataset via an analysis of the averaged envelope of the signal. The classifier using the refined dataset has an overall accuracy of 90%.

Sperm marking represents a valuable monitoring tool for genetic pest control strategies such as the Sterile Insect Technique, but also provides a key tool for reproductive biology studies. Sperm-marked lines can be generated by introducing transgenes that mediate the expression of fluorescent proteins during spermatogenesis. Homozygous lines established by transgenesis approaches are going through a genetic bottleneck that can lead to reduced fitness. Transgenic SIT approaches have mostly focused on Dipteran and Lepidopteran pests so far. With this study, we provide sperm-marked lines for the Coleopteran pest model organism, the red flour beetle Tribolium castaneum, based on the β2-tubulin promoter/enhancer driving red (DsRed) or green (EGFP) fluorescence. The obtained lines are reasonably competitive and were thus used for studies on reproductive biology confriming the phenomenon of ‘last male sperm precedence’ and that the spermathecae are deployed for long term sperm storage enabling the use of sperm from first matings even after secondary matings for a long period of time. The homozygosity and competiveness of the lines will enable future studies to analyze the controlled process of sperm movement into the long time storage organ as part of a post-mating cryptic female choice mechanism of this extremely promiscuous species.

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.

Calcineurin plays a key role in cardiovascular pathogenesis by exerting pro-apoptotic effects in cardiomyocytes; however, its involvement in the regulation of cardiomyocyte autophagy under chronic intermittent hypoxia (CIH) remains largely unknown. Here we showed that CIH induced calcineurin activity in H9C2 cells, resulting in the attenuation of adenosine monophos-phate-activated protein kinase (AMPK) signaling and inhibition of H9C2 cell autophagy. Au-tophagy, LC3-II levels, and AMPK phosphorylation were significantly elevated in response to CIH in H9C2 cells by day 3; however, these effects were reversed, and calcineurin activity and apoptosis were significantly increased by day 5. The calcineurin inhibitor, FK506, restored AMPK activation and LC3 protein levels, and reduced CIH-induced H9C2 cell apoptosis, while calcineurin overexpression significantly attenuated the increase in LC3 levels and enhanced H9C2 cell apop-tosis. Calcineurin inhibition failed to induce autophagy or alleviate apoptosis in H9C2 cells ex-pressing a dominant negative K45R AMPK mutant. Autophagy downregulation abrogated the protective effects of FK506-mediated calcineurin inhibition. These results indicated that calcineurin suppressed adaptive autophagy during CIH by downregulating AMPK activation. Our findings showed the underlying mechanisms of calcineurin and autophagy regulation during H9C2 cell survival in response to CIH, and suggested a new strategy for preventing CIH-induced cardiomyocyte damage.

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.

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.

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.

The use of botanical extracts of the plant Jatropha curcas (Euphorbiaceae) represents a valuable alternative to control insect pests and avoid the detrimental effects on the environment and health that arise due to synthetic chemical insecticides. Thus, we conducted a systematic review to summarize the published evidence on the bioactivity of J. curcas against insect pests. Electronic databases were searched to identify studies that assessed J. curcas extracts against insect pests in various types of crops. We included 39 articles that reported the insecticidal and insectistatic activity of several botanical extracts from J. curcas against insects of eight different taxonomic orders. The evidence demonstrates that aqueous and methanolic extracts from seeds and leaves, seed oil, and petroleum ether seed extracts were effective against insect pests of stored grains, aphids of cabbage, sorghum, fruit flies, and desert locusts. The extracts caused high mortality, controlled the populations, reduced oviposition, diminished hatchability, and increased the antifeedant effect. However, the type of solvent used to obtain the botanical extract and the method of application (contact or food) are fundamental to increase its bioactivity. Therefore, botanical extracts from seeds and leaves of J. curcas should be considered as an alternative against insect pests and may be incorporated into integrative and sustainable management for insect control.