Quantitative determination of the critical size of inclined coal pillar in old goaf water affected area is of great significance for water damage prevention and safe mining. The critical size of inclined waterproof coal pillar is derived by using theoretical analysis, numerical calculation and field engineering practice for the stability of the waterproof coal pillar in old goaf water affected area of 1303 working face of Dananhu I mine in Xinjiang region. Firstly, a force model of inclined waterproof coal pillar was established to reveal the law that the critical size of the coal pillar increases with the increase of coal seam inclination under the action of asymmetric load. Then, numerical simulation was applied to reveal the dynamic evolution process of plastic deformation-destabilization-destruction of section coal pillar under the influence of mining and single-side water pressure, and the critical size of waterproof coal pillar in study area was determined to be 19.09m. Finally, measures such as pumping and pressure relief and slurry reinforcement were adopted to reduce the deformation rate of the roadway on side of waterproof coal pillar, which ensured the stability of the coal pillar and roadway and the safe recovery of the working face.

Retinoic acid receptor-related orphan receptor γ (RORγ) is a transcription factor regulating the expression of the pro-inflammatory cytokine IL-17 in human T helper 17 (Th17) cells. Activating RORγ can induce multiple IL-17-mediated autoimmune diseases but may also be useful for anticancer therapy. Its deep immunological functions make RORɣ an attractive drug target. Over 100 crystal structures have been published describing atomic interactions between RORɣ and agonists and inverse agonists. In this review, we focus on the role of dynamic properties and plasticity of the RORɣ orthosteric and allosteric binding sites by examining structural information from crystal structures and simulated models. We discuss the possible influences of allosteric ligands on the orthosteric binding site. We find that high structural plasticity favors the druggability of RORɣ, especially for allosteric ligands.

To facilitate the computation of the uniaxial compressive strength value of the cemented paste backfill under the condition of high sand-cement ratio, and to analyze the size effect of the cemented paste backfill with high sand-cement ratio under varied aspect ratios, the cemented paste backfill specimens with sand-cement ratios of 8:1-24:1 and aspect ratios of 0.5, 1, and 2 were prepared. Through response surface experiments and finite element analysis, the influence of three aspect ratios on the cemented paste backfill strength was explored, and the failure characteristics and size effect mechanisms of cemented paste backfill with various aspect ratios were analyzed. The model of strength conversion between cemented paste backfill with different aspect ratios was established. The results show that the compressive strength of the cemented paste backfill decreases with the increase of the aspect ratio under the same mass concentration and sand-cement ratio. When the aspect ratio is 0.5 and 1, the splitting failure is the main factor; when the aspect ratio is 2, the shearing failure is the main factor. The three-dimensional stress caused by the end effect of the cemented paste backfill is the main reason for the high strength when the aspect ratio is 0.5. Due to the one-dimensional stress zone generated in the middle of the cemented paste backfill with an aspect ratio of 2 in the laboratory, its strength value is closer to the actual uniaxial compressive strength value of the cemented paste backfill. The strength values of the cemented paste backfill with aspect ratios of 0.5 and 1 were higher than the actual uniaxial compressive strength values in the laboratory. The rationality of the theoretical analysis was verified by the ABAQUS analysis results. According to the experimental results, a strength conversion model between different aspect ratios is established, which can provide a reference for the design of the uniaxial compressive strength of the cemented paste backfill.

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

The degree of ore rock fragmentation of mine blasting is an important index for evaluating the effect of engineering blasting. In order to study the effect of millisecond delayed blasting on the internal fragmentation of the ore rock, LS-DYNA numerical simulation software was used to obtain the damage characteristics of the ore rock in the blasting area using the RHT model. The Mohr-Coulomb strength damage criterion was applied to analyze the internal stress state of the ore rock, and the effects of 25ms, 50ms and 75ms delay time conditions on ore rock fragmentation were studied. The results show that, within a certain range of delay time, the degree of rock fragmentation increases with the increase of delay time. The stress state in the ore rock due to blasting is strengthened with the increase of delay time in the direction of the blast hole, which shows that the stress concentration is strengthened from the excavation face to the interior of the ore rock. The damage and the degree of fragmentation show a characteristic relationship of 25ms＜50ms＜75ms, which is verified by carrying out blasting experiments on site.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

Floods are among the most serious natural disasters worldwide; they cause enormous crop losses every year and threaten world food security. There are many studies focused on flood impact assessments for administrative districts but fewer on postdisaster impact assessments for specific crops. Therefore, this study used remote sensing data, including the normalized difference vegetation index (NDVI), elevation data, slope data, and rainfall data, combined with crop growing season data to construct a crop flood damage assessment index (CFAI). First, an analytic hierarchy process (AHP) was used to assign weights to the impact factors; then, the weighted composite score method was used to calculate the CFAI; and finally, the impact was classified as slight, moderate, or severe based on the magnitude of the CFAI . This method was used for the Missouri River floods of 2019 in the U.S. Due to the lack of measured data, the disaster vegetation damage index (DVDI) was used to validate the results. The combined approach achieved a high degree of consistency in spatial distribution. The CFAI can respond well to the degree of crop impact after flooding, providing new ideas and reference standards for agriculture-related departments.

The intentional damages to local Cultural Heritage sites carried out in recent months by the Islamic State have received wide coverage from the media worldwide. Earth Observation data provide important information to assess these damages in such non-accessible areas, and automated image processing techniques would be needed to speed up the analysis if a fast response is desired. This paper shows the first results of applying fast and robust change detection techniques to sensitive areas, based on the extraction of textural information and robust differences of brightness values related to pre- and post-disaster satellite images. A map highlighting potentially damaged buildings is derived, which could help experts at timely assessing the damages to the Cultural Heritage sites of interest. Encouraging results are obtained for two archaeological sites in Syria and Iraq.

The liver diseases are posing serious threat to human health associated with abusive use of allopathy medicines, especially in developing economies like Pakistan. The strengthening of detoxification system using natural products might be a suitable option to minimize the liver problems. In this current research, Zingiber officinale and Azadirachta indica were evaluated for their hepatoprotective role. For the purpose, 20 Sprague Dawley rats were equally divided into four groups i.e., negative control, paracetamol positive control, 2.5% ginger and 2% neem powder, respectively. During 42 days study, the levels of bilirubin and liver enzymes significantly elevated due to liver damage. Although, the values dropped (20-25%) in treatment group. Serum glucose and serum lipid profile increased in positive control group, but reduced (5-10%) in both ginger and neem groups. The serum protein profile declined in liver damage group, however, improved (~5%) in treatment groups. The hematological parameters slightly declined in liver damage group, but increased in ginger and neem groups. Moreover, the white blood cells differential count and renal parameters showed abnormal values in liver damage group, but improved after treatment. This study is promising and highlighted the hepato-protective role of neem and ginger that may open several avenues of research.

Many aging adults experience some form of hearing problems that may arise from auditory peripheral damage. However, it has been increasingly acknowledged that hearing loss is not only a dysfunction of the auditory periphery but results from changes within the entire auditory system, from periphery to cortex. Damage to the auditory periphery is associated with an increase in neural activity at various stages throughout the auditory pathway. Here, we review neurophysiological evidence of hyperactivity, auditory perceptual difficulties that may result from hyperactivity, and outline open conceptual and methodological questions related to the study of hyperactivity. We suggest that hyperactivity alters all aspects of hearing – including spectral, temporal, spatial hearing – and, in turn, impairs speech comprehension when background sound is present. By focusing on the perceptual consequences of hyperactivity and the potential challenges of investigating hyperactivity in humans, we hope to bring animal and human electrophysiologists closer together to better understand hearing problems in older adulthood.

Hybrid reinforcement in a composite material (CM), in many situations, allows better govern material mechanical properties. Polymer matrix CM plate is reinforced with small particles and macro-fibers. Particles are oil shale ash (OSA) powder, macro-fibers – basalt fiber threads im-pregnated by matrix material. With the goal to find out elastic properties of the matrix- polymer with OSA, samples with its different concentrations were experimentally fabricated and their elastic properties were experimentally measured. Obtained data were used in numerical model-ling. Was observed polymer matrix composite slab, reinforced with OSA and three-dimensional (3D) basalt fiber fabric. Fabric are forming threads impregnated by matrix (polymer resin mixed with OSA particles). Damage accumulation in the stretched slab was modelled. Impregnated thread, in the modelling, is observed as a macro-fiber (MF) with averaged elastic properties. With the load increase MF in the material began to break. At first, appeared isolated single breaks. A probabilistic sequential MF rupture accumulation model was accepted and numerical-ly realized. The geometry of the reinforcing knitted fabric was modeled using the Leaf and Glaskin approach. In the knitted fabric highly, stressed MF cross-sections are observed as po-tential location where thread breakage can occur. If one thread breaks, the cross-sections of the adjacent threads experience the overload caused by this rupture. More overloaded crossection in the adjacent overloaded thread breaks and we obtain two adjacent broken MF designated as a defect with the size j=2. The probabilities of obtaining defect consisting of at least 2, 3, … j adjacent broken MF in the plate were calculated. The calculations continued until the rupture process becomes unstable (j→∞). The overstresses on adjacent threads in the CM were calculat-ed using the FEM three-dimensional numerical approach. Analytical and stochastic methods were used for the load-carrying capacity determination and different size defects accumulation in the hybrid composite material (HCM) plate. Also, was calculated the probability of the plate rupture.

Based on PVDF (piezoelectric sensing techniques), this paper attempts to study the propagation law of shock waves in brittle materials during the process of three-wavelength laser irradiation of polysilicon, and discusses the formation mechanism of thermal shock failure. The experimental results show that the vapor pressure effect and the plasma pressure effect in the process of pulsed laser irradiation lead to the splashing of high temperature and high density melt. With the decrease of the laser wavelength, the laser breakdown threshold decreases and the shock wave is weakened. Because of pressure effect of the laser shock, the brittle fracture zone is at the edge of the irradiated area. The surface tension gradient and surface shear wave caused by the surface wave are the result of coherent coupling between optical and thermodynamics. The average propagation velocity of laser shock wave in polysilicon is 8.47×103m/s, and the experiment has reached the conclusion that the laser shock wave pressure peak exponentially distributes attenuation in the polysilicon.

A central hypothesis on brain functioning is that plasticity regulates the signals transfer function by modifying the efficacy of synaptic transmission. In the cerebellum, granular layer has been shown to control the gain of signals transmitted through the mossy fiber pathway. Until now, the impact of plasticity on incoming activity patterns was analyzed by combining electrophysiological recordings in acute cerebellar slices and computational modeling, unraveling a broad spectrum of different forms of synaptic plasticity in the granular layer, often along with forms of intrinsic excitability changes. Here, we attempt to provide a brief overview of the most prominent forms of plasticity at excitatory synapses formed by mossy fibers onto principal neurons (granule cells, Golgi cells and unipolar brush cells) in the granular layer. Specifically, we will highlight current understanding of the mechanisms and their functional implications of the synaptic and intrinsic plasticity, providing valuable insights into how inputs are processed and reconfigured at the cerebellar input stage.

Intratumoral heterogeneity is a major ongoing challenge in the effective therapeutic targeting of cancer. Accumulating evidence suggests that a fraction of cells within a tumor termed Cancer Stem Cells (CSCs) are primarily responsible for this diversity resulting in therapeutic resistance and metastasis. Adding to this complexity, recent studies have shown that there can be different subpopulations of CSCs with varying biochemical and biophysical traits resulting in varied dissemination and drug-resistance potential. Moreover, cancer cells can exhibit a high level of plasticity or the ability to dynamically switch between CSC and non-CSC states or among different subsets of CSCs. The molecular mechanisms underlying such plasticity has been under extensive investigation and the trans-differentiation process of Epithelial to Mesenchymal transition (EMT) has been identified as a major contributing factor. Besides genetic and epigenetic factors, CSC plasticity is also shaped by non-cell-autonomous effects such as the tumor microenvironment. In this review, we discuss the recent developments in understanding CSC plasticity in tumor progression at biochemical and biophysical levels, and the latest in silico approaches being taken for characterizing cancer cell plasticity with implications in improving existing therapeutic approaches.

Establishing macrometastases at distant organs is a highly challenging process for cancer cells, with extremely high attrition rates. A very small percentage of disseminated cells have the ability to dynamically adapt to their changing micro-environments through reversibly switching to another phenotype, aiding metastasis. Such plasticity can be exhibited along one or more axes – epithelial-mesenchymal plasticity (EMP) and cancer stem cells (CSCs) being the two most studied, and often tacitly assumed to be synonymous. Here, we review the emerging concepts related to EMP and CSCs across multiple cancers. Both processes are multi-dimensional in nature; for instance, EMP can be defined on morphological, molecular and functional changes, which may or may not be synchronized. Similarly, self-renewal, multi-lineage potential, and anoikis and/or therapy resistance may not all occur simultaneously in CSCs. Thus, arriving at rigorous functional definitions for both EMP and CSCs is crucial. These processes are dynamic, reversible, and semi-independent in nature; cells traverse the inter-connected high-dimensional EMP and CSC landscapes in diverse paths, each of which may exhibit a distinct EMP-CSC coupling. Our proposed model offers a potential unifying framework for elucidating the coupled decision-making along these dimensions and highlights a key set of open questions to be answered.

Social plasticity, defined as the ability to adaptively change the expression of social behavior according to previous experience and to social context, is a key ecological performance trait that should be viewed as crucial for Darwinian fitness. The neural mechanisms for social plasticity are poorly understood, in part due to skewed reliance on rodent models. Fish model organisms are relevant in the field of social plasticity for at least two reasons: first, the diversity of social organization among fish species is staggering, increasing the breadth of evolutionary relevant questions that can be asked. Second, that diversity also suggests translational relevance, since it is more likely that “core” mechanisms of social plasticity are discovered by analyzing a wider variety of social arrangements than relying on a single species. We analyze examples of social plasticity across fish species with different social organizations, concluding that a “core” mechanism is the initiation of behavioral shifts through the modulation of a conserved “social decision-making network”, along with other relevant brain regions, by monoamines, neuropeptides, and steroid hormones. The consolidation of these shifts may be mediated via neurogenomic adjustments and regulation of the expression of plasticity-related molecules (transcription factors, cell cycle regulators, and plasticity products).

We present a high-throughput nanoindentation study of in-situ bending effects on incipient plastic deformation behavior of polycrystalline and single-crystalline pure aluminum and pure copper at ultra-nano depths (<200nm). We find that hardness displays a statistically inverse dependence on in-plane stress for indentation depths smaller than 10nm, and the dependence disappears for larger indentation depths. In addition, plastic noise in the nanoindentation force and displacement displays statistically robust noise features, independently of applied stresses. Our experimental results suggest the existence of a regime in FCC crystals where ultra-nano hardness is sensitive to residual applied stresses, but plasticity pop-in noise is insensitive to it.

Oleuropein (OLE), a main constituent of olive, displays a pleiotropic beneficial dynamic in health and disease, based mainly on its antioxidant and hypolipidemic properties, and its capacity to protect myocardium during ischemia. Furthermore, OLE activates peroxisome proliferator-activated receptor (PPARα) in neurons and astrocytes, providing neuroprotection against noxious biological reactions that are induced following cerebral ischemia. Current study investigated the effect of OLE in the regulation of various neural plasticity indices, emphasizing the role of PPARα. For this purpose, 129/Sv wild-type (WT) and Pparα-null mice were treated with OLE for three weeks. The present findings revealed that chronic treatment with OLE up-regulated the brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the prefrontal cortex (PFC) of mice via activation of ERK1/2, AKT and PKA/CREB signaling pathways. No similar effects were observed in the hippocampus. The OLE-induced effects on BDNF and TrkB appear to be mediated by PPARα, because no similar alterations were observed in the PFC of Pparα-null mice. Notably, OLE did not affect the neurotrophic factors NT3 and NT4/5 in both brain tissues. Fenofibrate though, a selective PPARα agonist, up-regulated BDNF and NT3 in the PFC of mice, whereas the drug induced NT4/5 in both brain sites tested. Interestingly, OLE provided neuroprotection in differentiated human SH-SY5Y cells against β-amyloid and H2O2 toxicity independently from PPARα activation. In conclusion, OLE and similar drugs acting either as PPARα agonists or via PPARα independent mechanisms could improve synaptic function/plasticity mainly in the PFC and to a lesser extent in the hippocampus, thus beneficially affecting cognitive functions.

The cytoskeleton is a master organizer of cell cortex, organelles positioning and membrane trafficking. Therefore, playing a decisive role in establishment of apico-basal polarity. Septins are critical cytoskeleton components which function in apico-basal polarity remain weakly investigated. Here, using 3D culture system, we demonstrate that septin9 localizes at basolateral membrane (BM). Its depletion induces an inverted polarity phenotype, decreasing -catenin at BM and increasing the expression of the transforming growth factor (TGF) and the epithelial-to-mesenchymal transition (EMT) markers. Similar effects were observed upon deleting its two polybasic domains, and the mutant become cytoplasmic and apical. The cysts with an inverted polarity phenotype display an invasive phenotype, with src and cortactin accumulating at the peripheric membrane. Inhibition of TGF-receptor and RhoA rescues the polarized phenotype. Although the cysts from overexpressed-septin 9, overgrowth and present a filled lumen. Both phenotypes correspond to tumor features. This suggests that septin 9 expression and assembly through the two PB domains are essential for establishing and maintaining apico-basal polarity against tumor development through a mechanism involving TGF-dependent EMT and RhoA activity.

Clonal evolution and cellular plasticity are the genetic and non-genetic driving forces of tumor heterogeneity that in turn determines the tumor cell response towards therapeutic drugs. Several lines of evidence suggest that therapeutic interventions foster the selection of drug resistant neural crest stem-like cells (NCSCs) that establish minimal residual disease (MRD) in melanoma. Here we established a dual reporter system enabling the tracking of NGFR expression and mRNA stability, providing insights into the maintenance of NCSC-states. We observed that the transcriptional reporter that contained a 1kb fragment of the human NGFR promoter was activated only in a minor subset (0.72±0.49%, range 0.3-1.5) and ~2-4% of A375 melanoma cells revealed stable NGFR mRNA. The combination of both reporters provided insights into phenotype switching and revealed that both cellular subsets gave rise to cellular heterogeneity. Moreover, whole transcriptome profiling and gene set enrichment analysis (GSEA) of the minor cellular subset revealed hypoxia-associated programs that might serve as potential drivers of an in vitro switching of NGFR-associated phenotypes and relapse of post-BRAF inhibitor treated tumors. Concordantly, we observed that the minor cellular subset increased in response to dabrafenib over time. In summary, our reporter-based approach provided insights into plasticity and identified a cellular subset that might be responsible for the establishment of MRD in melanoma.

Constitutive models for plastic deformation of metals are typically based on flow rules determining the transition from elastic to plastic response of a material as function of the applied mechanical load. These flow rules are commonly formulated as a yield function, based on the equivalent stress and the yield strength of the material, and its derivatives. In this work, a novel mathematical formulation is developed that allows the efficient use of machine learning algorithms describing the elastic-plastic deformation of a solid under arbitrary mechanical loads and that can replace the standard yield functions with more flexible algorithms. By exploiting basic physical principles of elastic-plastic deformation, the dimensionality of the problem is reduced without loss of generality. The data-oriented approach inherently offers a great flexibility to handle different kinds of material anisotropy without the need for explicitly calculating a large number of model parameters. The applicability of this formulation in finite element analysis is demonstrated, and the results are compared to formulations based on Hill-like anisotropic plasticity as reference model. In future applications, the machine learning algorithm can be trained by hybrid experimental and numerical data, as for example obtained from fundamental micromechanical simulations based on crystal plasticity models. In this way, data-oriented constitutive modeling will also provide a new way to homogenize numerical results in a scale-bridging approach.

Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial-mesenchymal transition (EMT). Cells in these hybrid E/M phenotypes often combine epithelial and mesenchymal features and tend to migrate collectively commonly as small clusters. Such collectively migrating cancer cells play a pivotal role in seeding metastases and their presence in cancer patients indicates an adverse prognostic factor. Moreover, cancer cells in hybrid E/M phenotypes tend to be more associated with stemness which endows them with tumor-initiation ability and therapy resistance. Most recently, cells undergoing EMT have been shown to promote immune suppression for better survival. A systematic understanding of the emergence of hybrid E/M phenotypes and the connection of EMT with stemness and immune suppression would contribute to more effective therapeutic strategies. In this review, we first discuss recent efforts combining theoretical and experimental approaches to elucidate mechanisms underlying EMT multi-stability (i.e. the existence of multiple stable phenotypes during EMT) and the properties of hybrid E/M phenotypes. Following we discuss non-cell-autonomous regulation of EMT by cell cooperation and extracellular matrix. Afterwards, we discuss various metrics that can be used to quantify EMT spectrum. We further describe possible mechanisms underlying the formation of clusters of circulating tumor cells. Last but not least, we summarize recent systems biology analysis of the role of EMT in the acquisition of stemness and immune suppression.

Colistin is used in treatment against gram-negative bacteria. It causes toxic effects due to oxidative stress in a dose-dependent manner. Naringin is a flavonoid with strong antioxidant properties found naturally in many plants, especially citrus fruits. This study aimed to determine the protective effects of NRG in CLS-induced sciatic nerve injury. Thirty-five male Spraque rats were randomly divided into five groups: control, NRG, CLS, CLS+NRG50, and CLS+NRG100. CLS was administered orally at a 15mg/kg for seven days. NRG was administered orally at 50 or 100 mg/kg for seven days. CLS caused toxic damage in sciatic nerve tissue by increasing MDA and decreasing antioxidant capacity (SOD, CAT, GPx, and GSH); increasing NF-κB, TNF-α, nNOS release; increasing apoptotic factor (Caspase-3); decreasing HO-1 and nCAM; and inducing 8-OHdG, MAPK and GFAP. NRG, on the other hand, reversed all these changes in sciatic nerve tissue and reduced CLS-induced oxidative stress damage, inflammatory damage and apoptotic damage. These effects were more effective at the 100mg/kg dose of NRG than at the 50mg/kg dose. In sciatic nerve tissue, CLS-induced sciatic nerve toxicity with increased oxidative stress, inflammation, and apoptotic damage. NRG showed a protective effect against CLS-induced sciatic nerve toxicity.

Age-related brain deterioration and Alzheimer's disease (AD) pose major challenges as misfolded proteins are deposited in the brain, leading to a decline in cognitive abilities and disruption of neural networks crucial for memory. This article addresses the impact of disrupted spike-timing-dependent plasticity (STDP) mechanisms in Alzheimer's disease and highlights the role of Transcranial magnetic stimulation (TMS) in the study of cortico-cortical spike-timing-dependent plasticity. Amidst this adversity, the role of STDP emerges as a key player in memory formation by synchronizing neural activity. Progressive neuronal dysfunction decreases neural plasticity and impairs manual dexterity and speed, echoing more general problems in elderly people. The findings highlight the potential of neurally-driven cortico-cortical paired associative stimulation (ccPAS) to revitalize neural plasticity and improve motor performance in elderly people, bridging the gap between age-related challenges and Alzheimer's research. This work opens a door to potential rehabilitation strategies for aging populations by unlocking the aging brain's ability to improve motor performance.

Phenotypic switching in cancer cells has been found to be present across tumor types. Recent studies on Glioblastoma report a remarkably common architecture of four well-defined phenotypes coexisting within high levels of intra-tumour genetic heterogeneity. Tumours grown from any cell type recapitulate the original phenotypic composition. Similar dynamics have been shown to occur in breast cancer, melanoma and likely across further cancer types. Given the adaptive potential of phenotypic switching (PHS) strategies, understanding how it drives tumour evolution and how to break down these architectures is a major priority. Here we model the ecological dynamics behind PHS. The model is able to reproduce experimental results, and specific conditions for cancer progression and clearance reveal novel features of plastic tumours and its direct consequences on therapy resistance. Following our results we discuss \textit{transition} therapy as a novel scheme to target not only combined cytotoxicity but also the rates of phenotypic switching.

Following the occurrence of a typhoon, quick damage assessment related to residents can facilitate quick dispatch of house repair and disaster insurance works. Employing a deep learning method, this study used aerial photos of the Chiba prefecture obtained following the Typhoon Faxai in 2019 to automatically detect and evaluate the roof damage. This study comprised three parts: training deep learning model, detecting the roof damage using trained model, and classifying the level of roof damage. The detection object comprised roof outline, blue tarps, and roof completely destroyed. The roofs were divided into three categories: roof without damage, roof with blue tarps and roof completely destroyed. the F value obtained using the proposed method was higher than those obtained using other methods. In addition, it can be further divided into 5 levels from level 0 to 4. Finally, the spatial distribution of the roof damage was analyzed using ArcGIS tools. The proposed method is expected to provide certain reference for the real-time detection of the roof damage after the occurrence of a typhoon.

Typhulaceae Jülich is one of the cold-adapted fungal families in basidiomycetes. Typhula (Pers.) Fr. and Pistillaria Fr. representing the family are distinguished from the morphology of a stipe to a hymenium (Fries 1821). The hymenium of Typhula is distinguishable from the stipe, but indistinguishable and consecutive in the genus Pistillaria. This taxonomic criterion is ambiguous, and consequently the opinion of Karsten (1882) has been widely accepted; I the genus Typhula, basidiomata develop from sclerotia, while basidiomata develop directly from substrata in the genus Pistillaris. But, Corner (1970) observed basidiomata of Pistillaria petasitis S. Imai in Hokkaido, Japan, from sclerotia. We collected irregular sclerotia of Typhula hyperborea H. Ekstr. from Upernavik, West Greenland. This specimen had a stipe-like structure on a Poaceae plant, and sclerotia developed on its tip. In August, P. petasitis in Hokkaido, Japan, formed basidiomata directly from substrates on the ground. Similar phenomena were found from other Typhula spp. in Japan. All of these fungi had the potential to produce sclerotia in culture, and as well as the capacity of mycelial growth at ambient air temperatures in each locality when samples were collected. These findings suggest that Typhula spp. developed basidiomata not only from the sclerotia dispersed by the basidiospores but also mycelia generated by the spore germination formed basidiomata multiple times depending on their growth environments.

A paper recently published by eLife on forebrain cortical synaptic plasticity reports that retinoic acid (RA) alters synaptopodin-dependent metaplasticity in mouse dentate granule cells (Lenz et al., 2021). RA is the active form of vitamin A that functions as a ligand for nuclear RA receptors that directly bind genomic control regions to regulate gene expression (Chambon, 1996; Ghyselinck and Duester, 2019). However, some studies have suggested that RA may have nongenomic effects outside of the nucleus, particularly with regard to synaptic plasticity (Aoto et al., 2008; Zhang et al., 2018). The current results reported by Lenz et al. demonstrate that treatment with pharmacological levels of RA can alter synaptic plasticity which may be useful to treat neurological diseases (Lenz et al., 2021). However, the results reported here and those reported by others have not shown that endogenous RA is normally required for synaptic plasticity (or any other nongenomic effect) as there are no reports of genetic loss-of-function studies that remove endogenous RA in adult brain. The implication is that pharmacological levels of RA result in nongenomic effects, some of which may be helpful to treat certain diseases but in other cases this may cause unwanted side-effects.

Waddington’s epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of “landscape” in the context of dynamical system theory represents a high-dimensional cell state space, in which each cell phenotype is considered as an “attractor” that is determined by interactions among multiple variables (molecular players), and is buffered against environmental fluctuations. Further, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes. Here, we discuss these phenotypic transitions in cancer from a dynamical systems perspective and invoke the concept of “cancer attractors” – hidden stable states of the underlying regulatory network that are not occupied by normal cells. Using epithelial-to-mesenchymal transition (EMT), cancer stem-like properties, metabolic reprogramming and the emergence of drug/hormone resistance as examples, we illustrate how phenotypic plasticity in cancer cells enables them to acquire hybrid phenotypes (such as hybrid epithelial/mesenchymal and hybrid metabolic phenotypes) that tend to be more aggressive and notoriously resilient to drug/hormone treatment. Furthermore, we highlight multiple factors that may give rise to phenotypic plasticity in cancer cells, such as (a) multi-stability or oscillatory behaviors governed by underlying regulatory networks involved in cell-fate decisions in cancer cells, and (b) network rewiring due to conformational dynamics of intrinsically disordered proteins (IDPs) that are highly enriched in cancer cells. We conclude by discussing why a therapeutic approach that promotes ‘recanalization’, i.e. the exit from “cancer attractors” and re-entry into “normal attractors”, is more likely to succeed rather than a conventional approach that targets individual molecules/pathways.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Lineage plasticity, the switching of cells from one lineage to another has been recognized to be a cardinal property essential for embryonic development, tissue repair and homeostasis. However, such a highly regulated process goes awry when cancer cells exploit this inherent ability to their advantage, resulting in tumorigenesis, relapse, metastasis and therapy resistance. In this review, we summarize our current understanding on the role of lineage plasticity in tumor progression and therapeutic resistance in multiple cancers. Lineage plasticity can be triggered by treatment itself and is reported across various solid as well as liquid tumors. Here we focus on the importance of lineage switching in tumor progression and therapeutic resistance of solid tumors such as the prostate, lung, hepatocellular and colorectal carcinoma and the myeloid and lymphoid lineage switch observed in leukemias. Besides this, we also discuss the role of Epithelial-Mesenchymal Transition (EMT) in facilitating the lineage switch in biphasic cancers such as aggressive carcinosarcomas. We also discuss the mechanisms involved, current therapeutic approaches and challenges that lie ahead in taming the scourge of lineage plasticity in cancer.

In this paper, we present a comprehensive 4D study of the early stage of plastic deformation in a polycrystalline binary AlLi alloy. The entire microstructure is mapped with X-ray diffraction contrast tomography and a set of bulk grains is further studied via X-ray topotomography during mechanical loading. The observed contrast is analyzed with respect to the slip system activation and the evolution of the orientation spread is measured as a function of applied strain. The experimental observations are augmented by the mechanical response predicted by crystal plasticity finite element simulations to analyze the onset of plasticity in details. Simulation results show a general agreement of the individual slip system activation during loading and that comparison with experiments at the length scale of the grains may be used to fine tune the constitutive model parameters.

The pivotal role of the basolateral amygdala (BLA) in the emotional modulation of hippocampal plasticity and memory consolidation is well established. Specifically, multiple studies have demonstrated that the activation of the noradrenergic (NA) system within BLA governs these modulatory effects. However, most of the current evidence has been obtained by direct infusion of synthetic NA or beta-adrenergic agonists. In the present study, we aimed to investigate the effect of endogenous NA release in the BLA, induced by a natural aversive stimulus (coyote urine), on memory consolidation for a neutral hippocampal-dependent task. We combined a weak version of the object location task (OLT) with mild predator odor exposure (POE) for our experiments. To investigate the role of the BLA in memory modulation, a subset of the animals (Wistar rats) were treated with the non-selective beta-blocker propranolol at the end of the behavioral procedures. Hippocampal tissue was collected either 90 minutes after drug infusion or 24 hours after the OLT test. The samples were used to determine the levels of phosphorylated CREB (pCREB) and activity-regulated cytoskeleton-associated protein (Arc) - two molecular markers of experience-dependent changes in neuronal activity. The result suggests that POE is a behavioral paradigm suitable for studying the interaction between BLA and the hippocampus in memory prioritization and selectivity.

This experiment was conducted to study the effects of Cyfluthrin (Cy) exposure on neurobehaviour, hippocampal tissue and synaptic plasticity in Wistar rats. First, high-dose Cy exposure can cause nerve injury with symptoms such as deficits in learning and memory ability, spatial exploration and autonomic motor ability. Moreover, it was found that medium- and high-dose Cy exposure can cause disordered energy metabolism in hippocampal cells and an abnormal release of the neurotransmitter Glu. Second, pathological brain sections showed that the middle and high doses of Cy caused deformation, reduction and disorder of hippocampal pyramidal cells, a decrease in the number of Nissl bodies, pyknosis of the hippocampal cell nuclear membrane and serious damage to organelles, indicating that exposure to these doses of Cy may cause hippocampal tissue damage in rats. Third, with the increase in exposure dose, the morphological changes in hippocampal synapses were more obvious, including blurred synaptic spaces, decreased synaptic vesicles and a decreased number of synapses. Moreover, the expression levels of the key synaptic proteins PSD-95 and SYP also decreased in a dose-dependent manner, indicating obvious synaptic damage. Finally, the study found that medium and high doses of Cy could upregulate the expression of A2AR in the hippocampus, and the expression levels of inflammatory factors and apoptosis-related proteins increased in a dose-dependent manner. Moreover, the expression of A2AR mRNA was correlated with neurobehavioural indicators, inflammatory factors, synaptic plasticity factors and apoptosis factors, suggesting that Cy may cause nerve damage in rats and has a close relationship with A2AR.

Online identity-based theft is known to be one of the most serious and growing threats to victims, such as individuals and organizations, over the last 10 years due to the enormous economic damage these crimes have caused. The availability of personal information on the Internet has increased the chances of this cyber-crime. Online identity theft crime is the result of a combination of cyber-crimes on the one hand and lack of awareness and training of users on the other hand to protect personal data on the other. Education and awareness, which also contributes to early detection, is the strongest tool for consumers to safeguard themselves from online identity fraud. This paper provides a comprehensive explanation of online identity theft, the various approaches that thieves use to attack individuals and organizations and the types of fraud involved in this cyber-crime. The aim of this research is to evaluate the need for a reformulation of the concept of identity theft in order to be compatible with the evolution of behaviors and fraud.

Macromolecular crystallography at cryogenic temperatures has so far provided the majority of the experimental evidence that underpins the determination of the atomic structures of proteins and other biomolecular assemblies by means of single crystal X-ray diffraction experiments. One of the core limitations of the current methods is that crystal samples degrade as they are subject to X-rays, and two broad groups of effects are observed: global and specific damage. While the currently successful approach is to operate outside the range where global damage is observed, specific damage is not well understood and may lead to poor interpretation of the chemistry and biology of the system under study. In this work, we present a phenomenological model in which specific damage is understood as the result of a single process, the steady excitation of crystal electrons caused by X-ray absorption, which acts as a trigger for the bulk effects that manifest themselves in the form of global damage and obscure the interpretation of chemical information from XFEL and synchrotron structural research.

The review starts by highlighting the significance of nuclear power plants in contemporary world, especially its indispensable role in the global efforts to reduce CO2 emissions. Then, it describes the impact of irradiation on microstructure and mechanical properties of reactor structural materials. The main part provides the reader with a thorough overview of crystal plasticity models developed to address the irradiation effects so far. All three groups of most important materials are included. Namely, the Zr alloys used for fuel cladding, austenitic stainless steels used for reactor internals and ferritic steels used for reactor pressure vessel. Other materials, especially those considered for construction of future fission and fusion nuclear power plants, are also mentioned. The review pays also special attention to ion implantation and instrumented nanoindentation which are a common way to substitute costly and time-consuming neutron irradiation campaigns.

Single-particle tracking with quantum dots (QDs) constitutes a powerful tool to track the nanoscopic dynamics of individual cell membrane components unveiling their membrane diffusion characteristics. Here we tested the possibility of extracting from the nano-resolved (16 ms and 30 nm) population dynamics of several quantum dots, time-binned at the second time-scale, the rapid structural changes of the cell membrane surface. We used for this proof-of-concept study bright, small and stable biofunctional QD nanoconstructs recognizing the neuronal cannabinoid type 1 (CB1) receptor and a commercial point-localization microscope to reconstruct in 3D the dynamics of the plasma membrane surface of cultured cells with a spatial resolution of tens of nanometers. CB1 receptor was chosen because it’s a highly expressed and fast diffusing membrane protein. Therefore, rapid QD diffusion on the axonal plasma membrane of cultured hippocampal neurons allowed highly precise reconstruction of the membrane surface in less than one minute. QD nanoconstructs diffused into the membrane of synaptic clefts allowing the entire topological reconstruction of the presynaptic component. In addition, we demonstrated successful reconstruction of the remarkably high dynamics of membrane surface topology at the second time-scale both in HEK-293 cell filopodia and axons. Our results show that this novel technique, which we named nanoPaint, is a powerful precision tool for the study of the structural plasticity of cell membrane surfaces.

Background: Drought, N deficiency and herbivory are considered the most important stressors caused by climate change in the agro- and eco-systems and varied in space and time shaping a highly dynamic and heterogeneous stressful environments. This study aims to evaluate the to-mato morpho-physiological and metabolic responses to combined abiotic and herbivory at dif-ferent within-plant spatial levels and temporal scales. Methods: Leaf-level morphological, gas exchange traits and VOC profiles were measured in to-mato plants exposed to N deficiency and drought, T. absoluta larvae and their combination. Ad-ditive, synergistic or antagonistic effects of the single stress when combined were also evaluat-ed. Morpho-physiological traits and VOC profile were also measured on leaves located at three different positions along the shoot axes. Results: The combination of the abiotic and biotic stress has been more harmful than single stress with antagonistic and synergistic but non-additive effects for the morpho-physiological and VOC tomato responses, respectively. Combined stress also determined a high within-plant phenotypic plasticity of the morpho-physiological responses. Conclusions: These results suggest that the combined stress in tomato determined a “new stress state” and a higher within-plant phenotypic plasticity which could permit an efficient use of the growth and defence resources in the heterogeneous and multiple stressful environmental condi-tions.

Contradictory reports are available on vaccine-associated hyperstimulation of the immune system, provoking the formation of pathological autoantibodies. Despite being interconnected within the same network, the role of the quieter, yet important non-pathological; natural autoantibodies (nAAbs) is less defined. We hypothesize that upon a prompt immunological trigger, also physiological nAAbs exhibit a moderate plasticity. We investigated their inducibility through aged and recent antigenic triggers. Anti-viral antibodies (anti-MMR; n=1739 and anti-SARS-CoV-2 IgG; n=330) and nAAbs (anti-citrate synthase IgG, IgM; n=1739) were measured by in-house and commercial ELISAs, using Croatian (Osijek) anonymous samples with documented vaccination background. Results were subsequently compared for statistical evaluation. Interestingly, IgM isotype nAAb showed a statistically significant connection with anti-MMR IgG seropositivity (p< 0.001 in all cases), while IgG isotype nAAb levels were elevated in association with anti-SARS CoV-2 specific seropositivity (p= 0.019) and in heterogeneous vaccine regimen recipients (unvaccinated controls; vector/mRNA vaccines p= 0.002). Increasing evidence supports the interplay between immune activation and the dynamic expansion of nAAbs. Consequently, further questions may emerge regarding the ability of nAAbs silently shaping the effectiveness of immunization. We suggest re-evaluating the impact of nAAbs on the complex functioning of the immunological network.

The great pipefish Syngnathus acus is one of the most representative European syngnathid, being highly associated with seagrass and macroalgal beds. Surprisingly, the ecology of this ovoviviparous marine fish has received scanty attention. The population inhabiting three sites on Cíes Archipelago (Atlantic Islands National Park, NW Spain) was monitored in 2017-2018 for spatial and temporal changes in abundances, reproduction traits, trophic niche occupancy and dietary regimes across reproduction states through an isotopic (δ13C and δ15N) approach. Abundances were highly variable across seasons and sites, decreasing significantly from mid-autumn. The population consisted almost exclusively of large adults that migrate by the end of the breeding season, which extended from mid-spring to summer. Operational sex ratios suggest that the species is sex-role reversed. S. acus is a secondary consumer (Trophic position= 3.36 ± 0.05) preferring amphipods but displaying annual and seasonal dietary plasticity. Mature fish were less selective than immatures (especially females) with a higher preference for amphipods (36-68%) in the former. The second most preferred prey were carideans, copepods or isopods, depending on the year and reproduction state. Overall, the wider trophic niches in females and immature specimens compared to males and mature fish would indicate a higher variability in both the use of prey resources and/or their origin. The present study highlights the trophic plasticity and unique features of S. acus population in Cíes Archipelago, especially regarding the outstanding size of the fish and the exceptional occurrence of breeders.

Electrical transmission between neurons is largely mediated by gap junctions. These junctions allow the direct flow of electric current between neurons, and in mammals are mostly composed of the protein connexin (Cx)36. Circuits of electrically coupled neurons are widespread in these animals, plus, experimental and theoretical evidence supports the notion that, beyond synchronicity, these circuits are able to perform sophisticated operations like lateral excitation and inhibition, noise reduction, as well as the ability to selectively respond upon coincident excitatory inputs. Although once considered stereotyped and unmodifiable, we now know that electrical synapses are subject to modulation and, by reconfiguring neural circuits, these modulations can alter relevant operations. The strength of electrical synapses depends on gap junction conductance, as well as on its functional interaction with the electrophysiological properties of coupled neurons. In particular, voltage dependent channels of the non-synaptic membrane critically determine the efficacy of transmission at these contacts. Consistently, modulatory actions on these channels have been shown to represent relevant mechanisms of plasticity of electrical synaptic transmission. Here we review recent evidence on the regulation of electrical synapses of mammals, the underlying molecular mechanisms, and the possible ways in which they affect circuit function.

This paper focused on impact localization of composite structures, which possess more complexity in the guided wave propagation because of the anisotropic behavior of composite materials. In this work, a composite plate was manufactured by using a compression molding process with proper pressure and temperature cycle. Eight layers of woven composite prepreg were used to make the plate. A structural health monitoring (SHM) technique is implemented with piezoelectric wafer active sensors (PWAS) to detect and localize the impact on the plate. There are two types of impact event are considered in this paper (a) low energy impact event (b) high energy impact event. Two clusters of sensors recorded the guided acoustic waves generated from the impact. The acoustic signals are then analyzed using a wavelet transform based time-frequency analysis. The proposed SHM technique successfully detect and localize the impact event on the plate. The experimentally measured impact locations are compared with the actual impact locations. An immersion ultrasonic scanning method was used to visualize the composite plate before and after the impact event. A high frequency 10 MHz 1-inch focused transducer was used to scan the plate in an immersion tank. Scanning results show that there is no visible manufacturing damage in the composite plate. However, clear impact damage was observed after the high-energy impact event.

Excess weight, which is seen as the background cause of most diseases, is gradually becoming the most important problem in the world. The cafeteria diet is robust diet that mimics the western diet and provides rapid weight gain associated with the obesity, diabetes, and cancer. The relationship between obesity and cancer is well known. For this reason, it is of great importance to reveal the first molecular and metabolic alterations that occur before entering the obesity process with any factor to understand the pathology of many diseases and to treat them in the early period. The beneficial effects of probiotics are attributed to their metabolite content with antioxidant properties or the postbiotic metabolites produced by them. In this study, the effects of different dietary practices on the hepatic antioxidant system of rats in developmental period were investigated by real-time PCR, enzyme activity measurements, and quantitative measurements of metabolites. After all, it was observed that CAF caused serious impairments by affecting the hepatic antioxidant system at gene and protein levels, and these impairments were relatively reversed with SCD Probiotics supplementation. In addition, regardless of the CAF diet, the regulatory effect of SCD Probiotics supplementation on the hepatic antioxidant system is remarkable.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third-leading cause of cancer-related mortality. Currently, the global burden of nonalcoholic fatty liver disease (NAFLD) has dramatically overcome both viral and alcohol hepatitis thus becoming the main cause of HCC incidence. NAFLD pathogenesis is severely influenced by lifestyle and genetic predisposition. Mitochondria are highly dynamic organelles which may adapt in response to environment, genetics and epigenetics in the liver (“mitochondrial plasticity”). Mounting evidence highlighted that mitochondrial dysfunction due to loss of mitochondrial flexibility, may arise before overt NAFLD and since the early stages of liver injury. Mitochondrial failure not only promotes hepatocellular damage, but also release signals (mito-DAMPs) which trigger inflammation and fibrosis, generating an adverse microenvironment in which several hepatocytes select anti-apoptotic programs and mutations that may allow survival and proliferation. Furthermore, one of the key events in malignant hepatocytes is represented by remodeling of glucidic-lipidic metabolism combined to reprogramming of mitochondrial functions, optimized to deal with energy demand. In sum, this review will discuss how mitochondrial defects may be translated into causative explanations of NAFLD-driven HCC, emphasizing future directions for research purposes and for development of potential preventive or curative strategies.

The relative dislocation density of aluminum and copper samples is quantitatively measured using linear Resonant Ultrasound Spectroscopy (RUS). For each metallic group, four samples were prepared with different thermomechanical treatments in order to induce changes in their dislocation densities. The RUS results are compared with Nonlinear Resonant Ultrasound Spectroscopy (NRUS) as well as Second Harmonic Generation (SHG) measurements. NRUS has a higher sensitivity by a factor of two to six and SHG by 14% to 62%. The latter technique is, however, faster and simpler. As main a result we obtain a quantitative relation between the changes in the nonlinear parameters and the dislocation density variations, which in a first approximation is a linear relation between these differences. We also present a simple theoretical expression that explains the better sensitivity to dislocation content of the nonlinear parameters with respect to the linear ones. X-Ray diffraction measurements, although intrusive and less accurate, support the acoustics results.

We examined Neurite orientation dispersion and density imaging in patients with migraine. We found that patients with medication overuse headache exhibited lower orientation dispersion than those without. Moreover, orientation dispersion at the body of the corpus callosum was statistically negatively correlated with migraine attack frequencies. These findings indicate that neurite dispersion is damaged in patients with chronic migraine. Our study results indicate the orientation preference of neurite damage in migraine.

The DNA Damage Response (DDR) is a complex signaling network that comes into play when cells experience genotoxic stress. Upon DNA damage, cellular signaling pathways are rewired to slow down cell cycle progression and allow recovery. However, when the damage is beyond repair, cells activate complex and still not fully understood mechanisms, leading to a complete proliferative arrest or cell death. A number of conventional and novel anti-neoplastic treatments rely on causing DNA damage or on the inhibition of the DDR in cancer cells. However, the identification of molecular determinants directing cancer cells toward recovery or death upon DNA damage is still far from complete, and it is object of intense investigation. SPRY-COntaining RAN binding Proteins (Scorpins) RANBP9 and RANBP10 are evolutionarily conserved and ubiquitously expressed proteins whose biological functions are still debated. RANBP9 has been previously implicated in cell proliferation, survival, apoptosis and migration. Recent studies also showed that RANBP9 is involved in the Ataxia Telangiectasia Mutated (ATM) signaling upon DNA damage. Accordingly, cells lacking RANBP9 show increased sensitivity to genotoxic treatment. Although there is no published evidence, extensive protein similarities suggest that RANBP10 might have partially overlapping functions with RANBP9. Like RANBP9, RANBP10 bears sites putative target of PIK-kinases and high throughput studies found RANBP10 to be phosphorylated following genotoxic stress. Therefore, this second Scorpin might be another overlooked player of the DDR alone or in combination with RANBP9. This review focuses on the relatively unknown role played by RANBP9 and RANBP10 in responding to genotoxic stress.

To evaluate whether the extent of cardiac damage in severe aortic stenosis (AS) might be associated with the occurrence of conduction system disorders after TAVI. A total of 153 symptomatic patients with severe AS who had a TAVI were categorized before the procedure according to the extent of cardiac damage: stage 1 (13.5%): no or LV damage; stage 2 (58.8%): left atrial/mitral valve damage, atrial fibrillation (AF); stage 3 (27.7%): low-flow state, pulmonary vasculature/tricuspid valve/RV damage. After TAVI, 34% of patients exhibited LBBB and 10% high-degree atrioventricular block (HD-AVB). No patient in group 1 developed HD-AVD whereas new LBBB was frequent in groups 2 and 3. Twenty-one patients presented with resolutive paroxysmal AF with a higher rate for each group increment (group 1: n=0, 0%; group 2: n=11,15.7%; group 3: n=10, 30.3%) (p = 0.012). Patients in group 3 had the higher rate of permanent pacemaker implantation (PPMI) (group 1: n=1, 6.3%; group 2: n=7,10%; group 3: n=9, 27.3%) (p=0.012). No patient in group 1 died during the hospital stay. In conclusion, cardiac damage staging of AS might help identify patients at higher risk of conduction disorders and PPMI requirement after TAVI.

At present, the applications and efficacy of non-ionizing radiations (NIR) in oncotherapy are limited. In terms of potential combinations, the use of biocompatible magnetic nanoparticles as heat mediators has been extensively investigated. Nevertheless, the development of more efficient heat nanomediators that may exhibit high specific absorption rates still is an unsolved problem. Our aim was to investigate if externally applied magnetic fields and a heat-inducing NIR affect tumor cell viability. To this end, under in vitro conditions, different human cancer cells (A2058 melanoma, AsPC1 pancreas carcinoma, MDA-MB-231 breast carcinoma) were treated with the combination of electromagnetic fields (EMFs, using solenoids) and hyperthermia (HT, using a thermostated bath). The effect of NIR was also studied in combination with standard chemotherapy and targeted therapy. An experimental device combining EMFs and high intensity focused ultrasounds (HIFU)-induced HT was tested in vivo. EMFs (25 T, 4h) or HT (52C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approx. 16%, 50%, and 21% of controls values in A2058, AsPC1, and MDA-MB-231 cells, respectively. Increased lysosomal permeability, release of cathepsins into the cytosol and mitochondria-dependent activation of cell death are the underlying mechanisms. Cancer cells could be completely eliminated combining EMFs, HT and standard chemotherapy or EMFs, HT and anti-Hsp70-targeted therapy. As a proof of concept, in vivo experiments performed in AsPC1 xenografts showed that combination of EMFs, HIFU-induced HT, standard chemotherapy and a lysosomal permeabilizer induces a complete cancer regression.

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.

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.

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

Several clinically useful anticancer drugs selectively kill cancer cells by inducing DNA damage; the genomic instability and DNA repair defects of cancer cells make them more vulnerable than normal cells to the cytotoxicity of DNA-damaging agents. Because epoxide-containing compounds can induce DNA damage, we have used the MTT assay to evaluate the selective cytotoxicity of three epoxyalkyl galactopyranosides against A549 lung cancer cells and MRC-5 lung normal cells. Compound (2S,3S)-2,3-Epoxydecyl 4,6-O-(S)-benzylidene-β-D-galactopyranoside (EDBGP) showed the highest selective anticancer activity and was selected for mechanistic studies. After observing that EDBGP induced cellular DNA damage (comet assay), we found that cells deficient in nucleotide excision repair were hypersensitive to the cytotoxicity of this compound; this suggests that EDBGP may induce bulky DNA adducts. EDBGP did not inhibit glycolysis (glucose consumption and lactate production). Pre-treatment of lung cancer cells with several antioxidants did not reduce the cytotoxicity of EDBGP, thereby indicating that reactive oxygen species do not participate in the anticancer activity of this compound. Finally, EDBGP was screened against a panel of cancer cells and normal cells from several tissues, including three genetically modified skin fibroblasts with increasing degree of malignancy. Our results suggest that epoxyalkyl galactopyranosides are promising lead compounds for the development of new anticancer agents.

The paper describes an application of machine learning approach for parameter optimization. The method is demonstrated for the elasto-viscoplastic model with both isotropic and kinematic hardening. It is shown that the proposed method based on long-short term memory networks enabled to obtain reasonable agreement of stress-strain curves for cyclic deformation in low-cycle fatigue regime. The main advantage of the proposed approach over traditional optimization schemes lies in the possibility to get parameters for a new material without the necessity to conduct any further optimizations. As the power and robustness of the developed method was demonstrated on the very challenging problem (cyclic deformation, crystal plasticity, self-consistent model, isotropic and kinematic hardening), it is directly applicable to other experiments and models.

This article presents a novel computational approach to visualizing memristor dynamics within a simulated neural network. Memristors, known for their ability to emulate synaptic plasticity due to their variable resistance characteristics, are key components in neuromorphic computing and hold potential for advancing our understanding of neural processes. Our study introduces a sophisticated memristor model that incorporates non-linear resistance changes, simulating the complex behavior of synaptic connections in a neural network.The neural network, consisting of multiple interconnected neurons with memristor-based synapses, is subjected to a series of electrical stimuli. Each memristor's resistance is modulated in response to the applied voltage, mimicking the synaptic weight adjustments that occur during learning and memory formation in biological neural networks. To effectively illustrate these changes, we employ a high-contrast color mapping scheme, where the varying resistance of each memristor is represented by distinct colors, providing a clear and intuitive visualization of synaptic modifications over time.Our simulation runs through multiple iterations, demonstrating how synaptic weights evolve in response to different input patterns. The use of an extended voltage range and increased scaling factors ensures pronounced changes in memristance, enhancing the visibility of synaptic adaptations. The resulting visualizations offer a compelling representation of how memristors can mimic the dynamic nature of biological synapses, contributing to the field of neuromorphic engineering and deepening our comprehension of neural mechanisms underlying learning and memory.This work not only showcases the potential of memristors in simulating neural behavior but also provides a valuable educational tool for illustrating complex concepts in neuroscience and neuromorphic computing. The insights gained from this study pave the way for further exploration into the development of advanced neural network models and the design of memristor-based computing systems.

The classification of tumors in subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, cancer phenotypes are turning out to be far more heterogenous than initially thought, and the classification is continually being updated to include more subtypes. Tumors are indeed highly dynamic and they can evolve and undergo various changes in their characteristics during disease progression. The picture becomes even more complex when tumor responds to a therapy. In all these cases, cancer cells acquire the ability to trans-differentiate, changing subtype, and adapt to changing microenvironments. These modifications affect the tumor's growth rate, invasiveness, response to treatment, and overall clinical behavior. Studying tumor subtype transitions is crucial for understanding tumor evolution, predicting disease outcomes, and developing personalized treatment strategies. We discuss this emerging hallmark of cancer and the molecular mechanisms involved at the crossroads between tumor cells and their microenvironment, focusing on four different human cancers in which tissue plasticity causes a subtype switch: breast cancer, prostate cancer, glioblastoma and pancreatic adenocarcinoma.

Plants exhibit the capacity for adaptation through their metabolic processes to various changes in environmental conditions. Investigating these adaptations in current and future climatic scenarios is of great importance for ensuring productive agricultural crops. This adaptative potential is commonly employed as an indicator of genotypes with higher potential in breeding programs. However, the complexity and interaction of plant metabolic parameters pose a challenge to selection strategies. In this context, the aim of this study was to explore phenotypic plasticity within the germplasm of Hybrid Timor coffee. Additionally, we assessed the utility of the Phenotypic Plasticity Index (MVPi) as a promising tool to predict genotype performance across diverse climatic conditions. To achieve this, we evaluated the performance of seven accessions from the Hybrid Timor germplasm in comparison to the Rubi and IPR 100 cultivars, known for their susceptibility and resistance to drought, respectively. The experiment was conducted at greenhouse conditions, with two treatments: a control scenario, maintaining soil moisture near its maximum water-holding capacity, and a water deficit scenario involving irrigation cessation followed by rehydration. Data encompassing physiological, biochemical, and growth aspects were collected during three distinct stages: pre-application of water deficit, its imposition, and subsequent rehydration. Furthermore, field evaluations of the productivity of the same genotypes were carried out over two consecutive seasons. Based on physiological and biochemical assessments, the MVPi was computed, employing Euclidean distance between principal component multivariate analysis scores. Subsequently, this index was correlated with growth and productivity data through linear regressions. Our findings reveal that the more plastic genotypes, capable of significantly altering physiological and biochemical parameters in response to environmental stimuli, exhibited reduced biomass loss in both aerial and root parts, consequently positively influencing their productivity. Enhanced plasticity was particularly prominent in accessions from the MG Germplasm Collection: MG 311 - Hybrid Timor UFV 428-02, MG 270 - Hybrid Timor UFV 377-21, and MG 279 - Hybrid Timor UFV 376-31, alongside the Rubi MG 1192 cultivar. The MVPi emerged as a valuable instrument to assess genotype adaptability and predict their performance under varying climatic scenarios.

Attention Deficit-Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with high incidence in children and adolescents characterized by motor hyperactivity, impulsivity, and inattention. MRI-based evidences support that neuroanatomical abnormalities as the volume reduction of neocortex and hippocampus are shared by several neuropsychiatric diseases as schizophrenia, autism spectrum disorder and ADHD. In addition, it is well documented the abnormal development and postnatal pruning of dendritic spines of neocortical neurons in schizophrenia, autism spectrum disorder and intellectual disability. A recent report using the prenatal nicotine exposure murine model of ADHD support a delay in spine maturation in CA1 neurons correlated with impaired working memory and hippocampal long-term potentiation (LTP). In vivo spine imaging show that dendritic spines are dynamic structures exhibiting Hebbian and homeostatic plasticity triggering intracellular cascades involving glutamate receptors, calcium influx and remodeling of F-actin network. The LTP-induced insertion of postsynaptic glutamate receptors is associated to the enlargement of spine head and long-term depression (LTD) to the spine shrinkage. In this review, we summarize recent evidence emerged from meta-analysis of brain imaging data from ADHD patients, risk loci from global genome-wide analysis and new reports focused on spine molecular structure and dynamics using in vivo imaging in neocortex and hippocampus.

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique that modulates synaptic plasticity in the human motor cortex (M1). Since previous studies have primarily used motor evoked potentials (MEPs) as outcome measure, cortical correlates of PAS-induced plasticity remain unknown. Therefore, the aim of this observational study was to investigate cortical correlates of a standard PAS induced plasticity in the primary motor cortex by using a combined TMS-EEG approach in a cohort of eighteen healthy subjects. In addition to the expected long-lasting facilitatory modulation of MEPs amplitude, PAS intervention also induced a significant increase in transcranial magnetic stimulation evoked potentials (TEPs) P30 and P60 amplitude. No significant correlation between the magnitude of PAS-induced changes in TEP components and MEP amplitude were observed. However, the linear regression analysis revealed that the combined changes in P30 and P60 component amplitudes significantly predicted the MEP facilitation after PAS. The findings of our study offer novel insight into the neurophysiological changes associated with PAS-induced plasticity at M1 cortical level and suggest a complex relationship between TEPs and MEPs changes following PAS.

Working memory (WM) is a brain system for short-term storage and manipulation of information and plays an important role in complex cognitive tasks. In the synaptic theory of WM memorized elements are stored in the form of short-term potentiated connections in a sample population of neurons. In this paper, we show that such populations can be formed due to the mechanisms of spike-timing-dependent plasticity (STDP) – the phase dependence associated with the ratio of the pulse times of the interacting neurons. We propose a WM model considering two types of plasticity: short-term plasticity and STDP. We have shown formation of neuronal clusters encoding items in the WM model, that can be formed by external stimulation of a group of neurons due to the mechanisms of STDP and hold and reactivated by short-term plasticity mechanisms. The dynamic formation of neuronal clusters instead of pre-formed clusters gives additional flexibility to the model.

Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.

We have previously developed several successful decellularization strategies yielding porcine cardiac extracellular matrices (pcECMs), which exhibit tissue-specific bioactivity and bioinductive capacity when cultured with various pluri- and multipotent stem cells. Here, we studied the tissue-specific effects of the pcECM on seeded human mesenchymal stem cells (hMSCs) phenotype using reverse transcribed quantitative polymerase chain reaction (RT-qPCR) arrays for cardio-vascular related genes. We further corroborated interesting findings at the protein level (flow cytometry and immunological stains) as well as bioinformatically using several mRNA sequencing and protein databases of normal and pathologic adult tissue expression, as well as during human embryonic organogenesis. We discovered that upon seeding of human mesenchymal stem cells (hMSCs) on the pcECM they displayed partial MET toward endothelial phenotypes (CD31+) and morphologies, which were preceded by an early spike (~day 3 onward after seeding) in HAND2 expression at both the mRNA and protein levels compared to plate controls. CRISPR-Cas9 knockout (KO) of HAND2 and its associated antisense long non-coding RNA (HAND2-AS1) regulatory region resulted in proliferation arrest, hypertrophy, and senescent-like morphology. Bioinformatic analyses revealed that HAND2 and HAND2-AS1 are highly correlated in expression, are expressed in many different tissue types albeit at distinct yet tightly regulated expression levels. Deviation (down or up regulation) from these basal tissue expression levels are associated with a long list of pathologies. We thus suggest that HAND2 expression levels may finetune cell plasticity possibly affecting senescence and mesenchymal-to-epithelial transition states, through yet unknown mechanisms. Targeting this pathway may represent a promising new therapeutic approach for a wide range of diseases, including cancer, degenerative disorders, and aging. Nevertheless, further investigations are required to better understand the molecular players involved, potential inducers and inhibitors of this pathway, and eventually potential therapeutic applications.

Adipose tissue (AT) is a remarkably plastic and active organ with functional pleiot-ropism and high remodeling capacity. Although the expansion of fat mass, by defini-tion, represents the hallmark of obesity, the dysregulation of the adipose organ emerges as the forefront of the link between adiposity and its associated metabolic and cardio-vascular complications. The dysfunctional fat displays distinct biological signatures, which include enlarged fat cells (i.e., adipocyte hypertrophy), low-grade inflammation, impaired redox homeostasis, and cellular senescence. While these events are orches-trated in a cell-type, context-dependent and temporal manner, the failure of the adipose precursor cells to form new mature adipocytes appears the main instigator of the adi-pose dysregulation, which, ultimately, poses a deleterious milieu either by promoting ectopic lipid overspill in non-adipose targets (i.e., lipotoxicity) or by inducing an al-tered secretion of different adipose-derived hormones (i.e., adipokines and lipokines). This novel paradigm (“expandability hypothesis”) challenges and extends previous “adipocentric view”, which implies a reduced plasticity of the adipose organ at the nexus between “unhealthy” fat expansion and the development of obesity-associated comorbidities. In this review, we will briefly summarize the potential mechanisms by which adaptive changes to variations of energy balance may impair adipose plasticity and promote fat organ dysfunction. We will also highlight the conundrum with the perturbation of the adipose microenvironment and the development of cardio-metabolic complications by focusing on adipose lipoxidation and cellular senescence. Finally, we discuss the sci-entific rationale for proposing adipose organ plasticity as a target to curb/prevent adi-posity-linked cardio-metabolic complications.

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%.

The physical and mechanical properties of rocks will change significantly after being subjected to high temperatures, which poses safety hazards to underground projects such as coal underground gasification. In order to investigate the effect of temperature on the macroscopic and microscopic properties of rocks, this paper has taken sandstone as the research object and conducted uniaxial compression tests on sandstone specimens at different temperatures (20-1000 ℃) and different heating rates (5-30 ℃/min) at 1200 ℃. At the same time, the acoustic emission (AE) test system was used to observe the acoustic emission characteristics of the rock damage process, and the microstructural changes after high temperature were analyzed with the help of a scanning electron microscope (SEM). The test results show that the effect of temperature on sandstone is mainly divided into three stages: Ⅰ (20-500 ℃) stage is the strengthening zone, the evaporation of water and the contraction of primary fissures, sandstone densification is enhanced. Specifically, the compressive strength and elastic modulus increase, the macroscopic damage mode is dominated by shear damage, and the fracture micro-morphology is mainly brittle fracture. Stage II (500-600°C) is the transition zone, 500°C is the threshold temperature for compressive strength and modulus of elasticity, and the damage mode changes from shear to cleavage damage, and the sandstone undergoes brittle-ductile transition in this temperature interval. Stage III is the physicochemical deterioration stage. The changes in physical and chemical properties make the sandstone compressive strength and modulus of elasticity continue to decline, the macroscopic damage mode is mainly dominated by cleavage damage, and the fracture microscopic morphology is more toughness fracture. The effect of different heating rates on the mechanical properties of sandstone was further studied, and it was found that the mechanical properties of the rock were more deteriorated under higher heating rates.

This study explores the multifaceted influence of litter size, maternal care, exercise, and aging on rats' neurobehavioral plasticity and dentate gyrus microglia dynamics. Body weight evolution revealed a progressive increase until maturity, followed by a decline during aging, with larger litters exhibiting lower weights initially. Notably, exercised rats from smaller litters displayed higher body weights during mature and aged stages. Dentate gyrus volumes showed no significant differences among groups, except for aged sedentary rats from smaller litters, which exhibited a reduction. Maternal care varied significantly based on litter size, with large litter dams showing lower frequencies of caregiving behaviors. Behavioral assays highlighted the detrimental impact of a sedentary lifestyle and reduced maternal care/large litters on spatial memory, mitigated by exercise in aged rats from smaller litters. Microglial dynamics in the layers of dentate gyrus revealed age-related changes modulated by litter size and exercise. Exercise interventions mitigated microgliosis associated with aging, particularly in aged rats. These findings underscore the complex interplay between early-life experiences, exercise, microglial dynamics, and neurobehavioral outcomes during aging.

N6-methyladenosine (M6A) modification is the most abundant internal chemical modification on RNA molecules in eukaryotes and can affect mRNA metabolism and regulate RNA transcription, nuclear export, splicing, degradation, translation, ets, and has a significant impact on various aspects of physiology or pathobiology. Radiotherapy is the most common measure of tumor treatment, variety of cellular intrinsic mechanisms affect the responses of cells to ionizing radiation (IR) and effectiveness of cancer radiotherapy. In this review, we summarize and discuss the recent advances about the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage response, and outcomes of cancer radiotherapy. Insights into the RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy as well as radioprotection on normal tissues.

The fatigue delamination damage is one of the most important fatigue failure modes of laminated composite structures. However, the developments of the theoretical framework, mathematical/physical model and numerical simulation of fatigue delamination are still challenging issues, and there is a lack of systematic classification. This article reviews the experimental phenomena of the onset and propagation stage of delamination under fatigue loading, and summarizes the commonly used phenomenological models for laminated composite structures. The research methods, general modeling formulas and development prospects of the phenomenological models are presented in detail. In the light of the analysis of finite element model (FEM) for the laminated composite structures, a number of simulation methods of fatigue delamination crack propagation damage model are carefully classified. Furthermore, within the theoretical framework of strength theory model (SM), fracture mechanics model (FM), damage mechanics model (DM) and hybrid model (HM), the complete procedure, application, capability assessment, advantages and limitations of the models are also discussed in detail. Finally, several valuable suggestions are given for the research interests, and challenging technical problems that need to be overcome on the fatigue delamination prediction of laminated composite structures in the future.

The 2022-2023 Chilean summer showed increased temperatures and similar burned area, compared to the 2016-2017 season, where more than 500,000 hectares were compromised, mainly in the rural areas. After a brief review, it is revealed that the effects of forest fires on soil and hydrological properties are barely debated in Chile. Here, we showed a climatological analysis where temperature records in the 2016-2017 season were unusual, as well as another unexpected increase in the summer of 2022-2023, resulting in high-severity fires known as ‘mega-fires’ or “storm-fires”. Mega-fires affect forest plantations and native forests mainly from 33º S (Maule Region) to 39º S (Los Ríos Region) and they are expected to become frequent due to climate change, moving from the north to the south. We present an overview of the influence of wildfires on soil components in the most affected areas (inland, Coastal, and Andes ranges), their hydrological impacts, and potential erosion risk due to high winter precipitation. We propose several management practices that could help to prevent or mitigate these events, including pre-and post-fire interventions, such as afforestation and seeding, selective logging, mulching, erosion barriers, soil preparation, and dam monitoring. We argue that any effective plan in fire-prone and affected areas should include a combination of actions taken at the hillslope scale at integral ecosystem management, whose effectiveness should be monitored and verified regionally at the watershed scale.

This paper aims to provide an overall review of degradation, damage evolution and fatigue models in the literature of various engineering materials, mostly metals, and composites.

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.

Memristive spiking neural networks are a promising emerging technology in the field of deep learning. These models can be implemented using neuromorphic hardware and therefore offer low power consumption and low latency, crucial to edge-computing applications. These systems, however, pose several challenges, including on-chip training and connectivity reduction. The latter is essential to ease the manufacturing complexity of the system. On-chip training can be realized using synaptic plasticity enabled by memristors. In this work, we compare two methods of connectivity reduction applicable to memristive spiking networks: an ensemble-based approach and a probabilistic sparse connectivity approach. We evaluate both of these methods in conjunction with a three-layer spiking neural network on the handwritten and spoken digits classification tasks using two memristive plasticity models and a classical time-dependent plasticity rule. On the handwritten digits recognition task, both methods achieve the F1-score of 0.89–0.93, and yield the 0.80–0.96 F1-score on the spoken digits recognition task.

This paper conducts an extensive literature review focusing on the utilisation of crack tip plasticity as a crucial parameter in determining and enhancing crack growth models. The review encompasses a comprehensive analysis of various methodologies, predominantly emphasising numerical simulations of crack growth models while also considering analytical approaches. Although experimental investigations are not the focus of this review, their relevance and interplay with numerical and analytical methods are acknowledged. The paper critically examines these methodologies, providing insights into their advantages and limitations. Ultimately, this review aims to offer a holistic understanding of the role of crack tip plasticity in the development of effective crack growth models, highlighting the synergies and gaps between theoretical, experimental, and simulation-based approaches.

Direct cardiac reprogramming of fibroblasts into induced cardiomyocytes (iCMs) is a promising approach but remains a challenging technology of regenerative medicine for damaged myocardium. Efforts have been focused on improving the efficiency by understanding fundamental mechanisms. One of the major challenges is that the plasticity of cultured fibroblast varies batch to batch with unknown mechanisms. Here, we noticed that a portion of in vitro cultured fibroblasts have been activated to differentiate into myofibroblasts, marked by the expression of αSMA, even in the primary cell culture of tissues. Both forskolin, which activates adenylyl cyclase and increases cAMP concentration, and TGFbeta inhibitor SB431542 can efficiently suppress myofibroblast differentiation of cultured fibroblasts. However, SB431542 improved but forskolin blocked iCM reprogramming of fibroblasts that were infected with retroviruses of Gata4, Mef2c and Tbx5 (GMT). Moreover, inhibitors of cAMP downstream signaling pathways, PKA or CREB-CBP, significantly improved the efficiency of iCM reprogramming. Consistently, inhibition of p38/MAPK, another upstream regulator of CREB-CBP, also improved reprogramming efficiency. We then investigated if inhibition of these signaling pathways in primary cultured fibroblast could improve their plasticity for reprogramming, and found that preconditioning of cultured fibroblasts with CREB-CBP inhibitor significantly improved the cellular plasticity of fibroblasts to be reprogrammed, yielding ~2-fold amount of reprogrammed iCMs compared to that of untreated control cells. In conclusion, suppression of cAMP/PKA/CREB signaling axis improves fibroblast plasticity for direct cardiac reprogramming.

The 1060 aluminium alloy is widely applied to electronic industry, construction area, aerospace field, traffic engineering, decoration and consumption goods market for its good chemical, physical and mechanical properties. In general, excellent processing property is necessary and important for manufacturing of complicated panels. In this paper, a special 2D ultrasonic vibration incremental forming method is designed to improve its plasticity and mechanical properties. Three kind of processing methods including traditional single point incremental forming, longitudinal ultrasonic vibration incremental forming and 2D ultrasonic vibration incremental forming are conducted for flexible manufacture of conical parts of 1060 aluminium alloy sheet. Then micro-hardness tests, residual stress tests and scanning electron microscopy tests are carried out to probe its revolution of micro-structure and mechanical properties and to analysis the effects of different types of ultrasonic vibration on plasticity and fracture characteristic of 1060 aluminium alloy. It is proved that 2D ultrasonic vibration is facilitated to improvement of plasticity and surface qualities of 1060 aluminium alloy than the other two processing methods. So, the novel 2D ultrasonic vibration incremental forming possesses substantial application values on flexible and rapid manufacturing of complicated thin-walled component of aluminium alloy.

Huntington’s disease (HD) causes progressive movement disorders and cognitive deficits. Besides, sleep disturbances and emotional distress are prominent clinical signatures of HD. The experimental subjects and HD human brains display altered regenerative plasticity resulting from aberrant neurogenic and nonneurogenic areas. Sleep disorders, emotional disruption, and cognitive deficits have been linked to impaired cell cycle events of neural stem cells (NSC) in neurodegenerative disorders. In a physiological state, circadian clock gene pathways play important roles in the regulation of the proliferation and differentiation of NSC, whereas the irregular circadian clock pathway is attributed to impairment in the neurogenic process. The recent advancement of chemogenetic-based approaches represents a potential scientific tool to rectify the abnormal circadian clock which may aid in mitigating neurogenic failure in the brain. Notably, GABAergic vasoactive intestinal peptide (VIP)-expressing neurons in the brain plays a key role in the regulation of neuroplasticity and circadian rhythm. Thus, this conceptual review article addresses the potential link between sleep disorder and aberrant neurogenic events in HD and proposes chemogenetic kindling of vasoactive intestinal peptide (VIP) -expressing GABAergic neurons in the brain as a therapeutic strategy for reprogramming the clock gene pathways in mitigating the neurodegenerative failure in HD.

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).

This paper presents an efficient topology optimization approach considering fail-safe requirements in the framework of the solid isotropic material with penalization method. Existing methods either are computationally extremely expensive or do not consider fail-safe requirements in the optimization. The current approach not only obtains the fail-safe optimization structure, but also significantly improves the computational efficiency of fail-safe topology optimization. In this method, the worst-case compliance is considered to minimize as the optimization objective, using the Kreisselmeier–Steinhauser function to approximate the non-differentiable max-operator. The sensitivity is derived by the adjoint method, and a general fail-safe optimality criteria method is developed to update design variables. The damage scenarios greatly reduces in the process of failsafe strategy optimization by employing the density-based filter method. Finally, the effectiveness and computational efficiency of this method for fail-safe optimization is verified by several numerical examples.

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.

Schizophrenia is a spectrum of neuropsychiatric deformities, characterized by hallucination, delusion, mood disorders, speech pathology, and neurocognitive deficits. Among various clinical manifestations, hallucination has been recognized as a core psychotic symptom that occurs more frequently in schizophrenia. A significant number of subjects with neurocognitive disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and other neurological diseases like stroke and epileptic seizure also experience hallucinations. While aberrant neurotransmission has been linked to the neuropathogenic events of schizophrenia, the specific cellular mechanism contributing to hallucinations remains ambiguous. Neurodegeneration in the hippocampus of the brain has been identified as a predominant pathogenic determinant of dementia. While the scientific proof for the neurodegeneration in schizophrenia is limited, the occurrence of dementia in schizophrenia has become increasingly evident. To note, both neurodegenerative, neurodevelopmental, and neuropsychiatric disorders display impaired neurogenesis in the brain. Impaired neurogenesis in the hippocampus has been linked to dementia and mood disorders. Notably, the early phase of many neurodegenerative disorders has been characterized by reactive neuroblostosis and aberrant cell cycle activation in mature neurons leading to the fluctuation in neurogenic processes leading to abnormal synaptogenesis and neurotransmission in the brain. Thus, this article emphasizes a hypothesis that aberrant neurogenic processes could be an underlying mechanism of hallucination in schizophrenia and other neurological diseases.

Doped copper overpacks are planned to be utilized in the spent nuclear fuel repositories in Finland and in Sweden. The assessment of long-term integrity of the material is a matter of importance. Grain structure variations, segregation and any possible manufacturing defects in microstructure are relevant in terms of susceptibility to creep and damage from the loading evolution imposed by its operating environment. This work focuses on studying the microstructure level length-scale dependent deformation behavior of the material, of particular significance with respect to accumulation of plasticity over the extensive operational period of the overpacks. Reduced micromorphic crystal plasticity model, which is similar to strain gradient models, is used in this investigation. Firstly, the model’s size dependent plasticity effects are evaluated. Secondly, different microstructural aggregates presenting overpack sections are analyzed. Grain size dependent hardening responses, i.e., Hall-Petch like behavior, can be achieved with the enhanced hardening associated with the micromorphic model at polycrystalline level. It was found that the nominally large grain size in the base material of the overpack shows lower strain hardening potential than the fine grained region of the welded microstructure with stronger strain gradient related hardening effects. Size dependent regularization of strain localization networks is indicated as a desired characteristics of the model. The findings can be utilized to provide an improved basis for modeling the viscoplastic deformation behavior of the studied copper alloy and assess the microstructural origins of any integrity concerns explicitly by way of full field modeling.

DNA damage causes the mutations that are the principal source of genetic variation. DNA damage detection and repair mechanisms therefore play a determining role in generating the genetic diversity on which natural selection acts. Speciation, it is commonly assumed, occurs at a rate set by the level of standing allelic diversity in a population. The process of speciation is driven by a combination of two evolutionary forces: genetic drift and ecological selection. Genetic drift takes place under conditions of relaxed selection, and results in a balance between rates of mutation and rates of genetic substitution. These two processes, drift and selection, are necessarily mediated by a variety of mechanisms guaranteeing genome stability in any given species. One of the outstanding questions in evolutionary biology concerns the origin of the widely varying phylogenetic distribution of biodiversity across the tree of life, and how the forces of drift and selection contribute to shaping that distribution. The following examines some of the molecular mechanisms underlying genome stability and the adaptive radiations that are associated with biodiversity and the widely varying species richness and evenness in the different eukaryotic lineages.

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

The natural frequency of buildings decreases during a strong-motion earthquake, and the structure loses its stiffness. As a result, understanding the damaging process in the structure owing to changes in structural properties is critical during a seismic excitation. The time-frequency technique can detect the damaged building’s time-varying frequency contents. Wigner distributions (WD), Wigner-Ville distributions (WVD), pseudo-Wigner-Ville distributions (PWVD), smoothed pseudo-Wigner-Ville distributions (SPWVD), and synchrosqueezing transforms (SST) have all become popular in recent years for a variety of earthquake engineering applications, including building damage detection. This study proposes the local maximum synchrosqueezing transform (LMSST) for detecting frequency shifts in buildings during strong earthquakes. The data presented in the research show that the suggested method outperforms as compared to the conventional time-frequency methods for detecting frequency shifting in earthquake-damaged structures.

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.

The use of high strength to weight ratio laminated composites is emerging in marine industry and applications as a very efficient solution for improving productivity. Nevertheless, delamination between the layers is a limiting factor for the wider application of laminated composites, as it reduces the stiffness and strengths of the structure. Interleaving nanofibrous mats between layers of composite laminates has been proved to be an effective method for improving composites delamination resistance. This paper aims to characterize the effect of interleaved nanofiber on mode I interlaminar properties and failure mechanisms when subjected to static and fatigue loadings. For this purpose, virgin and nanomodified woven laminates were subjected to Double Cantilever Beam (DCB) specimens. Static and fatigue tests were performed and the tests were monitored by acoustic emission technique. The mechanical results showed a 130% increase of delamination toughness for nanomodified specimens in the static loadings and more crack growth resistance in the fatigue loading. The AE results revealed that different type of failure mechanisms was the cause of these improvements for the modified specimens compared with the virgin ones.

Alcohol abuse can result in detrimental multisystem effects. Chronic alcohol abuse is known to be associated with pathophysiological changes in multiple organs often resulting in life threatening clinical outcomes e.g. breast and colon cancer, pancreatic disease, cirrhosis of the liver, diabetes, osteoporosis, arthritis, kidney disease, immune system dysfunction, hypertension, coronary artery disease, alcohol-induced cardiomyopathy and heart failure as well as central nervous system disorders. In this review article, we will discuss the multisystemic effects of alcohol abuse and explore in greater detail alcohol’s impact on two main systems that result in pathophysiological changes i.e. the cardiovascular and central nervous systems.

Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. This paper provides deep insight into immune related adverse events (irAEs) posing a major challenge and drawback to ICIT, and presents right management strategies for very complex complications. Moreover, for the first time in literature, a non-linear mathematical model is introduced to measure the ICIT success rate and to decide about the optimum ICIT duration. Furthermore, a strategy is presented to overcome or to delay the progression after initial good response in a subset of patients.

Forensic anthropologists play a key role in skeletal trauma analysis and commonly use macroscopic features to distinguish between trauma types. However, this approach can be challenging, particularly in cases of highly comminuted or incompletely recovered fractures. Histological analysis of microscopic fracture characteristics in fractured bones may thus help provide additional information on trauma type and bone fracture biomechanics in general. This study analysed the extent of microcrack damage to osteons in long bones with blunt force trauma (BFT) and gunshot trauma (GST), from both traumatic death cases and post-mortem experimental fractures. We identified four types of osteonal damage (OD). In traumatic death cases, OD affecting the inside of the osteon and compromising the Haversian canal (type 1) was found to be indicative of BFT. Moreover, OD affecting the cement line (type 3) and interstitial lamellae (type 4) was more common in the GST samples. OD affecting the inside of the osteon without compromising the Haversian canal (type 2) was not found to be indicative of either trauma type. In cases of experimental fractures, our study revealed that post-mortem fractures in dry bone samples featured the highest amount of OD, particularly of type 4. This study also found that the experimentally produced GST featured similar OD pattern to GST death cases. These findings support our hypothesis that there are distinct osteonal damage patterns in human long bones with BFT and GST, which are of relevant value for trauma analysis in forensic anthropology.

In this study, an experiment was conducted on hoop pine (Araucaria cunninghamii), which is a common tree species in Taiwan. Holes with diameters of 4, 5, 7, 10, 12, and 14 cm were drilled in dry hoop pine timber with a diameter of 39 cm and a height of 57 cm, and an 800 MHz Ground Penetrating Radar (GPR) antenna were used to determine the minimum image resolution and the size of the holes in the wood. GPR images of the timber were subjected to a filtering process to obtain characteristic reflection curves of the damage to the timber. Curves with clear waveforms were observed in the GPR profiles of eccentric holes with a diameter of 4 cm. Profiles of the damage were obtained and profile images with the trunk radius at the centre were transformed into polar coordinate images. From these polar coordinate images, the location, size and diameter of the eccentric holes in the wood were identified, and the reflection curves were characterised by waveforms and irregular fluctuations. The risk levels of tree trunks were determined on the basis of their t/R (minimum normal wall thickness of the cross-section of the trunk/radius of the trunk) values and hole area ratios. A comparison between the GPR-based results and the actual diameters of the holes revealed that the filtered GPR profiles could be used for the efficient and accurate assessment of damage to hoop pine timber (average error rate ≤ 4%).

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.

Cancer-associated fibroblasts (CAF) form the basis of tumor microenvironment and possess immunomodulatory functions by interacting with other cells surrounding tumor, including T lymphocytes, macrophages, dendritic cells and natural killer cells. Ionizing radiation is a broadly-used method in radiotherapy to target tumors. In mammalian cells, ionizing radiation induces various types of DNA damages and DNA damage response. Being unspecific, radiotherapy affects all the cells in tumor microenvironment, including the tumor itself, CAFs and immune cells. CAFs are extremely radio-resistant and do not initiate apoptosis even at high doses of radiation. However, following radiation, CAFs become senescent and produce a distinct combination of immunoregulatory molecules. Radiosensitivity of immune cells varies depending on the cell type due to inefficient DNA repair in, for example, monocytes and granulocytes. In this minireview, we are summarizing recent findings on the interaction between CAF, ionizing radiation and immune cells in the tumor microenvironment.

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

Given the high prevalence of cutaneous genus beta human papillomavirus (β-HPV) infections, it is important to understand how they are manipulating their host cells. This is particularly true for cellular responses to UV damage, since our skin is continually exposed to UV. The E6 protein from β-HPV (β-HPV E6) decreases the abundance of two essential UV-repair kinases (ATM and ATR). Since β-HPV E6 reduces their availability, the impact on downstream signaling events has been uncertain. We demonstrate that β-HPV E6 decreases ATM and ATR activation. This inhibition extended to XPA, an ATR target necessary for UV repair, lowering both its phosphorylation and accumulation. β-HPV E6 hinders POLη phosphorylation and foci formation, critical steps in translesion synthesis. ATM’s phosphorylation of BRCA1 is also attenuated by β-HPV E6. However, β-HPV E6’s hindrance of ATM/ATR signaling during UV-associated cell cycle arrest was incomplete. While there was less phosphorylation of immediate downstream targets (CHK1), events further down the cascade were not decreased. These observations are consistent with β-HPV infections making UV radiation more deleterious and support the proposed role of β-HPV in early stages of non-melanoma skin cancer development.

The era of Internet of Things (IoT) has begun to evolve and with this the devices around us are getting more and more connected. Vehicular Ad-hoc NETworks (VANETs) is one of the applications of IoT. VANET allow vehicles within these networks to communicate effectively with each another. VANETs can provide an extensive range of applications that support and enhance passenger safety and comfort. It is important that VANETs are applied within a safe and reliable network topology; however, the challenging nature of reaching reliable and trustworthy agreement in such distributed systems is one of the most important issues in designing a fault-tolerant system. Therefore, protocols are required so that systems can still be correctly executed, reaching agreement on the same values in a distributed system, even if certain components in the system fail. In this study, the agreement problem is revisited in a VANET with multiple damages. The proposed protocol allows all fault-free nodes (vehicles) to reach agreement with minimal rounds of message exchanges, and tolerates the maximal number of allowable faulty components in the VANET.

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.

The rapidly expanding corona pandemic in 2020 brought the world to virtual economic stagna-tion. While the impact on the environment from suspended air traffic, idle industry and economic lockdown has been considerable, so have the economic and social consequences of the crisis. To make matters worse, the resulting state of stagnation is neither economically nor socially sustaina-ble. Nevertheless, we need to ask ourselves what we can learn from the situation in order to ex-plore the benefits of globalization, intercept similar crisis situations more effectively in the future and move towards more sustainable development on an ecological, economic and social level. This paper identifies the areas of expanded externality management needed to further improve environmental quality, digitalization, network expansion and basic income. These central issues need to be addressed both during and after the crisis in order to deal with problems of inequality and climate change mitigation for current and future generations. Concrete concepts will be put forward and discussed in the paper.

The advancement of mechanization in forestry has bolstered productivity within the sector while simultaneously precipitating impacts necessitating deeper comprehension for the attainment of heightened levels of environmental sustainability in forestry management. The aim of this study was to apply an instrument for assessing the environmental damage and impacts of forest harvesting in commercial Eucalyptus plantations, based on a combination of methodologies. The environmental impact assessment methodology for forest harvesting was applied by combining interaction network approaches and impact assessment matrices. This methodology was then applied to a commercial Eucalyptus plantation in the municipality of São Pedro, state of São Paulo, Brazil. The results show that timber transportation activities had the highest positive and negative environmental indices. The most significant negative impacts refer to the depletion of water resources and erosion, while the positive impacts are regional development and job creation. The most significant changes, both positive and negative, were observed in a greater number of environmental impacts for the physical and anthropic environment, with fewer for the biotic environment. The combination of methodologies has potential as an expedient tool for planning forestry operations, providing practical results for decision-making, making production more sustainable and applicable to different crops and production systems.

Water deficit is one of the factors that most influence plant growth and yield. Thus, this study aimed to evaluate the effect of silicon and salicylic acid application and water deficit on the growth and photosynthetic and osmoregulatory metabolism of Talisia esculenta Radlk seedlings and their recovery potential after the resumption of irrigation. Six treatments were performed: irrigation, irrigation suspension, irrigation suspension + silicon at 0.5 g L−1, irrigation suspension + silicon at 1.0 g L−1, irrigation suspension + salicylic acid at 50 mg L−1, and irrigation suspension + salicylic acid at 100 mg L−1. The evaluations were carried out at the beginning of the experiment (T0), at 10 and 15 (DIS) days after irrigation suspension, when the seedlings showed a photosynthetic rate close to zero, and at recovery (REC). The plants were submitted to water restriction for up to 15 days, being then re-irrigated until the recovery point, which was monitored based on the photosynthetic rate. Silicon application attenuated the harmful effects of water deficit on gas exchange, initial fluorescence, promoted proline accumulation in the leaf and root, and provided higher seedling quality. Salicylic acid application contributed to the maintenance of the relative water content of leaves during the water deficit period. Silicon and salicylic acid applications can attenuate the harmful effects of water stress, with silicon being the most effective agent in maintaining its growth and metabolism.