People living in areas of significant seismic risk seldom undertake sufficient preparations to safeguard their family. This is most problematic in remote communities such as those along the Dead Sea Fault, Israel, where self-reliance is a key factor in coping with disasters. To facilitate individual and familial involvement in earthquake preparedness in remote areas, we designed a tool for self-assessment of risk and preparedness. The personalized risk assessment is based on national hazard and building standards, and on personal input regarding structure characteristics. The risk and preparedness evaluations enhance awareness and provide immediate feedback to help users improve familial preparedness. Spatial analysis of the data collected is used to form high-resolution maps that expose specific challenges for emergency response. A study conducted in the town of Mitzpe Ramon exposed neighborhoods with relatively high risk of damage and low preparedness. Integrating these results with seasonal stress-factors such as peak tourism and extreme weather, provides new and important insights on the ability of the local community and emergency forces to cope with multi-hazard situations. Analysis of the heterogeneous distribution of expected hardship within a community should be implemented world-wide to improve risk mitigation.

Mammalian species possess sophisticated innate immune mechanisms that collectively combat a wide array of viral pathogens. Among these, the well-characterized interferon (IFN) response has been extensively researched; however, the role of antiviral RNA interference (RNAi) in mammals is emerging as an area of significant interest. Previous research has noted that Dicer, an enzyme crucial for processing double-stranded RNA (dsRNA), exhibits reduced activity in vitro, and that the IFN response may overshadow or inhibit the antiviral functions of RNAi in mammalian cells. Consequently, the functional relevance of RNAi in antiviral defense within mammalian somatic cells remains an open question. The evolution of antiviral systems in human populations reflects their substantial advantages, paralleling the evolutionary pressure on genomes encoding such defense mechanisms. While the well-studied protein-guided immune responses in mammals are essential for survival in viral environments, small RNA-mediated antiviral systems, which utilize complementary base pairing to silence non self-genetic material, also play a crucial role. In mammals, evidence suggests that microRNAs (miRNAs) regulate genes integral to antiviral responses, and emerging data indicate that small interfering RNAs (siRNAs), PIWI-interacting RNAs (piRNAs), and transfer RNAs (tRNAs) can directly target virus-derived nucleic acids. This review aims to highlight some of the recent progress in understanding mammalian antiviral RNAi mechanisms.

Social surveys are conducted to determine how annoyed people are in a certain noise situation. The results are typically presented as exposure-response curves showing the percentage of the area population that are highly annoyed as a function of the noise exposure level. It is a well-known fact that the survey results are not only dependent on the accumulated noise exposure, DNL, DENL, or similar, but also on various other factors such as maximum levels, exposure patterns, noise spectra, etc. A re-analysis of previously reported surveys shows that the results are also to a large extent dependent on survey-specific factors like wording of the annoyance questions, how the questionnaires are presented, response scales, methods of scoring highly annoyed, etc. This paper discusses and quantifies the influence of such factors and suggests ways of comparing results from surveys that have been conducted according to different protocols and different analysis methods.

Hemifacial spasm (HFS) is a rare disorder characterized by involuntary facial muscle contractions. The primary cause is mechanical compression of the facial nerve by nearby structures. Lateral spread response (LSR) is an abnormal muscle response observed during electromyogram (EMG) testing and is associated with HFS. Intraoperative monitoring of LSR is crucial during surgery to confirm successful decompression. Proper anesthesia and electrode positioning are important for accurate LSR monitoring. Stimulation parameters should be carefully adjusted to avoid artifacts. The disappearance of LSR during surgery is associated with short-term outcomes, but its persistence does not necessarily indicate poor long-term outcomes. LSR monitoring has both positive and negative prognostic value, and its predictive ability varies across studies. Early disappearance of LSR can occur before decompression and may indicate better clinical outcomes. Further research is needed to fully understand the implications of LSR monitoring in HFS surgery.

This letter introduces a frequency response characteristic (FRC) curve and its application in high renewable power systems. In addition, the letter presents a method for fast frequency response assessment and frequency nadir prediction without performing dynamic simulations using detailed models. The proposed FRC curve and fast frequency response assessment method are useful for operators to understand frequency response performance of high renewable systems in real time.

The integrated stress response (ISR) is an adaptational signaling pathway that is induced in response to different stimuli, such as accumulation of unfolded and misfolded protein, hypoxia, amino acid deprivation, viral infection and ultraviolet light. It has been known that viral infection can activate ISR, but the role of ISR during viral infection is still unclear. In some cases, ISR is a protective mechanism of host cell against infection with virus whilst ISR may be hijacked by viruses for facilitating its replication. In this review, we highlighted recent advances on induction of ISR upon viral infection and the downstream responses involved such as autophagy, apoptosis, formation of stress granules and innate immunity response. We then discussed the molecular mechanism of ISR regulating viral replication and how viruses antagonize this cellular stress response resulting from ISR.

Photosynthetic activities of the sago palm (Metroxylon sagu Rottb.) were studied to find out its sensitivity to changes in ambient air temperature. The minimum ambient air temperature designed for the experiment was 25–29⁰C, while the higher end was 29–33⁰C. Several photosynthetic parameters were studied to support our analysis in sago photosynthetic activity, including diurnal leaf gas exchange, assimilation rate vs. CO₂ concentration, leaf greenness, leaf chlorophyll content, and photosynthetic rate vs. irradiance. We found that sago palm photosynthetic activity tends to be more sensitive to minimum than to maximum ambient air temperature. The plants exposed to higher air temperatures had dark green leaf color associated with higher rates of diurnal photosynthesis, chlorophyll content, and rubisco limited photosynthetic activity. They also exhibited higher trend in optimum irradiance absorption level. Consequently, maximum light energy dissipation occurred at higher temperatures.

The successful vaccination implies the induction of effective specific immune responses. We intend to find biomarkers among various immune cell subpopulations, cytokines and antibodies which could be used to predict the levels of specific antibody- and cell-mediated responses after measles-mumps-rubella vaccination. We measured 59 baseline immune status parameters (frequencies of 42 immune cell subsets, levels of 13 cytokines, immunoglobulins) before vaccination and 13 response variables (specific IgA and IgG, antigen-induced IFN-γ production, CD107a expression on CD8+ T lymphocytes, and cellular proliferation levels by CFSE dilution) 6 weeks after vaccination for 19 individuals. Statistically significant Spearman correlations between some baseline parameters and response variables were found for each response variable (p<0.05). Due to the low number of observations relative to the number of baseline parameters and missing data for some observations, we utilized three feature selection strategies to select potential predictors of the post-vaccination responses among baseline variables: (a) screening of the variables based on the correlation analysis, (b) supervised screening based on the information of changes of baseline variables at day 7, (c) implicit feature selection is performed using regularization-based sparse regression. We identified optimal multivariate liner regression models for predicting the effectiveness of vaccination against measles-mumps-rubella using the baseline immune status parameters. It turned out that the sufficient number of predictor variables ranges from one to five depending on the response variable of interest.

Background and introduction: Lung cancer is a prevalent and deadly disease globally. Non-small cell lung cancer (NSCLC) is the most common subtype, comprising 85% of cases; Case report: A 65-year-old ex-smoker man presented to our facility with nocturnal cough. Various investigations revealed that he had metastatic NSCLC, for which he underwent chemotherapy with cisplatin and gemcitabine, followed by immunotherapy with Nivolumab. He achieved a complete response to the therapy and has remained free from recurrence for over 7 years since the initial diagnosis; Discussion and Conclusion: The treatment of metastatic NSCLC remains a significant therapeutic challenge, but the implementation of new therapeutic techniques has expanded the possibilities of achieving complete and durable eradication of the disease.

Cucumber (Cucumis sativus L.) is a vital economic vegetable crop, and TRM (TONNEAU1 Recruiting Motif) gene plays a key role in cucumber organ growth. However, the pan-genomic characteristics of the TRM gene family and their expression patterns under different stresses have not been reported in cucumber. In this study, we identified 29 CsTRMs from the pan-genomes of 13 cucumber accessions, with CsTRM29 existing only in PI183967. Most CsTRM proteins exhibited differences in sequence length, except five CsTRMs having consistent protein sequence lengths among the 13 accessions. All CsTRM proteins showed amino acid variations. Analysis of CsTRM gene expression patterns revealed that six CsTRM genes strongly changed in short-fruited lines compared with long-fruited lines. And four CsTRM genes strongly responded to salt and heat stress, while CsTRM14 showed responses to salt stress, powdery mildew, gray mold and downy mildew. Some CsTRM genes were induced or suppressed at different treatment timepoint, suggesting that cucumber TRM genes may play different roles in responses to different stresses, with expression patterns varying with stress changes. Remarkably, the expression of CsTRM21 showed considerable change between long and short fruit and in responses to abiotic stresses (salt stress, heat stress) as well as biotic stresses (powdery mildew, gray mold), suggesting a dual role of CsTRM21 in both fruit shape determination and stress resistance. Collectively, this study provided a base for further functional identification of CsTRM genes in cucumber plant growth and stress resistance.

During the SARS-CoV-2 vaccination campaign, people with CF (pwCF) were considered a clinically vulnerable population. However, data on immunogenicity of anti-SARS-CoV-2 vaccines in pwCF are lacking. We conducted a prospective study enrolling all patients aged >12 and followed-up in our CF centre, who received two doses of the BNT162b2 vaccine in March-­­­October 2021. They underwent a blood sample for quantification of antibodies to the SARS-CoV-2 spike protein receptor binding domain immediately before receiving the first dose and after 3 and 6 months from the second dose. We enrolled 143 patients (median age: 21 years, range: 13-38); of whom 16 had a previous infection. Median antibody titer (interquartile range) after 3 months from vaccination was 1288 U/mL (730-2115) and decreased to 918 U/mL (534-1488) after 6 months (P<0.0001). Median values were higher among previously infected patients as compared to those naïve to SARS-CoV-2 (9107 vs 1229 U/mL at 3 months and 4810 vs 829 U/mL at 6 months, P<0.0001) with no significant differences in the rate of decline over time (P=0.135). All pwCF mounted an antibody response after two-doses of BNT162b2 vaccine that waned at 6 months from vaccination. Age ≥30 years and use of inhaled corticosteroids were associated with a lower humoral response.

Conformal radiotherapy is a primary treatment in head and neck cancer, which putative adverse effects depend on relatively low doses of radiation delivered to increased volumes of normal tissues. Systemic effects of such treatment include radiation-induced changes in serum lipid profile, yet dose- and volume-dependence of these changes remain to be established. Here we analyzed levels of choline-containing phospholipids in serum samples collected consecutively during the radiotherapy used as the only treatment modality. The LC-MS approach applied in the study enabled the detection and quantitation of 151 phospholipids, including (lyso)phosphatidylcholines and sphingomyelins. No statistically significant differences were found in the pre-treatment samples from patients with different location and stage of cancer. To compensate for potential differences between schemes of radiotherapy the biologically effective doses were calculated and used in the search of correlations with specific lipid levels. We found that the levels of several phospholipids depended on the maximum dose delivered to the gross tumor volume and total radiation energy absorbed by the patient’s body. Increased doses correlated with increased levels of sphingomyelins and reduced levels of phosphatidylcholines. Noteworthy, serum phospholipid levels were associated mainly with volumes of normal tissues irradiated with relatively low doses (i.e., total accumulated dose 20 Gy), which indicated the importance of such effects on the systemic response of the patient’s organism to IMRT.

Production of biofuel from lignocellulosic biomass is relatively low due to the limited knowledge about natural cell wall loosening and cellulolytic processes in plants. Industrial separation of cellulose fiber mass from lignin, its saccharification and alcoholic fermentation is still cost-ineffective and environmental unfriendly. Assuming that the green transformation is inevitable and that the new sources of raw materials for biofuels are needed, we decided to study cell death - a natural process occurring in plants in a context of reducing the recalcitrance of lignocellulose for production of second generation bioethanol. “members of the enzyme families responsible for lysigenous aerenchyma formation were identified during the root hypoxia stress in Arabidopsis thaliana cell death mutants. The cell death regulatory genes, LESION SIMULATING DISEASE 1 (LSD1), PHYTOALEXIN DEFICIENT 4 (PAD4) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) conditionally regulate the cell wall when suppressed in transgenic aspen. During four years of growth in the field the following effects were observed: lignin content was reduced, the cellulose fiber polymerization degree increased and the growth itself was unaffected. The wood of transgenic trees was more efficient as a substrate for saccharification, alcoholic fermentation and bioethanol production. The presented results may trigger the development of novel biotechnologies in the biofuel industry.

In recent times, there has been a growing interest in the use of control charts as a feedback process monitoring technique. Particularly, CUSUM schemes have been proven to be efficient for monitoring processes where the magnitude of the sustained mean shifts is small or moderate. However, because of the constant control limits, the detection ability of CUSUM schemes becomes slow at the initial set-up of the process. The fast initial response FIR feature has often been used to enhance it at the process startup. Meanwhile, the dynamism of real-life problems has always encouraged a more sensitive CUSUM scheme capable of detecting process shifts more rapidly. In this paper, an improved CUSUM scheme for monitoring process mean is proposed. This scheme will be substantial for monitoring processes whose observations are obtained at a distant time interval for example hourly, daily or weekly and where the sustained shifts are assumed to be small or moderate. To demonstrate the practical applications of the proposed scheme, we present its real-life application using datasets from a bottling company and petroleum refinery laboratory.

Immune dysfunction has long been reported by medical professionals regarding astronauts suffering from opportunistic infections both during their time in space and a short time period afterwards once back on Earth. Various species of prokaryotes on board these space missions or cultured in a microgravity analogue exhibit increased virulence, enhanced formation of biofilms, and in some cases develop specific resistance for specific antibiotics. This poses a substantial health hazard to the astronauts confined in constant proximity to any present bacterial pathogens on long space missions with a finite number of resources including antibiotics. Furthermore, some bacteria cultured in microgravity develop phenotypes not seen in Earth gravity conditions, providing novel insights into bacterial evolution and research.

Nonhost disease resistance is the most common type of plant defense mechanism against potential pathogens. In this study, the metabolic enzyme formate dehydrogenase (FDH1) was identified to be involved in nonhost disease resistance in Nicotiana benthamiana and Arabidopsis thaliana. In Arabidopsis, AtFDH1 was highly upregulated in response to both host and nonhost bacterial pathogens. Arabidopsis Atfdh1 mutants were compromised in nonhost resistance, basal resistance, and gene-for-gene resistance. The expression patterns of salicylic acid (SA) and jasmonic acid (JA) marker genes after pathogen infections in Atfdh1 mutant indicated that SA is most likely involved in the FDH1-mediated plant defense response to both host and nonhost bacterial pathogens. Previous studies reported that FDH1 localizes to only mitochondria, or both mitochondria and chloroplasts. Our results showed that the AtFDH1 localized to mitochondria and the amount of FDH1 localized to mitochondria increased upon infection with host or nonhost pathogens. Interestingly, the subcellular localization of FDH1 was observed in both mitochondria and chloroplasts after infection with a nonhost pathogen in Arabidopsis. We speculate that FDH1 plays a role in cellular signaling networks between mitochondria and chloroplasts to produce coordinated defense responses such as SA-induced reactive oxygen species (ROS) generation and hypersensitive response (HR)-induced cell death against nonhost bacterial pathogens.

Respiratory Syncytial Virus is a common respiratory pathogen known for causing respiratory illnesses, ranging from mild symptoms to severe lower respiratory tract infections in infants and the elderly. This virus is responsible for one-third of pneumonia deaths in the pediatric population, but there are currently only a few effective vaccines and pharmacological treatments. The frac-talkine (CX3CL1) receptor (CX3CR1) is a co-receptor for RSV expressed by airway epithelial cells and a diversity of immune cells. Recent research has highlighted the role of CX3CR1 in the host immune response to RSV infection, and its potential role in the development of an efficient vaccine and novel treatments.

Host immunological pathways have been proposed including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. Besides TH2 and TH9 immune responses which are against multicellular parasites, host immunological pathways against viruses, intracellular micro-organisms (bacteria, protozoa, and fungi), and extracellular micro-organisms can use programmed cell death pathways to trigger immune reactions or to execute effective strategies to eliminate these pathogens. These programmed cell deaths include apoptosis, autophagic death, pyroptosis, ferroptosis, necroptosis, and NETosis. Apoptosis is related to host anti-virus eradicable THαβ immunity. Autophagic death is related to host anti-virus tolerable TH3 immunity. Pyroptosis is related to host anti-intracellular micro-organism eradicable TH1 immunity. Ferroptosis is related to host anti-intracellular micro-organism tolerable TH1-like immunity. Necroptosis is related to host anti-extracellular micro-organism eradicable TH22 immunity. NETosis is related to host anti-extracellular micro-organism tolerable TH17 immunity.

Food allergies are a growing public health concern worldwide, especially in children and young adults. Allergen-specific IgE plays a central role in the pathogenesis of food allergies, but their titers poorly correlate with allergy development. Host immune systems yield allergen-specific immunoglobulin (Ig)A, IgE and IgG subclasses with low or high affinities and differential Fc N-glycosylation patterns that can affect the allergic reaction to food in multiple ways. High affinity IgE is required to induce strong mast cell activation eventually leading to allergic anaphylaxis while low affinity IgE can even inhibit the development of clinically relevant allergic symptoms. IgA and IgG antibodies can inhibit IgE-mediated mast cell activation through various mechanisms, thereby protecting IgE-positive individuals from allergy development. The production of IgE and IgG with differential allergenic potential seems to be affected by the signaling strength of individual B cell receptors, and by cytokines from T cells. This review provides an overview of the diversity of the B cell response and the diverse roles of antibodies in food allergy.

Like other organisms, fungi produce extracellular vesicles (EVs) that are involved in various biological processes, including intercellular communication and the transport of molecules between cells. These EVs can be applied in fungal pathogenesis, virulence, and interactions with other organisms, including host cells, in the case of fungal infections. While some types of mycoses are relatively common and easily treatable, certain neglected mycoses pose significant public health challenges, such as sporotrichosis, chromoblastomycosis, and paracoccidioidomycosis. These infectious diseases can cause significant morbidity and disability, leading to a reduced quality of life for the patients. So, research about the virulence factor is essential to understand how fungi escape the immune system. In this context, this manuscript reviews the study of fungi EVs, their cargo, their obtaining, and their role during the infectious process, which is extremely important for understanding this neglected mycosis.

Leishmaniasis is a complex infectious parasitic disease caused by protozoa of the genus Leishmania, belonging to a group of neglected tropical diseases. It poses significant global health challenges, particularly in socio-economically disadvantaged regions. Macrophages, as innate immune cells, play a crucial role in initiating the inflammatory response against the pathogens responsible for this disease. Macrophage polarization, the process of differentiating macrophages into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, is essential for the immune response in leishmaniasis. The M1 phenotype is associated with resistance to Leishmania infection, while the M2 phenotype is predominant in susceptible environments. Notably, various immune cells, including T cells, play a significant role in modulating macrophage polarization by releasing cytokines that influence macrophage maturation and function. Furthermore, other immune cells can also impact macrophage polarization in a T-cell-dependent manner. Therefore, this review comprehensively examines macrophage polarization's role in leishmaniasis and other immune cells' potential involvement in this intricate process.

We present a new perspective of the link between QED and Maxwell's equations. We demonstrate that the interpretation of $\mathbf{D}=\varepsilon_{0} \mathbf{E}$ as vacuum polarization is consistent with QED. A free electromagnetic field polarizes the vacuum, but the polarization and magnetization currents cancel giving zero source current. The speed of light is a universal constant, while the fine structure constant, which couples the electromagnetic field to matter, runs as it should.

Aim: This study aimed to understand the role of workforce agility as a coping strategy to curtail the COVID-19 pandemic. Method: The study reviewed and integrated two lines of literature to develop a theoretical framework to help business organizations to respond, adapt, and recover from the COVID-19 pandemic crisis. Results: The results showed that there are several commonalities between the workforce agility literature and the crisis management literature, mostly manifested in the speed of responding to uncertain and unpredictable, adverse events in the business environment. A thorough review of key themes in both kinds of literature led to developing a theoretical framework that links crisis drivers, crisis enablers, crisis capabilities, and response strategy. Workforce agility can be used as a coping strategy to deal with the COVID-19 pandemic crisis. Both kinds of literature evolve to respond to any crisis; the crisis management literature focuses on Meso-level (organizational level) or collective actions to mitigate the crisis, while the workforce agility literature focuses on the Micro-level (individual level). However, the successful response to any crisis requires the synergy of both actions. Future Studies: The results of this research are of prime importance for both researchers and practitioners. Researchers can use the theoretical framework as a baseline for building empirical research design. The current study also sets the context for future researchers who are interested in workforce agility to test the validity of agile work behaviors in real adverse context. It also opens a new stream of debate by deconstructing understudied links between workforce agility, resilience, and crisis management. Mangerial implication: For practitioners to ensure a successful response to any impending crisis, they must develop their employees’ agile behaviors. Practitioners can also redesign their recruitment strategy to select the right individuals with the right agile attributes, abilities, and behaviors to easily alter their behaviors according to the progressing crisis phases. Finally, practitioners can design continual learning interventions to include required agile skills and competencies to prepare their employees for future crises.

Abstract: With the continuous integration of various energy systems and the reform of energy trading marketization, the traditional power demand response can no longer meet the needs of multi-energy coupling. For the joint response problem of multi-energy, this paper proposes a comprehensive demand response optimization incentive model considering the user response characteristics, with the complete energy service providers and multiple users as the participants of the comprehensive demand response, to solve the response strategy for the optimal goal of all parties. The implementation architecture of integrated demand response and the electrothermal energy hub model is introduced first. Secondly, the integrated demand response collaborative optimization strategy of the integrated energy service providers and users is established, and the existence and uniqueness of the optimal solution are proved. Finally, the example analysis demonstrates that the proposed strategy can reduce the integrated energy service providers' response cost and user dissatisfaction under multiple scenarios.

Mechanical power and motion are often transmitted by the gear-rotor-bearing system. When there are fitting clearances between the housing and outer ring in bearings, complex vibration responses will be generated, which makes the operating status difficult to identify. Therefore, for analyzing dynamic responses, a dynamic model of gear-rotor-bearing systems with bearing fitting clearances is proposed. In the model, the bearing system with fitting clearances and gear pair system are combined, and the coupling relationship is determined by the gyroscopic mo-tion of the shaft. The friction force and collision force caused by fitting clearances are also con-sidered, which are simulated by the Coulomb friction model and Hertz theory. The result shows that the meshing stiffness will also be excited by the bearing displacement. When there are fit-ting clearances on the bearing, the amplitude modulation of the bearing outer raceway to the system time-domain response is intensified, and the multiple harmonic frequency of bearings and gear pairs are generated on the spectrum, as well as defect frequencies of gear pairs. As the fitting clearance is increased, the higher multiple harmonic responses will be caused. Although the response amplitude of the gearbox is increased by raising the input speed, multiple harmon-ic responses are suppressed, which makes the system mainly vibrate at the fundamental fre-quency. Then, the dynamic model and the vibration analysis are experimentally verified.

The role of the immune response to SARS-CoV-2 infection is not yet well known, in particular about the persistence of circulating antibodies. The aim of the study is to compare the results of two automated systems for the determination of IgG antibodies against SARS CoV-2 and to assess the time course of the IgG response after the onset of symptoms for a period longer than that evaluated to date. IgG were measured in 98 specimens of 55 subjects with COVID-19 (time from the onset of symptoms from 3 to 109 days) using the automated tests "Abbott SARS-COV-2 IgG" and the "MAGLUMI 2019-nCoV IgG". The two methods had a concordance of 91.8%, but the quantitative correlation showed very dispersed results. All the specimens resulted positive after 17 days from the onset of the synptoms. However, the median concentrations of IgG, after a rapid increase up to about 20 days, quickly decrease to about 15% of the maximum for Maglumi. The same samples measured by Architect showed a quite constant trend up to 80 day, and then an only moderate decline. The titer of IgG against SARS-CoV-2 in patients exposed to COVID-19 may significantly and rapidly decrease, with a different time-course depending on the method used for the determination.

The human innate immune response to the pore-forming toxin of Vibrio cholerae VCC, is currently under study. Here, in vitro studies on a human macrophage cell line (THP-1), helped explore the activated pathways involved on the onset the innate immune response towards the cytotoxin. The secreted monomeric 65 KDa form interacts with mature macrophages in pg/ml concentrations, determined by dose response experiments after treatments under 1 h. Non vacuolating concentrations (pg/ml) were applied to the cells; immunoblots revealed activation of MAPKs: early overexpression of p38 and ERK. Cell lysis by release of lactate dehydrogenase (LDH) was not apparent in the first hour, nonetheless it was positive after 24 h. Finally, to discern whether the VCC stimulates transcriptional activators via MAPKs pathway, NF-κB and AP-1 were studied by real time quantitation. Increased expression of p50 (NF-κB), cJun and cFos (AP-1) was observed. Given that NF-κB is the transcription factor initiating inflammation of innate immune response and in turn, AP-1 is responsible for cell surviving response, results from this study lead us to conclude that VCC in vitro treatments, induce a pro-inflammatory and a surviving response, in less than one hour on activated macrophages.

Background: Cytokines and chemokines are critical regulators of innate and adaptive immunities during viral infection. We examined innate and adaptive immune responses to hepatitis C virus (HCV) and hepatitis B virus (HBV) at baseline and against controls. Methods: Twenty-seven cytokines were evaluated before treatment in 27 patients with chronic hepatitis C(CHC) [genotype1 (n=20), genotype2 (n=7), HCVRNA 5.72IU/ml] and 12 chronic hepatitis B(CHB) [e-antigen (Ag) (+) (n=5), e-Ag (-) (n=7), HBVDNA 6.191.31Logcopies/ml] and against controls(n=5). Results: Th1 and Th2 cytokines were significantly higher (p<0.05) in CHB than in CHC. The levels of IL-IL10 in CHC and CHB, and IL15 in CHC(genotype2) and CHB were significantly lower (p<0.05) than in controls. The levels of CXCL8 in CHC and CHB, IL12 in CHC and CHB [e-Ag (-)] and CXCL10 in CHC and CHB were significantly higher (p<0.05) than in controls. IFN-γwas higher in CHB than in controls. Conclusion: Cytokines levels differed between CHB and CHC before treatment. Innate immune responses were impaired in CHB with HBeAg(-) and CHC, but not in CHB with HBeAg(+) with high viral loads. Adaptive immune responses were impaired in CHB and CHC and appear to reflect the distinct state of virus-host immune interactions between CHB and CHC.

Background/Objectives: The Perilla frutescens plant has historically been used to protect against inflammation and redox stress. This has been attributed in part to the high content of various polyphenols. Despite this, the complement of polyphenolic components in Perilla extract is not yet fully defined. The aim of this study was to characterise the polyphenolic composition in Perilla extract, and its effect on the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which during inflammation and oxidative stress binds to the antioxidant response element (ARE) found on the promoter of phase II antioxidant enzymes. Methods: Following extraction using four solvents of different properties, the total phenolic, flavonoid and ortho-diphenolic content of Perilla extract were determined. Individual phenolic compounds were identified and quantified by RP-HPLC. Dual Luciferase assay using a reporter plasmid containing a human NQO1 ARE-luciferase fusion was employed to determine the potential protective effect of the Perilla fractions against redox stress. Results: HPLC analysis revealed that the highest phenolic content was present in the polar extracts. A total of 35 distinct polyphenolic compounds were identified, with rosmarinic acid being the major constituent. On cells in vitro, the methanol Perilla fraction showed protection against redox stress, with the luciferase assay displaying up to 1.5 fold increase in the induction of the human NQO1 ARE-luciferase reporter. Conclusions: While Perilla extract seems to be mainly protecting against inflammation and redox stress through the action of rosmarinic acid, further work is required on the synergystic effects between different polyphenols.

Background: Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune responses. Body: This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.

In mountain-gorge areas, the rock creep is the critical process for high rock slopes failure. During long-term rock creep, slopes might encounter earthquakes and form further creep after earthquakes. This complex mechanical response process can easily lead to the slope failure. Based on a high rock slope in the Nujiang River Basin, this paper analyzes deformation characteristics and dynamic response characteristics by using FLAC3D software, considering combined effects of multiple earthquakes and long-term creep. Results show that when the amplitude increases, the shear strength of the slope decreases and the risk of instability increases under combined actions of creep and earthquakes. Earthquakes promote the development of creep and induce the accumulation of damage on the slope surface and in the slope. The delayed effect becomes more pronounced as the slope height increases. We need to consider deformation differences of the slope further. The ground motion response on the slope surface is stronger than those in the slope, with the peak occurring at the top of the slope. Earthquakes have a greater impact on the middle and top of the slope surface, where cumulative damage and crack development begin. Reinforcement should be considered in these two places. Vertical earthquake has a great effect on the dynamic response. The phenomenon of slope resonance leads to a larger MPGA in the vertical direction than in the horizontal direction. Nonlinear and damping characteristics of the slope and the frequency of seismic waves cause the MPGA to decrease with the increase of amplitudes. This study could promote the development of high rock slope failure mechanism and provide references for the prevention of landslides in the Nujiang River Basin.

In today's digital landscape, cybersecurity has become a priority, with attacks becoming increasingly sophisticated. Traditional security approaches are no longer enough, requiring a more dynamic and advanced response. In this context, integrating Artificial Intelligence (AI) and Machine Learning (ML) appears key to addressing this growing threat. However, despite their high effectiveness, there is a developed problem: the integration of various data sources and technologies for comprehensive protection. This article presents an in-depth review of integrating Artificial Intelligence and Machine Learning in cybersecurity, focusing particularly on Open Extended Detection and Response (Open XDR) technology. The literature review in this article was meticulously conducted with specific criteria in mind. It focused on sourcing peer-reviewed journals, authoritative cybersecurity publications, and recent conferences that primarily concentrate on the advancements in AI and ML within the cybersecurity domain, particularly from 2018 to 2023. This timeframe was chosen to ensure the inclusion of the most current and relevant developments in Open XDR technology, Intrusion Detection Systems, Endpoint Detection and Response, and Security Information and Event Management systems. Additionally, the review gave special attention to studies and reports highlighting practical implementations and real-world applications of these technologies, thereby ensuring a comprehensive understanding of their impact and effectiveness in enhancing cybersecurity resilience. The methodology used is a detailed literature review, examining how various cybersecurity components interact and function. These components include Intrusion Detection Systems (IDS), which monitor networks for malicious activities; Endpoint Detection and Response (EDR), which focuses on detecting and investigating security incidents on endpoints; and Security Information and Event Management (SIEM), systems that provide real-time analysis of security alerts. The review also considers the role of Active Directory, a directory service for Windows domain networks, and the process of log forwarding, where log files are transmitted to a central server for analysis, in the context of AI and ML. The paper delves into the development of AI and ML, underscoring their roles in cybersecurity for advanced data processing, pattern recognition, and predicting threats. It explores both supervised (where the model is trained on labeled data) and unsupervised learning (where the model learns from unlabeled data) in ML, and how these techniques bolster cybersecurity measures. The article highlights the significance of Open XDR as a critical innovation that integrates data from multiple sources for comprehensive security analysis. Further, the review discusses how the integration of AI and ML into various cybersecurity tools, such as IDS, EDR, and SIEM, augments capabilities in threat detection and response. It addresses the challenges and opportunities that AI and ML present in the cybersecurity domain, focusing on ethical issues, data privacy concerns, and the necessity for ongoing professional development in this rapidly advancing field. The paper concludes by affirming the effectiveness of merging AI and ML with these cybersecurity tools within the Open XDR framework.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

For marine vessels, a propeller shaft system, also known as a propulsion shaft system, is an essential changer in engine torque and propeller thrust. The propeller shaft system is subjected to transverse, longitudinal, and torsional excitations during operation. These sources of excitations originate from alternating thrust generated by the propeller, operation of a propeller in a stern flow field which is non-uniform in time and space, misalignment of components such as shafts, bearings, and keyholes in the assembly, excitations in the form of rotational motion, and the whirling motion of the shafts. These dynamic excitations posed a challenging issue for the integrity and reliability of a marine vehicle. Thus, it is crucial to analyze the dynamic response of the propulsion shaft system. The dynamic analysis of the propulsion shaft system is typically conducted using numerical /analytical models. At present, Finite Element Model (FEM) as a numerical model plays a vital role in analyzing the dynamic response of the structure. The computed response and the modal parameters from the FE model are reliable only if accurate boundary conditions, such as stiffness, can be imposed on the model. However, the numerical FE model deviates from the experimental results because of uncertainties in the stiffness values of the bearings and other connectors. This paper uses the Response Surface Optimization (RSO) technique to estimate the unknown stiffness of the bearings used in the propulsion shaft system. The experimental model of the propeller shaft system is constructed from the steady-state response of the system using the step sine excitation. The natural frequencies and the amplitude of vibrations in the FE model are updated using the parametric RSO technique. The updated model shows that the difference in natural frequencies and vibration amplitude is less than 10% between the optimized and experimental models. Propeller Shaft, Vibrations, Optimization, Response Surface

The recent outbreak of Nipah virus in India in 2023 had affected the Kozhikode district in Kerala, with a total of 6 confirmed cases and 2 deaths. The source of the outbreak was traced to fruit bats that contaminated date palm sap, a common drink in the region. The outbreak was contained by rapid detection, isolation, and contact tracing of the cases, as well as public health education and social distancing measures. It also highlighted the need for improved surveillance, diagnostics, and therapeutics for Nipah virus. This letter highlights the latest insights gained from the epidemiological, clinical, and laboratory investigations of the outbreak.

COVID-19 pandemic outbreak challenged the global public health in last couple of years. Throughout the pandemic period, numbers of mutant strains of SARS- CoV-2 created challenges for the infected patients with diverse pathophysiology and immune response. Variant of Concern (VOC) alpha (B.1.1.7), delta (B.1.617.2) and omicron (B.1.1.529) grew most notable for causing the epidemiological manifestations, which eventually caused elevated infectivity resulting in significant mortality. This review indicates the comparative analysis of the immune-pathophysiological mechanisms in respect to the aforementioned strains of SARS-CoV-2.

Salmonella is the intracellular pathogen and etiological known for the cause of asymptomatic carriage, gastroenteritis, systemic disease (typhoid fever), in severe cases death may also occur. Altered function of mitochondria due to Salmonella infection impacts the immune response. Mitochondria which are recognized as the “powerhouse” of the cells are also know to play central role in the immune metabolism. Mitochondrial dynamics such as fusion, fission, signaling, transport and mitophagy influences the immune system and also maintains the cellular integrity. Mitochondrial DNA and Reactive oxygen species formation also elicits the inflammatory responses. This review discusses the immune metabolism and effect of altered mitochondrial dynamics in case of Salmonella infection.

The influence of four levels of dietary supplementation on the development of the immune response and on the biology of Haemonchus contortus and Trichostrongylus colubriformis was evaluated in Dorper lambs under serial artificial mixed-infections with 1000 infective larvae (L3) of each species, given every three days for 12 weeks. For each of the four diets formulated, one infected group (n=7) and one control group (n=4) were set up. Diets 1, 2, 3 and 4 contained 0%, 25%, 50% and 75% of concentrate, respectively. There was an evident immune response to infection in all groups, manifested through eosinophilia and production of anti-L3 immunoglobulins. There was a significant inverse relationship between the levels of nutrients in the diets and the numbers of late fourth-stage larvae, early fifth-stage larvae and adults of H. contortus. Most of the H. contortus parasite population was in hypobiosis at the early-fourth stage, representing 59.5%, 75.8%, 83.3% and 86.3% of the total Haemonchus worm burden, respectively, in the Diets 1, 2, 3 and 4. In the case of T. colubriformis, hypobiosis was not observed and the diet had no influence on establishment of the parasite.

Salvia hispanica (chia) is a highly nutritious food source and has gained popularity due to its high omega-3 fatty acid content. Red spider mites are a serious problem in the production of S. hispanica. However, no study has been conducted to analyse the defensive response to the infestation of red spider mites in S. hispanica. To elucidate the molecular mechanisms of the defensive response of S. hispanica to red spider mites, we performed a transcriptomic analysis of S. hispanica when infested by red spider mites. In the comparative assessment of leaf transcriptomes, a total of 1743 differentially expressed genes (DEGs) were identified between control and mite-infested S. hispanica. From these, 1208 (69%) transcripts were up-regulated and 535 (31%) were down-regulated. The DEGs included transcription factors, defense hormones, and secondary metabolites that were either suppressed or activated in response to spider mite herbivory. Gene Ontology (GO) enrichment analysis revealed that plant secondary metabolites such as glucosinolates, and signalling pathways, including the jasmonic acid signalling pathway, may play an important role in the defence against red spider mites. This study provides novel insights into the defence response of S. hispanica in response to insect herbivory and could be a resource for the improvement of pest resistance in the chia.

In Μay 2022, for the first time, multiple cases of mpox were reported in several non-endemic countries. The first ever case of the disease in Greece was confirmed on 8 June 2022 and a total of 88 cases were reported in the country until the end of April 2023. A multidisciplinary response team was established by the Greek National Public Health Organization (EODY) to monitor and manage the situation. EODY’s emergency response focused on enhanced surveillance, laboratory testing, contact tracing, medical countermeasures, and education of health care providers and the public. Even though management of cases was considered successful and the risk from the disease was down-graded, sporadic cases continue to occur. Here, we provide epidemiological and laboratory features of the reported cases to depict the course of the disease notification rate, that suggests measures for raising awareness as well as vaccination of high-risk groups of the population should be continued.

One of the significant challenges today in the brain-machine interface using invasive methods is the stability of the chronic record. In recent years, polymer-based electrodes have gained notoriety for achieving mechanical strength values close to that of brain tissue, promoting a lower immune response to the implant. In this work, we fabricated fully polymeric electrodes based on PEDOT:PSS for neural recording in Wistar rats. We characterized the electrical properties and both in-vitro and in-vivo functionality of the electrodes. Also, we employed histological processing and microscopical visualization to evaluate tecidual immune response in 7, 14, and 21 days post-implant days. Electrodes with 400-micrometer channels showed a 12dB signal-to-noise ratio. Local field potentials were characterized under two conditions: anesthetized and free-moving. There was a proliferation of microglia to the tissue-electrode interface in the first days, with a decrease after 14 days. Astrocytes also migrated to the interface, but there was no continuous recruitment of these cells in the tissue, showing inflammatory stability at 21 days. The signal was not affected by this inflammatory action, demonstrating that fully polymeric electrodes can be an alternative to prolong the valuable time of neural recordings.

Bunyaviruses represent the largest group of RNA viruses, and are the causative agent of a variety of febrile and hemorrhagic illnesses. Originally characterized as a single serotype in Africa, the number of described bunyaviruses now exceeds over 500, with its presence detected around the world. These predominantly tri-segmented, single-stranded RNA viruses are transmitted primarily through arthropod and rodent vectors, and can infect a wide variety of animal and plants. Although encoding for a small number of proteins, these viruses can inflict potentially fatal disease outcomes, and have even developed strategies to suppress the innate antiviral immune mechanisms of the infected host. This short review will attempt to provide an overall description of the order Bunyavirales, describing the mechanisms behind their infection, replication and their evasion of the host immune response. Furthermore, the historical context of these virus will be presented, starting from their original discovery almost 80 years ago, to the most recent research pertaining to viral replication and host immune response.

Deaths and property damage from the flood have increased drastically in the past two decades due to various reasons such as increased population, unplanned development and climate change. Losses from floods can be reduced by having accurate intelligence of an emerging flood situation in order to make timely decisions for issuing early warnings and responding efficiently. This paper presents a thorough analysis of the types and sources of intelligence required for flood warning and response processes and technology solutions that can be used for capturing such intelligence. A structured review, covering a more comprehensive range of published literature on Flood Early Warning and Response Systems (FEWRS), was conducted to identify the necessary intelligence and the technology that can be used to capture intelligence required for various phases of a flood hazard as it develops. Twenty-seven different types of key intelligence required in the flood cycle were identified. A conceptual architecture was identified that illustrates how relevant technology solutions can be used to extract intelligence at various stages of a flood event for decision making for early warnings and response.

Background: We aimed to identify overexpressed genes or related pathways associated with good responses to anti-HER2 therapy and to suggest a model for predicting drug response in neoadjuvant therapy with trastuzumab in HER2-positive breast cancer patients. Methods: We recruited 64 women with breast cancer and categorized them into three groups according to anti-HER2 therapy response. RNA from twenty core needle biopsy paraffin-embedded tissues and four cultured cell was extracted, reverse transcribed, and subjected to microarray. The obtained data were analyzed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and database for annotation, visualization, and integrated discovery. Results: In total, 6,656 genes differentially expressed between trastuzumab-susceptible and trastuzumab-resistant cell lines (3,224 upregulated and 3,432 downregulated). Expression changes in 34 genes in several pathways were found to be related to the response to trastuzumab-containing treatment, interfering with adhesion to other cells or tissues (focal adhesion) and regulating extracellular matrix interactions and phagosome action. Thus, decreased tumor invasiveness and enhanced drug effects might be the mechanisms explaining the better drug response in complete response group. Conclusions: This multigene assay-based study provides insights into breast cancer signal transduction and the possible prediction of treatment response to targeted therapies such as trastuzumab.

Molecular iodine (I2) induces apoptotic, antiangiogenic, and antiproliferative effects in breast cancer cells. Little is known about its effects on the tumor immune microenvironment. We studied the effect of oral (5 mg/day) I2 supplementation alone (I2) or together with conventional chemotherapy (Cht+I2) on the im-mune component of breast cancer tumors from a previously published pilot study conducted in Mexico. RNA-seq, I2 and Cht+I2 samples showed significant increases in expression of Th1 and Th17 pathways. Tumor immune composition determined by deconvolution analysis revealed significant increases in M0 macrophages and B lymphocytes in both I2 groups. Real-time RT-PCR showed that I2 tumors overexpress T-BET (p = 0.019) and interferon-gamma (IFNγ; p = 0.020) and silence tumor growth factor-beta (TGFβ; p = 0.049); whereas in Cht+I2 tumors, GATA3 is silenced (p = 0.014). Preliminary methylation analysis shows that I2 activates IFNγ gene promoter (by increasing its unmethylated form) and silences TGFβ in Cht+I2. In conclusion, our data showed that I2 supplements induce the activation of the immune response and that when combined with Cht, the Th1 pathways are stimulated. The molecular mechanisms involved in these responses are being analyzed, but preliminary data suggest that methylation/demethylation mechanisms could also participate.

A highly efficient reduction process of Cr (VI) with biochar was conducted in this paper. The results showed that nearly 100% Cr (VI) was reduced at selected reaction conditions: the dosage of biochar at m (C)/m(Cr) = 3.0, reaction temperature of 90 ℃, reaction time at 60 min and concentration of H2SO4 of 20 g/L, respectively. The reduction kinetics analysis demonstrated that the reduction of Cr (VI) fitted well with the pseudo-first-order model and the apparent activation energy was calculated to 40.24 kJ/mol. Response surface methodology confirmed that all the experimental parameters had positive effect on the reduction of Cr (VI). The influence of each parameter on the reduction process followed the order: dosage of biochar> Concentration of H2SO4 > Reaction Temperature > Reaction Time. This paper provided a versatile strategy for treatment of wastewater containing Cr (VI) and showed a bright tomorrow for wastewater treatment.

Purpose: This study aimed to determine the efficacy and safety of Oncoxin as an antitumoral supplement, and to describe its mechanism of action. Methods: We performed this scoping review according to the recommendations of the Joanna Briggs Institute and included patients older than 18 years-old who have any kind of tumor and receive Oncoxin as a supplement. We focused on the efficacy in terms of antitumoral properties, quality of life and survival, safety in terms of adverse events, and the mechanism of action. We did not limit for language or setting. We searched MEDLINE (Pubmed), EMBASE (Scopus), LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to nowadays. Results: We found a promising increment of survival when taking Oncoxin as a supplementary treatment. Additionally, the quality of life increased in terms of Karnofsky and EORTC scales. Regarding the mechanism of action, studies suggest it modifies inflammatory mediators’ expression, as evidenced by the reduction of COX-2, IL-1β, IL-6, TNF-α, IL-1β, IL-12, and IFN-γ. Besides, it promotes an arrest in the progression of cells from G1 into S, along with an increase in p27 and a decrease in cyclin D1 and pRb. Conclusions: We found promising complementary effects of Oncoxin to the standard treatment of cancer patients in diverse scenarios, with putative robust mechanisms of action. In addition to clinically relevant impacts verified in clinical trials, as well as it decreases the levels of pro-inflammatory cytokines, it can also decrease cytokines with antitumor activity such as IFN-γ, which should be further explored in larger trials and the long term.

Background: The COVID-19 has put global health institutions on alert. Organizations such as the CDC and WHO have developed preparedness and prevention checklist of 2019-nCoV infection to be used by public and healthcare professionals. Since COVID 19 pandemic is unexpected and no country aware of it prior to outbreak, there is limited information on the overall preparations of healthcare providers in Ethiopia. Therefore, the aim of this study was to assess early healthcare professionals’ preparedness and response to COVID 19 Pandemic in Oromia regional state, Ethiopia. Methods: The study was conducted on healthcare professionals working in public hospitals of Oromia regional state. The study was carried out by online questionnaire prepared using SurveyMonkey©. The collected data was analyzed and One-way ANOVA was used to determine the significant differences between health professionals working in different hospitals. The statistical significance associations of variables of interest was determined at 95% confidence intervals. Results: Healthcare professionals in the public hospitals of Oromia regional state, Ethiopia perceived that they are not yet well prepared and may not respond to the pandemic quickly and efficiently. Even though, they have positive response towards identifying signs and symptoms, provide education and utilization of PPE, they are still lacking in practical responses like managing cases, implementing emergency plans and isolation procedures from many others. Conclusion: As the Federal Ministry of Health, Ethiopia Public health institute and Oromia health bureau are vigilant and continually conducting preventive measures programs, extensive and maximum effort should be done to improve healthcare providers’ preparedness and response towards any emergency related to COVID-19 pandemic.

Optical conductivity of an interacting polaron gas is calculated within an extended random phase approximation which takes into account mixing of collective excitations of the electron gas with LO phonons. This mixing is important for the optical response of strongly polar crystals where the static dielectric constant is rather high, as in the case of strontium titanate. The present calculation sheds light on unexplained features of experimentally observed optical conductivity spectra in $n$-doped SrTiO$_{3}$. These features appear to be due to dynamic screening of the electron-electron interaction by polar optical phonons and hence do not require additional mechanisms for their explanation.

Adenosine to inosine (A-to-I) RNA editing is a highly conserved regulatory process carried out by adenosine-deaminases (ADARs) on dsRNAs. Although a considerable fraction of the transcriptome is edited, the function of most editing sites is unknown. Previous studies indicate changes in A-to-I RNA editing frequencies following exposure to several stress types. However, the overall effect of stress on the expression of ADAR targets is not fully understood. Here, we performed high-throughput RNA sequencing of wild-type and ADAR mutant C. elegans worms after heat-shock to analyze the effect of heat-shock stress on the expression pattern of genes. We found that ADAR regulation following heat-shock does not directly involve heat-shock related genes. Our analysis also revealed that lncRNAs and pseudogenes, which have a tendency for secondary RNA structures, are enriched among upregulated genes following heat-shock in ADAR mutant worms. The same group of genes is downregulated in ADAR mutant worms under permissive conditions, which is likely, considering that A-to-I editing protects endogenous dsRNA from RNA-interference (RNAi). Therefore, temperature increases may destabilize dsRNA structures and protect them from RNAi degradation, despite the lack of ADAR function. These findings shed new light on the dynamics of gene expression under heat-shock in relation to ADAR function.

The response of plasmonic metal particles to an electromagnetic wave undergoes significant features at the nanoscale level. Different properties of the internal composition of a metal, such as its ionic background and the free electron gas, begin to manifest more prominently. As the dimensions of the nanostructures decrease, the classical local theory gradually becomes inadequate. Therefore, Maxwellʹs equations need to be supplemented with a relationship determining the dynamics of current density which is the essence of nonlocal plasmonic models. In this field of physics, the standard (linearized) hydrodynamic model (HDM) has been widely adopted with great success, serving as the basis for a variety of simulation methods. However, ongoing efforts are also being made to expand and refine it. Recently, the GNOR (general nonlocal optical response) modification of the HDM has been used, with the intention of incorporating the influence of electron gas diffusion. Clearly, from the classical description of fluid dynamics, a close relationship between viscosive damping and diffusion arises. This offers a relevant motivation for introducing the GNOR modification in an alternative manner. The standard HDM and its existing GNOR modification also do not include the influence of interband electron transitions in the conduction band and other phenomena that are part of many refining modifications of the Drude‐Lorentz and other models of metal permittivity. In this article, we present a modified version of GNOR‐HDM that incorporates the viscosive damping of the electron gas and a generalized Drude‐Lorentz term. In the selected simulations, we also introduce Landau damping which corrects the magnitude of the standard damping constant of the electron gas based on the size of the nanoparticle. We have chosen a spherical particle as a suitable object for testing and comparing HD models and their modifications because it allows finding precise analytical solutions for the interaction and, simultaneously, it is a relatively easily fabricable nanostructure in practice. Our contribution also includes our own analytical method for solving the HDM interaction of a plane wave with a spherical particle. This method forms the core of calculations of the characteristic quantities, such as the extinction cross‐sections and the corresponding components of electric fields and current densities.

Considering the large number of candidates in vaccine testing studies against different pathogens and the amount of time spent in the pre- and clinical trials, there is a pressing need to develop an improved in vivo system to quickly screen vaccine candidates. The model of a polyester-polyurethane sponge implant provides a rapid analysis of the specific stimulus-response, allowing the study of a compartmentalized microenvironment. The sponge implant’s defined measurements were standardized as a compartment to assess the immune response triggered by vaccinal antigen. The LBSap vaccine (composed by Leishmania braziliensis antigens associated with saponin adjuvant) was used in the sponge model to assess the antigen-specific immunological biomarker, including memory generation after initial contact with the antigen. Mice strains (Swiss, BALB/c, and C57BL/6) were previously immunized using LBSap vaccine followed by an antigenic booster performed inside the sponge implant. The sponge implants were assessed after 72 hours, and the immune response pattern was analyzed according to leukocyte immunophenotyping and cytokine production. After LBSap vaccination, the innate immune response of the antigenic booster in the sponge implants demonstrated higher levels in the Ly+ neutrophils and CD11c+ dendritic cells with reduced numbers of F4/80+ macrophages. Moreover, the adaptive immune response in Swiss mice demonstrated a high CD3+CD4+ T-cells frequency consisting of an effector memory component in addition to a cytoxicity response (CD3+CD8+ T-cells), displaying the central memory biomarker. The major cell surface biomarker in the BALB/c mice strain was related to CD3+CD4+ effector memory while the increased CD3+CD8+ effector memory was highlighted in C57/BL6. The cytokine profile was more inflammatory in Swiss mice, with the highest levels of IL-6, TNF, IFN-g, and IL-17, while the same cytokine was observed in in C57BL/6 yet modulated by enhanced IL-10 levels. Similar to Swiss mice, BALB/c mice triggered an inflammatory environment after the antigenic booster in the sponge implant with the increased levels in the ILL-6, TNF, and IFN-g. The results highlighted how genetic background can influence populations involved in the immune response and indicated that it is possible to use this model to optimize and monitor the innate and adaptive immune responses of vaccine candidates. In this sense, these results could guide the choice of the most appropriate experimental model in biomolecule tests, considering that the particularities of each mouse strain influenced the dynamics of the immune response.

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some in-dividuals do not experience anticipated improvements despite weight loss. Bi-omarkers to identify such individuals at early stages are lacking. IGF-1 and IGFBP-1 were shown to predict T2DM onset in prediabetes. We assessed if these markers also predict the success of lifestyle interventions, thereby possibly guid-ing personalized strategies. We analyzed fasting serum levels of IGF-1, IGFBP-1 and IGFBP-2 in relation to changes in metabolic and anthropometric parameters, including intrahepatic li-pids (IHL) and visceral adipose tissue (VAT) volume measured by MRI, in 345 high-risk prediabetic participants (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), significance set at p

Due to the long duration and high cost of traditional pumping tests, the response of well water level to seismic wave, earth tide, and barometric pressure provides a feasible method for determining continuous changes in aquifer hydraulic parameters. Aiming at the problem that the response phase shift of well BB water level to tidal tide M2 is greater than that of tide O1, this paper preferentially calculated the time series changes of S, Be, n and BKu based on the response mechanism of well water level to barometric pressure and earth tide and with the help of smooth moving method. Then by using the mixed flow model, the variation of transmissivity and leakage coefficient over time were simultaneously obtained, and the evolution process and characteristics of aquifer parameters near well BB caused by the Wenchuan earthquake were ultimately discussed. The calculation results are basically consistent with the previous pumping test, and have been verified and compared by using other scholars' methods. This solving process avoids the problems such as excessive dependence on initial values, multiple solutions, and unstable tide O1, which has a promoting effect on the study of the impact of seismic activity on aquifer systems.

Abstract: The centrepiece of this analytical review is the metabolism of hydroxyapatite in its natural, bone, and synthetic forms, where the mitochondria-mediated mechanism may serve as the leading mechanism. The possibility that osteoblast mitochondria play an important role in the initial stages of bone mineralisation is discussed. Furthermore, the paper highlights the key role of mitochondria in the metabolism of synthetic hydroxyapatite.Differences between the results of in vivo and in vitro studies using synthetic hydroxyapatite of different morphologies are also detailed. It is noted that long-term infiltration with immune cells and in vivo studies are necessary to adequately evaluate hydroxyapatite as a bone-plastic material.Particular attention is given to the interaction of hydroxyapatite with immune cells and its ability to affect the ribosomes and mitochondria of cells. Due to its mechanical properties, scalability and potential use for the treatment of extensive bone defects of tumor origin, hydroxyapatite is a promising material.This study also highlights the importance of further development of in vitro research methods in the context of their biomimeticity. Overall, this work offers a theoretical direction for future studies of hydroxyapatite as a bone grafting material and emphasises the value of in vivo studies.

This study examined infants' neural responses to emotional prosody in natural speech. A multi-feature oddball paradigm was used with 34 3~11 month-old infants. Results showed distinct early (100-200 ms) and late (300-500 ms) mismatch responses to different emotional prosodies. Older infants had more negative early responses with happy and angry prosodies evoking stronger responses compared to sad prosody while younger infants showed a clearer distinction between angry and sad prosodies. In the late time window, angry prosody elicited more negative responses than sad prosody with younger infants showing more distinct responses between these two prosodies. Males exhibited stronger early mismatch responses than females. These findings call for further research on the implications for socio-emotional and language development.

Food and drinks can be contaminated with pollutants such as lead and strontium and this poses a serious danger to human health. For this reason, a number of effective sensors have been developed for the rapid and highly selective detection of such contaminants. TBA, a well-known aptamer developed to selectively target and thereby inhibit the protein of clinical interest -thrombin, is receiving increasing attention for sensing applications, particularly for the sensing of different cations. Indeed, TBA, in the presence of these cations, folds into the stable G-quadruplex structure. Furthermore, different cations produce small but significant changes in this structure that result in changes in the electrical responses that TBA can produce. In this article we produce an overview of the expected data regarding the use of TBA in the detection of lead and strontium, calculating the expected electrical response using different measurement techniques. Finally, we conclude that the TBA should perform better as a detector of strontium rather than lead.

Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, in which inflammation and demyelination lead to neurodegeneration and progressive disability. The treatment target is slowing down the disease course and mitigating the symptoms. Approximately 30 to 50% of patients do not respond optimally to Disease Modifying Therapies (DMTs), in which therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of HLA DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3), was used to classify therapeutic response. Patients were classified as follows: a) control: patients who achieved NEDA-3 b) case: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were: GG 50.5%, GA 34.3% and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p=0.6). We concluded that in Mexican patients with MS, HLA DRB1*0403 was not associated with therapeutic response to DMTs.

The noncoding RNAs (ncRNAs) are small transcript sequences that do not encode proteins but participate in the regulation of gene expression at the post-transcriptional level playing important biological roles such as proliferation and differentiation. In the tumor microenvironment, the dysregulated immunological response can participate in the progression and negative phenotype of cancer, the variability of switch cell differentiation and activation of the different immune cell lineages showed differential regulation by the type of cancer. Recent evidence showed that the upregulation of lncRNA can be used as a biomarker and predictive indicator for cancer progression. The use of lncRNA to turn off the tumor immune response and activate the anti-tumoral immune response is day by day a promising reality for the control of cancer. However, is imperatively elucidated the role of each ncRNA identified as well as its respective molecular pathways regulated, including the immune checkpoints, before its application at the clinical level. The correct delivery of lncRNA or mimics to inhibit its expression using the most efficient carriers to the cell or cellular organelle is a science that should continue to be developed.

Ransomware is continually evolving. The most recent tactic is to combine crypto-ransomware with data exfiltration, mandate fraud, and other such schemes to steal from victims and attempt to blackmail them. This paper examines the new trend, its underlying motives, and proposes practical recommendations to help organizations defend against this menace

We select four important waves of new entrants that knocked on the door of European electricity markets to illustrate how market rules need to be continuously adapted to allow new entrants to come in and push innovation forward. The new entrants that we selected are utilities venturing into neighbouring markets after establishing a strong position in their home market, utility-scale renewables project developers, asset-light software companies aggregating the assets of smaller consumers and producers, and different types of communities. We show that well-intentioned rules designed for certain types of market participants can (unintentionally) become obstacles for new entrants. We conclude that the evolution of market rules illustrates the importance of dynamic regulation. At the start of the liberalisation process the view was that we would deregulate or re-regulate the sector after which the role of regulators could be reduced. But their role has only increased. New players might also present new risks that require intervention by regulators.

Background: Twitter is a major tool for communication in emergencies such as natural disasters. This online social network allows the user to produce content, and it is not designed exclusively for news releases, as opposed to other service providers. Aim: The aim of this study is to investigate Twitter uses in natural disasters and pandemics. Methods: The included studies reported the role of Twitter in natural disasters. The studies that report in settings other than the natural disasters (such as man-made disasters) and other social media were excluded. Electronic databases for a comprehensive literature search including MEDLINE, Web of Science, CINAHL, PsycINFO, Cochrane Register of Controlled Trials (CENTRAL) and EMBASE were used to identify the records that match the mentioned inclusion criteria published till May 2020. The study characteristics were extracted from the qualified studies including year of publication, findings, and geographical location of the study conduct. A narrative synthesis for this literature review was used. Results: The search identified 822 articles of which 780 articles were removed, 256 were not available, 311 papers were not relevant, 16 were duplicated articles, and 197 were non-related to the emergencies. 45 articles met the selection criteria and were included in the review. eleven themes were found in the narrative synthesis including early warning, disseminating information and misinformation, advocacy, personal gains, assessment, various roles of organizations, public mood, geographical analysis, charity, using influencers, and trust. Conclusions: It is recommended that influential individuals be identified in each country and community before disasters occur so that the necessary information can be disseminated in response to disasters. Preventing the spread of misinformation is one of the most important issues in times of disaster, especially pandemics. Disseminating accurate, transparent, and prompt information from relief organizations and governments can help. Also, analyzing Twitter data can be a good source for understanding the mental state of the community, estimating the number of injured people, estimating the points affected by natural disasters, and modeling the prevalence of epidemics. Therefore, various groups such as politicians, the government, non-governmental organizations, aid workers, and the health system can use this information to plan and implement interventions.

Coronavirus disease 2019 (COVID-19) since its declaration as a pandemic by world health organization (WHO) has spread across the various continent with little known about the most effective public health response for containing and mitigating the transmission of the epidemic. It is important to state that some authors have published on the lessons learned from transmission and management of COVID-19 infection but only a few considered it from the Africa perspective. Despite the late arrival of the pandemic in Africa and the notion that the virus may not thrive because of the high temperature in the continent; today the narrative has changed with the number of infected patients increasing daily. Herein, the authors have shared their perspectives and opinions on the dynamics and response to COVID-19 from Africa context to create more awareness and approach in mitigating the spread of the virus should the continent becomes the epicenter of COVID-19.

A divergent selection experiment on environmental sensitivity was performed in rabbits. The aim of this study was to estimate the correlated response in kits’ weight and its survival, and weight distance from birth to weaning. Weight distance was calculated as the absolute values of the differences between the individual value and the mean value of its litter. Also, relationship between probability of survival at 4 d of age and weight at birth was studied. Environmental sensitivity was measured as litter size variability. A total of 2484 kits from 127 does of the low line (selected for reducing litter size variability) and 1916 kits of 114 does of the high line (selected for increasing litter size variability) of the 12th generation were weighed. Bayesian methodology was used to estimate the correlated response to selection, and LOGISTIC procedure of SAS was used to estimate the relationship between weight and probability of survival. Both lines showed similar individual weight at birth and at weaning, and similar survival at birth and at 4 d of age. Survival at weaning was higher in the low line than in the high line (0.67 and 0.62; P= 0.93). Weight distance was higher at birth but lower at weaning in the low line (47.8 g and 54.1 g; P=0.98). Kit’s weight at birth affected its survival. In conclusion, selection for environmental sensitivity showed correlated response in kits survival and in homogeneity of litter weight at weaning.

In 2014, the outbreak of adenoviral pneumonia occurred in Korean military training center. However, there is limited data on characteristics of fever and its response to antipyretics therapy in immunocompetent adults with adenoviral positive community-acquired pneumonia (CAP). Medical records of patients who were admitted to Armed Forces Chuncheon Hospital for treatment of CAP between January 2014 and December 2016 were retrospectively analyzed. We evaluated demographics, clinico-laboratory findings and radiologic findings at admission were compared between adenovirus positive (Adv) group and adenovirus negative (non-Adv) group. Out of 251 military personnel with CAP during the study periods, 67 were classified into Adv group while 184 were Non-Adv group. Patients with Adv group had a longer duration of fever after admission and symptom onset. Adv group patients had a higher mean temperature at admission and more observed over 40 and 39 to 40℃. Adv group patients had more commonly observed no response to antipyretic treatment and adverse events after antipyretics use. Length of hospital stay had no significant difference between two groups and no patient died in both groups. In our study, Adv positive CAP in patients with immunocompetent military personnel had distinct characteristics of fever and response to antipyretic treatment.

The present work aims at the comprehensive application of stochastic and optimization tools with the support of Information and Communication Technologies (ICT) through a case study in a logistics process for electronic goods; simulation and Response Surface Methodology (RSM) are applied for this purpose. The problem to be evaluated is to define an optimal distribution cost for products shipped to wholesale customers located in different cities in Mexico from a manufacturing plant in Tijuana, Mexico. The factors under study are the product allocation for each distribution center, finished good inventory level and on time deliveries, which are supposed to be significant to get the objective. The methodology applied for this problem considers the design of a discrete event simulation model to represent virtually the real life of logistics process, which is considered a complex system due to different activities are interrelated to carry it out. This model is used to execute the different experiments proposed by the RSM. The results obtained from simulation model were analyzed with the RSM to define the mathematical model that allows identifying the parameters of the factors in order to optimize the process. The findings prove how the ICT facilitate the application of stochastic tools with the purpose of process optimization.

Imperatorin is a chemical compound belong to Linear furan coumarins. Imperatorin is attracting considerable attention because of its anti-tumor, antibacterial, anti-inflammatory, anticoagulant and inhibition of myocardial hypetrophy and other pharmacological efficacy. However, imperatorin has limited water solubility and preferable lipid solubility, we decided to design and synthesize imperatorin lipid microsphere, to optimize preparation conditions. The aim was to develop and formulate imperatorin lipid microsphere through nano emulsion technology and apply the response surface-central composite design to optimize the imperatorin lipid microsphere formulation. Influence of content of amount of egg lecithin(A), amount of poloxamer188(B), soybean oil for injection accounted for the total percentage of oil phase(C) were investigated. Integrated effect of dependent variables including particle size(Y₁), polydispersity index(Y₂), Zeta potentials(Y₃), drug loading(Y₄), encapsulation efficiency(Y₅). Data of overall desirabiities were fitted to a second-order polynomial equation, through which three dimensional response surface graphs were described. Optimum experimental conditions were calculated by Design-Expert 8.06. Results indicated that the optimum preparation conditions were as follows: egg lecithin amount 1.39 g, poloxamer188 amount 0.21 g, soybean oil for injection amount 10.57%. Preparation of imperatorin lipid microsphere according to the optimum experimental conditions resulted in an overall desirability of 0.7286, while the particele size (168±0.54) nm, polydispersity index (PDI) (0.138±0.02), Zeta potentials (−43.5±0.5) mV, drug loading (0.833±0.27) mg·mL⁻¹, encapsulation efficiency (90±1.27)%. The difference between observed and predicted values of the overall desirability of the optimum formulation was in range from 2.4% to 4.3%. Subsequently, using the Scanning electron microscopy to observe the micromorphology of imperatorin lipid microsphere, the result shows that round globular of relatively uniform and sizes within 200nm.The proliferation study of imperatorin lipid microsphere on MDA-MB-231 was investigated by MTT method. Furthermore, pharmacokinetics in Sprague Dawley rats were evaluated using orbital bleeding. A sensitive and reliable liquid chromatography with High Performance Liquid Chromatography (HPLC) method was established and validated for the quantification of imperatorin in rat plasma samples. The data were calculated by DAS (Drug and statistics) pharmacokinetic software version3.2.6 (China). Results demonstrated that imperatorin lipid microsphere can significantly enhance the bioavailability of imperatorin and can significantly inhibit MDA-MB-231 cell proliferating. In conclusion, our results suggersted that the response surface-central composite design is suitable for the optimized lipid microspere formulation. Imperatorin Lipid microsphere can improve the bioavailability of imperatorin and inhibit the proliferation of MDA-MB-231 than that of imperatorin.

Phononic crystals are periodic composite structures with specific resonant features that are gaining strength in the field as liquid sensors. The introduction of a structural defect in an otherwise periodic regular arrangement can generate a resonant mode, also called defect mode, inside the characteristic band gaps of phononic crystals. The morphology, as well as the frequency in which these defect modes appear, can give useful information on the composition and properties of an analyte. Currently, only gain, and frequency measurements are performed using phononic crystal sensors. Other measurements like the transient response have been implemented in resonant sensors such as quartz microbalances showing great results and proving to be a great complimentary measure to the gain and frequency measurements. In the present paper, a study of the feasibility of using the transient response as a measure to acquire additional information about the analyte is presented. Theoretical studies using the transmission line model were realized to show the impact of variations in the concentration of an analyte, in this case, lithium carbonate solutions, in the transient time of the system. Experimental realizations were also performed showing that the proposed measurement scheme presents significant changes in the resulting data, indicating the potential use of this measure in phononic crystal sensors. This proposed measure could be implemented as a stand-alone measure or as a compliment to current sensing modalities.

Improved understanding of climate-growth relationships of multi-species is fundamental to understand and predict response of forest growth to future climate change. Forests are mainly composed of conifers in Northwestern Yunnan Plateau, but variations of growth response to climates among the species are not well understood. To detect growth response of multiple species to climate change, we developed residual chronologies of four major conifers, i.e. Abies georgei, Picea likiangensis, Pinus densata and Larix potaninii at upper distributional limits in Shika Snow Mountain. By using dendroclimatology method, we analyzed correlations between the residual chronologies and climate variables. The results showed that conifer radial growth was influenced by both temperature and precipitation in Shika Snow Mountain. Previous November temperature, previous July mean maximum temperature (T_max) and current June precipitation were the common climatic factors, which had consistent influences on radial growth of four species. Temperature in previous post growing season (September–October) and current growing season (June-August), and precipitation in previous August were the common climatic factors, which had divergent impacts on four species radial growth. Current May T_max and early growing season (April-May) precipitation showed positive and negative influences on growth of P. likiangensis, respectively. Temperature in current post growing season positively affected growth of A. georgei. According to the prediction of climate models and our understanding in growth response of four species to climate variables, we may understand growth response to climate change at species level. It is difficult to predict future forest growth in the study area, since future climate change might cause both increases or decreases for four species and indirect effects of climate change on forest should be considered.

Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

To better cope with stress in emergencies, emergency personnel undergo virtual reality (VR) stress trainings. Such trainings typically include visual, auditory and sometimes tactile impressions, whereas olfactory stimuli are mostly neglected. This concept paper therefore examines whether odors might be beneficial for further enhancing the experience of presence and immersion into a simulated environment. The aim is to demonstrate the benefits of VR civilian stress trainings for emergency personnel and to investigate the role of odors as stressors by manipulating the degree of perceived psychophysiological stress via olfactory impressions. Moreover, the current paper presents the development and validation of a convenient and portable fragrance dosing system that allows personalized odor presentation in VR. The presented system can transport reproducible small quantities of an air-fragrance mixture close to the human nose using piezoelectric stainless steel micropumps. The results of the fluidic system validation indicate that the micropump is suitable to release odors close to the nose with constant amounts of odor presentation. Furthermore, the theoretical background and the planned experimental design of VR stress training including odor presentation via olfactory VR technology is elucidated.

The focus of recent research shifts towards complex ‘whole organism’ responses (i.e., in multiple functional traits) in adaptation to or to defend against stressors under complex environmental conditions. This increasing complexity is challenging to analyse and demands sophisticated tools to drive meaningful conclusions from those data. Trait-based regression models, multivariate analyses, like principal component analyses, and plasticity indices can be used to tackle challenges with those complex investigations. But those methods have substantial limitations, like the need for high sample size, multi-dimensionality of results or the need for trait coordination in high-dimensional space, or the calculation on the population level, which might buffer or cover the de facto occurring individual effects. To improve and simplify studies on ‘whole organism’ responses, analyses, and their interpretation, we developed the Index for Adaptive Responses. This straightforward framework can unite all traits of an organism in one number. A newly developed transformation method, included in this framework, comprises a normalisation and standardisation to a baseline or control without changing the data or variance structure of the original data. We assessed the performance and accuracy of the framework with an application in an extensive predator-prey case study, with simulations and application examples using literature data. We show that the Index for Adaptive Responses respects adaptations as well as maladaptations and outperforms established approaches. The framework is robust against outliers and non-gaussian distribution. We further show that the qualitative prediction of the adaptiveness of included traits is highly accurate, even under challenging conditions, e.g., low replicate numbers. Functions and algorithms of the framework are provided with an R package but can easily be translated into other programming languages. The Index for Adaptive Responses will simplify future research on complex adaptive responses and improves our understanding of these responses’ ecological as well as evolutionary implications.

A calibrated mathematical model of antiviral immune response to SARS-CoV-2 infection is developed. The model considers the innate and antigen-specific responses to SARS-CoV-2 infection. Recently published data sets from human challenge studies with SARS-CoV-2 were used for parameter estimation. Understanding the regulation of multiple intertwined reaction components of the immune system is necessary for linking the clinical phenotypes of COVID-19 with the kinetics of immune responses. Consideration of multiple immune reaction components in a single calibrated mathematical model allowed us to address some fundamental issues related to pathogenesis of COVID-19, i.e. sensitivity of the peak viral load to parameters characterizing the specific response components, the kinetic coordination of the individual responses, and the factors favoring a prolonged viral persistence. The model provides a tool for predicting the infectivity of patients, i.e. the amount of virus which is transmitted via droplets from the person infected with SARS-CoV-2, depending on the time of infection. The thresholds in the relative unbalance between innate and adaptive response parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic response synchrony/coordination were identified.

Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pre-treated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1), by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS.

Trichoderma atroviride is a strong necrotrophic mycoparasite antagonizing and feeding on a broad range of fungal phytopathogens. It further beneficially acts on plants by enhancing growth in root and shoot and inducing systemic resistance. Volatile organic compounds (VOCs) are playing a major role in all those processes. To date, T. atroviride IMI 206040 and T. atroviride P1 are among the most frequently studied T. atroviride strains and hence are used as model organisms to study mycoparasitism and photoconidiation. However, there are no studies available, which systematically and comparatively analyzed putative differences between these strains regarding their light-dependent behavior. We therefore explored the influence of light on conidiation and the mycoparasitic interaction as well as the light-dependent production of VOCs in both strains. Our data show that in contrast to T. atroviride IMI 206040 conidiation in strain P1 is independent of light. Furthermore, significant strain-and light-dependent differences in the production of several VOCs between the two strains became evident, indicating that T. atroviride P1 could be a better candidate for plant protection than IMI 206040.

Abstract: In this study, we present an analytical tool that can be used to predict the nonlinear structural response of seaplanes advancing through sinusoidal head-sea waves. Seaplanes exhibit a unique instability phenomenon known as porpoising, which is an oscillatory motion along the heave and pitch axes that can cause serious structural damage. The heaving and pitching equations of motion are presented in the form of coupled, forced, and nonlinear Duffing-type equations with cubic nonlinearity. The analytical model developed in this study leverages the Poincaré–Lindstedt perturbation method to express the amplitude and frequency of motion in terms of all physical parameters. The accuracy and reliability of the proposed model were validated through computational fluid dynamics (CFD) simulations based on incompressible unsteady Reynolds-averaged Navier–Stokes (RANS) equations. The results show a strong agreement between the analytical tool and the CFD simulations, with minor discrepancies due to assumptions inherent in the 2D simulations, particularly the assumption that seawater only passes beneath the hull, resulting in increased buoyancy forces and reduced damping. This study offers a novel and practical method for predicting the dynamic stability of seaplanes under realistic sea conditions, potentially enhancing safety and operational efficiency by mitigating the risks associated with porpoising.

Background This study aimed to examine the acute effects of different pre-ST strategies on muscular performance and blood pressure (BP) responses in recreationally strength-trained women. Methods: Twelve overweight women with normal-to-elevated BP were recruited and performed six exper-imental protocols in a randomized order: 1) control protocol (CC) – BP assessed without exercises performed, 2) strength training (ST), 3) foam rolling warm-up followed by strength training (FR+ST), 4) specific warm-up followed by strength training (SW+ST), 5) aerobic exercise followed by strength training (AE+ST), and 6) stretching exercises followed by strength training (SE+ST). Strength training consisted of three sets at 80% of 10RM with a self-suggested rest interval between sets for bench press, back squat, bench press 45º, front squat, lat pull-down, leg press, shoulder press, and leg extension. Results: All experimental protocol had a lower total training volume, fa-tigue index, and repetitions performance in relation to ST (p

RM (red mud) was acidified with sulphuric acid and the acidified ARM (acidified red mud) was utilized as an innovative adsorption material for treating antibiotic-contained wastewater. The adsorption conditions, kinetics, isotherms, thermodynamics, and mechanism of ARM for CIP (ciprofloxacin) were investigated. Characterization of the ARM involved techniques such as scanning electron microscopy(SEM), transmission electron microscope(TEM), brunauer- emmett-teller (BET), X-ray diffraction (XRD), X-ray fluorescence (XRF), thermogravimetric analysis (TGA) and NH3-TPD analysis. Adsorption studies were conducted employing response surface methodology (RSM) for experimental design. The results showed that ARM can absorb CIP effectively. The RSM optimal experiment indicated that the most significant model terms influencing adsorption capacity were solution pH, CIP initial concentration and ARM dosage, under which the predicted maximum adsorption capacity achieved 7.30 mg/g. The adsorption kinetics adhered to a pseudo-second-order model, while equilibrium data fitted the Langmuir-Freundlich isotherm, yielding maximum capacity values of 7.35 mg/g. The adsorption process occurred non-spontaneously and absorbed heat, evidenced by ΔG0 values between 2.06 and 0.87 kJ/mol, ΔS0 at 39.41 J/mol/K, and ΔH0 at 13.8 kJ/mol. Analysis using attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) indicated there existed complex reaction between Al-O in ARM and the ester group –COO in CIP. The C=O bond in CIP was likely to undergo a slight electrostatic interaction or be bound to the internal spherical surface of ARM. The findings indicate that ARM is a promising and efficient adsorbent for CIP removal from wastewater.

Nowadays, Multi-needle electrospinning has used to be an efficient method for producing nanofiber membranes. But in the process, the fluctuation errors in electrospinning fluid flow rate have directly influence the membrane quality, which bringing instability and still have not been solved yet. For finding out the solution to the inaccurate flow control in multi-needle, it is necessary to develop a multi-stage flow runner spinneret for large-scale production of nanofiber membrane. At first, the paper uses the finite element software COMSOL to numerically simulate the polymer flow in the runner of spinneret. Based on it, the velocity field distribution curve was draw and the velocity instability coefficient of the polymer flow was attained, which are providing theoretical guidance for the optimal design of spinneret. Next, the response surface analysis method (RSM) was used to establish a regression model between the average diameter of the nanofiber membrane and the process parameters. Then, above regression model used to perform variance data processing between the average diameter and the process parameter configuration. After that, the 2D and 3D response surface profiles and the significance analysis were completed. Finally, the stability of the nanofibers production was improved, which attained the optimal adjustment of process configuration in multi-needle electrospinning.

The prevailing challenge in our current era is climate change, a crisis recognized by the global community that has prompted immediate actions to confront and mitigate its consequences. There is a consensus among scientists that human activities, driven by developmental ambitions, are the driving force behind the ongoing climate crisis. “The well-documented aftermath, including the rise in sea levels, coastal erosion, reduced agricultural yields, compromised access to clean water, and health implications, emphasizes the intricate and wide-ranging effects of climate change.” Furthermore, there is an increasing recognition that climate change gives rise to distinct social, economic, and divergent consequences. “Although all countries worldwide will undergo the impacts of climate change, the distribution of these effects will differ among regions, generations, age groups, income levels, occupations, and genders.” Notably, the adverse consequences will disproportionately impact the impoverished, predominantly situated in developing nations. “This paper explores the effects of climate change on displacement and the ensuing refugee dilemma.” It aims to scrutinize the inclusion of climate-induced displacement in the present international framework, encompassing both climate change and refugee regimes. The paper promotes a human rights-centred approach to tackling displacement stemming from climate change.

Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like te-mozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glio-blastoma sensitivity to REGO and elucidate the underlying molecular mechanisms involved in tumor resistance or responsiveness to treatment. 3D glioblastoma organoids (GB-EXPs) obtained from 18 patients’ resected recurrent glioblastoma tumors were treated with TMZ and REGO. Drug responses were evaluated using NAD(P)H FLIM, stratifying tumors as responders (Resp) or non-responders (NR). Whole-exome sequencing was performed on 16 tissue samples, and whole-transcriptome analysis on 13 GB-EXPs treated and untreated. We found 35% (n=9) and 77% (n=20) of tumors responded to TMZ and REGO, respectively, with no instances of TMZ-Resp be-ing REGO-NR. Exome analysis revealed a unique mutational profile in REGO-Resp tumors compared to NR tumors. Transcriptome analysis identified distinct expression patterns in Resp and NR tumors, impacting Rho GTPase and NOTCH signaling, known to be involved in drug response. In conclusion, recurrent glioblastoma tumors were more responsive to REGO com-pared to TMZ treatment. Importantly, our approach enables a comprehensive longitudinal ex-ploration of the molecular changes induced by treatment, unveiling promising biomarkers in-dicative of drug response.

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.

A wide variety of bioactive peptides have been identified in the central nervous system and several peripheral tissues in the ascidian Ciona intestinalis type A (Ciona robusta). However, hemocyte endocrine peptides have yet to be explored. Here, we report a novel 14-amino acid peptide, CiEMa, that is predominant in the granular hemocytes and unilocular refractile granulocytes of Ciona. RNA-seq and qRT-PCR revealed the high CiEma expression in the adult pharynx and stomach. Immunohistochemistry further revealed the highly concentrated CiEMa in the hemolymph of the pharynx and epithelial cells of the stomach, suggesting biological roles in the immune response. Notably, bacterial lipopolysaccharide stimulation of isolated hemocytes for 1-4 hours resulted in increased CiEMa secretion. Furthermore, CiEMa-stimulated pharynx exhibited mRNA upregulation of the growth factor (Fgf3/7/10/22), vanadium binding proteins (CiVanabin1 and CiVanabin3), and forkhead and homeobox transcription factors (Foxl2, Hox3, and Dbx), but not antimicrobial peptides (CrPap-a and CrMam-a) or immune-related genes (Tgfbtun3, Tnfa, and Il17-2). Collectively, these results suggest that CiEMa plays roles in signal transduction involving tissue development or repair in the immune response, rather than in the direct regulation of immune-response genes. The present study identified a novel Ciona hemocyte peptide, CiEMa, providing insights into the molecular and functional diversity of the immune response in chordates.

Micro/Nano Robot is an intelligent and efficient microrobot that can perform specific tasks under the influence of external stimuli. Depending on the application scenarios, the microrobot can adaptively transform into appropriate functional forms under different external stimuli, thus perfectly matching the needs. To date, microbots have been widely used in targeted therapy, drug delivery, tissue engineering, environmental remediation, and other fields. Although the applications of microrobots are promising, there are only a few reviews that can focus on the preparation methods and driving mechanisms. Therefore, it is necessary to outline the current status of the development of these microrobots in order to provide some new insights for the further development of the field. Therefore, this paper reviews the research progress of microrobots in terms of preparation methods, stimulus response mechanisms and applications, and highlights the applicability of different preparation methods and stimulus types. Finally, the current challenges faced by microrobots are highlighted and possible solutions are proposed to facilitate the practical application of microrobots.

In recent years, the emergence of the concept of immunometabolism has shed light on the pivotal role that cellular metabolism plays in both the activation of immune cells and the development of immune programs. The antiviral response, a widely distributed defense mechanism used by infected cells, serves to not only control infections but also to attenuates their deleterious effects. The exploration of the role of metabolism in orchestrating the antiviral response represents a burgeoning area of research, especially considering the escalating incidence of viral outbreaks coupled with the increasing prevalence of metabolic diseases. Here, we present a review of current knowledge regarding immunometabolism and the antiviral response during viral infections. Initially, we delve into the concept of immunometabolism by examining its application in the field of cancer—a domain that has long spearheaded inquiries into this fascinating intersection of disciplines. Subsequently, we explore examples of immune cells whose activation is intricately regulated by metabolic processes. Progressing with a systematic and cellular approach, our aim is to unravel the potential role of metabolism in antiviral defense, placing significant emphasis on the innate and canonical interferon response.

Atopic dermatitis (AD), a T2 inflammatory skin condition, is widely recognized as one of the most prevalent chronic and recurrent skin disorders. One of the most effective therapy for treating moderate-to-severe AD is Dupilumab, a monoclonal antibody that blocks both IL-4 and IL-13 signaling. At the same time, no comprehensive analysis of cytokines profile was made in AD patients undergoing Dupilumab therapy. The primary objective of our research was to examine the levels of main cytokines to better understanding systemic immune response in AD and to identify potential biomarkers of the effectiveness of Dupilumab treatment. AD patients demonstrated significant clinical improvements one year after initializing of Dupilumab therapy. We identified 16 cytokines that showed major difference between Dupilumab-treated patients and patients without Dupilumab therapy. Six cytokines showed correlation with AD severity and the efficacy of Dupilumab therapy. Jointly revealed cytokines could potentially predict the effectiveness of Dupilumab treatment and help to choose the precision target therapy in AD patients as well.

In the dairy cattle sector, the evaluation of the effects induced by heat stress is still one of the most impactful and investigated aspects as it is strongly connected to both sustainability of the production and animal welfare. On the other hand, more recently, the possibility of collecting large dataset made available by the increasing technology diffusion is paving the way for the application of advanced numerical techniques based on machine learning or big data approaches. In this scenario driven by rapid change there could be the risk of dispersing the relevant information represented by the physiological animal component, which should maintain the central role in the development of numerical models and tools. In the light of this, the present literature review aims to consolidate and synthesize existing research on the physiological consequences of heat stress in dairy cattle. The present review provides, in a single document, an overview as complete as possible of the heat stress-induced responses in dairy cattle with the intent of filling the existing research gap for extracting the veterinary knowledge present in the literature and make it available to those who are developing numerical models and tools.

Radiotherapy is the primary treatment modality for non-metastatic nasopharyngeal carcinoma (NPC) across all TNM-stages. Locoregional control rates have been impressive even from the 2D-radiotherapy (RT) era, except when the ability to deliver optimal dose coverage to the tumor is compromised. However, short- and long-term complications following head and neck RT are potentially debilitating, and thus, there had been much research investigating technological advances in RT delivery over the past decades, with the primary goal of limiting normal tissue damage. On this note, with a plateau in gains of therapeutic ratio by modern RT techniques, future advances have to be focused on individualization of RT, both in terms of dose prescription and delineation of target volumes. In this review, we analyzed the guidelines and evidence related to contouring methods, and dose prescription for early and locoregionally-advanced (LA-) NPC. Next, with the preference for induction chemotherapy (IC) in patients with LA-NPC, we assessed the evidence concerning radiotherapy adaptations guided by IC response, as well as functional imaging and contour changes during treatment. Finally, we discussed on RT individualization that is guided by EBV DNA assessment, and its importance in the era of combinatorial immune checkpoint blockade therapy with RT.

This paper presents a novel approach for individual design perception modeling using the YUKI-trained Fuzzy Inference System. The study focuses on understanding how individuals perceive design based on personality traits, particularly openness to experience. The proposed YUKI algorithm optimizes the FCM clustering algorithm, enhancing its ability to handle uncertain and imprecise data. The YUKI-trained FIS generates several Sugeno-type FIS models to predict design perception, to minimize the Root Mean Squared Error between the model prediction and the actual design perception of participants. The results demonstrate that the YUKI-trained FIS offers more accurate predictions compared to the traditional FCM-trained FIS, and the RMSE values for individual design perceptions fall within a satisfactory range of 0.84 to 1.32. The YUKI-trained FIS proves effective in clustering individuals based on their level of openness, providing insights into how personality traits influence design perception.

In their natural environment, bacteria are exposed to various stresses. The stress-response sigma factor SigB of gram-positive Bacillus subtilis is the best-characterized example. Unlike Bacillus subtilis, the gram-positive bacterium Streptomyces coelicolor A3(2) contains nine SigB homologues (SigBFGHIKLMN) with a major role in differentiation and response to osmotic stress. We previously constructed a two-plasmid system to identify promoters recognized by these sigma factors. Interestingly, almost all identified promoters were recognized by two or more SigB homologues. However, no specific sequences characteristic for these recognition groups were found. To examine this cross-recognition in vivo in S. coelicolor A3 (2), one of these promoters was cho-sen, which drives the expression of the sporulation-specific gene ssgB. The ssgBp promoter was inserted into a luciferase reporter plasmid and conjugated to S. coelicolor M145 and nine mutant strains containing deleted individual sigB homologous genes. Luciferase reporter activity indi-cated differential activity of this promoter in these mutant strains, suggesting overlapping pro-moter recognition by these SigB homologues. To determine which nucleotides in the ̶ 10 re-gion are responsible for the selection of a specific SigB homologue, several mutant promoters with altered last three nucleotides in this region were prepared and tested in the two-plasmid system. Some mutant promoters were specifically recognized by some SigB homologues. Mutant promoters were inserted into a luciferase reporter plasmid and conjugated to S. coelicolor A3(2) and these nine mutant strains. Luciferase reporter activity indicated differential activity of these ssgBp mutant promoters, indicating overlapping promoter recognition by these SigB homologues in S. coelicolor A3(2).

Studies evaluating candidate tick-derived proteins as anti-tick vaccines in natural hosts have been limited due to high costs. To overcome this problem, animal models are used in immunization tests. The aim of this article was to review the use of rabbits as an experimental model for the evaluation of tick-derived proteins as vaccines. A total of 57 tick proteins have been tested for their immunogenic potential using rabbit as model for vaccination. The most commonly used rabbit breeds were New Zealand (73.8%), Japanese white (19%), Californians (4.8%) and Flemish lop-eared rabbit (2.4%). Anti-tick vaccines efficacy resulted in up to 99.9%. Haemaphysalis longicornis (17.9%) and Ornithodoros moubata (12.8%) were the most common tick model in vaccination trials. Experiments in rabbits have revealed that some proteins (CoAQP, OeAQP, OeAQP1, Bm86, GST-Hl, 64TRP, serpins and voraxin) can induce immune responses against various tick species. In addition, in some cases it was possible to determine that the vaccine efficacy in rabbits was similar to experiments performed in natural hosts (e.g. Bm86, IrFER2, RmFER2, serpins and serine protease inhibitor). In conclusion, results have shown that prior to performing anti-tick vaccination trials using natural hosts, rabbits can be used as suitable experimental models for these studies

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). The current vaccine strategy for KTRs seems to be unable to provide effective protection against coronavirus disease 2019 (COVID-19) [2] and the occurrence of severe COVID-19 in some vaccinated KTRs suggested a lack of immunity. We analized here the antibody response in a group of 32 kidney transplant recipients (KTR) followed at the Nephrology and Dialysis unit of the Hospital Pio XI of Desio, Italy, compared with a group of 23 healthy workers classified as Late responders (HCW-LR) (10 males age 27-62) and 13 females (age 46-64). We observed that the patients need additional vaccine boosters due to their immunocompromised status and therapy to protect them from infections related to viral variants, in accordance with the literature.

The objective of this study was to evaluate the glycemic index and the satiety response of three Mexican kinds of honey. The values of fructose ranged from 272.40-395.10 g/kg, while the glucose value ringed 232.20-355.50 g/kg. The ratio F/G of sample honey was 1.45, 1.00, and 1.17 for Highland, Multifloral, and Avocado honey, respectively. Twenty-six participants completed this study, which was previously approved by the ethics committee of the Facultad de Salud Pública y Nutrición (CE 2/2018-19). Highland and Avocado honey is classified as medium-GI (69.204.07 and 66.365.74, respectively), while Multifloral honey is classified as high-GI (74.245.98). The Highland honey presented the best satiety response. The difference in IG values and the effect of the satiety response of Highland honey could be explained by the different fractions of carbohydrates in samples and other components such as phytochemicals.

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

Antimicrobial peptides (AMPs) can directly kill Gram-positive bacteria, Gram-negative bacteria, mycobacteria, fungi, enveloped viruses and parasites. At sublethal concentrations some AMPs and also conventional antibiotics can stimulate bacteria response to increase their resilience, also called the hormetic response. That can include stimulation of growth, mobility, and biofilm production. Here, we have discovered AMPs that stimulate the growth of certain mycobacteria. Peptide 14 for example showed growth stimulating effect on M. tuberculosis, M. bovis, M. avium subsp. paratuberculosis (MAP), M. marinum, M. avium-intracellulare, M. celatum and M. abscessus. The effect was more pronounced at low bacterial inocula. The peptides induce a faster transition from the lag phase to the log phase and keep the bacteria longer in the log phase before entering the stationary phase compared to non treated control. In some cases, an increase in the division rate was observed. An initial screen using MAP and a collection of 75 peptides revealed 13 peptides with a hormetic effect. For M. tuberculosis a collection of 25 artificial peptides were screened and 9 were found to reduce the time to positivity (TTP), improving growth. A screen of 43 naturally occurring peptides, 11 fragments of naturally occurring peptides and 5 designed peptides, all taken from the APD3, identified a further 44 peptides that also lowered TTP by at least 5%. Lasioglossin LL-III (Bee) and Ranacyclin E (Frog) were the most active natural peptides, the human cathelicidin LL37 fragment GF-17 and a porcine cathelicidin protegrin-1 fragment was the most active fragment of naturally occurring peptides. Peptide 14 showed growth-stimulating activity between 50 ng/ml and 10 µg/ml whereas the stability-optimised peptide 14D had a narrow activity range of 0.1 - 1 µg/ml. Peptides identified in this study are now part of novel products improving the diagnosis of mycobacteria in humans and animals.

Electricity generation from renewable energy sources is emerging as a result of global carbon emission reduction policies. However, most renewable energy sources are non-dispatchable and cannot be adjusted to meet the fluctuating electricity demands of society. A flexible operation process has been proposed as an effective solution to compensate for the unstable nature of renewable energy sources. Thermal load fluctuations during flexible operation may cause creep-fatigue damage to the high-temperature components of thermal power plants, as they are designed with a focus on creep damage under a constant power level. This study investigated the residual life of high-temperature components, such as a superheater tube and a reheater header, to failure under flexible operation conditions using finite element analysis and empirical models. First, we determine an analytical solution for the straightened superheater tube under thermal conditions and compare it with the numerical solution to verify the numerical models. Through the verified finite element model, the creep-fatigue life of the reheater header is estimated by considering flexible operation factors and employing the Coffin-Manson and Larson-Miller models. Although fatigue damage increases with decreasing minimum load and ramp rate, we confirmed that creep damage significantly affects the residual life during flexible operation. In addition, a surrogate model was proposed to evaluate the residual life of the reheater as a function of the flexible operation factors using the machine learning methodology, based on the results of finite element methods. It can be used to predict its residual life without performing complex thermal-structure analysis and relying on empirical models for fatigue and creep life. We expect our findings to contribute to the efficient operation of thermal power plants by optimizing the flexible operation factors.

Minute Virus of Mice (MVM) is an autonomous parvovirus of the Parvovirus family that replicates in mouse cells and transformed human cells. MVM genomes localize to cellular sites of DNA damage with the help of their essential non-structural phosphoprotein NS1 to establish viral replication centers. MVM replication induces a cellular DNA damage response that is mediated by signaling through the ATM kinase pathway, while inhibiting induction of the ATR kinase signaling pathway. However, the cellular signals regulating virus localization to cellular DNA damage response sites has remained unknown. Using chemical inhibitors to DNA damage response proteins, we have discovered that NS1 locallization to cellular DDR sites is independent of ATM or DNA-PK signaling, but is dependent on ATR signaling. Pulsing cells with an ATR inhibitor after S-phase entry leads to attenuated MVM replication. These observations suggest that the initial localization of MVM to cellular DDR sites depends on ATR signaling before it is inactivated by vigorous virus replication.

Background: Different investigations have shown an association between the eating behavior of children and adolescents, and their nutritional status. The objective is to identify eating behavior patterns associated with nutritional status diagnosed by anthropometry in a sample of Spanish schoolchildren. Methods: A cross-sectional study in 283 Spanish schoolchildren (6 to 16 years old). Methods: The sample was assessed anthropometrically by Body Mass Index (BMI), Waist-to height ratio (WHtR) and body fat percentage (%BF). Eating behavior was analyzed using the CEBQ "Children's Eating Behavior Questionnaire" answered by parents or guardians. Results: A positive association was found between excess weight, abdominal obesity, high adiposity, lower scores in anti-intake subscales and higher scores in pro-intake subscales. These were mainly associated with lower satiety response, higher food intake, higher food enjoyment, higher eating speed, and emotional overeating. Conclusion: Our results support the usefulness of the CEBQ as an easy-to-use tool to identify eating behaviors associated with the development of childhood and adolescent obesity. Its use in future research could help to understand behavioral phenotypes in schoolchildren and guide nutrition education and obesity prevention initiatives

Human trafficking is the third most lucrative form of trafficking in the world (just behind drugs and counterfeit goods). Multiple outbreaks of unrest between October 2016 and August 2017 in the Rakhine State of Myanmar triggered around 745,000 influxes of Rohingyas crossing into Bangladesh through the border boundaries at Teknaf and Ukhiya sub-districts of Cox’s Bazar. In this regard the media confirmed that over a thousand Rohingya people particularly women and girls were victims of human traffickers. This research aims to explore the underlying cause of human trafficking (HT) during emergency response and seeks how the knowledge and capacity of the refugee, local administration and law enforcement agencies in Bangladesh can be improved in promoting counter trafficking (CT) and safe migration processes. In order to achieve the objectives, this research starts with reviewing acts, rules, policies and action plans of the Government of Bangladesh on the HT, CT and safe migration processes. Then, a case study method has been applied to present ongoing the CT and safe migration programs of a NGO called Young Power in Social Action (YPSA) that received funding and technical support from the International Organization of Migration (IOM) for this purpose, the research in this paper will later evaluate the effectiveness of the program through conducting key informant interviews (KII) and focus group discussion (FGDs) with beneficiary and non-beneficiary participants from refugees, law-enforcing agencies (LEA) and non-governmental organizations’ (NGOs) in Teknaf, and Ukhyia sub-districts in Bangladesh. Thus, this research identified program level strengths and weaknesses in relation to the CT, and safe migration process and provide key directions how they can be improved.

When exposed to a viral infection, the attacked cells promptly set up defence mechanisms. Part of antiviral responses, the innate immune interferon pathway and associated interferon stimulated genes are notably allowing the production of proteins bearing an antiviral activity. Numerous viruses are able to evade the interferon response, highlighting the importance of controlling this pathway to ensure their efficient replication. Several viruses are also known to manipulate the metabolism of infected cells to optimize the availability of amino acids, nucleotides and lipids. They then benefit from a reprogramming of the metabolism that favours glycolysis instead of mitochondrial respiration. Given the increasingly discussed crosstalk between metabolism and innate immunity, we wondered whether this switch from glycolysis to mitochondrial respiration would be beneficial or deleterious for an efficient antiviral response. We used a cell based model of metabolic reprogramming. Interestingly, we showed that increased mitochondrial respiration was associated with an enhanced interferon response following poly:IC stimulation. This suggests that during viral infection, the metabolic reprogramming towards glycolysis is also part of the virus' strategies to inhibit the antiviral response.