Background: Current prostate cancer evaluation can be inaccurate and burdensome. Quantitative evaluation of MRI sequences non-invasively helps prostate tumor assessment. However, including Dynamic Contrast Enhancement in the examined MRI sequence set can add complications, inducing possible side effects from the IV placement or injected contrast material, and prolongs scanning time. Purpose: Predict the risk of developing Clinically Significant (Insignificant) prostate cancer CsPCa (CiPCa) and International Society of Urologic Pathology (ISUP) grade using processed Signal to Clutter Ratio (SCR) derived from spatially registered bi-parametric MRI (SRBP-MRI) and thereby enhance non-invasively management of prostate cancer. Methods: This pilot study retrospectively analyzed 42 consecutive prostate cancer patients from the PI-CAI data collection. BP-MRI (Apparent Diffusion Coefficient, High B-value, T2) were resized, translated, cropped, and stitched to form spatially registered SRBP-MRI. Efficacy of noise reduction was tested by regularizing, eliminating principal components (PC), and minimizing elliptical volume from the covariance matrix to optimize the SCR. MRI guided biopsy (MRBx), Systematic Biopsy (SysBx), combination (MRBx+SysBx), or radical prostatectomy determined the ISUP grade for each patient. ISUP grade >=2 (<2) was judged as CsPCa (CiPCa). Linear and Logistic regression were fitted to ISUP grade and CsPCa/CiPCa SCR. Correlation Coefficients (R) and Area Under the Curves (AUC) for Receiver Operator Curves (ROC) evaluated the performance. Results: High correlation coefficients (R) (>0.55) and high AUC (=1.0) for linear and/or logistic fit from processed SCR and z-score for SRBP-MRI greatly exceed fits using prostate serum antigen, prostate volume, and patient age (R~0.17). Patients assessed with combined MRBx+SysBx and from individual MRI scanners achieved higher R (R=0.207+/-0.118) than using all patients in the fits. Conclusions: In the first study to date to apply and test hyperspectral approaches for assessing tumor aggressiveness on SRBP-MRI, high values of R and exceptional AUC to fit the ISUP grade and CsPCA/CiPCA were comparable or better than those from artificial intelligence in other studies.

Cancer is considered nowadays one of the main causes of human death worldwide, being characterized by an alteration of the oxidative metabolism. Many natural compounds with anti-tumor attributes have been described, many of them from plant origin. Among them, capsaicin, which is the molecule responsible for the pungency in hot pepper fruits, has been reported to show antioxidant, anti-inflammatory and analgesic activities, as well as anti-proliferative properties against cancer. Thus, in this work the potential anti-proliferative activity of pepper (Capsicum annuum L.) fruits from diverse varieties with different capsaicin content (California < Piquillo < Padrón < Alegría riojana) against several tumor cell lines (lung, melanoma, hepatoma, colon, breast, pancreas, and prostate) has been investigated. The results showed that the capsaicin content in pepper fruits did not correspond with their anti-proliferative activity against tumor cell lines. By contrast, the greatest activity was promoted by the pepper tissues which contained the lowest capsaicin amount. This indicates that other compounds different from capsaicin have this anti-tumor potentiality in pepper fruits. Based on this, green fruits from the variety Alegría riojana, which has negligible capsaicin levels, was used to study the effect on the oxidative and redox metabolism of tumor cell lines from liver (Hep-G2) and pancreas (MIA PaCa-2). Different parameters from both lines treated with pepper fruit crude extracts were determined including, among others, protein nitration and protein S-nitrosation (two post-translational modifications (PTMs) promoted by nitric oxide), the antioxidant capacity, as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX). Besides, the activity of the NADPH-generating enzymes glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and NADP-isocitrate dehydrogenase (NADP-ICDH) was followed. Our data revealed that the treatment of both cell lines with pepper fruit extracts altered their antioxidant capacity, enhanced the catalase activity, and considerably reduced the activity of the NADPH-generating enzymes. As a consequence, less H2O2 and NADPH seem to be available to cells, thus avoiding cell proliferation and possibly triggering cell death in both cell lines.

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by persistent deficits in social interaction and communication, repetitive movements, abnormal focusing on objects, or activity that can significantly affect the quality of life of the afflicted. Brain neuronal and glial cells have been implicated. It has a genetic component but can also be triggered by environmental factors or drugs. For example, prenatal exposure to valproic acid (VPA) or acetaminophen (APAP) or ingestion of propionic acid (PPA) can increase the risk of ASD. Recently, epigenetic influences on ASD have been brought to the forefront of investigations on the etiology, prevention, and treatment of this disorder. Epigenetics refers to DNA modifications that alter gene expression without making any changes to the DNA sequence. Although an increasing number of pharmaceuticals and environmental chemicals are being implicated in the etiology of ASD, here we specifically focus on the molecular influence of the above-mentioned drugs on epigenetic alterations in neuronal and glial cells and their potential connection to ASD. It is concluded that a better understanding of these phenomena can lead to more effective interventions in ASD.

Metabolic dysfunction associated fatty liver disease (MAFLD) has gained worldwide attention as a public health problem. Nonetheless, lack of enough mechanistic knowledge restrains effective treatments. It is known that T3 regulate hepatic lipid metabolism, and mitochondrial function. Liver dysfunction of T3 contributes to MAFLD, but its role is not fully understood. Objective: To evaluate the role of T3 dysfunction in the progression of MAFLD in an animal model. Method-ology: Male/adult Sprague Dawley rats (n=20) were allocated to a control group (standard di-et–2.93kcal/g) and diet group (CDHF–4.3kcal/g). Euthanasia took place in the 28th week. D3 ac-tivity and expression, UCP2 and D1 expression, REDOX status, mitochondrial, Krebs cycle and endoplasmic reticulum homeostasis in liver tissue were measured. Results: We observed an in-crease in D3 activity/expression (P<0.001) related to increased TBARS and carbonyls and GSH reduction in the MAFLD group (P<0.05). There was a T3-dependent decrease in UCP2 expression (P=0.01), mitochondrial capacity, respiratory activity with increased endoplasmic reticulum stress in the MAFLD group (P < 0.001). Surprisingly, in and environment with lower T3 levels we observed an augmented alpha-ketoglutarate dehydrogenase (KGDH) and glutamate dehydro-genase (GDH) enzymes activity (P<0.05). Conclusion: Induced D3, triggered by changes in the REDOX state, decreases T3 availability, and hepatic mitochondrial capacity. The Krebs cycle en-zymes were altered as well as reticulum stress. Taken together, these results shed new light on the role of T3 metabolism in MAFLD and new treatment opportunities.

Abstract: Toxicity of emerging organic pollutants to photosystems of aquatic plants are still not well clarified. This study aimed to develop a novel ecotoxicological experimental protocol based on nanoscale electrochemical mapping of photosynthetic oxygen evolution of aquatic plants by SECM (scanning electrochemical microscopy). The protocol was also checked by confocal laser scanning microscopy (CLSM), the traditional Clark oxygen electrode method and chlorophyll fluorescence technique. The typical persistent organic pollutant 2,4-dichlorophenol (2,4-DCP) in water environment and the common aquatic Microsorium pteropus (M. pteropus) were chosen as the model organic pollutant and tested plant, respectively. It was found that the SECM method could well discriminated the responses of stoma micromorphology and spatial pattens of photosynthetic oxygen evolution on single stoma. The shape of stoma blurred with increasing 2,4-DCP concentration, which was in good agreement with the CLSM images. The dose-response curves and IC50 values obtained from the SECM data were verified by the data measured by the traditional Clark oxygen electrode method and chlorophyll fluorescence test. The IC50 value of single stoma oxygen emission of 24 h exposed plant leave, which was derived from the SECM current data (32535 μg L-1), was close to those calculated from the maximum photosynthetic efficiency (Fv/Fm) measured by chlorophyll fluorescence test (33963 μg L-1), and the Clark oxygen electrode method photosynthetic oxygen evolution rate (32375 μg L-1). The 72 h and 96 h 2,4-DCP exposure data further confirmed the reliability of the nanoscale stoma oxygen emission mapping methodology for ecotoxicological assessment. In this protocol, the procedures for how to collect effective electrochemical data and how to extract useful information from the single stoma oxygen emission pattern were well established. This study showed that SECM is a feasible and reliable ecotoxicological tool for evaluation of toxicity of organic pollutants to higher plants with unique nanoscale visualization advantage over the conventional methods.

Gas and power networks are tightly coupled and interact with each other due to physically interconnected facilities. In an integrated gas and power network, a contingency observed in one system may cause iterative cascading failures, resulting in network wide disruptions. Therefore, understanding the impacts of the interactions in both systems is crucial for governments, system operators, regulators and operational planners, particularly, to ensure security of supply for the overall energy system. Although simulation has been widely used in the assessment of gas systems as well as power systems, there is a significant gap in simulation models that are able to address the coupling of both systems. In this paper, a simulation framework that models and simulates the gas and power network in an integrated manner is proposed. The framework consist of a transient model for the gas system and a steady state model for the power system based on AC-Optimal Power Flow. The gas and power system model are coupled through an interface which uses the coupling equations to establish the data exchange and coordination between the individual models. The bidirectional interlink between both systems considered in this studies are the fuel gas offtake of gas fired power plants for power generation and the power supply to LNG terminals and electric drivers installed in gas compressor stations and underground gas storage facilities. The simulation framework is implemented into an innovative simulation tool named SAInt (Scenario Analysis Interface for Energy Systems) and the capabilities of the tool are demonstrated by performing a contingency analysis for a real world example. Results indicate how a disruption triggered in one system propagates to the other system and affects the operation of critical facilities. In addition, the studies show the importance of using transient gas models for security of supply studies instead of successions of steady state models, where the time evolution of the line pack is not captured correctly.

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances which have investigated the contribution of cell intrinsic mechanisms as well as of the immune system to myeloid leukemogenesis in this specific subset of AML. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes for these patients

Due to the extraordinary mechanical properties of ultra-high-performance concrete (UHPC), the shear stirrups in UHPC beams could potentially be removed. The aim of this study is to determine the effect of beam height and steel fiber volume content on the shear behavior of non-stirrup UHPC beams under a larger shear span-depth ratio (up to 2.8). Eight beams were designed and fabricated, including six non-stirrup UHPC beams and two comparing stirrup-reinforced normal concrete (NC) beams. The experimental results demonstrated that the volume content of steel fiber could be a crucial factor affecting the ductility, cracking strength, and shear strength of non-stirrup UHPC beams and altering their failure modes. Additionally, the height of the beam had a considerable effect on its shear resistance. This study revealed that the French standard formulae were more accurate for the UHPC beams with larger shear span-depth ratios and PCI-2021 formulae greatly overestimate the shear capacity of UHPC beams with larger shear span-depth ratios. Xu’s formulae were more accurate for the steel fiber-reinforced UHPC beams with larger shear span-depth ratios.

Long span cable-stayed bridge is the main bridge type with a span of more than 400 meters. It is generally designed as a double tower long-span structure with good spanning capacity and economic performance. Wind resistance safety performance is the main index to control the long-span cable-stayed bridge structure. During the operation of long-span cable-stayed bridge structure, because the service life of the cable is far less than the design life of the structure, the wind resistance performance of the structure will inevitably deteriorate significantly, which will seriously affect the structural service performance of symmetric cable-stayed bridge. Based on symmetric reliability theory, this paper takes flutter and static wind stability of long-span cable-stayed bridge structure as the main design control index, uses positive reliability theory to calculate the reliability index of symmetric cable-stayed bridge structure, uses inverse reliability theory to calculate the safety factor of symmetric cable-stayed bridge structure, and evaluates the wind resistant time-varying performance of long-span cable-stayed bridge structure by comprehensively considering the reliability index and safety factor. Taking a practical project of a long-span cable-stayed bridge as a specific case, the wind resistant time-varying reliability of the bridge during its operation for more than 30 years is analyzed, and the parameter sensitivity is analyzed. The results show that the wind resistance performance of the cable-stayed bridge structure is obviously affected by the cable, and the degradation of the cable performance will have an important impact on the wind resistance time-varying performance of the structure, especially the critical wind speed of the structure has obvious time-varying characteristics. The safety factor and reliability index can objectively evaluate the wind resistance time-varying performance of the long-span cable-stayed bridge structure.

Ant rescue behaviour belongs to the most interesting subcategories of prosocial and altruistic behaviour encountered in the animal world. Several studies suggested that ants are able to identify what exactly restrains the movements of another individual and to direct their rescue behaviour precisely to that object. To shed more light on the question how precise is the identifi-cation of the source of restraint of another ant, we investigated rescue behaviour of workers of the red wood ant Formica polyctena using a new version of an artificial snare bioassay in which a nestmate victim was bearing on its body two wire loops, one placed on the petiole and acting as a snare, and an additional one on the leg. The tested ants did not direct preferentially their rescue behaviour to the snare. Moreover, the overall strategy adopted by the most active rescuers was not limited to precisely targeted rescue attempts directed to the snare, but consisted of attempts to find a solution to the victim’s problem through frequent trial-and-error switching between various subcategories of rescue behaviour. These findings highlight the importance of precise identifica-tion of cognitive processes and overall behavioural strategies for better understanding of causal factors underlying animal helping behaviour.

The interactions of chemotherapeutic drugs with nanocage protein apoferritin (APO) are the key features in the effective encapsulation and release of highly toxic drugs in APO-based controlled drug delivery systems. The encapsulation enables mitigating the drugs side effects, collateral damage to healthy cells, and adverse immune reactions. Herein, the interactions of anthracycline drugs with APO were studied to assess the effect of drug lipophilicity on their encapsulation excess n and in vitro activity. Anthracycline drugs, including doxorubicin (DOX), epirubicin (EPI), daunorubicin (DAU), and idarubicin (IDA), with lipophilicity P from 0.8 to 15, were investigated. We have found that in addition to hydrogen-bonded supramolecular ensemble formation with n = 24, there are two other competing contributions that enable increasing n under strong polar interactions (APO(DOX)) or under strong hydrophobic interactions (APO(IDA) of the highest efficacy). The encapsulation/release processes were investigated using UV-Vis, fluorescence, circular dichroism, and FTIR spectroscopies. In vitro cytotoxicity/growth inhibition tests and flow cytometry corroborate high apoptotic activity of APO(drugs) against targeted MDA-MB-231 adenocarcinoma and HeLa cancer cells, and low activity against non-tumorigenic MCF10A cells, demonstrating targeting ability of nanodrugs. A model for molecular interactions between anthracyclines and APO nanocarriers was developed, and the relationships derived compared with experimental results.

Heavy metals constitute pollutants particularly common in air, water, and soil. They are present in both urban and rural environments, on land and in marine ecosystems, causing serious environmental problems since they do not degrade easily, remain almost unchanged for long periods, and bioaccumulate. Detection, though especially quantification, is a systematic process as monitoring of their levels needs to be carried out at regular intervals since there is often seasonal variation. The need for rapid and low-cost determination of metals is therefore considerable. In the present study atomic absorption spectroscopy (AAS), using a flame or graphite furnace, and square wave anodic stripping voltammetry (SWASV), using a bismuth thin film electrode, a sensitive voltammetric method is being compared and analytically validated. Atomic absorption spectroscopy (AAS) represents a well-established analytical technique while anodic stripping voltammetry is being criticized for its applicability in complicated sample matrices such as soil samples. This sample-handling challenge is being investigated in the present study. The results show that both methods AAS and ASV were satisfactorily correlated and showed that the concentration of metals is lower than the limit values, but with increasing trend. Therefore, continuous monitoring of metal levels in the urban complex of the city is necessary and a matter of great importance. Regarding Cd, the detection limits of Cd are lower compared to those of AAS when using the graphite furnace, while an overestimation was noted when using flame-AAS in comparison with those found with SWASV. The SWASV method has the advantage of being cheaper and faster, enabling the simultaneous determination of heavy elements across the range of concentrations that these elements can occur in Mediterranean soils. Additionally, we applied a dsDNA-modified electrode which can be used in the speciation analysis of Cu(I) and Cu(II). The changes in the characteristic peaks of guanine and adenine can be applied in the redox speciation analysis of copper in soil which represents an issue of great importance.

Acetaminophen use during pregnancy and early childhood was accepted in the 1970s, but is now a subject of considerable concern. Careful analysis shows that initial acceptance of the drug was based on false assumptions and ignorance of the impact of the drug on brain development. Fourteen studies now indicate that prenatal exposure to acetaminophen is associated with neurodevelopmental problems. Based on corrections for confounding factors applied to the analyses of available data, it can be concluded that prenatal exposure to acetaminophen causes statistically significant risks of one subtype of autism spectrum disorder (ASD), developmental delays, and attention deficit hyperactivity disorder. In contrast, data regarding postnatal exposure to acetaminophen are limited, and several factors impede a classic multivariate analysis of data to resolve the issue. However, circumstantial evidence regarding postnatal exposure to the drug is abundant, and it can be concluded beyond a reasonable doubt that postnatal exposure to acetaminophen in susceptible children is responsible for many if not most cases of ASD. Circumstantial evidence includes at least three otherwise unexplained temporal relationships, data from laboratory animal studies, several miscellaneous and otherwise unexplained correlations, and the lack of alternative suspects that fit the evidence-derived profile.

Abstract: Objective: We aimed to look for the mortality of Black and White Neonates and compare the Black and White neonates' mortalities after stratifying the population by many significant epidemiologic and hospital factors. We utilized the National Inpatient Sample (NIS) dataset over seven years from 2012 through 2018 for all neonates ≤ 28 days of age in all hospitals in the USA. Design/Method: We utilized the National Inpatient Sample (NIS) dataset over seven years from 2012 through 2018 for all neonates ≤ 28 days of age in all hospitals in the USA. Neonatal characteristics used in the analysis included ethnicity, sex, household income, and type of healthcare insurance. Hospital characteristics were urban teaching, urban non-teaching, and rural. Hospital location was classified according to the 9 U.S. Census Division regions. Results: Neonatal mortality continues to be higher in Black: 21,975 (0.63%) and in White was: 35495 (0.28%), Government-supported health insurance was significantly more among Black populations when compared to White (68.8% vs. 35.3% p<0.001). Household income differed significantly; almost half (49.8%) of the Black population has income ≤ 25th percentile vs. 22.1% in White. There was a significant variation in mortality in different U.S. locations. In the Black population, the highest mortality was in the West North Central division (0.72%), and the lower mortality was in the New England division (0.51%), whereas in the White population, the highest mortality was in the East South-Central division (0.36%), and the lowest mortality was in the New England division (0.21%). Trend analysis showed a significant decrease in mortality in Black and White populations over the years, but when stratifying the population by sex, types of insurance, the household income, the type of hospitals, the mortality was consistently higher in Black groups throughout the study years, Conclusions: Disparities in neonatal mortality continue to be higher in Black; There was a significant variation in mortality in different U.S. locations. In the Black population, the highest mortality was in the West North Central division, and the lower mortality was in the New England division, whereas in the White population, the highest mortality was in the East South-Central division, and the lowest mortality was in the New England division. There has been a significant decrease in mortality in Black and White populations over the years, but when stratifying the population by many significant epidemiologic and hospital factors, the mortality was consistently higher in Black groups throughout the study years.

In the context of improving aircraft safety, this study focuses on the development and evaluation of a graphene-based ice detection system using an environmental chamber. The research is driven by the need for more accurate and efficient ice detection methods, crucial in mitigating in-flight icing hazards. The methodology employed involves testing flat graphene-based sensors in a controlled environment, simulating a variety of climatic conditions that could be experienced in an aircraft during its entire flight. The environmental chamber enabled precise manipulation of temperature and humidity levels, thereby providing a realistic and comprehensive test bed for sensor performance evaluation. The results were significant, revealing the graphene sensors’ heightened sensitivity and rapid response to the subtle changes in environmental conditions, especially the critical phase transition from water to ice. This sensitivity is the key to detecting ice formation at its onset, a critical requirement for aviation safety. The study concludes that graphene-based sensors, tested under varied and controlled atmospheric conditions, exhibit a remarkable potential in enhancing ice detection systems for aircraft. Their lightweight, efficient and highly responsive nature makes them a superior alternative to traditional ice detection technologies, paving the way for more advanced and reliable aircraft safety solutions.

The 2-oxoglutarate dehydrogenase complex (OGDHc) is a key enzyme in the TCA cycle and represents one of the major regulators of mitochondrial metabolism through NADH and reactive oxygen species levels. The OGDHc impacts cell metabolic and cell signaling pathways through the coupling of 2-oxoglutarate metabolism to gene transcription related to tumor cell proliferation and aging. DHTKD1 is a gene encoding 2-oxoadipate dehydrogenase (E1a), which functions in the L-lysine degradation pathway. The potentially damaging variants in DHTKD1 have been associated to the (neuro) pathogenesis of several diseases. Evidence was obtained for the formation of a hybrid complex between the OGDHc and E1a, suggesting a potential cross talk between the two metabolic pathways and raising fundamental questions about their assembly. Here we reviewed the recent findings and advances in understanding of protein-protein interactions in OGDHc and 2-oxoadipate dehydrogenase complex (OADHc), an understanding that will create a scaffold to help design approaches to mitigate the effects of diseases associated with dysfunction of the TCA cycle or lysine degradation. A combination of biochemical, biophysical and structural approaches such as chemical cross-linking MS and cryo-EM appears particularly promising to provide vital information for the assembly of 2-oxo acid dehydrogenase complexes, their function and regulation.

The primary objective of this study is to synthesize, elucidate the structural properties, and ex-plore the biological activity of novel metal complexes derived from 6-methyl-2-thiouracil and 6-propyl-2-thiouracil. The paper outlines a synthesis method and assesses the antimicrobial activ-ity of newly formed Cu(II) and Pd(II) complexes with two substituted 2-thiouracil ligands. The structural attributes of these newly developed compounds are thoroughly discussed based on data derived from melting point analysis, MP-AES for Cu and Pd, UV-Vis, IR, ATR, 1H NMR, 13C NMR and Raman spectroscopy. The interpretation of the complex spectra is assisted by the data for 6-methyl-2-thiouracil and 6-propyl-2-thiouracil obtained from 1H-1H COSY, DEPT-135, HMBC and HMQC spectra. In addition, the antimicrobial activity of these complexes and the free ligands are assessed against both Gram-positive and Gram-negative bacteria, as well as yeasts.

The complexity of modern power grids, exacerbated by integrating diverse energy sources, espe-cially inverter-based resources (IBRs), presents a significant challenge to grid operation and plan-ning since linear models fail to capture the intricate IBR dynamics. This study employs the Sparse Identification of Nonlinear Dynamics (SINDy) method to bridge the gap between theoretical un-derstanding and practical implementation in power system analysis. It introduces the novel Volterra-based Nonlinearity Index (VNI) to examine system-level nonlinearity comprehensively. The distinction of dynamics into first-order linearizable terms, second-order nonlinear dynamics, and third-order noise elucidates the intricacy of power systems. The findings demonstrate a fundamental shift in system dynamics as power sources transit to IBRs, revealing system-level nonlinearity compared to module-level nonlinearity in conventional syn-chronous generators. The VNI quantifies nonlinear-to-linear relationships, enriching our comprehension of power system behavior and offering a versatile tool for distinguishing between different nonlinearities and visualizing their distinct patterns through the proposed VIN profile.

The efficiency of a new composite material of the layered double hydroxide (LDH) of ZnMgAl and rice husk biochar (RHB) for the removal of Cu(II) and Pb(II) ions from synthetic wastewater was investigated in this study. The images of scanning electron microscope showed extremely fine crystalline LDH particles decorated on the rough surface of the RHB while the succesful formation of the composite adsorbent (LDH/RHB) was confirmed by the corresponding energy dispersive X-ray and the Fourier-transform infrared spectroscopy. An equilibrium contact time of 30 and 15 min for Cu2+ and Pb2+, respectively, was proposed for the optimum performance of the batch adsorption process. The dose of the LDH/RHB adsorbent was optimized at 0.4 g yielding maximum adsorption capacities of 117 and 124 mg g-1 for Cu2+ and Pb2+, respectively, with corresponding maximum removal efficiencies of nearly 94% and 99%. The initial meta concentrations was optimized at 50 or 60 mg L-1 corresponding to maximum removal efficiencies or adsorption capacities. For the changing initial metal’s concentration, the removal efficiencies remained unchanged for up to 50 mg L-1 and decreased by about 50% by increasing the initial concentrations from 50 to 100 mg L-1. The adsorption capacities observed a linear increasing trend by increasing the initial concentrations from 5 to 60 mg L-1 and remained unchanged afterward up to 100 mg L-1. A solution pH of 6.0 yielded optimum results with an increasing trend in adsorption capacities and percentage removal by changing the solution pH from 2.0 to 7.0. Based on the best-fit of the pseudo second-order kinetic model to the experimental data, the chemisorption was suggested to be the controlling mechanism of adsorption. The fitting of the Langmuir model suggested a monolayer sorption of Cu2+ and Pb2+ in addition to a heterogeneous adsorption as supported by the fitting of the Temkin isotherm. The application of the Dubinin–Radushkevich isotherm proposed a physical adsorption (mean free energy of adsorption less than 8 kJ mol−1) of both heavy metal ions on the surface of the LDH/RHB adsorbent.

This paper introduces a new destriping algorithm for remote sensing data. The method is based on combined Haar Stationary Wavelet transform and Fourier filtering. State-of-the-Art methods based on the discrete wavelet transform (DWT) may not always be effective and may cause different artifacts. Our contribution is three-fold: i) we propose to use the Undecimated Wavelet transform (UWT) to avoid as much as possible shortcomings of the classical DWT; ii) we combine a spectral filtering and UWT using the simplest possible wavelet, the Haar basis, for a computational efficiency; iii) we handle 2D fields with missing data, as commonly observed in ocean remote sensing data due to atmospheric conditions (e.g., cloud contamination). The performances of the proposed filter are tested and validated on the suppression of horizontal strip artifacts in cloudy L2 Sea Surface Temperature (SST) and ocean color snapshots.

With the fintech industry growing at an unprecedented rate, it is critical to protect cybersecurity and ensure data privacy. The research presented here offers a thorough examination of the challenges faced by financial technology companies, highlighting the growing risks posed by malware, phishing, and network vulnerabilities. As essential components of a proactive defense plan, the report promotes strong cybersecurity measures like frequent security assessments, encryption, and stringent access controls. The findings highlight how important it is for fintech companies to give cybersecurity equal importance with open and honest data privacy policies in order to win over customers. In order to protect the industry from cybersecurity risks regulatory compliance, intrusion detection systems, and collaborative information sharing are considered essential components. The article advises businesses to include cybersecurity and data privacy into their core business operations and customer relations, highlighting the critical role these factors play in sustaining success in the rapidly evolving fintech industry.

(1) Introduction: The COVID-19 pandemic presented unique challenges for patients and healthcare providers, especially for those working with obesity and related health problems. E-health has emerged as a crucial tool for the follow-up of users undergoing bariatric surgery during this period, allowing remote monitoring of users' health status and providing access to virtual consultation with health professionals. This study aims to analyze the impact of the use of telemedicine during the COVID-19 pandemic on the results of bariatric surgery and user satisfac-tion with this follow-up. (2) Method: Observational study with retrospective data collection. The variables were divided into several groups: health data, associated comorbidities, quality of life, quality of sleep and satisfaction with telemedicine monitoring. (3) Results: Surgery significantly affected weight loss, in general more than 75% loss of excess weight. Comorbidities, like the qual-ity of life, were reversed over time, with 50% of subjects maintaining excellent levels. Although most users were satisfied with the monitoring, the variables had no relationship. (4) Conclusions: The follow-up assured by telemedicine did not alter the results of bariatric surgery, which may allow us to infer that it may be an option to consider for regular monitoring of the post-bariatric surgery process.

Succinic semialdehyde dehydrogenase (SSADH) is a mitochondrial enzyme involved in the catabolism of the neurotransmitter γ-amino butyric acid. Pathogenic variants in the gene encoding this enzyme cause SSADH deficiency, a developmental disease manifesting as hypotonia, autism and epilepsy. SSADH deficiency patients usually have family-specific gene variants. Here, we describe a family exhibiting four different SSADH variants, Val90Ala, Cys93Phe, and His180Tyr/Asn255Asp (a double variant). We provide a structural and functional characterization of these variants and show that Cys93Phe and Asn255Asp are pathogenic variants that affect the stability of the SSADH protein. Due to impairment of the cofactor NAD+ binding, these variants show a highly reduced enzyme activity. However, Val90Ala and His180Tyr exhibit normal activity and expression. The His180Tyr/Asn255Asp variant exhibits a highly reduced activity as a recombinant species, is inactive and shows a very low expression in eukaryotic cells. A treatment with substances that support protein folding by either increasing chaperone protein expression or by chemical means was not capable of increasing the expression of the pathogenic variants of the SSADH deficiency patient. However, stabilization of the folding of pathogenic SSADH variants by other substances may provide a treatment option for this disease.

We presented unusual case of double left ventricular false aneurysm complicating late presentation AMI successfully treated with the combination of urgent surgical drainage of tamponade, staged PCI of non-culprit lesion, preventive implantation of ICD-DR, guideline directed heart failure medical therapy and delayed but effective reconstructive operation.

Two new coordination compounds of Mn(II) and Cu(II) viz. [Mn(bz)2(Hdmpz)2(H2O)] (1) and [Cu(crot)2(Hdmpz)2] (2) (where, bz = benzoate, crot = crotonate, Hdmpz = 3, 5-dimethyl pyrazole) have been synthesized and characterized using single crystal X-ray diffraction technique, FT-IR, electronic spectroscopy, TGA and elemental analyses. Compounds 1 and 2 crystallize as mono-nuclear coordination compounds of Hdmpz based penta-coordinated Mn(II) and hexa-coordinated Cu(II) respectively containing distorted trigonal bipyramidal and distorted octahedral geome-tries. Crystal structure analysis of compound 1 reveals the presence C‒H⋯π and π-stacking in-teractions along with O‒H⋯O, N‒H⋯O and C‒H⋯O H-bonding interactions which stabilizes the layered assembly of the compound. Similarly, the presence of hydrogen bonding along with π-stacking interactions stabilizes the crystal structure of compound 2. We have carried out theo-retical investigations to analyze π⋯π H-bonding and antiparallel CH···π non-covalent interac-tions observed in the compounds. DFT calculations were performed to evaluate strength of these interactions energetically. Moreover, QTAIM and non-covalent interaction (NCI) plot index computational tool were used to characterize them and evaluate the contribution of the H-bonds.

Inferring algorithmic structure in data is essential for discovering causal generative models. In this research, we present a quantum computing framework using the circuit model, for estimating algorithmic information metrics. The canonical computation model of the Turing machine is restricted in time and space resources, to make the target metrics computable under realistic assumptions. The universal prior distribution for the automata is obtained as a quantum superposition, which is further conditioned to estimate the metrics. Specific cases are explored where the quantum implementation offers polynomial advantage, in contrast to an indispensable exhaustive enumeration in the corresponding classical case. The unstructured output data and the computational irreducibility of Turing machines make this algorithm impossible to approximate using heuristics. Thus, exploring the space of program-output relations is one of the most promising problems for demonstrating quantum supremacy using Grover search that cannot be dequantized. Experimental use cases for quantum acceleration are developed for self-replicating programs and algorithmic complexity of short strings. With quantum computing hardware rapidly attaining technological maturity, we discuss how this framework will have significant advantage for various genomics applications in meta-biology, phylogenetic tree analysis, protein-protein interaction mapping and synthetic biology. This is the first time experimental algorithmic information theory is implemented using quantum computation. Our implementation on the Qiskit quantum programming platform is copy-left and can be found on https://github.com/Advanced-Research-Centre/QPULBA

In this article we explore the limiting behavior of the universal prior distribution obtained when applied over multiple meta-level hierarchy of programs and output data of a computational automata model. We were motivated to alleviate the effect of Solomonoff's assumption that all computable functions or hypotheses of the same length are equally likely, by weighing each program in turn by the algorithmic probability of their description number encoding. In the limiting case, the set of all possible program strings of a fixed-length converges to a distribution of self-replicating quines and quine-relays - having the structure of a constructor. We discuss how experimental algorithmic information theory provides insights towards understanding the fundamental metrics proposed in this work and reflect on the significance of these result in digital physics and the constructor theory of life.

Japan Aerospace Exploration Agency (JAXA) is going to launch Advanced Land Observing Satellite 3 (ALOS-3) after 2022. ALOS-3 satellite is capable of observing global land areas with wide swath (4000 km along-track direction and 70 km cross-track direction) at high spatial resolution (panchromatic: 0.8m, multispectral: 3.2m). Maintenance and updating of land cover and vegetation information at national level is one of the major goals of the ALOS-3 mission. This paper presents the potential of simulated ALOS-3 images for the classification and mapping of land cover and vegetation types at Genus-Physiognomy-Ecosystem (GPE) level. We acquired and simulated WorldView-3 images according to the configuration of the ALOS-3 satellite sensor and the simulated ALOS-3 images were utilized for the classification and mapping of land cover and vegetation types in three sites (Hakkoda, Zao, and Shiranuka) in northern Japan. This research dealt with 17 land cover and vegetation types in Hakkoda site, 25 land cover and vegetation types in Zao site, and 12 land cover and vegetation types in Shiranuka site. Ground truth data were newly collected in three sites, and we employed eXtreme Gradient Boosting (XGBoost) classifier with the implementation of 10-fold cross-validation method for assessing the potential of ALOS-3S images. The classification accuracies obtained in Hakkoda, Zao, and Shiranuka sites in terms of f1-score were 0.810, 0.729, and 0.805 respectively. The fine scale (3.2m) land cover and vegetation maps produced in the study sites showed clear and detailed view of the distribution of plant communities. Regardless of the limited number of the temporal images, ALOS-3S images showed high potential (at least 0.729 F1-score) for the land cover and vegetation classification in all three sites. The availability of more cloud free temporal scenes is expected for improved classification and mapping in the future.

Climate change, biodiversity loss, and other social and environmental problems pose grave risks. Progress so far has been incremental and insufficient, and as a result scientists, global policy experts, and the general public increasingly conclude that bold change is required across all sectors of society. At least two kinds of bold change are conceivable: reform of existing societal systems (e.g., financial, economic, legal, and governance systems), including their institutions, policies, rules, and priorities; and transformation, understood as the de novo development of and migration to new, improved systems. This paper is the second in a series of three that together propose a novel science-driven research and development program aimed at societal transformation. Moreover, the series advances a conceptual framework and formal mechanics by which societal transformation might be approached. Two of the underlying hypotheses are that new societal systems can be developed in a science-driven process to be fit for purpose, and system fitness can be compared across designs. Societies are viewed as superorganisms, and systems are viewed as a societal cognitive architecture. The first paper in the series provides definitions, aims, hypotheses, and a worldview. This paper discusses motivations, the role of science in societal transformation, a theory of change, and fitness metrics. The proposed R&amp;D program and theory of change are sound, viable, and affordable. The local-global-viral strategy invites the global science community to play a unique co-leadership role with local communities in the development, testing, and monitoring of new societal systems. Systems are implemented via a novel civic club model, where participation is voluntary. Clubs grow and replicate based on merit and aided by club networks, whose systems are also viewed as societal cognitive architectures. Benefits of the program and strategy are discussed.

The core of risk aggregation in the Solvency II Standard Formula is the so-called square root formula. We argue that it should be seen as a means for the aggregation of different risks to an overall risk rather than being associated with variance-covariance based risk analysis. Considering the Solvency II Standard Formula from the viewpoint of linear geometry, we immediately find that it defines a norm and therefore provides a homogeneous and sub-additive tool for risk aggregation. Hence Euler's Principle for the reallocation of risk capital applies and yields explicit formulas for capital allocation in the framework given by the Solvency II Standard Formula. This gives rise to the definition of diversification functions, which we define as monotone, subadditive, and homogeneous functions on a convex cone. Diversification functions constitute a class of models for the study of the aggregation of risk, and diversification. The aggregation of risk measures using a diversification function preserves the respective properties of these risk measures. Examples of diversification functions are given by seminorms, which are monotone on the convex cone of non-negative vectors. Each L^p norm has this property, and any scalar product given by a non-negative positive semidefinite matrix does as well. In particular, the Standard Formula is a diversification function and hence a risk measure that preserves homogeneity, subadditivity, and convexity.

Multimission satellite altimetry (e.g. ERS, Envisat, TOPEX/Poseidon, Jason) data have enabled a synoptic view of ocean variations in the past decades, including sea-level rise and mesoscale circulations. Since 2016, the Sentinel-3 mission has provided better spatial and temporal sampling compared with its predecessors. The Sentinel-3 Ku/C Radar Altimeter (SRAL) is one of the synthetic aperture radar altimeters (SAR Altimeter) which is more precise in coastal and lake observations. In this study, we validate Sentinel-3 Level-2 products in Baltic Sea coastal areas and two lakes in Estonia. Moreover, the Copernicus Marine Environment Monitoring Service (CMEMS) Level-3 sea-level anomaly data and the Nucleus for European Modelling of the Ocean (NEMO) reanalysis model outcomes are compared with measurements from a tide gauge network. A dense in situ water level network deployed along the coast for geodetic observation was utilised to provide ground truths for validating altimetry results. Three validation methods were used for Level-2 data: (i) collocated Sentinel-3 and GNSS ship measurements; (ii) a national geoid model (EST-GEOID2017) with sea-level anomaly correction; (iii) collocated Sentinel-3 and buoy measurements. The validations were carried out in seven Sentinel-3A/B overpasses in 2019. Our results show that the uncertainty of the Sentinel-3 Level-2 altimetry product is below decimetre level on the Estonian coast and the targeted lakes. Results from CMEMS Level-3 showed a correlation of 0.8 (RMSE 0.19 m) and 0.91 (RMSE 0.27 m) when compared against tide gauge measurements and NEMO model, respectively.

This report demonstrates the first-time asymmetric synthesis of enantiopure structured triacylglycerols (TAGs) of the ABC type presenting three non-identical fatty acids, two of which unsaturated. The unsaturated fatty acids included the monounsaturated oleic acid (C18:1 n-9) and the polyunsaturated linoleic acid (C18:2 n-6). This was accomplished by a six-step chemoenzymatic approach starting from (R)- and (S)-solketals. The highly regioselective immobilized Candida antarctica lipase (CAL-B) played a crucial role in the regiocontrol of the synthesis. The synthesis also benefited from the use of the p-methoxybenzyl (PMB) ether protective group that enabled incorporation of two different unsaturated fatty acids to the glycerol skeleton. The total of six such TAGs were prepared, four constituting the unsaturated fatty acids in the sn-1 and sn-2 positions with a saturated fatty acid in the remaining sn-3 position of the glycerol backbone. In the two remaining TAGs the different unsaturated fatty acids accommodated the sn-1 and sn-3 end positions with the saturated fatty acid present in the sn-2 position. Enantiopure TAGs are urgently demanded as standards for enantiospecific analysis of intact TAGs in fats and oils.

Background. Escalating global plastic production, expected to reach 34,000 million tons by 2050, poses a significant threat to human and environmental well-being, particularly in aquatic ecosystems. Microplastics (MP) and nanoplastics (NP), which originate from the degradation of plastics, are of concern due to their potential bioaccumulation and uptake of pollutants. This study addresses identification methods and focuses on insect meal, a raw material for aquaculture feed. Methods. By using different techniques, the study was able to detect MP and NP in insect meal samples. Chemical digestion with KOH at 60°C efficiently removed organic matter without affecting the synthetic polymer polyethylene (PE). Filtration, confocal Raman microscopy, SEM and TEM were used for comprehensive analysis and integrity tests on PE films were performed using Raman and FTIR spectroscopy. The results showed the presence of PE microplastic particles in the insect meal, which was confirmed by correlative Raman and SEM mapping on a positively charged surface. In addition, the increased resolution of the Raman microscope identified submicrometric PE NP (800 nm). Transmission electron microscopy (TEM) with energy dispersive X-ray spectroscopy (EDX) confirmed plastic-like structures in the insect meal, highlighting the presence of PE plastics characterized by irregular shapes and some agglomeration. The higher carbon concentration in the EDX analysis supported the plastic nature, which was also confirmed by Raman spectroscopy. Conclusions. The study provides a robust method for the detection of MP and NP in insect meal and provides valuable insight into the possible presence of plastics in insect-based aquafeeds. The combination of different analytical methods increases the reliability of the results and sets the stage for future investigations that could focus on the quantification of NP and the assessment of their potential environmental impact.

In systems biology, biological phenomena are often modeled by ODE and distributed in the de facto standard file format SBML. The primary analyses performed with such models are dynamic simulation, steady-state analysis, and parameter estimation. These methodologies are mathematically formalized, and libraries for such analyses have been published. Several tools exist to create, simulate, or visualize models encoded in SBML. However, setting up and establishing analysis environments is a crucial hurdle for non-modelers. Therefore, easy access to perform fundamental analyses of ODE models is a significant challenge. We developed SBMLWebApp, a web-based service to execute SBML-based simulations, steady-state analysis, and parameter estimation directly in the browser without the need for any setup or prior knowledge to address this issue. SBMLWebApp visualizes the result and numerical table of each analysis and provides a download of the results. SBMLWebApp allows users to select and analyze SBML models directly from the BioModels Database. Taken together, SBMLWebApp provides barrier-free access to an SBML analysis environment for simulation, steady-state analysis, and parameter estimation for SBML models. SBMLWebApp is implemented in Java™ based on an Apache Tomcat® web server using COPASI, the SBSCL, and LibSBMLSim as simulation engines. SBMLWebApp is licensed under MIT with source code available from https://github.com/TakahiroYamada/SBMLWebApp. The program runs online at http://simulate-biology.org.

Background: A malfunction of the innate immune response in COVID-19 is associated with eosinopenia particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils.. Methods: Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16 and CD62L) in the absence or presence of a formyl peptide (fNLF). 45 SARS-CoV-2 PCR positive patients were grouped based on disease severity. PCR negative patients with proven bacterial (n=20) or other viral (n=10) infections were used as disease controls. Eosinophils were identified with the use of the FlowSom algorithm. Results: Low blood eosinophil numbers (<100 cells/microL; p<0.005) were found both in patients with COVID-19 and with other infectious diseases albeit less pronounced. Two discrete eosinophil populations were identified in healthy controls both before and after activation with fNLF based on the expression of CD11b. Before activation, the CD11bbright population consisted of 5.4% (CI95% = 3.8, 13.4) of total eosinophils. After activation, this population of CD11bbright cells comprised nearly half the population (42.21%, CI95% = 35.9, 54.1). Eosinophils in COVID-19 had a similar percentage of CD11bbright cells before activation (7.6%, CI95% = 4.5, 13.6), but were clearly refractory to activation with fNLF as a much lower percentage of cells end up in the CD11bbright fraction after activation (23.7%, CI95% = 18.5, 27.6; p<0.001). Conclusion: Low eosinophil numbers in COVID-19 are associated with refractoriness in responsiveness to fNLF, which is likely caused by migration of fully functional cells to the tissue. Such homing might be beneficial as eosinophils have been implicated in viral killing.

This paper focus on the modeling and time-domain analyzing method of piecewise-smooth fractional-order circuit systems. Firstly, an analytical framework is constructed based on a generalized piecewise-smooth two-port impedance network model, which takes the topological characteristics of Dickson type switched-capacitor converters (SCCs) as examples, and considers the fractional-order characteristics of class-2 X7R ceramic capacitors, which are widely used in SCCs. Secondly, the time-domain analyzing method for such a piecewise-smooth fractional-order circuit system is developed, numerical solutions are obtained, and the influence of the fractional-order capacitor on the power conversion efficiency of the system are revealed. Finally, in order to validate the analysis, both numerical simulation and experiments are provided in the work, the results of which confirm that, the proposed fractional-order analytical framework can capture the power loss mechanism of piecewise-smooth fractional-order circuit systems more effectively than the traditional integer-order based approach, thus benefiting the design of circuit systems.

This paper discusses two major applications of SU(3) theory, the first being the question of quantum brachistochrones and problems in time optimal control theory, the second being the use of spherical tensor decompositions of the special functions which are associated to SU(3) via the isotropic oscillator. We discuss the derivation of the quantum brachistochrone problem more generally from the perspective of von Neumann equations and matrix mechanics, arriving at an equivalent formulation to the Lagrangian method. Discussion is given to the application of such advanced methods in quantum computation, and some future directions that may be amenable to a similar sort of an

The paper presents a new type of hydraulic clutch operating with magnetorheological (MR) fluids and the results achieved from both theoretical analysis and experimental measurement. The hy-draulic clutch system of its own design with MR working fluid and a rotating magnetic field lo-cated is designed. The principle of this clutch is to use a rotating magnetic field created by an al-ternating current electromagnet to set the MR fluid in motion. In the tests of the hydraulic clutch with a rotating magnetic field, MR fluid produced on their own, consisting of solid iron particles of various diameters mixed with a silicone oil, are used as working fluids. The rheological properties of MR fluids are assessed on the basis of tests carried out with a Brookfield DV2T rheometer equipped with a magnetic device for generating the magnetic field of its own design. The char-acteristics of the hydraulic clutch with MR working fluid and the rotating magnetic field are tested on a specially built test stand. As a result of the research, it has been found that the torque transmitted by the clutch is the greater, the higher the rotational speed of the magnetic field and the lower the rotational speed of the beaker in which the working fluid is placed, and that the greatest torque occurs for the working fluid with the highest iron content. Based on the analysis of the structure and characteristics of the clutch in which the magnetic field is used, it has been shown that the design of the developed clutch is similar to that of an induction clutch, and its characteristics correspond to the characteristics of the eddy current clutch. Therefore, the proposed new clutch working with MR fluid and the rotating magnetic field can be applied to stationary power transmission system similarly to an eddy current clutch.

Leukemia represents as one of the most common primary malignancies of the hematologic system in both children’s and adults and remains a largely incurable or relapse disease. The elucidation of disease subtypes based on mutational profiling, has not improved clinical outcomes. IDH1/2 are key enzymes of TCA cycle that produces α-ketoglutarate (αKG), however their mutated version, are well reported in various cancer types including leukemia, produces D-2 hydroxyglutarate (D-2HG), an oncometabolite. Recently, some studies have shown that wild type IDH1 is highly expressed in non-small cell lung carcinoma (NSCLC), primary glioblastomas (GBM) and several hematological malignancies and corelates with disease progression. In this work, we have showed treatment of wild type IDH1 leukemia cells with specific IDH1 inhibitor switched leukemic cells towards gly-colysis from oxidative phosphorylation (OXPHOS) phenotype. We also noticed reduction in αKG in treated cells possible suggesting inhibition of IDH1 enzymatic activity. Further, we found that IDH1 inhibition reduces the metabolites related to one carbon metabolism, essential to maintain global methylation in leukemic cells. Finally, we observed that metabolic alteration in IDH1 inhibitor treated leukemic cells promotes reactive oxygen species (ROS) formation along with loss of mito-chondrial membrane potential, leading towards apoptosis in leukemic cells. Overall, we showed that wild type IDH1 targeting in leukemic cells promote metabolic alterations that can be exploited for combination therapies for better outcome.

Plasmodium falciparum dihydroorotate dehydrogenase (PfDODH) is one of the enzymes currently explored in the treatment of malaria. Although there is currently no clinically approved drug targeting PfDODH, many of the compounds in clinical trials have [1, 2, 4,] triazolo [1, 5-a] pyrimidin-7-amine backbone structure. This study sought to design new compounds from the fragments of known experimental inhibitors of PfDODH. Nine experimental compounds retrieved from Drug Bank online were downloaded and broken into fragments using Schrodinger power shell; the fragments were recombined to generate new ligand structures using BREED algorithm. The new compounds were docked with PfDODH crystal structure, after which the compounds were filtered with extensive drug-likeness and toxicity parameters. A 2D-QSAR model was built using the multiple linear regression method and externally validated. The compounds electronic behaviours were studied using DFT calculations. Structural investigation of the six designed compounds, which had lower binding energies than the standard inhibitors, showed that five of them had [1, 2, 4,] triazolo [1, 5-a] pyrimidin-7-amine moieties and interacted with essential residues at the PfDODH binding site. In addition to their drug-like and pharmacokinetic properties, they also showed minimal toxicities. The externally validated 2D-QSAR model with R² and Q² values of 0.6852 and 0.6691, confirmed the inhibitory prowess of these compounds against PfDODH. The DFT calculations showed regions of the molecules prone to electrophilic and nucleophilic attack. The current study thus provides insight into the development of a new set of potent PfDODH inhibitors.

Relapses and resistance to therapeutic agents are major barriers for treatment of acute myeloid leukemia (AML) patients. This unfavorable circumstance emphasizes the need for new strategies targeting drug-resistant cells. As IDH mutation is present in the preleukemic stem cells and systematically conserved at relapse, targeting mutant IDH cells would be essential to achieve a long-term remission in the AML subgroup with IDH mutation. Here, using a panel of human AML cell lines and primary AML patient specimens harboring IDH mutation, we showed that the presence of IDH mutation through the production of an oncometabolite (R)-2-HG induces vitamin D receptor related transcriptional programs, priming these AML cells to differentiate with pharmacological doses of ATRA or/and VD. This activation occurs in a CEBP-dependent manner. Accordingly, our findings illuminate potent and cooperative effects of IDH mutation and vitamin D pathway to differentiate in AML, revealing a novel therapeutic approach easily transferable/immediately applicable in clinics for this subgroup of AML patients.

Background: Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is mainly associated with SDHB gene mutation and sometimes with SDHC or SDHD mutation. However, only three case of SDHA-deficient RCC have been reported, and the relation of SDHA mutation to RCC has not been clarified. Methods: We investigated SDHA/B/C/D gene mutations in 72 human RCCs by targeted next-generation sequencing, and also assessed SDHA and nuclear factor erythroid 2–related factor 2 (Nrf2) protein expression in 30 tumors. Results: NGS revealed SDHA gene mutations associated with amino acid sequence variations in 12 tumors, while no tumors had SDHB/C/D mutations. The SDHA gene mutations were identical in somatic and germline DNA of all 12 patients. Tumors with SDHA mutations showed a decrease of SDHA protein (p = 0.0177) and an increase of Nrf2 protein (p = 0.0120), with an inverse correlation between SDHA and Nrf2 protein expression (p = 0.0321). Tumor cells with SDHA mutations characteristically had eosinophilic cytoplasm and showed various patterns of proliferation. Conclusions: Our observations suggested that germline SDHA gene mutations might be linked to hereditary RCC associated with mitochondrial dysfunction.

In paper I, we showed that the observed (LCDM) Universe can be modeled as a local Black Hole (BH) Universe (BHU) of fixed mass M, without Dark Energy (DE): cosmic acceleration is caused by the BH event horizon rS=2GM. %The same BHU solution can be used to model the interior of a stellar or galactic BHs. Here, we propose that our BHU could form from the hierarchical free-fall collapse of regular matter. We argue that the singularity could be avoided with a Big Bounce explosion, caused by neutron degeneracy pressure (Pauli exclusion principle). This happens at GeV energies, like in core collapse supernova, well before the collapse reaches Planck energies (1E19 GeV). If our universe formed this way, there is no need for cosmic Inflation or a singular start (The Big Bang). Nucleosynthesis and recombination follow a hot expansion, like in LCDM, but cosmological measurements, which are free parameters in LCDM, could be estimated from first principles. Dark Matter could be made up of a wide mass range of primordial compact objects (BHs and Neutron stars), remnants of the collapse and bounce, which can provide a faster start for galaxy formation. We present a simple prediction to explain the observed value of Lambda and the coincidence problem.

Bridge load testing is crucial in evaluating bridge load-carrying capacity and construction quality. However, conventional techniques have many limitations such as the need for direct contact and low acquisition frequency. This study provides a comprehensive examination of the static and dynamic load tests of a multi-span cable-stayed bridge utilizing a ground-based radar inter-ferometer (GB-radar). The case study was conducted at the Fifth Nanjing Yangtze River Bridge (FNYRB), which is recognized as the world's first lightweight steel-concrete composite cable-stayed bridge, with two spans measuring 600 m. To enhance measurement accuracy, a method was proposed to detect and recover radar phase jumps caused by vehicle motion. Furthermore, precise geometry projection was employed to acquire vertical displacements from GB-radar which were taken along the line-of-sight (LOS) direction. Moreover, during the static load test, a continuous deformation was observed with a maximum pace of 0.31 mm/min, indicating a post-construction settlement caused by soft soil consolidation. This case study highlights the high sampling frequency, high measurement accuracy, and exceptional weatherproof ability of GB-radar, thereby demonstrating its potential to be an alternative to the structural health monitoring (SHM) system.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

The effectiveness of combining strength-specific training with endurance training to enhance the performance of endurance runners remains uncertain. This study aimed to analyze effect of practising maximum-strength (MAX), explosive strength (EXP) or both combined (COMB) on seven runners’ performance-indicators: vertical jump (VJ), one-repetition-maximum-squat (1RM), peak-velocity/peak-running-speed (PV), lactate-threshold (over incremental-test-protocols, LT), middle-distance-time-trial (TT), maximum-oxygen-consumption (VO2max), running-economy (RE). Systematic-review (Scopus, Wed of Science, Sports Discuss, PubMed) with meta-analysis was conducted following PRISMA standards. Inclusion-criteria (PICOS) were: recreational or well-trained athletes aged 18-45 performing concurrent-training ≥five-week. Used search-terms were related to different types of strength/endurance, participants’ age, sport-modality. 20 manuscripts were selected, quality-assessed with PEDro. MAX training is more effective than EXP, COMB in improving VJ, 1RM, PV, while COMB is more effective than MAX, EXP to enhance TT. MAX is more effective than EXP in improving LT. Concurrent-workouts do not provide additional benefits to VO2max. It is unknown which strength-modality (MAX, EXP or COMB) is more effective in improving RE. Concurrent-training is more effective than single-mode-endurance-training for enhancing specific performance-variables in adult-endurance-runners. Middle-, long-distance-runners may consider incorporating MAX-training to target specific goals, e.g., improving VJ, 1RM, LT, PV while utilizing COMB-training to enhance TT. Certain variables may benefit from EXP. New randomized-controlled-trials are required to confirm these findings.

Cross-species investigations on cancer invasiveness are a new approach that identified new biomarkers potentially useful for improving tumor diagnosis and prognosis in clinical medicine and veterinary science. In this study, we combined proteomic analysis of four experimental rat malignant mesothelioma (MM) tumors with analysis of ten patient-derived cell lines to identify common features associated to mitochondrial proteome rewiring. The comparison of significant abundance changes between invasive and non-invasive rat tumors rat tumors gave a list of 433 proteins, including twenty-six proteins reported to be exclusively located in mitochondria. Next, we analyzed the differential expression of genes encoding the mitochondrial proteins of interest in five primary epithelioid and five primary sarcomatoid human MM cell lines, and the most impressive increase was observed in the expression of the long-chain acyl coenzyme A dehydrogenase (ACADL). To evaluate the role of this enzyme in the migration/invasiveness, two epithelioid and two sarcomatoid human MM cell lines derived from patients with the highest and lowest overall survival were studied. Interestingly, sarcomatoid vs epithelioid cell lines were characterized by higher migration and fatty oxidation rates, in agreement with ACADL findings. These results suggest that evaluating mitochondrial proteins in MM specimens might identify tumors with higher invasiveness.

The experiences gathered during the past 30 years support the operational use of irrigation scheduling based on frequent multi-spectral image data. Currently, the operational use of dense time series of multispectral imagery at high spatial resolution makes monitoring of crop biophysical parameters feasible, capturing crop water use across the growing season, with suitable temporal and spatial resolutions. These achievements, and the availability of accurate forecasting of meteorological data, allow for precise predictions of crop water requirements with unprecedented spatial resolution. This information is greatly appreciated by the end users, i.e. professional farmers or decision-makers, and can be provided in an easy-to-use manner and in near-real-time by using the improvements achieved in web-GIS methodologies. This paper reviews the most operational and explored methods based on optical remote sensing for the assessment of crop water requirements, identifying strengths and weaknesses and proposing alternatives to advance towards full operational application of this methodology. In addition, we provide a general overview of the tools which facilitates co-creation and collaboration with stakeholders, paying special attention to these approaches based on web-GIS tools.

This paper describes the load capacity of short fiber-reinforced polymer lugs with Ti-6Al-4V selective laser-melted bushings with the original embedded element surface roughness and after sandblasting and vibratory finishing. Lugs are an important part of pin-joints. Adhesion between PA6 and SLM produced titanium is not fully studied. The cohesive zone material Mode II model parameters were calibrated experimentally by extruding a cylindrical bushing along the lug axis. The values of the maximum equivalent tangential contact stress were fitted for cases with investigated embed element roughness. The critical fracture energy for tangential slip was also estimated. Validation of the constructed CZM Mode II models with the results of strength experiments was performed. In both the experiment and the calculation, greater bushing roughness provides greater lug load-bearing capacity. The presented models can be used for the preliminary evaluation of SFRP PA6 parts with titanium embedded elements bearing capacity.

In this part of the series of two papers, we extend the theorems discussed in part I for infinite series. We then use these theorems to develop distinct novel results involving the Hurwitz zeta function, Riemann zeta function, Polylogarithm and Fibonacci numbers. In continuation, we obtain some zeros of the newly developed zeta functions and explain their behaviour using plots in complex plane. Furthermore, we provide particular cases for the theorems and corollaries which show that our results generalise the currently available functions and series such as the Riemann zeta function and the geometric series. Finally, we provide four miscellaneous examples to showcase the vast scope of the developed theorems.

Let $(A,\Delta)$ be a {\it weak multiplier Hopf algebra} as introduced in [VD-W3] (see also [VD-W2]). It is a pair of a non-degenerate algebra $A$, with or without identity, and a coproduct $\Delta$ on $A$, satisfying certain properties. If the algebra has an identity and the coproduct is unital, then we have a Hopf algebra. If the algebra has no identity, but if the coproduct is non-degenerate (which is the equivalent of being unital if the algebra has an identity), then the pair would be a multiplier Hopf algebra. If the algebra has an identity, but the coproduct is not unital, we have a weak Hopf algebra. In the general case, we neither assume $A$ to have an identity nor do we assume $\Delta$ to be non-degenerate and so we work with a {\it genuine} weak multiplier Hopf algebra. It is called {\it regular} if its antipode is a bijective map from $A$ to itself. \snl In this paper, we {\it continue the study of weak multiplier Hopf algebras}. We recall the notions of the source and target maps $\varepsilon_s$ and $\varepsilon_t$, as well as of the source and target algebras. Then we investigate these objects further. Among other things, we show that the canonical idempotent $E$ (which is eventually $\Delta(1)$) belongs to the multiplier algebra $M(B\ot C)$ where $B=\varepsilon_s(A)$ and $C=\varepsilon_t(A)$ and that it is a {\it separability idempotent} (as studied in [VD4.v2]). If the weak multiplier Hopf algebra is regular, then also $E$ is a {\it regular} separability idempotent. \snl We also consider {\it special cases and examples} in this paper. In particular, we see how for any weak multiplier Hopf algebra $(A,\Delta)$, it is possible to make $C\ot B$ (with $B$ and $C$ as above) into a new weak multiplier Hopf algebra. In a sense, it forgets the 'Hopf algebra part' of the original weak multiplier Hopf algebra and only remembers the source and target algebras. It is in turn generalized to the case of any pair of non-degenerate algebras $B$ and $C$ with a separability idempotent $E\in M(B\ot C)$. We get another example using this theory associated to any discrete quantum group (a multiplier Hopf algebra of discrete type with a normalized cointegral). Finally we also consider the well-known 'quantization' of the groupoid that comes from an action of a group on a set. All these constructions provide interesting new examples of weak multiplier Hopf algebras (that are not weak Hopf algebras).

In this paper, two double Jordan-type inequalities are introduced based on the papers [1]-[5]. These inequalities generalize the inequalities obtained in [1]-[5]. As a result, some new upper and lower bounds of the sinc function are obtained. This extension of Jordan’s inequality is enabled by considering the corresponding inequalities through the concept of stratified families of functions elaborated in [6]. Based on this approach, some optimal approximations of the sinc function are derived by determining corresponding minimax approximants, also described in the paper [6].

This paper considers a new approach to the modeling of the vacuum infusion process at the manufacturing three-dimensional composite parts of complex shape. The developed approach and numerical methods are focused on the reliable prediction with the needed accuracy and elimination the unrecoverable defect of composite structure such as the dry spots. The paper presents some experimental results, which demonstrate two cases of dry spots formation in large aircraft composite panels, and analyses the reasons of these defects arising. Our numerical technique is based on the vacuum infusion of the liquid resin into porous preform as the two phase flow, which is described by the phase field equation coupled with the Richards equation describing the fluid motion in unsaturated soils with spatially varied pressure dependant porosity and saturation. This problem statement allowed to correctly reconstruct the resin front motion and formation of inner and outer dry spots depending on its movement. For the rapid detection of preform zones that are suspicious for defect formation two indicators calculated during process simulation are proposed and tested at the numerical experiments. The auxiliary program tool has been developed in MATLAB environment to correctly detect the times of formation, localization and dimensions of the arising dry spots by using the results of the finite element model simulation.

This dissertation presents a method for the synthesis of substituted indoles bearing heterocyclic substituents onto the 3- position. The route for the synthesis of the heterocyclic substituents indoles starts from 3-acetyl indole nucleus depend on two parts. One part: Reaction of 3-acetylindole 1 with hydrazide compounds such as phenyl hydrazine, hydrazine hydrate, and thio-semicarbazide, to yield 3-(1-(2-phenylhydrazono) ethyl)-1H-indole 2, 3-(1-hydrazonoethyl)-1H-indole 6, and thiosemicarbazone 10 respectively. 3-(1-Hydrazonoethyl)-1H-indole 6 reacted with thiophene-2-carboxaldeyde, isatin and 3-acetyl indole. In the same way, 3-(1-(2-phenylhydrazono) ethyl)-1H-indole 2 reacted with thioglycollic acid, glycine and benzaldehyde. 3-Acetylindole 1 thiosemicarbazone reacted with acetic anhydride, piperidine, concentration of hydrochloric acid and thiophene-2-carboxaldeyde. Second part. Reaction of 3-acetyl indole 1 with amines compounds such as p-nitroaniline to formed Schiff base 15 which it reacted with thioglycollic acid to give compound 16. 3-Acetyl indole 1 reacted with ethylene diamine to afford bis imine indole to afford compound 17. The reports of this docking study revealed that the new compounds exhibit good antibacterial activity. The synthesized compounds screened in vitro for their antibacterial activity revealed remarkable inhibitory effects against the selected microorganisms. And also an anti-oxidant activity studying for some synthesized compounds. Structures of the newly synthesized compounds examination by spectral data (IR, 1H- NMR and 13C -NMR).

Wireless Sensor Networks (WSNs) are being increasingly adopted in critical applications, where verifying the correct operation of sensor nodes is a major concern. Undesired events may undermine the mission of the WSNs. Hence their effects need to be properly assessed before deployment to obtain a good level of expected performance and during the operation in order to avoid dangerous unexpected results. In this paper we propose a methodology to support design and deployment of dependable WSNs by means of an event-based formal verification technique. The methodology includes a process to guide designers towards the realization of a dependable WSN and a tool ("ADVISES") to simplify its adoption. The tool allows to generate automatically formal specifications used to check correctness properties and evaluate dependability metrics at design time and at runtime. During the runtime we can check the behavior of theWSN accordingly to the results obtained at design time and we can detect sudden and unexpected failures, in order to trigger recovery procedures. The effectiveness of the methodology is shown in the context of two case studies, aiming to illustrate how the tool is helpful to drive design choices and to check the correctness properties of theWSN at runtime

Cells have metabolic flexibility that allows them to adapt to changes in substrate availability. Two highly relevant metabolites are glucose and fatty acids (FA), and hence, glycolysis and fatty acid oxidation (FAO) are key metabolic pathways leading to energy production. Both pathways affect each other, and in the absence of one substrate, metabolic flexibility allows cells to maintain sufficient energy production. Here we show that glucose starvation or sustained pyruvate dehy-drogenase (PDH) activation by dichloroacetate (DCA) induce a large genetic remodeling to pro-pel FAO. The extracellular signal-regulated kinase 5 (ERK5) is a key effector of this multistep metabolic remodeling. First, there is an increase in the lipid transport by expression of low-density lipoprotein receptor-related proteins (LRP), e.g. CD36, LRP1 and others. Second, an increase of the expression of members of the acyl-CoA synthetase long-chain (ACSL) family acti-vates FA. Finally, the expression of the enzymes that catalyze the initial step in each cycle of FAO, i.e. the acyl-CoA dehydrogenases (ACADs), is induced. All of these pathways lead to enhanced cellular FAO. In summary, we show here that different families of enzymes, which are essential to perform FAO, are regulated by the signaling pathway, i.e. MEK5/ERK5, which transduces changes from the environment to genetic adaptations.

Antimicrobial resistance (AMR) poses one of the significant challenges for the progress of modern medicine not only by its myriad manifestations on a microbiological plane but also due to its demand for a complex, multisectoral approach for its annulment. While some nations have been actively involved in the deployment of counter measures against AMR, the same have yet to be implemented in India. This can be attributed due to a combination of its epitomizing multivariate nature and the challenges encountered on a ground-level in policy implementation. This review surveys mechanisms and factors promoting incidence of AMR, potential Artificial Intelligence (AI) implementation alongside evaluating the efficacy of the One Health approach on national and state levels in curbing the rise of AMR.

This study aimed to elucidate the similarities and differences between amyloid-forming corpora amylacea (CA) in the prostate and lung, examine the nature of CAs in cystic tumors of the atrioventricular node (CTAVN), and clarify the distinctions between amyloid-forming CA and spheroid-type amyloid deposition. We conducted proteomics analyses using liquid chromatography–tandem mass spectrometry with laser microdissection and immunohistochemistry to validate the characteristics of CAs in the lung and prostate. Our findings revealed that CAs in these organs primarily consist of common proteins (β2-microglobulin and lysozyme) and locally produced proteins. Moreover, we observed a discrepancy between the histopathological and proteomic analysis results in CTAVN-associated CAs. In addition, while the histopathological appearance of amyloid-forming CAs and spheroid-type amyloid deposits were nearly identical, the latter deposition lacked β2-microglobulin and lysozyme, and exhibited evident destruction of surrounding tissue. A literature review further supported these findings. These results suggest that amyloid-forming CAs in the lung and prostate are formed through a shared mechanism, serving as waste containers (wasteosomes) and/or storage for excess proteins (functional amyloids). In contrast, we hypothesize that while amyloid-forming CA and spheroid-type amyloid deposits are formed, in part, through common mechanisms, the latter are pathological.

RNA pol II assembly occurs in the cytoplasm before the translocation of the enzyme to the nucleus. Affecting assembly influences mRNA transcription in the nucleus and mRNA decay in the cytoplasm. However, very little is known about the consequences on ncRNA synthesis. In this work, we show that impairment of RNA pol II assembly leads to a decrease in cryptic non-coding RNAs (preferentially CUTs and SUTs). This alteration is partially restored upon overcoming the assembly defect. Notably, this drop in ncRNAs is only partially dependent on the nuclear exosome, which suggests a major specific effect of enzyme assembly. Our data also point out a defect in transcription termination and lead as to proposes that CTD phosphatase Rtr1 could be involved in this process.

In this study, the term dimension is introduced on fuzzy (neutrsophic) graphs. The classes of these specific graphs are chosen to obtain some results based on dimension. The types of crisp notions and fuzzy (neutrsophic) notions are used to make sense about the material of this study and the outline of this study uses some new notions which are crisp and fuzzy (neutrsophic).

Solar neutrinos have played a central role in the discovery of the neutrino oscillation mechanism. They still are proving to be a unique tool to help investigate the fusion reactions that power stars and further probe basic neutrino properties. The Borexino neutrino observatory has been operationally acquiring data at Laboratori Nazionali del Gran Sasso in Italy since 2007. Its main goal is the real-time study of low energy neutrinos (solar or originated elsewhere, such as geo-neutrinos). The latest analysis of experimental data, taken during the so-called Borexino Phase-II (2011-present), will be showcased in this talk - yielding new high-precision, simultaneous wide band flux measurements of the four main solar neutrino components belonging to the "pp" fusion chain (pp, pep, ⁷Be, ⁸B), as well as upper limits on the remaining two solar neutrino fluxes (CNO and hep).

Omega-3 fatty acids (ω-3 FAs) are important fatty acids having the beneficial roles in human health including reducing blood pressure, lowering the risk of cardiovascular disease and exerting anti-inflammation activities. Omega-3 FAs were mainly found in fish oils, therefore, determination of these FAs is very important. This study highlighted the employment of FTIR spectroscopy combined with multivariate data analysis for determination of ω-3 FAs in fish oils. Fish oils were obtained from the extraction of corresponding fishes and subjected to purification. The oils were further subjected to FTIR spectroscopic measurement at mid infrared region (4000-450 cm-1). Fatty acid compositions of ω-3 FAs namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were determined using gas chromatography with flame ionization (GC-FID), and the results from GC-FID were used as actual values. Two multivariate regressions along with wavenumbers regions or their combinations were optimized and compared to provide the best condition for prediction of EPA and DHA in fish oils. The results showed that partial least square regression (PLSR) was suitable for prediction of DHA applying the variable of absorbance values of the second derivative spectra, with the values of coefficient of determination (R2) of 0.9916 and 0.9316 in calibration and validation models, respectively. The values of root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) obtained were 0.789 and 2.53. While, prediction of EPA was performed using principal component regression with R2 value of &gt; 0.72 and low values of RMSEC and RMSEC. It can be concluded that the combination of FTIR spectra and multivariate regression provides the effective tools and alternative GC-FID method for the prediction of EPA and DHA in fish oils.

Synthesis of new series of 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea derivatives and its in vitro antiproliferative activities against NCI-60 human cancer cell lines of nine different cancer types are described. Fourteen compounds 5a-n have been synthesized with three different hydrogen bondable moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea. Different substituents with different π and σ values were added on the terminal phenyl group. Compounds with 4-hydroxymethylpiperidine moiety showed higher mean percentage inhibition values over the 60-cell line panel at 10-µM concentration. They showed broad-spectrum antiproliferative activity over many cell lines of different cancer types. For instance, compound 5a elicited some lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line by 146.1, 108.7, 136.2, 134.8, 116.6 % at 10 µM, respectively. Compounds 5a-e exhibited superior antiproliferative activity than Paclitaxel and Gefitinib against the most sensitive cell lines. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose testing mode to determine their IC₅₀ values. The data revealed that 5a and 5d urea compounds are the most active derivatives with significant efficacies and superior potencies than Paclitaxel in 21 different cancer cell lines, belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than Gefitinib in 38 and 34 cancer cell lines, respectively; belonging particularly to colon cancer, breast cancer and melanoma cell lines.

For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The International Agency for Research on Cancer (IARC) continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene belong to these potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages while β-myrcene occurs naturally as a constituent of essential oils of plants such as hops, lemongrass and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using data from own nuclear magnetic resonance (NMR) analysis and literature review. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg) and in some fish products (about 10 mg/kg) while among beverages, wines contained between 1–10 mg/L with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is either very old or based on single sample analysis, and currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.

This article discusses the use of a hand held electronic nose to obtain information on the presence of some aromatic defects in natural cork stoppers, such as haloanisoles, alkylmethoxypyrazines and ketones. The proposed prototype has been developed as an instrumentation system with up to eight commercial gas sensors. Machine learning algorithms such as k-nearest neighbors and artificial neural networks has been used. The use of this system tries to improve the current aromatic defect detection process in the cork stopper industry, which is done by gas chromatography or human test panels.

The transition to sustainable mobility is a recognized socio-economic and environmental challenge, particularly among young adults in low- and middle-income countries (LMICs). This paper addresses the lack of comprehensive research on mobility patterns for LMICs by examining the travel patterns of students, staff, and lecturers at the National Advanced School of Public Works, Yaoundé (NASPW) to understand transport mode choices and barriers to the use of public and active transport modes. Data was collected through online questionnaires from 425 participants. Findings revealed that most students (27.5%) used multiple modes of transport, with moto-taxis being the most common (21%). Lecturers primarily used private cars (50%), while staff relied on taxis or multiple modes (33%). Accessibility, vehicle speed, and flexibility appeared as the most important reasons for the preferred modes of transport. Barriers included long waiting times and traffic congestion for public transport, and distance and inadequate infrastructure for active mobility. The usage of public transportation was encouraged by its affordability and reduced travel time, whilst active options were preferred due to their cost savings and health benefits. To promote sustainable mobility for campus travel, it is crucial to encourage active modes, develop mass transport systems, and raise awareness through symposiums and conferences among students and staff.

As part of the Fabaceae project of northeastern Mexico, today we present the compendium of legumes of the subfamilies Caesalpinioideae, Cercidoideae and Detarioideae from this region. As in our previous work on the Mimosoideae Clade, new nomenclatural changes and retypification of genera of the subfamily Caesalpinioideae are included. Also, based on new scientific information published, the taxonomic changes in new genera, recently segregated from the genus Caesalpinia (Conzattia, Coulteria, Denisophytum, Erythrostemon, Guilandina, Hoffmannseggia, and Pomaria) are included. Based on field work, collection of botanical samples over the past 37 years, and reviewing botanical materials in national and international herbaria, the diversity of legumes of the subfamilies Caesalpinioideae, Cercidoideae, and Detarioideae in northeastern Mexico has been recorded. The subfamily Caesalpinioideae includes two tribes, the tribe Caesalpinieae with 12 genera (Caesalpinia, Ceratonia, Coulteria, Delonix, Denisophytum, Erythrostemon, Gleditsia, Guilandina, Hoffmannseggia, Haematoxylum, Parkinsonia, and Pomaria), and 26 species and the tribe Cassieae, which includes three genera (Cassia, Chamaecrita, and Senna) and 28 species. The subfamily Cercidoideae include two genera (Bauhinia and Cercis), and eight species and the subfamily Detarioideae, includes only one genus and one species (Tamarindus indicus). The total flora of these three subfamilies comprize 18 genera and 63 species, it includes 56 native species and seven exotic ones: Bauhinia variegata, Cassia fistula, Ceratonia siliqua, Delonix regia, Erythrostemon gilliesii, Senna alata, and, Tamarindus indicus. The endemism of both subfamilies includes a total of 20 species and 10 infraspecific categories.

Experimental systems to simulate future elevated CO2 conditions in the field often have large, rapid fluctuations in CO2. To examine possible impacts of such fluctuations on photosynthesis, intact leaves of field grown plants of five species were exposed to two-minute cycles of CO2 between 400 and 800 mol mol-1 lasting a total of 10 minutes, with photosynthesis, stomatal conductance and PSII fluorescence measured at the end of each half-cycle, and also 10 minutes after the end of the cycling. Prior to the cyclic CO2 treatments, steady-state responses of leaf gas exchange and fluorescence to CO2 were determined. In four of the five species, in which stomatal conductance decreased with increasing CO2, the cyclic CO2 treatments reduced stomatal conductance. In those species, both photosynthesis and the photochemical efficiency of PSII were reduced at limiting internal CO2 levels, but not at saturating CO2. In the fifth species, there was no change in stomatal conductance with CO2, and no change in either photosynthesis or PSII efficiency at any CO2 level with CO2 cycling. It is concluded that in many, but not all, species fluctuations in CO2 may reduce photosynthesis at low CO2 partly by decreasing the photochemical efficiency of photosystem II, as well as by decreasing stomatal conductance.

Hybrid metal-organic compounds as relatively new and prosperous magnetoelectric multiferroics provide opportunities to improve the polarization, magnetization and magneto-electric coupling at the same time, which usually have some limitations in the common type-I and type-II multiferroics. In this work we investigate the crystal of guanidinium copper(II) formate [C(NH2)3]Cu(HCOO)3 and give novel insights concerning the structure, magnetic, electric and magneto-electric behaviour of this interesting material. Detailed analysis of crystal structure at 100 K is given. Magnetization points to the copper(II)-formate spin-chain phase that becomes ordered below 4.6 K into the canted antiferromagnetic (AFM) state, as a result of super-exchange interaction over different formate bridges. The performed ab-initio colinear density functional theory (DFT) calculation confirm the AFM-like ground state as a first approximation and explain the coupling of spin-chains into the AFM ordered lattice. In versatile measurements of magnetization of a crystal, including transverse component besides the longitudinal one, very large anisotropy is found that might originate from canting of the coordination octahedra around copper(II) in cooperation with the canted AFM order. With cooling down in zero fields the generation of spontaneous polarization is observed step-wise below 270 K and 210 K and the effect of magnetic field on its value is observed also in the paramagnetic phase. Measured polarization is somewhat smaller than the DFT value in the c-direction, possibly due to twin domains present in the crystal. The considerable magneto-electric coupling below the magnetic transition temperature is measured with different orientations of the crystal in magnetic field, giving altogether the new light onto the magneto-electric effect in this material.

Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). In part II we report the optimization of a potent and selective hydroxamic acid meprin α inhibitor probe which may help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition.

Let f : V → V be a Cohomological Expanding Mapping¹ of a smooth complex compact homogeneous manifold with $ dim_{\mathbb{C}}(\Vc)=k \ge 1$ and Kodaira Dimension $\leq 0$. We study the dynamics of such mapping from a probabilistic point of view, that is, we describe the asymptotic behavior of the orbit $ O_{h} (x) = \{h^{n} (x), n \in \mathbb{N} \quad \mbox{or}\quad \mathbb{Z}\}$ of a generic point. Using pluripotential methods, we have constructed in our previous paper \cite{Armand4} a natural invariant canonical probability measure of maximal Cohomological Entropy $ \nu_{h} $ such that ${\chi_{2l}^{-m}} (h^m)^\ast \Omega \to \nu_h \qquad \mbox{as} \quad m\to\infty$ for each smooth probability measure $\Omega $ in $\Vc$ . We have also studied the main stochastic properties of $ \nu_{h}$ and have shown that $ \nu_{h}$ is a smooth equilibrium measure , ergodic, mixing, K-mixing, exponential-mixing. In this paper we are interested on equidistribution problems and we show in particular that $ \nu_{h}$ reflects a property of equidistribution of periodic points by setting out the Third and Fourth Main Results in our study. Finally we conjecture that $$\nu_h:=T_l^+ \wedge T_{k-l}^-,$$ $$\dim_\HH(\nu_h)= \Psi h_{\chi}(h) , $$ $$\dim_\HH( \mbox{Supp} T_l^+) \geq 2(k-l) + \frac{\log \chi_{2l}}{\psi_l},$$ $$|\langle \nu_m^x-\nu_h,\zeta\rangle|\leq M \Big[1+\log^+{1\over D(x,\Tc)}\Big]^{\beta/2}\|\zeta\|_{\Cc^\beta} \gamma^{-\beta m/2}$$ and $$|\langle \nu_m^x-\nu_h,\zeta\rangle|\leq M \Big[1 +\log^+{1\over D(x,E_\gamma)}\Big]^{\beta/2}\|\zeta\|_{\Cc^\beta} \gamma^{-\beta m/2}.$$

The new NICE guideline for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), published in October 2021, makes significant changes in treatment recommendations. It acknowledges the complexity of this chronic medical condition, which always impacts quality of life and can be profoundly disabling, recognising the prejudice and stigma that people with ME/CFS often experience in the absence of any specific diagnostic test. The guideline outlines steps for accurate diagnosis, recognising post-exertional malaise as a core symptom; importantly, ME/CFS can now be diagnosed after just 3 months in a bid to improve long-term health outcomes. It recommends the need for individual, tailored management by a multi-disciplinary team, ensuring that the wellbeing of the individual is paramount. The guideline makes clear that any programme based on fixed incremental increases in physical activity or exercise, for example graded exercise therapy (GET), should not be offered as a treatment for ME/CFS and emphasises that cognitive behavioural therapy (CBT) should only be offered as a supportive intervention. Because of the rigorous methodology required by NICE Committee review and the inclusion of the testimony of people with lived experience as committee members, this guideline will influence the future diagnosis and management of ME/CFS in the UK and beyond.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

The coastal zone of the Valparaíso Region has been historically threatened by its natural and anthropogenic conditions, which demands efficient management for the adaptation and mitigation of the impacts that occur on the coast, especially in the face of the growing effects of climate change. As a contribution to decision makers in the development of strategic actions through adaptation plans, this study presents an approach to coastal vulnerability in the southern part of the region, applying the Coastal Vulnerability Index considering the variables geomorphology, coastal slope, changes in sea level, coastal erosion, tidal range, and wave height. The result illustrates a sectorization of the coast according to the degree of vulnerability, where the sectors formed by fine sandy beaches near river mouths and estuaries present greater risks to climatic events than those rocky stretches with medium-low cliffs.

Taxanes have been shown to be the most effective treatment for recurrent or metastatic breast cancer. However, for patients pretreated with taxanes, more active and possibly less toxic drugs are needed. In this retrospective study, we investigated on the effectiveness and safety of eribulin mesylate in 91 taxane-refractory subjects, extracted from the ESEMPIO database, which included 497 metastatic breast cancer patients treated with eribulin allover the Italy. This analysis included only those patients who have shown disease progression while receiving taxane therapy (primary refractory), or those who achieved a response followed by progression while still on therapy (taxane failure). Overall, 41/91 patients (45.2%) showed a clinical benefit; 1 complete response (2.2%) and 16 partial responses (17.6%) were observed. The median progression free survival was 3.1 months (95% CI: 2.8–3.5) and the median overall survival was 11.6 months (95% CI: 8.7–16.7). With regard to toxicity, 53 patients (58%) experienced asthenia/fatigue, 23 (25%) showed peripheral neurotoxicity, 18 (20%) alopecia, 12 (13%) mild constipation and 27 (30%) neutropenia. The toxicity related to the treatment led to eribulin dose reduction in 19 (21%) and discontinuation in 9 (10%) patients, respectively. In conclusion, this study suggests that eribulin is effective and well tolerated also in taxane-refractory patient.

To get more data concerning the influence of fertilizers (organic and mineral) on different forage plants existing in North-eastern Romanian grassland, the mass fractions of 14 essential, enzymatic, or considerd toxic elements was determined by Instrumental Neutron Activation Analysis together with the amount of crude proteins, ash, fibres as well as ether fact extract. Final results showed a significant variance of the content of analysed elements on organic as well as on mineral fertilized experimental plots, i.e. the content increased in 24% of plots, decreased in 23%, and remained unchanged in 45% while in 8% of plots their content was below the detection limits, as the case of Se. At the same time, an increase content of crude protein and ether extract was evidenced in fertilized grasses for all applied fertilizers while other global indicators such as neutral and acid fibre of sufuric lignin content decreased, suggesting significant higher nutritional values of fertilized forage plant.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

Background: The validation of laser usage during laparoscopic procedures, notably by Camran Nezhat in the late 1980s, has been significant. Lasers offer precision and depth control in tissue vaporization without bleeding. Surgical intervention remains central in managing endometrio-sis-associated pain and infertility, especially for patients unresponsive to hormonal therapy. Methods: This retrospective cohort study included 200 patients with SPE who underwent laparo-scopic laser vaporization. Surgery was performed using a CO2 laser, and histological confirma-tion of endometriosis was obtained for all cases. Pain scores and SF-36 questionnaire domains were assessed preoperatively and postoperatively. Fertility outcomes were evaluated among pa-tients desiring pregnancy. Results: Significant improvements in pain score and SF-36 questionnaire domains were ob-served postoperatively (p-value

Conventional monitoring relies on "in vivo" (non-destructive) measurements of aboveground organ traits (such as stems, branches, and leaves) to analyze plantation growth trends and assess the effectiveness of management practices like watering and fertilization. This study reveals the necessity of “ex vivo” (destructive) approaches, post-excavation, to ensure fully reliable monitoring of plantation performance, including belowground organ growth and development trends. We showcase the effectiveness of dendrometric analysis, which measures the annual ring width in the secondary xylem (wood) of the taproot and stem. Monitoring above- and belowground organ growth trends allow for the exploration of similarities and differences in how different tree organs respond to internal and external factors. Such monitoring is especially crucial for assessing plantation performance in challenging climates, such as those found in arid and semi-arid lands.

Background: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of neonatal hyperbilirubinemia. The aim of the study is to evaluate the clinical findings of glucose 6 phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) deficiency, to prevent further examinations for prolonged jaundice, and to contribute by regulating its treatment. At the same time, it is to determine whether systemic-immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) can be used in addition to conventional complete blood count (CBC) parameters in the diagnosis of neonatal prolonged jaundice. Methods: In full term neonates with hyperbilirubinemia who were admitted to Medicine Hospital between January 2019 and January 2024 with the complaint of jaundice, 167 infants with a serum bilirubin level above 5 mg/dL, whose jaundice persisted after the 10th day, were included in the study. Results: 63.5% of the patients were male and the mean age was 31±6 days. G6PD was negatively perfectly correlated with NLR (r: -1; p

Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A. We found that PI 3-kinase activation promoted cell cycle progression, especially when growth signals were limiting, as well as cell migration, both in a collective monolayer and as single cells. Furthermore, we showed that KMT2D inactivation had relatively little influence on these processes, except for single cell migration that KMT2D inactivation promoted in synergy with PI 3-kinase activation. Combination of these two genetic alterations induced expression of the ARPC5L gene that encodes a subunit of the Arp2/3 complex. ARPC5L depletion fully abolished the enhanced migration persistence exhibited by double-mutant cells. Our reconstitution approach in MCF10A has thus revealed both the cell function, single cell migration, and the underlying Arp2/3-dependent mechanism, which are synergistically regulated when KMT2D inactivation is combined with the activation of the PI 3-kinase.

The asymmetric synthesis of polyunsaturated triene C18:3 n-3 and C18:3 n-6 methoxylated ether lipids (MEL) of the 1-O-alkyl-sn-glycerol type is described as possible structural candidates for a triene C18:3 MEL of an unknown identity found in a mixture of shark and dogfish liver oil. Their C18:3 hydrocarbon chains constitute an all-cis methylene skipped n-3 or n-6 triene framework, along with a methoxyl group at the 2'-position and R-configuration of the resulting stereogenic centre. The methoxylated polyenes are attached by an ether linkage to the pro-S hydroxymethyl group of the glycerol backbone. The syntheses were based on the polyacetylene approach that involves a semi-hydrogenation of the resulting triynes. Both syntheses were started from our previously described enantio- and diastereomerically pure isopropylidene-protected glyceryl glycidyl ether, a double-C3 building block that was designed as a head group synthon for synthesis of various types of MELs.

NS-3 is one of the most used Network Simulators because it includes different modules, applications and protocols to simulate a wide range of network. Since new proposals usually involve a large number of simulations, a procedure to automatize the simulation process and extract statistics is very useful. "Statistical Framework" (SF) is an important module of NS-3 because it fulfills this need. SF allows us to collect simulation data and obtain statistical reports for NS-3. In this report, we present a detailed description of statistical framework module and two useful examples of its configuration.

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating acquisition of a rapid supply of ATP for proliferation in AML. Therefore, targeting of mesothelin presents a potentially promising approach for mitigating the progression of AML through inhibition of glycolysis and mitochondrial respiration in myeloid cells.

Prestressed concrete sleepers (or railroad ties) are principally designed in order to carry wheel loads from the rails to the ground of railway tracks. Their design takes into account static and dynamic loading conditions. In spite of the most common use of the prestressed concrete crossties in railway tracks, there have always been many demands from rail engineers to improve serviceability and functionality of concrete crossties. For example, signaling, fiber optic, equipment cables are often damaged either by ballast corners or by tamping machine. There has been a need to re-design concrete crosstie to cater cables internally so that they would not experience detrimental or harsh environments. Also, many concrete crossties need a retrofit for automatic train control device and similar signaling equipment. In contrast, the effects of holes and web openings on structural capacity of concrete crossties have not been thoroughly investigated. This paper accordingly highlights the effect of holes and web openings on the toughness and ductility of concrete crossties. The outcome of this research enables better decision making process for retrofiting prestressed concrete crossties with holes and web opening in practice.

The objective was to analyze the effects of adding anthocyanin delphinidin-3-O-sambubioside and cyanidin-3-O-sambubioside of Hibiscus sabdariffa L. in animal diets. Scientific articles published before 2021 in clinics, pharmacology, nutrition, and animal production were included. The grains/concentrate, metabolic exigency, and caloric stress contribute to increasing the reactive oxygen species (ROS); the excess of ROS unbalance the oxidants and antioxidants. Cyanidin-3-O-sambubioside and delphinidin-3-O-sambubioside have antioxidant, antibacterial, antiviral, and anthelmintic activities. In the rumen, anthocyanin might show interactions and/or synergisms with substrates, microorganisms, and enzymes which could reduce the fiber degradability, but increase the potential methane (CH4) emissions; since anthocyanin interferes in the biohydrogenation of fats, they increase the fat milk and meat quality. Anthocyanins reduce plasma oxidation and deposit in tissues, increasing the milk and meat antioxidant activities. Cyanidin-3-O-sambubioside and delphinidin-3-O-sambubioside act as inhibitors of the angiotensin-converting enzyme (ACEi) and rennin expression which may improve milk yield (there is not enough evidence in ruminants, though). Polyphenols affect the reproductive potential. Sub products of HS contain as many amounts of polyphenols as calyces, and their inclusion in diets would positively affect the average daily gain and fat meat quality. Including HS in ruminant diets can improve the meat and milk quality.

The Bacillus megaterium LVN01 species native to Colombia has demonstrated the ability to metabolize different co-products or industrial waste (such as fique juice, cane molasses, residual glycerol) and accumulate polyhydroxybutyrate (PHB), giving it potential in the bioplastics industry. In this research, the potential of liquid digestate as a carbon source for the production of PHA in fermentation processes with this bacterial strain was evaluated. Favorably, it was found that B. megaterium utilizes the nutrients from this residual substrate to multiply appropriately and efficiently synthesize poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV). Bench scale aerobic batch fermentation, under the operational conditions of this research [Volume: 3L; Temperature: 30.8°C; Agitation: 400 rpm; pH: 7.0 ± 0.2; Disolved Oxygen: 100% saturation; Antifoam 10% (v/v)], generated maximum values of DCW (0.56 g cell L-1) at 60 h, while the maximum PHB yield (360 mg PHB L-1) occurred at 16 h, which is very favorable for sustainable degradable bioplastics production. Additionally, GC-MS and NMR analyses confirmed that the PHBV copolymer synthesized by B. megaterium is made up of the monomers 3-hydroxybutyrate (3HB) and 3-hydroxyvalerate (3HV). Furthermore, the thermal properties determined by TGA (Tonset=283.1 ºC, Tendset= 296.98 ºC. Td =290.114 °C) and DSC (Tm= ºC155.7 °C, ΔHf= 19.80 J g-1, Xcr = 18.17%), indicate that it is a thermally stable biopolymer with low percentages of crystallinity, providing flexibility that facilitates molding, adaptation, and application in various industrial sectors.

A conjugate compound 5, (E)-6-hydroxy-2-oxo-2H-chromen-7-yl 3-(4-hydroxy-3-methoxyphenyl)acrylate, of 6,7-hydroxycoumarin (esculetin) 3 and (E)-3-(4-hydroxy-3-methoxyphenyl)- acrylic acid (ferulic acid) 1 was prepared in 61% yield by the esterification reaction of a protected ferulic acid 2a with esculetin 3 in the presence of triethylamine in dichloromethane for 3 h, followed by deprotection using 3M HCl. The structure of compound 5 was confirmed by 1H, 13C NMR spectroscopy, mass-spectrometry and elemental analysis.

The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs, and able to perfectly integrate with the host’s organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials: they exhibit good features in terms of impermeability, deformability and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration: however, this kind of materials lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these mate-rials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields: in the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance and patency will be herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance will be been disclosed.

Orthohepadnavirus causes chronic hepatitis in a broad range of mammals, including primates, cats, woodchucks, and bats. Hepatitis B virus (HBV) X protein inhibits type-I interferon (IFN) signaling, promoting HBV escape from the innate immune system to establish persistent infection. However, whether X proteins of Orthohepadnavirus viruses in the other species have similar inhibitory activity remains unknown. Here, we investigated the anti-IFN activity of 17 Orthohepadnavirus X proteins derived from various hosts. We observed conserved activity of Orthohepadnavirus X proteins in inhibiting TIR-domain-containing adaptor protein inducing IFN-β (TRIF)-mediated IFN-β signaling pathway through TRIF degradation. X proteins from domestic cat hepadnavirus (DCH), a novel member of Orthohepadnavirus, inhibited mitochondrial antiviral signaling protein (MAVS)-mediated IFNβ signaling pathway comparable with HBV X. These results indicate that inhibition of IFN signaling is conserved in Orthohepadnavirus X proteins.

LPA3 receptors were expressed in TREx HEK 293 cells, and their signaling and phosphorylation were studied. The agonist, lysophosphatidic acid (LPA), increased intracellular calcium and ERK phosphorylation through pertussis toxin-insensitive processes. Phorbol myristate acetate, but not LPA, desensitizes LPA3-mediated calcium signaling. The agonists and the phorbol ester-induced LPA3 internalization. Pitstop 2 (clathrin heavy chain inhibitor) markedly reduced LPA-induced receptor internalization; in contrast, phorbol ester-induced internalization was only delayed. LPA induced rapid β-arrestin-LPA3 receptor association. The agonist and the phorbol ester induced marked LPA3 receptor phosphorylation, and phosphorylation sites were detected using mass spectrometry. Phosphorylated residues were detected in the intracellular loop 3 (S221, T224, S225, and S229) and in the carboxyl terminus (S321, S325, S331, T333, S335, Y337, and S343). Interestingly, phosphorylation sites are within sequences predicted to constitute β-arrestin binding sites. These data provide insight into LPA3 receptor signaling and regulation.

Chronic kidney disease (CKD) is actually considered a public health priority according to the increasing number of patients affected by this condition: this casuistry is not only related to specific glomerular, tubular or autoimmune diseases or a consequence of acute kidney injury (AKI) episodes leading to organ failure, but it is tied to the progression of life expectancy and the impact of comorbidities such as cardiovascular disease, diabetes and cancer. CKD and its comorbidities promote low grade inflammatory status with an impact on patients’ clinical conditions, reducing their possibility for kidney transplantation or graft survival and their survival when receiving renal replacement therapies such as hemodialysis (HD) or peritoneal dialysis (PD). CKD is often referred to as an ageing accelerator: innate immune system dysregulation, in the uraemic proinflammatory milieu, is involved in this accelerated senescence phenomena and pentraxins, particularly Pentraxin-3 (PTX-3), are of particular interest in the development of kidney disease. A complete understanding of the mechanism of CKD progression, innate immune system involvement and a proper definition of PTX-3 role in kidney disease, could redefine the approach for diagnosis and a more centered patients’ management to slow down CKD progression over time and reduce its clinical and social impact.

Preeclampsia (PE) is a common pregnancy complication. It is associated with high maternal morbidity and mortality rates and intrauterine foetal growth restriction. This condition is characterised by high blood pressure and urinary protein levels. Apelin and galectin-3 (Gal- 3) are peptides involved in the regulation of body fluid homeostasis, inflammation and cardiovascular functions. This study aimed to determine the correlations amongst serum apelin and Gal-3 levels and insulin resistance (IR) in women with PE. Sixty patients with PE and 30 healthy controls participated in this study. The PE group had significantly lower apelin levels (p < 0.01) and higher Gal-3 levels (p < 0.05) than the control group. The PE group had higher serum glucose levels and β-cell functions than the control group. Moreover, patients with PE exhibited dyslipidaemia. Correlation analysis indicated that apelin and Gal-3 levels were not significantly correlated. Moreover, no correlation existed between the apelin levels and any measured parameters of the PE group. In conclusion, the elevations in serum Gal-3 levels with increments in IR-related parameters and lipid profiles reflect the possible contribution of Gal-3 to the harmful effects of IR and dyslipidemia levels on women with PE.

In descriptive statistics, U -statistics arise naturally in producing minimum-variance unbiased estimators. In 1984, Serfling considered the distribution formed by evaluating the kernel of the U -statistics and proposed generalized L-statistics which includes Hodges-Lehamnn estimator and Bickel-Lehmann spread as special cases. However, the structures of the kernel distributions remain unclear. In 1954, Hodges and Lehmann demonstrated that if X and Y are independently sampled from the same unimodal distribution, X − Y will exhibit symmetrical unimodality with its peak centered at zero. Building upon this foundational work, the current study delves into the structure of the kernel distribution. It is shown that the kth central moment kernel distributions (k > 2) derived from a unimodal distribution exhibit location invariance and is also nearly unimodal with the mode and median close to zero. This article provides an approach to study the general structure of kernel distributions.

This article is the second part of a scientific project under the general name "Geometrized vacuum physics". On the basis of the Algebra of Stignatures presented in the previous article [1], this article develops the main provisions of the Algebra of Signatures. Both of the above algebras are aimed at studying the properties of an ideal vacuum, but at the same time they are universal and can be applied in various branches of knowledge. It is shown that the signature of a quadratic form is related to the topology of the metric space for which the given quadratic form is a metric. Conditions are given under which an additive imposition of metric spaces with different topologies (or signatures) leads to a total Ricci flat space similar to a Calabi-Yau manifold. A spin-tensor representation of metrics with different signatures is considered and a Dirac bundle of quadratic forms is presented. This article does not contain physical applications of the Algebra of Signatures, but the potential power of this mathematical apparatus will be demonstrated in subsequent articles of this project.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

We discuss the implementation of a suite of virtual diagnostics at the FACET-II facility currently under commissioning at SLAC National Accelerator Laboratory. The diagnostics will be used for prediction of the longitudinal phase space along the linac, spectral reconstruction of the bunch profile and non-destructive inference of transverse beam quality (emittance) using edge radiation at the injector dogleg and bunch compressor locations. These measurements will be folded in to adaptive feedbacks and ML-based reinforcement learning controls to improve the stability and optimize the performance of the machine for different experimental configurations. In this paper we describe each of these diagnostics with expected measurement results based on simulation data and discuss progress towards implementation in regular operations.

Molecule radiation can be used as a tool to study colder regions in switching arc plasmas like arc fringes in contact to walls and ranges around current zero (CZ). This is demonstrated in the present study for the first time for the case of ablation-dominated high–current arcs as key elements of self–blast circuit breakers. The arc in a model circuit breaker (MCB) in CO2 with and an arc in a long nozzle under ambient conditions with peak currents between 5 and 10 kA were studied by emission and absorption spectroscopy in the visible spectral range. The nozzle material was polytetrafluoroethylene (PTFE) in both cases. Imaging spectroscopy was carried out either with high-speed cameras or with intensified CCD cameras. A pulsed high-intensity Xe lamp was applied as background radiator for the broad-band absorption spectroscopy. Emission of Swan bands from carbon dimers was observed at the edge of nozzles only or across the whole nozzle radius with highest intensity in the arc center, depending on current and nozzle geometry. Furthermore, absorption of C2 Swan bands and CuF bands were found with the arc plasma serving as background radiator. After CZ, only CuF was detected in absorption experiments.

We examine data assimilation coupling between meteorology and chemistry in the stratosphere from both weak and strong coupling strategies. The study was performed with the Canadian operational weather prediction Global Environmental Multiscale (GEM) model coupled online with the photochemical stratospheric chemistry developed at the Belgian Institute for Space Aeronomy, described in Part I. Here, the Canadian Meteorological Centre’s operational variational assimilation system was extended to include errors of chemical variables and cross-covariances between meteorological and chemical variables in a 3D-Var configuration, and we added the adjoint of tracer advection in the 4D-Var configuration. Our results show that the assimilation of limb sounding observations from the MIPAS instrument on board Envisat can be used to anchor the AMSU-A radiance bias correction scheme. Also, the added value of limb sounding temperature observations on meteorology and transport is shown to be significant. Weak coupling data assimilation with ozone-radiation interaction is shown to give comparable on meteorology whether a simplified linearized or comprehensive ozone chemistry scheme is used. Strong coupling data assimilation, using static error cross-covariances between ozone and temperature in a 3D-Var context, produced inconclusive results with the approximations we used. We have also conducted the assimilation of long-lived species observations using 4D-Var to infer winds. Our results showed the added value of assimilating several long-lived species, and an improvement in the zonal wind in the Tropics within the troposphere and lower stratosphere. 4D-Var assimilation also induced a correction of zonal wind in the surf zone and a temperature bias in the lower tropical stratosphere