In this paper, the influence of the various degradation conditions, on the molecular and supramolecular structure of polybutylene succinate (PBS) and polybutylene succinate adipate (PBSA) copolymer during degradation time is described. Experiment was carried out by the use injection molded samples and normalized conditions of biodegradation in soil, composting and artificial weathering. Materials were studied by using size-exclusion chromatography (SEC) coupled with multiangle laser light scattering (MALLS) detection and wide-angle X-ray diffraction (WAXD). Additionally, the physical and mechanical properties of the samples were determined. The performed experiments clearly show difference impact of selected degradation condition on the macroscopic, supramolecular and molecular parameters of studied aliphatic polyesters. The structural changes in PBS and PBSA explain the observed changes in the physical and mechanical properties of the obtained injection molded samples.

We have found a region in the northwestern Japan Sea near the Subpolar Front where mesoscale eddies regularly form and circulate. The anticyclonic eddy with a strong dynamic feature, vertically extended to the bottom (~3500 m), multilayer core structure and extreme values of temperature and salinity was sampled there in the cruise in May 2004. The altimetry-based eddy tracking showed that it had a life span of nine months with the size reaching 120 km. CTD observational data were used to explore the eddy’s features and vertical structure. The eddy had a multilayer core with different thermohaline characteristics which could be originated by eddy interaction with the surrounding waters during its life. The evolution of the eddy has been studied and analyzed with the help of altimetry-based Lagrangian indicators of water motion. Performing the particle-tracking numerical experiments, we computed the Lagrangian maps that contain information on the origin of water inside the eddy core and its ‘age’ on every day of the eddy’s life. Inspecting daily-computed Lagrangian maps, we documented the essential events in the evolution of the eddy including its formation, splitting, merger, entrainment and detrainment of water, erosion and eventual decay. All these observations have been verified with the infrared satellite images. The new Lagrangian technique has been applied to calculate day by day the content of water of various origin (coastal, subtropical and subarctic) entrained into the eddy core. It has been found that the surface core has been filled mainly with subtropical water originated in the southern flank of the Subpolar Front. The episodes with cardinal changes of ratio of different water types have been recorded and verified with the infrared satellite images and maps of the origin of water inside the eddy core.

Background: Although Tuberculosis (TB) is one of the oldest diseases known to mankind, many practitioners are still unaware of various aspects of management of TB including drug resistant TB. To be able to make an impact on the disease burden we need to understand the knowledge, attitude and practices (KAP) of practitioners, both in government and private sector, towards TB case management. Methodology: A random cross-sectional survey of 99 respondents to assess the KAP towards TB case management using a digital semi-structured questionnaire which was pre-tested and administered to allopathic practitioners from across States in North and Central India. Results: 77% responders were government doctors and 23% were private practitioners. Chest physicians accounted for 61% of the responders. 26% of government and 78% of private doctors relied on sources which are difficult to validate for their knowledge on drug resistant TB management. There were large variations seen in knowledge on modes of transmission, standard precautions, extent of drug resistant TB, diagnostics as well as treatment regimen for drug resistant TB. Conclusion: The knowledge of both sector doctors especially amongst private practitioners with respect to the awareness of extent, diagnosis, and treatment and infection control measures for drug resistant TB is suboptimal which translates to poor diagnostic, therapeutic and infection control choices amongst private practitioners. If India has to achieve the targets for TB Elimination by 2025, serious work needs to be done to upgrade the knowledge of the private sector doctors on drug resistant tuberculosis. The Ministry of Health and Family Welfare, GoI needs to have regular educational programs for the private practitioners coupled with awareness campaigns and frequent surveys to assess the knowledge, attitude and practices being followed in the private sector for TB management including drug resistant TB.

According to this study, approximately half of Africa's forests are utilized primarily or partially for the production of wood and non-wood commodities. Aims to evaluate Africa's forestry and forest products, namely Wood Forest Products (WFPs) and Non-wood Forest Products (NWFPs) in the sixteen (16) West African countries. While adhering to the following guidelines: wood extraction and preparation, analyzing wood primarily used as an energy source in Africa, identifying non-wood forest products in Africa, the state of export, trade, and customs procedures in West Africa, and examining the role of forests and forest stakeholders in Africa's low-carbon economy transition. An exploratory literature review of selected wood forest products and non-wood forest products (plants and animals) in West Africa identifying the country, the natural land area with the natural habitat issues of the forest, the species most harvested and traded in the West African sub-region. The study reemphasized some government legislation, policies, and market trade failures and limitations while also stating that trees may help in the low-carbon revolution through interventions aimed at maintaining, improving, and restoring natural capital have demonstrated that high environmental requirements of sustainable forest management (SFM) may be met in both natural and planted forests. The study identified a systematic assessment of the most common forest products (wood and non-wood forest products) considering the available data on the national forest reserves of the selected countries in West Africa. The study also revealed the need for biodiversity conservation of the available forest reserves to help mitigate the impact of global warming targeting the United Nation’s Sustainable Development Goal 13- Climate Action. Which is focused on integrating climate change mitigation, adaptation, impact reduction, and early warning signs into the national policies, improving forest planning and management education, awareness-raising, and institutional capacity within the sub-region.

The purpose of this study was to identify potential causes of violence and crime in informal settlements and residents’ strategies for response and prevention to these issues, as perceived by women living in Mathare informal settlement in Nairobi, Kenya. A total of 55 in-depth interviews were conducted with women living in the informal settlement in 2015-2016. A modified grounded theory approach was used to guide data collection and analysis. The most common contributor to violence and crime identified by women in Mathare informal settlement was idle youth, but leadership and government challenges, corruption and/or inadequacy of police, community barriers, tribalism, and lack of protective infrastructure also emerged as contributing factors. Despite facing many economic, environmental, and day-to-day challenges, women in Mathare identified violence and crime as predominant issues; thus, developing effective response and prevention strategies to these issues in informal settlements is paramount. Women suggest there are many strategies and initiatives to reduce and prevent violence and crime in informal settlements, but also identified barriers to implementing them. Findings suggest there is a need for trust-building between formal and informal organizations and institutions, systems of accountability, and long-term investment to foster sustainable and effective violence and crime response and interventions in these settlements.

Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress, and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect the tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation, including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and 5-AZA group. MiR-18a, miR-21, miR-34a and miR-146a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRNs profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRNs expression levels. Relating to prognostic risk factors, high risk MDS groups (high IPSS-R, high cytogenetic risk, high molecular risk (HMR) mutations tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRNs expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRNs deregulation involved in the MDS development, that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRNs expression levels in MDS patients.

Natural cytokinins are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of novel cytokinin analogs with alkyl substituents at various positions of the aromatic moiety, as well as with oxygen-containing groups, and tested their antiproliferative activity in MDA-MB-231, A-375, and U-87 MG cell lines, and cytoprotective properties in H2O2 and CoCl2 models. Two amino-linked compounds were anti-proliferative with the ability to act synergistically with doxorubicin, and two carbamate-based ones were cytoprotective. According to the molecular docking data, anti-proliferation was based on the A2AR and APRT inhibition and cytoprotection on the CDK2 inhibition. The obtained results are promising for the development of novel anti-cancer therapeutics.

With the rapid growth of the global mask market, consumers have put forward higher requirements for the functionality and ingredients of mask products. Conventional facial masks generally use ordinary non-woven fabrics as the mask base fabric, are frequently used with essence and contain preservatives. At the same time, they are susceptible to the influence of the external environment and are easily oxidized, which will cause the mask to deteriorate and skin allergic reactions. In addition, conventional facial masks exhibit poor skin fit, limited breathability, inadequate absorption of nutrient solutions, and easy to drip. The nanofiber mask prepared by electrospinning technology has a high specific surface area and high porosity, which enabling improved nutrient absorption by the skin, superior skin fit, and exceptional breathability. Nanofiber facial mask products can effectively solve consumer pain points and promote the high-end development of facial mask products. Therefore, this research combines needleless electrospinning technology to develop a novel solid-state, preservative-free, and quick-dissolving nanofiber facial mask that can be prepared on a large scale. Based on needleless electrospinning technology, this research deeply explores the process parameters and influencing mechanisms of quick-dissolving nanofiber facial masks, ultimately achieving the consistent production of nanofiber facial masks with optimal morphology. Comprehensive and evaluation of the structure and performance of nanofiber facial masks from micro and macro perspectives. The experimental results show that the mask morphology is optimal under the process conditions of using a spinning liquid of 20% collagen peptide solution, a spinning voltage of 30kV, a collection distance of 19cm, and a liquid supply speed of 130ml/h.

The new hybrid composite materials for PEM fuel cell were synthesized by UV-polymerization of acrylic monomers (acrylonitrile (AN), acrylic acid (AA), ethylene glycol dimethacrylate (EGDMA)) and sulfo aromatic monomer – sodium styrene sulfonate (SSS), and tetraethoxysilane/3-methacryloxypropyltrimethoxysilane (TEOS/MAPTMS)-based sol-gel system. By means of X-ray spectroscopy fractal structure of the obtained materials was characterized. Proton conductivity and viscoelastic properties of the materials were investigated depending on the content of inorganic component in nanocomposites. On the basis of impedance studies, an equivalent scheme is proposed that successfully describes the proton conductivity in the synthesized composite electrolyte membranes.

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anti-cancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O alkyl silybins derivatives were synthesized by Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4) and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of new eighteen derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by DPPH assay, showed a very pronounced activity depending on the tyrosyl moiety (HTYR>MTYR>>TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

Three-dimensional (3D) models with improved biomimicry are essential to reduce animal experimentation and drive innovation in tissue engineering. In the current study, we investigate the use of alginate-based materials as polymeric inks for 3D bioprinting of osteogenic models using human bone marrow stem/stromal cells (hBMSCs). A composite bioink incorporating alginate, nano-hydroxyapatite (nHA), type I collagen (Col) and hBMSCs was developed and for extrusion-based printing. Rheological tests perfomed on crosslinked hydrogels confirm the formation of solid-like structures consistently indicating a higher storage modulus compared to the loss modulus. The swelling behaviour analysis showed that the addition of Col and nHA into an alginate matrix can enhance the swelling rate of the resulting composite hydrogels, which maximizes cell proliferation within the structure. The LIVE/DEAD assay outcomes demonstrate that the inclusion of nHA and Col did not detrimentally affect the viability of hBMSCs over seven days post-printing. PrestoBlueTM revealed a higher hBMSCs viability in the alginate-nHA-Col hydrogel compared to the remaining groups. Gene expression analysis revealed that alginate-nHA-col bioink favoured a higher expression of osteogenic markers, including secreted phosphoprotein-1 (SPP1) and collagen type 1 alpha 2 chain (COL1A2), in hBMSCs after 14 days, indicating the pro-osteogenic differentiation potential of the hydrogel. This study demonstrates that the incorporation of nHA and Col into alginate enhances osteogenic potential and provides a bioprinted model to systematically study osteogenesis and the early stages of tissue maturation in vitro.

Determining the maturity of compost and other organic fertilizers is very important because of possible phytotoxic or phytostimulative effects. The maturity of the compost can be assessed on the basis of chemical analyses, and the germination test with different test plants is most often used to determine phytotoxicity. In this research, using the results of chemical analyses, the maturity of compost produced from plant residues after maintenance of green public areas was assessed. At the same time, a germination test was carried out with 4 test plant species (cucumber, garden cress, triticale, barley) to determine the phytotoxicity of compost (i.e. compost extract in a ratio of 1:2.5 and 1:10) and 3 ammonium N solutions (in concentrations of 200, 400 and 600 mg/L NH4-N). According to the chemical properties of compost, primarily the C/N and NH4-N/NO3-N ratios, as well as the NH4-N concentration, and the germination test with cu-cumber and garden cress, we can conclude that the tested compost was mature and that we do not expect a phytotoxic effect. The choice of the plant is very significant because the germination test with compost extract shows an undoubted phytostimulative effect on garden cress and cu-cumber with more pronounced phytostimulative effect of compost 1:10 than 1:2.5 extract. No such effect was found on the monocotyledonous test plants triticale and barley since the 1:10 ex-tract had no significant effect, and the 1:2.5 extract had a phytotoxic effect, moderate on triticale and high on barley. The conclusion is that garden cress and cucumber are suitable test plants for determining phytostimulative effect of compost, but they are not suitable for determining phytotoxicity for monocotyledonous plants, especially if the cause of phytotoxicity is some non-ammonium component. Barley is the most suitable species for determining non-ammonium phytotoxicity of compost and phytostimulative or phytotoxic effect of ammonium form of nitrogen. It would be very useful to conduct a comparative germination test with compost extracts in the ratio 1:2.5 and 1:10, whereby the 1:2.5 extract is used as a test for phytotoxicity, and the 1:10 extract for testing phytostimulative effect.

Dreams and positive symptoms of schizophrenia are similar in many aspects, such as bizarre-ness, impairment of reality testing, intense emotional participation. Hallucinations, delusions, and disorganized thoughts have been proposed to be an intrusion of the dreaming state in wake-fulness: conversely, psychotic patients’ abnormal cognitive and behavioral features could over-flow into sleep, transferring peculiar features to their dreams which would differ, in quantity and quality, from those of healthy people. Here we assess this latter hypothesis by analyzing the dreams of 46 patients, hosted in a residential facility or in a day-treatment center, affected by disorders of the schizophrenic spectrum with psychotic symptoms, versus those of 28 healthy controls, in terms of several quantitative and qualitative characteristics. In patients, we also in-vestigated whether dream variables correlated with the severity of symptoms assessed via the Brief Psychiatric Rating Scale. Overall, patients reported fewer and shorter dreams than controls, with a reduction of many ele-ments like characters and settings. The greatest differences regarded emotions, which were less frequent in patients and inversely correlated with symptoms’ severity. This evidence supports the hypothesis that dreams are crucial for emotion regulation during wakefulness and that this func-tion could be totally or partially ineffective in psychoses.

Micro-Raman spectroscopy was carried out to evaluate the localized residual stresses in commercial Gallium Nitride-based devices, specifically AlGaN/GaN High Electron Mobility Transistors (HEMTs) in a novel packaging design provided by STMicroelectronics S.r.l. The packaging plays a key role in protecting the device core against the external environment, thus minimizing damages caused by mechanical shocks, exposure to light, and contact with chemicals, conjointly achieving an efficient heat dissipation rate. Even though the packaging is a required step for the proper functioning of ready-to-use electronic devices, its application typically may introduce mechanical stress to AlGaN/GaN HEMTs, which can result in various reliability issues. In this paper, we investigate the impact of packaging on residual stress by analyzing the frequency shift of the E2 Raman peak along GaN layers and at the GaN/Si interface. An extensive evaluation was conducted using both a packaged device and a wafer-level device. The correlation between Raman frequency shifts of the E2 mode was accurately quantified, revealing a stress mitigation of approximately 0.1 GPa. This reduction is ascribed to the compressive stress introduced by the packaging, which partially offsets the intrinsic tensile stress of the wafer-level device. The proposed methodology could, in principle, be implemented to improve the development of a packaging.

Background and Objectives: Clinical trials are a critical step in the development of new medicines and medical devices, testing the efficacy and safety of new treatment regimens. However, if the results of clinical trials are not made public, the evidence base on interventions is incomplete and possibly distorted, which lead to suboptimal treatment choices and negatively affect public health. This study analyses and contrasts the laws and regulations governing clinical trial registration and reporting in China and the United States. Methods: We used desk research to compile, assess and compare current laws, regulations, compliance patterns, and enforcement mechanisms and actions in China and the United States (U.S.). Policy documents were downloaded from Chinese and U.S. government websites. A spreadsheet analysis was utilized for direct comparison. Results: Both China and the U.S. have laws and regulations governing clinical trial registration and reporting. Chinese legislation covers a broader range of trials. In the U.S. trial results must be disclosed to both the national regulator and the public, while Chinese law mandates disclosure to the regulator alone. Cross-country comparisons of regulatory compliance by trial sponsors are impossible due to the opacity of the Chinese data platform. Neither country effectively ensures that all clinical trial results are made public as required by the Declaration of Helsinki and recommended by the WHO. Interpretation: While neither country is perfect, both may be able to learn from each other. There is a major gap in the literature regarding the extent of non-publication of clinical trial results by sponsors operating in China.

In addition to its use as a food additive, sesame is also very popular in conventional drugs because of its antifungal, anticancer, analgesic, antioxidant, and antiproliferative, vitamin B and E supplier, serum cholesterol and blood pressure-lowering, wound healing potential. In this study, the cytotoxicity, wound healing, and anticancer (antiproliferation) properties of the ex-tract obtained from in vitro cultures of Sesamum orientale L. cv. "Gökova" were investigated using in L929 fibroblast, MCF-7 breast, and A549 lung epithelial cell lines. In our study, the cisplatin was also used as a control group to compare the anticancer efficacy of our plant extract. The IC50 values obtained from cell treatments were 922.73 µg.ml-1 (plant extract) and 33.09 µg.ml-1 (cispla-tin) for A549 µg.ml-1, 1837.07 µg.ml-1 (plant extract) and 19.27 µg.ml-1 (cisplatin) for MCF-7, and 154.70 µg.ml-1 (plant extract) for L929, respectively. The subcytotoxic doses of the treated plant extract provided the healing of artificially created wounds on L929 fibroblast cell cultures within 48 hours. For the evaluation of the anticancer activity, it was also determined that transcriptomic analyzes of BCL-XL gene, which is negatively correlated with apoptotic pathway, and Cas3 and Cas9 genes, which are positively correlated with apoptotic pathway, showed a statistically sig-nificant increase in A549 and MCF-7 cell lines treated with plant extract or cisplatin. In the light of the results obtained from the present study, it was seen that sesame plant extract may have wound healing potential at decreasing doses and anticancer activity potential at increasing dos-es. The present study can be a useful resource for the development of a drug with wound healing and/or antiproliferative potential, with applications to be made in different cell lines in the future.

Molecular analysis of growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

This study aimed to produce single-chain recombinant eel follicle-stimulating hormone (rec-eel FSH) analogs with high activity in Chinese hamster ovary DG44 (CHO DG44) cells. We recently reported that an O-linked glycosylated carboxyl-terminal peptide (CTP) of the equine chorionic gonadotropin (eCG) β-subunit plays contributes on high activity and time-dependent secretion in mammalian cells. We constructed a mutant (FSH-M) in which a linker including the eCG β-subunit CTP region (amino acids 115 to149) was inserted between the β-subunit and α-subunit of wild-type single chain eel FSH (FSH-wt). Plasmids containing eel FSH-wt and eel FSH-M were transfected into CHO DG44 cells. Single cells expressing each protein were isolated from 10 and 7 clones, respectively. Secretion increased gradually during the cultivation period and peaked at 4,000–5,000 ng/mL on day 9. The molecular weight of eel FSH-wt was 34–40 kDa, while that of eel FSH-M increased substantially, with two bands at 39–46 kDa. Treatment with PNGase F to remove the N glycosylation sites decreased the molecular weight remarkably to approximately 8 kDa. The EC50 value and maximal responsiveness of eel FSH-M were approximately 1.23- and 1.06-fold higher than those of eel FSH-wt, indicating that the mutant showed slightly higher biological activity. Phosphorylated extracellular regulated kinase (pERK1/2) activation exhibited a sharp peak at 5 min, followed by a rapid decline. These findings indicate that the new rec-eel FSH molecule with the eCG β-subunit CTP linker showed potent activity and could be produced in massive quantities using the stable CHO DG44 cell system.

Mucus plugging of the respiratory tract occurs in airway diseases, including asthma, chronic obstructive pulmonary disease and cystic fibrosis. It can cause blockage of airways, leading to breathlessness and lung failure. Here, we demonstrate the effect of BromAc® in dissolving mucus plugs in an novel ex-vivo ovine obstructive lung model using a ventilatory setup. Mucus simulant was filled into the trachea of freshly slaughtered ovine lungs and ventilated via an endotracheal tube (ETT) using Continuous Mandatory Ventilation. Predetermined single or repeated doses of Bromelain, Acetylcysteine (Ac), BromAc® and saline control were administered via an Aerogen® vibrating nebuliser and ventilated for 30 or 60 minutes. Ventilatory recording of resistance, compliance, tidal volume was conducted and rheology pre and post treatment were measured. A significant decline in airway resistance (p<0.0001) compared to saline control was observed when treated with Bromelain, Ac and BromAc®, with the latter showing a stronger mucolytic effect than single agents. The decline in resistance was also effective in shorter timepoint (p<0.05) at lower doses of the drugs. Changes in compliance, peak pressure and tidal volume was not observed post-administration of the drugs. Rheology measurements revealed that BromAc®™ significantly reduced the viscosity of the mucin at the end of 30-minute and 60-minute time points (p<0.001) compared to the saline control. BromAc® showed complete dissolution of the respiratory mucus simulant and improved ventilatory airflow parameters in the ex-vivo ovine model.

The BRAFV600E mutation, found in approximately 50% of melanoma cases, is associated with aggressive tumor behavior and poor prognosis. This study aimed to assess its impact on immunogenic cell death (ICD), a pivotal cytotoxic process triggering anti-tumor immune responses. Through comprehensive in silico analysis of The Cancer Genome Atlas data, we explored the association between the BRAFV600E mutation, immune subtype dynamics, and tumor mutation burden (TMB). Our findings revealed that the mutation correlated with a lower TMB, indicating a reduced generation of immunogenic neoantigens. Investigation into immune subtypes reveals an exacerbation of immunosuppression mechanisms in BRAFV600E-mutated tumors. To assess the response to ICD inducers, including doxorubicin and Me-ALA-based photodynamic therapy (PDT), compared to the non-ICD inducer cisplatin, we used distinct melanoma cell lines with wild-type BRAF (SK-MEL-2) and BRAFV600E mutation (SK-MEL-28, A375). We demonstrated a differential response to PDT between the WT and BRAFV600E cell lines. Further transcriptomic analysis revealed upregulation of IFNAR1, IFNAR2, and CXCL10 genes associated with the BRAFV600E mutation, suggesting their involvement in ICD. Using a gene reporter assay, we showed that PDT robustly activated the IFN-1 pathway through cGAS-STING signaling. Collectively, our results underscore the complex interplay between the BRAFV600E mutation and immune responses, emphasizing a putative correlation between tumors carrying the mutation and their responsiveness to therapies inducing the IFN-1 pathway, such as the ICD inducer PDT, possibly mediated by the elevated expression of IFNAR1/2 receptors.

Chronic fatigue and fibromyalgia symptoms frequently occur in major depressive disorder (MDD). The pathophysiology of these symptoms may in part, be ascribed to activated immune pathways, although it is unclear whether muscular factors play a role in their onset. The aim of the present study is to examine the role of muscle proteins in major depression in association with symptoms of chronic fatigue and fibromyalgia. We measured serum levels of agrin, talin-2, titin, and creatine phosphokinase (CPK) as well as the FibroFatigue (FF), the Hamilton Depression Rating Scale (HAM-D) and the Beck Depression Inventory (BDI-II) in 60 MDD patients and 30 healthy controls. The results show a significant increase in agrin and talin-2 in MDD patients as compared with controls. There were highly significant correlations between agrin and HAM-D, BDI-II and FF scores. Agrin, but not talin or titin, was significantly and positively associated with all 12 items of the FF scale. We found that a large part of the variance in HAM-D (47.4%), BDI-II (43.4%) and FF (43.5%) scores was explained by the regression on agrin, smoking, female sex (positively associated) and education (inversely associated). CPK was significantly and inversely associated with the total FF score and with muscle and gastro-intestinal symptoms, fatigue, a flu-like malaise, headache and memory, autonomic and sleep disturbances. These results suggest that aberrations in neuromuscular (NMJs) and myotendinous junctions may play a role in MDD and that the aberrations in NMJs coupled with lowered CPK may play a role in symptoms of chronic fatigue and fibromyalgia in MDD. Moreover, the increase of agrin in MDD probably functions as part of the compensatory immune-regulatory system (CIRS).

This study was conducted to investigate the effect of supplementing different types of methionine (L and D-type) and its precursor (HMBi) on milk protein synthesis using immortalized bovine mammary epithelial cell line (MAC-T Cell); D-methionine (D-Met), L-methionine (L-met) and 2-hydroxy-4-methylthiobutanoic acid I (HMBi), an isopropyl ester of the hydroxy analogue precursor of methionine. The underlying mechanism of milk protein synthesis by adding D- and L-type amino acid as well as HMBi was elucidated through omics analysis to verify the metabolism pathway. Results showed that HMBi group showed the highest beta casein mRNA expression levels compared to D- and L-Met groups and highest medium protein although not different with the L-Met treatment. The observed upregulated (>2 protein expression vs. control) and downregulated (<0.5 protein expression vs. control) proteins in L-Met, D-Met and HMBi treated groups were: 39, 77; 46, 68; and 40, 78, respectively. Interestingly, based on protein pathway analysis, L-Met treated group stimulated the ATP synthesis, PI3 kinase and pyruvate metabolism. On the other hand, the D-Met group stimulated fructose-galactose metabolism, glycolysis pathway, PI3 kinase and pyruvate metabolism. And lastly HMBi-treated group stimulated pentose phosphate pathway and glycolysis pathway. Metabolite analysis revealed that L-Met treated group resulted in the increase in 11 metabolites. On the other hand, D-Met treated group showed increase in 7 metabolites and decreased of uridine monophosphate (UMP). HMBi supplementation caused increases of 3 metabolites and decreased of UMP and N-acetyl-L-glutamate Addition of different isoforms of Met stimulated the production of intermediate metabolites for energy production. Addition of L-Met stimulated the production of energy metabolites such as pyruvate, malate, and fumarate, well-known as intermediates of Krebs cycle. On the other hand, HMBi supplementation resulted in increases of energy metabolite glucose 1-phosphate and 6-phosphogluconate. Results showed that HMBi-treated group exhibited highest expression of β-casein mRNA expression by stimulating proteins and metabolites as well as protein and metabolic pathways involved in protein and energy synthesis. As a result, HMBi-treated group resulted in highest protein concentration but not significantly different with L-Met. Both the D- and L-isoforms has considerably the same medium protein concentration and β-casein mRNA expression higher than the control. So, D- and L-Met isoforms can be used alternatively without any significant change in protein synthesis efficiency in bovine mammary epithelial cells.

Baía de Todos os Santos is the second largest bay in Brazil and is home to important ecosystems, including estuarine systems and mangroves. However, studies on the seasonal variability of its soil properties and composition are still scarce. For this study, soil and leaf samples were seasonally collected from mangrove forests at four sites (Cacha Prego, Ponta Grossa, Ilha de Maré, and Pitinga), which are representative of different environmental conditions within the BTS. Soil physicochemical properties, soil composition and partition of Fe forms were determined, and analysis of minerals by Scanning Electron Microscope, was performed on soil samples. Isotopic ratios (δ13C, δ15N) were also determined on soil and leaf samples. Soils showed significant spatial and temporal changes affecting both their properties (pH, Eh) and their composition (TOC, pyrite and Fe oxyhydroxide contents). Clear spatial changes were observed in redox potential, significantly affecting the concentrations of the different geochemical forms of Fe, particularly the concentrations of crystalline oxyhydroxydes and pyrite in one of the studied sites. In three of the study sites, pyrite crystals showed clear evidence of degradation associated with sandy soils. Finally, δ13C and N/C ratios in soils seem to suggest a mixed origin of organic matter.

Anthocyanins are among the best-known phenolic compounds and possess remarkable biological activities, including antioxidant, anti-inflammatory, anticancer, and antidiabetic effects. Despite their therapeutic benefits, they are not widely used as health-promoting agents due to their insta-bility, low absorption, and thus, low bioavailability and rapid metabolism in the human body. Recent research suggests that the application of nanotechnology could increase their solubility and/or bioavailability, and thus, their biological potential. Therefore, in this review, we decided to provide, for the first time, a comprehensive overview of in vitro and in vivo studies on nanocarriers used as delivery systems of anthocyanins, and their aglycones, i.e., anthocyanidins alone or com-bined with conventional drugs to the treatment or management of chronic diseases.

Chemotherapy is a standard therapeutic option for triple-negative breast cancer (TNBC); however, its effectiveness is often compromised by drug-related toxicity and resistance development. Herein, we aimed to evaluate whether an improved antineoplastic effect could be achieved in vitro and in vivo in TNBC by combining dovitinib, a multi-kinase inhibitor, with calcitriol, a natural anti-cancer hormone. In vitro, cell proliferation and cell-cycle distribution were studied by sulforhodamine B-assays and flow cytometry. In vivo, dovitinib/calcitriol effects on tumor growth, angiogenesis and endothelium activation were evaluated in xenografted mice by caliper measures, Itgb3-immunohistochemistry and 99mTc-RGD2-tumor uptake. The drug combination elicited a synergistically improved antiproliferative effect in TNBC-derived cells, which allowed a 7-fold dovitinib dose-reduction. Mechanistically, the co-treatment induced cell death and accumulation in S and G2/M phases, while inhibited tumor growth to a greater extent than each compound alone. Tumor uptake of 99mTc-RGD2 was reduced by dovitinib, suggesting angiogenesis inhibition, which was corroborated by decreased endothelial cell growth and tumor vessel density. In summary, calcitriol synergized dovitinib anticancer effects in vitro and in vivo, allowing for a significant dose-reduction of dovitinib, while maintaining its antiproliferative potency. Our results suggest the beneficial convergence of independent antitumor mechanisms of dovitinib and calcitriol to inhibit TNBC-tumor growth.

Review of the existing bibliography shows that the direction and magnitude of the long-term trends of UV irradiance, and their main drivers, vary significantly throughout Europe. Analysis of total ozone and spectral UV data recorded at four European stations during 1996 – 2017 reveals that long-term changes in UV are mainly driven by changes in aerosols, cloudiness, and surface albedo, while changes in total ozone play a less significant role. The variability of UV irradiance is large throughout Italy due to the complex topography and large latitudinal extension of the country. Analysis of the spectral UV records of the urban site of Rome, and the alpine site of Aosta reveals that differences between the two sites follow the annual cycle of the differences in cloudiness and surface albedo. Comparisons between the noon UV index measured at the ground at the same stations and the corresponding estimates from the DWD forecast model and OMI/Aura observations reveal differences of up to 6 units between individual measurements, which are likely due to the different spatial resolution of the different datasets, and average differences of 0.5 – 1 unit, possibly related to the use of climatological surface albedo and aerosol optical properties in the retrieval algorithms.

Diabetes mellitus is the fifth deadliest disease in the developing countries. Even with all the research and new drugs available, combating diabetes is still challenging. There are successes in finding new cost effective drugs without side effects, even if not perfect. In our investigation we studied binding mechanism of secondary metabolite of T. chebula in silico. It was observed that three compounds out of 16 have a higher binding affinity for the target proteins. Ellagic acid showed highest binding affinity with alpha amylase, beta glucosidase and alpha glucosidase with lesser binding energies -4.5kcal/mol, -5.36kcal/mol and -4.48kcal/mol respectively. Arjungenin has lesser binding energy of 4.77 kcal/mol with glucokinase while luteoline has binding energy of -7.25kcal/mol for enzyme glycogen synthase kinase. These entire compounds interacted with non-covalent interaction. Petroleum ether extract showed the significant alpha amylase inhibitory activity i.e. 51.22% as compared to standard drug (65.99%).TLC analysis revealed the presence of total 9 compounds in different plant extracts one of them might be a lead compound which could be further exploited for the development of novel safer and potent antidiabetic drug.

African swine fever virus (ASFV) continues to spread globally causing severe economic losses to the pig farmers. Vietnam licensed two live attenuated vaccines based on the ASFV strains ASFV-G-ΔI177L and ASFV-G-ΔMGF, to control the ongoing ASF outbreaks. In 2023, newly emerging highly virulent recombinant ASFV viruses containing genetic elements from both ASFV p72 genotype I and II (rASFV I/II) strains were reported from Northern Vietnam. This study evaluated if the two vaccine strains were able to protect the pigs against the emerging rASFV I/II strain VNUA/rASFV/TN1/23. Pigs vaccinated with ASFV-G-ΔMGF or ASFV-G-ΔI177L, when challenged with rASFV I/II, succumbed to the infection, or developed signs of chronic ASF. The findings from this study show that both vaccine strains that are licensed and used in Vietnam, are unlikely to protect pigs from the emerging highly virulent rASFV I/II strains. This complicates the ongoing efforts to control ASF in Asia and globally and emphasizes the urgent need for a novel vaccine that can effectively protect pigs from the rASFV I/II strains.

Honeypots are vital security tools that enable cybersecurity specialists to scrutinize the tactics employed by attackers. By doing so, they can get valuable insights into existing and upcoming internet dangers. Cyber-attacks are in a perpetual evolution, increasingly sophisticated and tailored to exploit specific vulnerabilities. Hence, it is imperative for both organizations and individuals not only to consider but also implement methods to safeguard themselves against cyberattacks and malware. This paper assesses a specific group of honeypot systems by considering detection range, emulation accuracy, data quality, dependability, scalability, performance, extensibility, installation options, setup difficulty, and maintenance requirements. Furthermore, it provides conclusions regarding the relative effectiveness of diverse honeypot systems in different situations. As a part of the research, it analyzes the latest progress and innovations in honeypot development, including enhancements in machine learning, heightened automation, integration with other security tools, cloud-based honeypots, and deception technology by using simulated assaults to showcase the logging and recording capabilities of these honeypots in capturing attack information. After carefully analyzing each honeypot, each has unique advantages, disadvantages, and special characteristics.

In response to the increasing complexity and sophistication of cyber threats, particularly those enhanced by advancements in artificial intelligence, traditional security methods are proving insufficient. This paper explores the zero-trust cybersecurity framework, which operates on the principle of "never trust, always verify" to mitigate vulnerabilities within organizations. Specifically, it examines the applicability of zero-trust principles in environments where large volumes of information are exchanged, such as schools and libraries, highlighting the importance of continuous authentication, least privilege access, and breach assumption. The findings highlight avenues for future research that may help preserve the security of vulnerable organizations.

Graph query languages such as Cypher are widely adopted to match and retrieve data in a graph representation, due to their ability of retrieving and transforming information. Despite the most natural way to match and transform information is through rewriting rules, those are scarcely or partially adopted in graph query languages. Their inability of doing so has a major impact on the subsequent way the information is structured, as it might then appear more natural to provide major constraint over the data representation so to consequently constraint the way the information should be represented. On the other hand, recent works are starting to move towards an opposite direction, as the provision of a truly general semistructured model (GSM) allows to both represent all the available data formats (Network-Based, Relational, and Semistructured) as well as support an holistic query language expressing all major queries in such languages. In this paper, we show that the usage of GSM enables the definition of a general rewriting mechanism which can be expressed in current graph query languages only at the cost of adhering the query to the specificity of the underlying data representation. We formalise the proposed query language in terms graph rewriting mechanisms described as a set of production rules $L\to R$ while providing restriction to the characterization of L, while extending it to support structural graph nesting operations, useful to aggregate similar information around an entry-point of interest. We discuss how GSM, by fully supporting index-based data representation, allows for a better physical model implementation leveraging the benefits of columnar database storages. Preliminary benchmarks shows the scalability of this proposed implementation in comparison with state-of-the-art implementations.

We introduce the Ising Network Opinion Formation (INOF) model and apply it for the analysis of networks of 6 Wikipedia language editions. In the model, Ising spins are placed at network nodes/articles and the steady-state opinion polarization of spins is determined from the Monte Carlo iterations in which a given spin orientation is determined by in-going links from other spins. The main consideration is done for opinion confrontation between capitalism, imperialism (blue opinion) and socialism, communism (red opinion). These nodes have fixed spin/opinion orientation while other nodes achieve their steady-state opinions in the process of Monte Carlo iterations. We find that the global network opinion favors socialism, communism for all 6 editions. The model also determines the opinion preferences for world countries and political leaders, showing good agreement with heuristic expectations. We also present results for opinion competition between Christianity and Islam, and USA Democratic and Republican parties. We argue that the INOF approach can find numerous applications for directed complex networks.

Glaucoma is one of the primary causes of blindness worldwide. Canal opening surgery, a type of minimally invasive glaucoma surgery (MIGS) applied in cases of mild to moderate glaucoma, has gained increasing popularity in recent years due to its efficacy in reducing intraocular pressure, its safety profile, the simplicity of its technique, and the reduced likelihood of compromised vision. Nevertheless, the existing body of histopathological studies remains insufficient for a comprehensive understanding of post-surgical wound healing. Consequently, debates persist among researchers regarding the mechanism through which Schlemm’s canal opening surgery reduces intraocular pressure, as well as the surgical techniques that may impact the outcomes and the factors influencing surgical success. As the history of MIGS is relatively short and lacks sufficient systemic reviews or meta-analysis evaluating the influence of individual factors, this review was conducted to illuminate disparities in the researchers’ opinions at the current stage of research.

We investigated the dynamics of a simple master equation describing the evolution of a probability distribution between two states, \( p_1 \) and \( p_2 \) (with \( p_1 + p_2 = 1 \)). Our focus is on the behavior of the entropy \( S \), the distance \( D \) from the uniform distribution (\( p_1 = p_2 = 1/2 \)), and the free energy \( F \). We define two ratios, \( \eta_S = \frac{dS/dt}{dF/dt} \) and \( \eta_D = \frac{dD/dt}{dF/dt} \), and find that both diverge to plus-minus infinity as the system evolves towards the uniform distribution. This divergence marks a critical transition point where the master equation temporarily loses physical meaning. However, after this divergence, the system settles into a new, well-behaved regime where the solutions stabilize at finite values, representing a new equilibrium or steady state. This two-regime behavior underscores the intricate dynamics of simple probabilistic systems as they approach and surpass equilibrium, providing insights into the complex interplay of entropy, distance, and free energy in statistical mechanics.

in the context of advanced nanomaterials research, nanogels have recently gained considerable attention for their versatility and promising biomedical applications. To date, a significant number of nanogels have been developed to meet the growing demands in various fields of biomedical research. Summarising preparation methods, physicochemical and biological properties and recent applications of nanogels may be useful to help exploring new directions for their development. This article presents a comprehensive overview of the latest nanogel synthesis methodologies, highlighting advances in formulation with different types of hydrophilic or amphiphilic polymers. It also underlines recent biomedical applications of nanogels in drug delivery and imaging, with a short section dedicated to biosafety considerations of these innovative nanomaterials. In conclusion, this article summarises recent innovations in nanogel synthesis and their numerous applications, highlighting their considerable potential in the biomedical field.

This qualitative research explores negotiation dynamics within procurement, focusing on strategies, challenges, and outcomes in contemporary business environments. Negotiation in procurement plays a crucial role in shaping organizational strategies, supplier relationships, and operational efficiencies. In a globalized economy characterized by rapid technological advancements and market uncertainties, effective negotiation practices are essential for organizations seeking competitive advantage and sustainable growth. Through semi-structured interviews with procurement professionals, supply chain executives, and industry experts, this study examines the nuanced strategies employed in negotiation processes. Thematic analysis of the data reveals key themes including negotiation strategies (e.g., preparation, flexibility), challenges (e.g., price volatility, regulatory constraints), and outcomes (e.g., cost savings, innovation incentives). Relationship management emerges as pivotal, highlighting the importance of trust, transparency, and mutual respect in fostering collaborative supplier partnerships. The study also explores contextual factors (e.g., organizational culture, industry dynamics) and emotional dimensions (e.g., emotional intelligence, interpersonal dynamics) that influence negotiation effectiveness.

Animals use dietary lipids to sustain their growth and survival. Insects can synthesize fatty acids (FAs) and are autotroph for a number of lipids, but auxotroph for specific lipids classes (e.g. sterols, polyunsaturated FAs). Once ingested, lipids are hydrolyzed in the intestinal lumen and taken up into intestinal cells within specific regions of the insect digestive tract. These lipids can be either stored in the intestinal cells or exported through the haemolymph circulation to specific organs. In this chapter, we describe the various lipids provided by insect diets, their extracellular hydrolysis in the gut lumen and their intake and metabolic fate in the intestinal cells. This review emphasizes the critical role of the digestive tract and its regionalization in processing dietary lipids prior to their transfer to the requiring tissues.

Non-conventional resonances, both acoustic and photonic, are found in metallic particles with a toroidal nanopropeller geometry that is generated by sweeping a three-lobed 2D-shape along a spiral with twisting angle, α. For both optical and acoustic cases, the spectral location of resonances experiences a red-shift as a function of α. We demonstrate that the optical case can be understood as a natural evolution of resonances as the spiral length of the toroidal nanopropeller increases with α, implying a huge helicity dependent absorption cross section. In the case of acoustic response, two red-shifting breathing modes are identified. Additionally, even a small α allows the appearance of new low-frequency resonances, whose spectral dispersion depends on a competition between length of the generative spiral and the pitch of the toroidal nanopropeller.

This paper presents a comprehensive bibliometric analysis of research on form and typology in architectural publications, spanning from 1999 to 2024. Utilizing the Web of Science database and the bibliometrix package in R, the study examines trends, influential works, and thematic evolution in the field. The findings reveal a progression from foundational themes such as "architecture," "culture," and "planning" to more specialized and diverse topics, including "sustainability," "parametric design," and "digital fabrication." Key influential works by authors like Jane Jacobs, Kevin Lynch, and Bill Hillier are highlighted. The study also underscores the collaborative nature of contemporary architectural research, with significant international co-authorship. While providing valuable insights into the research landscape, the study acknowledges limitations, such as database reliance and the need for qualitative analysis. The paper concludes with recommendations for future research, emphasizing the exploration of emerging technologies, interdisciplinary collaborations, and regional research dynamics.

This study explores the barriers and opportunities faced by women in supply chain leadership, a field traditionally dominated by men. Through in-depth interviews and thematic analysis, it uncovers the pervasive cultural and societal biases that undermine women's perceived competence and suitability for leadership roles. These biases, often rooted in deep-seated stereotypes, influence hiring and promotion decisions, creating significant obstacles for women. Structural and organizational barriers, such as the lack of formal diversity policies, flexible working arrangements, and adequate mentorship, further hinder women's career progression. The dual burden of professional and domestic responsibilities also disproportionately affects women, limiting their availability for work-related travel and extended hours, which are often required in supply chain roles. Despite these challenges, the study identifies several pathways to promote gender diversity in supply chain leadership. Organizational commitment to diversity and inclusion, flexible working policies, and comprehensive mentorship programs are crucial in supporting women's advancement. Education and professional development opportunities are essential in equipping women with the necessary skills for leadership roles. Additionally, fostering an inclusive corporate culture that values diverse perspectives and addresses discrimination is vital for creating a supportive environment. Broader societal and policy-level changes, such as government and industry initiatives promoting gender diversity, are also necessary. The integration of emerging areas like sustainability, entrepreneurship, emotional intelligence, marketing, and supplier relationship management offers new opportunities for women to contribute to the industry's evolution. By addressing these barriers and leveraging the identified opportunities, it is possible to create a more inclusive and equitable supply chain industry, benefiting both the industry and society.

The objective of this study is to analyze the assessment practices in primary education and how they relate to the valuation of the learning process. It seeks to understand the perceptions of teachers and students regarding assessment and to observe classroom activities, as well as to analyze the assessment instruments used. The method used is a mixed approach that combines qualitative interpretations of the participants’ realities with a phenomenological analysis to reflect on the evaluative practices. The results indicate a contradiction between what is said and what is done in terms of evaluation, with a tendency to use written tests and traditional exams instead of a combination of techniques that allow for a significant evaluation of student learning. In addition, significant differences are observed among teachers regarding the importance they give to evaluation within their practices and evaluative models.

The rodents of Saudi Arabia consist of 20 species and 12 genera within four families (Gliridae, Dipodidae, Muridae, and Hystricidae). Details on the past and present distribution of the rodents were included along with available data on their habitat preference and biology. The eastern central part of Saudi Arabia covering Tuwiq mountains plateau, including the vicinity of Riyadh, hosts the highest number of rodent species. Analysis of the rodent fauna of Saudi Arabia revealed that they have four major zoogeographical affinities; Palaearctic-Oriental (one species), Afrotropical- Palaearctic (six species), Palaearctic (four species), endemic to Saudi Arabia and Yemen (three species), Afrotropical-Palaearctic-Oriental (three species) and three cosmopolitan species. According to the National Red List, the Euphrates Jerboa, S. euphratica, is listed as Endangered, Near Threatened for the Indian Crested Porcupine, H. indica, three species as Data Deficient, while the rest are considered as Least Concern.

Defining integrals over volume element in curved spacetime together with the mass and energy densities within that region of spacetime is apparently equivalent to the given energy and mass of that body or particle. With this in mind equations involving energies and masses can be rewritten in terms of their densities and the integral over the curved space-time volume element. The idea find its place in quantum mechanical frameworks systematically accounting for the effect of spacetime volume structures and gravity on dynamics of quantum systems. This article briefly explores these concepts and runs through various frameworks and equations relevant to this idea including the quantum stress energy tensor, and expressing Schrodinger’s equation in ways that are tied to general relativity it also discusses the cosmological constant and the cosmological constant problem.

Theoretical and experimental approaches have been applied to study the polymer physics under-lying compaction of DNA in the bacterial nucleoid. Knowledge of the compaction mechanism is necessary to obtain a mechanistic understanding of the process of segregation of replicating chromosome arms (replichores) during the cell cycle. In the first part of this review light microscope observations are discussed that have demonstrated that the nucleoid has a lower refractive index and thus a lower density than the cytoplasm. A polymer-physical explanation for this phenomenon was given by the theory of Theo Odijk pro-posed in 1998. By assuming a phase separation between nucleoid and cytoplasm and by imposing equality of osmotic pressure and chemical potential between the two phases, a minimal energy situation is obtained in which soluble proteins are depleted from the nucleoid, thus explaining its lower density. The theory is compared with recent views for DNA compaction that are based on mere exclusion of polyribosomes from the nucleoid or on the transcriptional activity of the cell. These new views raise the question of whether they can still explain the lower refractive index or density of the nucleoid. In the second part of this review the question is discussed how DNA segregation occurs in Esche-richia coli, in the absence of the so-called active ParABS system, present in the majority of bacteria. How is entanglement prevented of nascent chromosome arms, generated at the origin in the pa-rental network of the E. coli nucleoid? The observations of the groups of Sherratt and Hansen in 2006, that the four nascent chromosome arms synthesized in the initial replication bubble, segre-gate to opposite halves of the sister nucleoids implies that extensive intermingling of daughter strands does not occur. Based on the hypothesis that leading and lagging replichores synthesized in the replication bubble, fold into micro-domains that do not intermingle, a passive "four-excluding-arms model" for segregation is proposed. This model implies that the key for seg-regation already lies in the structure of the replication bubble at the very start of DNA replication; it explains the different patterns of chromosome arms as well as the segregation distances between replicated loci as experimentally observed.

Data Meshes is an approach to data architecture and organization that treats data as a product and focuses on decentralizing data ownership and access. It has recently emerged as a field that presents quite a few challenges related to data ownership, governance, security, monitoring, and observability. To address these challenges, this paper introduces an innovative algorithmic framework leveraging data blueprints to enable the dynamic creation of Data Meshes and Data Products in response to user requests, ensuring that stakeholders will have access to specific portions of the Data Mesh as needed. Ownership and governance concerns are addressed through a unique mechanism involving Blockchain and Non-Fungible Tokens (NFTs). This facilitates secure and transparent transfer of data ownership, with the ability to mint time-based NFTs. By combining these advancements with the fundamental tenets of Data Meshes, this research offers a comprehensive solution to the challenges surrounding data ownership and governance. It empowers stakeholders to navigate the complexities of data management within a decentralized architecture, ensuring a secure, efficient, and user-centric approach to data utilization. The proposed framework is demonstrated using real-world data from a poultry meat production factory.

The present minireview assessed the benefits of using artificial intelligence applications in healthcare at predicting the targets of bioactive small molecules in human. Method. The tool is a tuned algorithm, with novel data in web interface. Results. We used tables to order the information of Swiss Target Prediction that allow predictions on combination of chemotherapies and probable side effects. This tool is useful to understand the molecular mechanisms underlying a given phenotype or bioactivity, to rationalize possible favorable or unfavorable side effects and to predict off-targets of known molecules as well as to clear the way for drug repurposing. Predictions are done using a ligand-based approach to compare the similarity between a query molecule and the known ligands of a large collection of protein targets. Conclusion. This study allowed us to formulate recommendations for the use of some of the chemotherapeutic agent groups in cancer patients at a low cost. It is very important and beneficial for patients that take medicine for a longer period and on whose lives depend on such treatment.

Weak interaction processes continue to be hot topics in fundamental physics research. In this paper, we briefly review some recent advances in the theoretical study of beta and double-beta decays that include both the nuclear and atomic part of these processes. On the nuclear side, we present a statistical approach for the computation of the nuclear matrix elements (NME) for neutrinoless double-beta (0νββ). A range of NME values, the most probable value for NME, and the associated theoretical uncertainty are given. Correlations with other related observables are shown as well. On the atomic side, we first briefly review the methods used to get the electrons’ wave functions. Further, we use them for the computation of some relevant kinematic quantities such as Fermi functions, electron spectra and angular correlation between the emitted electrons. Then, we present applications of these calculations to the experimental data analysis related to the search of the Lorentz invariance violation in two-neutrino double-beta (2νββ) decay and description of the decay rates and decay rate ratios for allowed and unique forbidden electron capture (EC) processes.

GCN1 is recognized as a factor that is essential for the activation of GCN2, which is a sensor of amino acid starvation. This function is evolutionarily conserved from yeast to higher eukaryotes. However, recent studies have revealed non-canonical functions of GCN1 that are independent of GCN2, such as its participation in cell proliferation, apoptosis, and the immune response, beyond the borders of species. Although it is known that GCN1 and GCN2 interact with ribosomes to accomplish amino acid starvation sensing, recent studies have reported that GCN1 binds to disomes (i.e. ribosomes that collide each other), thereby regulating both the co-translational quality control and stress response. We propose that GCN1 regulates ribosome-mediated signaling by dynamically changing its partners among RWD domain-possessing proteins via unknown mechanisms. We recently demonstrated that GCN1 is essential for cell proliferation and whole-body energy regulation in mice. However, the manner in which ribosome-initiated signaling via GCN1 is related to various physiological functions warrants clarification. GCN1-mediated mechanisms and its interaction with other quality control and stress response signals should be important for proteostasis during aging and neurodegenerative diseases, and may be targeted for drug development.

Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 74% of the world's population still uses plant-based medicines, indicating the ongoing significance of phytochemicals for human health. The study emphasizes the growing body of research examining the role of polyphenols in uncovering their anti-adipogenic and anti-obesity properties. Functions of polyphenols including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids are distinct due to changes in chemical diversity, and structural characteristics. This review methodically investigates the mechanism of how naturally occurring polyphenols mediate obesity and metabolic function. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role in part in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function. The effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required for prudent and precise mechanisms underlying polyphenols' therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes the holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.

We evaluate performance of Isogeometric analysis (IGA) for structural deformation and automobile crash. In automobile crash analysis, ensuring the accuracy of the acceleration, velocity and load in time series as well as the deformation behavior is important. To maintain the aforementioned consistency, accurately reproducing the bending and buckling of structural members is indispensable. In this study, we firstly compute the bending and buckling of structural members using IGA and validate its performance by comparing the results with conventional finite element analysis and experiments. In addition, we utilize IGA for the crash analysis of an automobile body.

Energy transition is one of the greatest challenges facing humanity today. All micro, small, medium and large enterprises in operation will have to face it, and some can al-ready boast the first successes in this regard. This paper focuses on the involvement of these smallest players in energy transition. Micro and small entities are the largest part of the economy, having a great influence on its development. Looking at the wide scale of their activities, these entities are distinguished by a specific owner-manager relationship. This means that the final decision-making is influenced by business goals, but also by the manager's approach, their awareness of changes, and personal and other factors. Based on a structured and standardized survey questionnaire, the research was carried out using the Computer-Assisted Telephone Interviewing technique between April and May 2022 among owners of micro and small enterprises operating in Poland. The survey showed that active engagement of micro and small enterprises in energy efficiency initiatives is related to their market success and financial health.

Starting 1994, the debate for regulating organic agriculture in Brazil was officially recognized in May 1999. Still, only in 2003, when the law # 10,831 was instituted, the country reached an effective milestone on organic production, both internally and externally. Since the industry regulation, the legislation underwent many modifications, constantly reviewing and adjusting. The current study examined the institutionalization of organic production in Brazil and what the current regulations can be used as a reference for those interested in this sector. The most recent update of Organic legislation and its implication on practice were also discussed. A case study on production of strawberry in organic system is presented and discussed.

Recognizing trust as a pivotal element for success within Human-Robot Collaboration (HRC) environments, this article examines its nature, exploring the different dimensions of trust, analysing the factors affecting each of them, and proposing alternatives for trust measurement. To do so, we designed an experimental procedure involving 50 participants interacting with a modified 'Inspector game' while we monitor their brain, electrodermal, respiratory, and ocular activities. This procedure allowed us to map dispositional (static individual baseline) and learned (dynamic, based on prior interactions) dimensions of trust considering both demographic and psychophysiological aspects. Our findings challenge traditional assumptions regarding the dispositional dimension of trust and establish clear evidence that the first interactions are critical for the trust-building process and the temporal evolution of trust. By identifying more significant psychophysiological features for trust detection and underscoring the importance of individualized trust assessment, this research contributes to understanding the nature of trust in HRC. Such insights are crucial for enabling more seamless human-robot interaction in collaborative environments.

The advent of AI in medicine has transformed various medical specialties, including orthodontics. AI has shown promising results in enhancing the accuracy of diagnoses, treatment planning, and predicting treatment outcomes. With the growing number of AI applications and commercially available tools, there is an increase in their usage in orthodontic practices worldwide. This review aims to explore the principles of artificial intelligence (AI), its applications in the diagnostic process of modern orthodontic practices, and concerns associated with the implementation of AI algorithms in clinical practice. A comprehensive review of the literature was conducted, focusing on five categories where AI has been applied in orthodontics: dental diagnostics, cephalometric evaluation, skeletal age determination, temporomandibular joint (TMJ) evaluation, and extraction decision making. AI has demonstrated high efficacy in all those fields. However, variations in performance and the necessity of manual supervision indicate that AI should be used cautiously in clinical settings. Nevertheless, the high complexity and potential unpredictability of AI algorithms call for cautious implementation and regular manual validation of results. Continuous AI learning, proper governance, and addressing privacy and ethical concerns are crucial for the successful integration of AI into orthodontic practice.

As yin and yang, cancer and diabetes are metabolic disorders characterized by deregulated, yet opposing, metabolic alterations. These metabolic shifts reflect a complex network of defective underlying signaling pathways, which ultimately orchestrate both disease pathogenesis and progression. The Warburg effect portrays the chief metabolic phenotype in cancer and is reflected by the dominance of aerobic glycolysis over minimal-to-no viable oxidative phosphorylation in cancer. Conversely, during the pathogenesis of type 2 diabetes (T2D), oxidative phosphorylation is constantly heightened. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, with exacerbating metabolic alterations affecting oxidative phosphorylation in a tissue-specific manner. Promising nutritional adjuvants, such as alpha-lipoic acid and flavonoids, can reprogram metabolism and exert antitumor and antidiabetic effects. Other pharmacological agents, such as metformin, have therapeutic effects on cancer and T2D. Herein, we discuss the molecular mechanisms and signaling pathways involved in the metabolic shifts in cancer and T2D, and explore the therapeutic strategies under investigation that aim to reverse the metabolic shift in both disease scenarios.

As part of a project ordered by the Ministry of Science, Technology and Innovation of Brazil, an assessment of Brazilian biological collections was conducted by the Brazilian Societies of Botany, Microbiology, Virology and Zoology to obtain data on the current state of these collections. The goal was to provide subsidies for future public policies, including financial support and prioritization policies. Herein, we present the results of the microbiological collections, which play a fundamental role in the ex situ conservation of biodiversity and support research, development and innovation. A survey was sent to public and private institutions in Brazil and answered by 168 microbiological collections from 79 different institutions. Among these, 73 comprise public research institutions and universities, demonstrating the State's importance in preserving and safeguarding Brazilian microbial diversity. The main taxonomic groups are bacteria (present in 70.24% of the collections) and fungi (52.98% of the collections) from different Brazilian ecosystems and biomes, including several type strains. Furthermore, the collections preserve microorganisms with biotechnological potential for application in environmental protection, public health, industry, and agribusiness. However, despite all these economic and biotechnological potentials, the data analysis showed serious limitations and fragilities, especially regarding physical infrastructure and human resources, and raises alerts about the risk that Brazilian collections are subjected to.

Chloroquine (CQ) and its derivate hydroxychloroquine (HCQ), the compounds with recognized ability to suppress autophagy, have been tested in experimental works and in clinical trials as adjuvant therapy for the treatment of cancers of different origin to increase the efficacy of cytotoxic agents. Such strategy can be effective to overcome the resistance to standard chemotherapy or anti-angiogenic therapy. This review presents the results of combined application of CQ/HCQ with conventional chemotherapy drugs (doxorubicin, paclitaxel, platinum-based compounds, gemcitabine, tyrosine kinases and PI3K/Akt/mTOR inhibitors, and other agents) for the treatment of different malignancies obtained in experiments on cultured cancer cells and on animal xenograft models, with a few examples of clinical trials. The effects of such approach on viability of cancer cells and tumor growth, as well as autophagy-dependent and independent molecular mechanisms underlying cellular responses of cancer cells to CQ/HCQ are summarized. Although the majority of experimental studies in vitro and in vivo have shown that CQ/HCQ can effectively sensitize the cancer cells to cytotoxic agents and increase the potential of chemotherapy, the results of clinical trials are often inconsistent. Although pharmacological suppression of autophagy remains a promising tool for increasing the efficacy of standard chemotherapy, the development of more specific compounds is required.

Abstract Objectives To investigate histopathological changes and serous carcinoma precursors such as secretory cell outgrowths (SCOUTs) and p53 signature in bilateral tubal ligation (BTL) materials performed during cesarean section (S/C). Materials and Methods 138 patients who underwent S/C and tubal sterilization (TS) between October 2020 and May 2021 at Konya City Hospital. Patients’ data were obtained from the haospital’s system. All data andd findings were investigated and statistically evaluated. Results The mean age was 34.62 years (22 - 44), the mean gravity was 4.89 (2-15) and the mean parity was 3.46 (1-10). 5.79% SCOUT, 7.24% atypia and 9.42% p53 signatures were observed. Significant correlations were shown between epithelial cell lineage and age and between KI-67, SCOUT, and gravity, between KI-67 results and gravity and parity, and between P53 score and age. Conclusion TS is a common, safe, and effective method worldwide. Today, BTL is increasing along with increasing S/C ratios. In addition to the reduced risk of ovarian cancers with ligation alone, precursor lesions such as hyperplasia, SCOUT, p53 signature, and STIL/ Serous tubal intraepithelial carcinoma (STIC) are encountered in the ampulla materials obtained. Considering the low rates of re-anastomosis, tubal excision may be recommended instead of ligation in women of relatively higher gravity and age.

Traumatic brain injury (TBI) is among the leading causes of mortality and long-term impairment globally. TBI has a dynamic pathology encompassing a variety of metabolic and molecular events that occur in two phases, primary and secondary. An external forceful blow to the brain initiates the primary phase, which is followed by a secondary phase that involves the release of calcium ions (Ca2+) and the initiation of a cascade of inflammatory processes, including mitochondrial dysfunction, rise in oxidative stress, activation of glial cells, and damage to the blood-brain barrier (BBB), resulting in paracellular leakage. There is currently no FDA-approved drug for TBI, but existing approaches rely on delivering small and macromolecular treatments, which are severely constrained by the BBB, poor retention, off-target toxicity, and complex pathology of TBI. Therefore, there is a demand for innovative and alternative therapeutics with effective delivery tactics for diagnosis and treatment of TBI. Tissue engineering and use of biomaterials is one such alternative approach. With this approach, neuronal stem cell therapy is combined with synthetically generated tissue materials such as hydrogels, self-assembling peptides, and electrospun nanofibers, which may induce neurite outgrowth, differentiation of human neural stem cells, and nerve gap bridging in TBI. This review examines tissue engineering and the use of biomaterials as potential treatments for TBI, including their synthesis, mechanisms of action, and limitations. The review also discusses challenges facing tissue engineering and biomaterial technology including survival rate of transplanted stem cells and the development of biodegradable, biocompatible, and mechanically flexible biomaterials. A better understanding of the mechanisms and drawbacks of these novel therapeutic approaches will help guide the design of future TBI therapies.

We prove that a diffeological space is diffeomorphic to the categorical join of any generating family of plots.

This article explores how digitalisation is impacting the hospitality industry and assesses the evolving role of Information Technology (IT) strategy in the digitalisation process. The research approach is qualitative and inductive, based on six in-depth interviews with senior IT professionals in the hospitality industry. Findings indicate significant differences in the role of IT strategy in guiding digitalisation in the companies studied. The depth of information provided by the interviewees supports the development and application of a model that profiles the companies regarding their degree of digitalisation and technology integration. Analysis of interview material allows the identification of key properties for successful digitalization: process agility, workforce adaptability, and technology manageability, along with a clear data culture and ensured cybersecurity. However, disparate systems and technologies, and a lack of data integrity, are key issues that leave hospitality companies with difficult choices in progressing digitalisation initiatives. The applied model and identification of key properties for successful digitalisation contribute to the development of related theory and can also be used as a reference point for senior IT professionals working in the industry.

Urban agriculture is an early practice, especially for cities in the Global South that are expanding at an unprecedented rate, and in African cities, it can be a way to attend to essential social and health needs. However, it is unclear whether architects and urban planners have expressed interest or already incorporated urban farming within their designs of African cities. This literature review was conducted to understand to what extent architects and urban planners have researched urban agriculture and health. Comprehensive searches based on urban agriculture, health, and Africa were conducted in Scopus, PubMed, and Web of Science from 2000 to December 2020. Zotero, Mozilla Firefox search engine, and Google Chrome were used to collect paper metadata. The duplicate articles were excluded, and all the n = 240 publications remaining were included in the analysis. Food security and the immediate health impact of urban agriculture on health were the most addressed topics. These studies reported the harmful effects of urban agriculture on malaria and the wastewater irrigation of plants. The evidence on urban agriculture is increasing from public health researchers, but not in the field of urban planning or architecture. Future research on urban agriculture's impacts on urban health should be increasingly done by architects and planners to help shape urban planning practices and regulations that could help create urban agriculture that benefits urban health.

Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is the secreted and membrane-associated proteins, which regulate diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence revealed that excess SEMA3A expression and subsequent signaling pathway aggravates kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports demonstrated that inhibition of SEMA3A ameliorated kidney injury via reduction of cell apoptosis, fibrosis and inflammation, thus SE-MA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized current knowledges regarding the role of SEMA3A signaling in kidney pathophysiology and their potential use in kidney diseases.

Signaling modules that integrate the diverse extra- and intracellular inputs to control cell proliferation are essential during both development and adult stages to guarantee organism homeostasis. Mobs are small adaptor proteins that participate in several of these signalling pathways. Here we review recent advances unraveling Mob4 cellular functions, a highly conserved non-catalytic protein, that plays a diversity of roles in cell proliferation, sperm cell differentiation and simultaneously is involved in synapse formation and neural development. In addition, the gene is often overexpressed in a wide range of tumors and is linked to poor clinical outcomes. Nevertheless, Mob4 molecular functions remain poorly defined, although it integrates the core structure of STRIPAK, a kinase/phosphatase protein complex, that can act upstream of the Hippo pathway. In this review we focus on the recent findings of Mob4 functions, that have begun to clarify its critical role on cell proliferation and development of tissues and individuals.

The famous Wigner’s friend experiment considers an observer – the friend– and a superobserver – Wigner– who treats the friend as a quantum system and her interaction with other quantum systems as unitary dynamics. This is at odds with the friend describing this interaction via collapse dynamics, if she interacts with the quantum system in a way that she would consider a measurement. These different descriptions constitute the Wigner’s friend paradox. Extended Wigner’s friend experiments combine the original thought experiment with non-locality setups. This allows for deriving local friendliness inequalities, similar to Bell’s theorem, which can be violated for certain extended Wigner’s friend scenarios. A Wigner’s friend paradox and the violation of local friendliness inequalities require that no classical record exists, which reveals the result the friend observed during her measurement. Otherwise Wigner agrees with his friend’s description and no local friendliness inequality can be violated. In this article, I introduce classical communication between Wigner and his friend and discuss its effects on the simple as well as extended Wigner’s friend experiments. By controlling the properties of a (quasi) classical communication channel between Wigner and the friend one can regulate how much outcome information about the friend’s measurement is revealed. This gives a smooth transition between the paradoxical description and the possibility of violating local friendliness inequalities, on the one hand, and the effectively collapsed case, on the other hand.

One of the most promising advancements in healthcare is the application of digital twin technology. Digital twins are virtual replicas of real-world human patients and can be used for monitoring, and diagnosis, and as a tool to design treatment strategies tailored to individual patients. Furthermore, digital twins could also be helpful in finding novel treatment targets and predicting the effects of drugs and other chemical substances in development. This review article delves into the various data sources and methodologies that contribute to the construction of digital twins. Each data source, including blood glucose levels, heart MRI and CT scans, cardiac electrophysiology, written reports, and multi-omics data, comes with different challenges regarding standardization, integration, and interpretation. We showcase how various datasets and methods are used to overcome these obstacles and generate a digital twin. While digital twin technology has seen significant progress, there are still hurdles in the way to achieving a fully comprehensive patient digital twin. Developments in non-invasive and high-throughput data collection, as well as advancements in modeling and computational power will be crucial to improve digital twin systems. We discuss a few critical developments in light of the current state of digital twin technology. Despite challenges, digital twin research holds great promise for personalized patient care and has the potential to shape the future of healthcare innovation.

During early embryonic development, fertilized one-cell embryos develop into preimplantation blastocysts and subsequently establish three germ layers through gastrulation during post-implantation development. In recent years, stem cells have emerged as a powerful tool to study embryogenesis and gastrulation without the need for eggs, allowing the generation of embryo-like structures known as synthetic embryos or embryoids. These in vitro models closely resemble early embryos in terms of morphology and gene expression and provide a faithful recapitulation of early pre- and post-implantation embryonic development. Synthetic embryos can be generated through a combinatorial culture of three blastocyst-derived stem cell types, such as embryonic stem cells, trophoblast stem cells, and extraembryonic endoderm cells, or totipotent-like stem cells alone. This review provides an overview of the progress and various approaches in studying in vitro embryogenesis and gastrulation using stem cells. Furthermore, recent findings and breakthroughs in synthetic embryos and gastruloids are outlined. Despite ethical considerations, synthetic embryo models hold promise for understanding mammalian (including human) embryonic development and have potential implications for regenerative medicine and developmental research.

Sclerotinia sclerotiorum is a devastating fungal pathogen that causes severe crop losses worldwide. It is of vital importance to understand its pathogenic mechanism for disease control. Through a forward genetic screen combined with next-generation sequencing, a putative protein kinase, SsCak1, was found to be involved in growth and pathogenicity of S. sclerotiorum. Knockout and complementation experiments confirmed that deletions in SsCAK1 caused defects in mycelium and sclerotia development, as well as appressoria formation and host penetration, leading to complete loss of virulence. These findings suggest that SsCak1 is essential for growth, development and pathogenicity of S. sclerotiorum. Therefore, SsCak1 could serve as a potential target for the control of S. sclerotiorum infection through host-induced gene silencing (HIGS), which could increase crop resistance to the pathogen.

The education landscape is an environment prone to change due to the volatile and ever-changing nature of the digital society in which we all live. Although the world moves at a different pace and any generalization is bound to have several exceptions, there is evidence from research conducted in different places and contexts that educational methods are becoming increasingly digitized and driven by technological innovation. Among technological trends fuelled in many cases by the COVID-19 pandemic and the need to stay at home but online, augmented reality solutions received an additional push as a valid and versatile educational technology worth exploring and eventually integrating into several teaching methods already in use. Although the technology still faces problems related to its affordability, accessibility, and the technical skills required of users, some ongoing projects have already provided evidence that using augmented reality solutions as teaching and learning tools can improve teachers’ and students’ learning outcomes by increasing their engagement and interactivity. The same issues arose when personal computers, tablets, and smartphones were first discussed as valuable tools for education and have now found their way into most classrooms. This paper reviews some of the key concepts related to augmented reality, as well as some current trends, benefits, and concerns related to its inclusion in educational contexts in areas such as life sciences, engineering, and health. The work carried out and presented in this paper provides an interesting insight into a technology that has led to global phenomena, such as Pokémon Go, and is constantly improving in terms of portability, usability, and overall user experience. Throughout the paper and in the conclusions section, we discuss the relevance of using the best features of augmented reality and how they can contribute to positive educational outcomes.

This analysis takes into account a significant chapter of the history of elites and eugenics from Transylvania during the interwar period. In his famous „Black Notebook”, Alexandru Vaida-Voevod, one of the most important personalities of the Romanian Great Union generation, wrote some surprising reflections about eugenics, race, and Romanian national superiority. In different ways, his reflections underline an invitation to analyze Romanian elites from the interwar period, as well as their way of thinking and feeling. Vaida's "Black Notebook" can therefore be considered "a torn page" from an important chapter in the history of the Romanian eugenics movement. It also represents an important key for understanding the history of Romanian freemasonry in Transylvania from the first two decades of the 20th century.

It is yet unknown how the formation of aneurysm inside the human body occurs. Thus, the understanding and analysis of the Coanda effect will result in a better overview of the overall fluid mechanics that develops inside such a structure, leading not only to better treatment plans, but also to diminished postoperative risks. This paper presents how the fluid behaves in this situation, and takes into consideration how this physical phenomenon influences the hemodynamics inside numerous anatomical regions, located in the central nervous system, where aneurysms usually develop. Analyzing the three main areas in which cerebral aneurysms form the Coanda effect can potentially lead to the rupture of the aneurysm, by changing the blood flow trajectory, it should be taken into consideration when choosing a treatment plan, especially in postoperative care. In addition, there are other factors that can influence the evolution of an aneurysm such as shape, size, localization and the patient’s health condition. Understanding and analysis of the Coanda effect will result in a better overview of the overall fluid mechanics that develops inside such a structure, leading not only to better treatment plans, but also to diminished postoperative risks.

Targeted radionuclide therapy is become increasingly prominent as a nuclear medicine subspe-cialty. For many decades, treatment with radionuclides has been mainly restricted to the use of iodine-131 in thyroid disorders. Currently, radiopharmaceuticals, consisting of a radionuclide coupled to a vector that binds to a desired biological target with high specificity, are being de-veloped. The objective is to be as selective as possible at the tumor level, while limiting the dose received at the healthy tissue level. In recent years, a better understanding of molecular mecha-nisms of cancer, as well as the appearance of innovative targeting agents (antibodies, peptides, small molecules) and the availability of new radioisotopes, have enabled considerable advances in the field of vectorized internal radiotherapy with a better therapeutic efficacy, radiation safety and personalized treatments. For instance, targeting the tumor microenvironment, instead of the cancer cells, now appears as particularly attractive. Several radiopharmaceuticals for therapeutic targeting have shown clinical value in severals types of tumors and have been or will soon be approved and authorized for clinical use.

As in other parts of the world, natural disasters are increasingly causing significant loss of life and economic damage in Turkey. Natural disasters such as earthquakes, floods, storms, fires, and hailstorms have been occurring since ancient times, but now they are being compounded by factors such as climate change and the deterioration of natural environments. This has led to an increase in the frequency and severity of natural disasters and the resulting damage. It is important to finance the economic consequences of natural disasters that threaten individuals, commercial enterprises, and the country's administration. The frequency of the public's exposure to natural disasters, insurance awareness, the financial size of the disasters, the risk management policies of insurance companies, and the competence and willingness of the state and local governments to cover the damage are decisive factors. Prior to the increase in natural disasters, the country's administration was active and involved in first aid, rescue, and damage financing. However, it now has difficulty in financing the damage caused by natural disasters to individual, commercial, industrial, and agricultural assets and does not want to provide full assurance. This is because the dangers awaiting humanity in the future cannot be fully predicted. Private insurance companies undertake the task of taking over and distributing the risk in financing natural disaster losses and ensuring sustainability. Although this is a modern and rational solution, the problem is the insufficient number of insurance policies and insufficient premium production in countries where insurance awareness is not sufficiently developed. To increase premium production and geographical distribution of the risk, the state includes natural disaster insurances within the scope of compulsory insurances and mandates pre-disaster insurance policies. Following the earthquake disaster in the Marmara Region on 17.08.1999, compulsory insurance against earthquakes was introduced in Turkey with the Decree Law No. 587, which entered into force on 27.09.2000. This eliminated the obligation of the state to pay earthquake-related payments for the buildings determined by Turkish Natural Catastrophe Insurance Pool (TNCIP). Citizens have obtained modern, reliable, and regular insurance protection against earthquake damage. Naturally, the success or failure of Compulsory Earthquake Insurance (CEI) and Turkish Natural Catastrophe Insurance Pool (TNCIP) can be questioned after a major disaster. Since TNCIP is a new institution and other countries have not yet adopted it as an example, precedent institutions and past data cannot be included in the literature.

Risk protection and precaution are noticeable present, especially in times of a pandemic like Covid 19. However, it is not only in times of abruptly upcoming and unexpected situations like Corona that companies and economic entities are exposed to opportunities and threats. Internal and external developments that could influence the organization’s aims are defined as risks. Hence, it is important to emphasize that every operational activity is associated with risks and is consequently a challenge for companies. The purpose of this paper is to contribute to the identification and classification of individual risks. In this regard, the objectives and relevance of risk management are highlighted. Through the accomplishment of a classic literature review and the application of a comparative methodology the procedure of how hedging instruments are applied, is elaborated. The analysis indicates that various business concerns have a high awareness of risks inherent in business transactions, although they are still very hesitant to insert hedging instruments. Their uncertainties consist in defining and classifying the relevant risks plus identifying the appropriate hedging methods for them. Thus, this research can add new dimensions to hedging transactions and, particularly, express the benefits and opportunities of hedge accounting.

The nervous system is composed of neurons, which conduct the signals, and glial cells that provide metabolic and functional support and protection to neurons. An important component of the nervous system is the myelin sheath, an insulating layer around the nerves of the brain and spinal cord, which allows a fast and efficient nerve conduction and therefore the proper transmission of signal to all tissues and organs. Myelin is made of protein and fatty substances and gives protection for the propagation of the electrical impulse. Myelin alterations determine the onset of several neuropathies as the electrical signal can be slowed or stopped. Myelin is formed by oligodendrocytes in the central nervous system (CNS) and by Schwann cells in the peripheral nervous system (PNS). Differences in myelination in the CNS and PNS have been found and molecules involved in membrane trafficking such as SNAREs and rabs have been proved to contribute to several aspects regarding the formation of myelin or dysmyelination. Here, I will describe the role of these proteins in regulating membrane trafficking and nerve conduction, myelin biogenesis and maintenance.

A non-steady state mathematical model of amino acid (phenylalanine (Phe)) and mineral salt (NaCl) solution separation by neutralization dialysis (ND) carried out in a batch mode is proposed. The model takes into account the characteristics of membranes (thickness, ion-exchange capacity and conductivity) and solutions (concentration, composition), as well as the flow rate of the solution in the dialyzer compartments. As compared to previously developed models, the new one considers the local equilibrium of Phe protolysis reactions in solutions and membranes and, also, the transport of all the phenylalanine forms (zwitterionic, positively and negatively charged) through membranes. A series of experiments on ND demineralization of NaCl and Phe mixed solution was carried out. In order to minimize Phe losses, the solution pH in the desalination compartment was controlled by changing the concentrations of the solutions in the acid and alkali compartments of the ND cell. The validity of the model was verified by comparison of simulated and experimental time dependencies of solution electric conductivity and pH, as well as the concentration of Na+, Cl– ions and Phe species in the desalination compartment. Based on the simulation results, the role of Phe transport mechanisms in the losses of this amino acid during ND was discussed.

Dietary iron assimilation is critical for health and essential to prevent iron deficient states and related comorbidities, such as anemia. The bioavailability of iron is limited, while its absorption and metabolism are tightly controlled to keep body iron stores within a relatively narrow range. Genetic inactivation of the iron hormone hepcidin causes hereditary hemochromatosis, an endocrine disorder of iron overload characterized by chronic hyperabsorption of dietary iron, with deleterious clinical complications if untreated. The impact of high dietary iron intake and elevated body iron stores in the general population is not well understood. Herein, we summarize epidemiological data suggesting that high intake of heme iron, which is abundant in meat products, poses a risk factor for metabolic syndrome pathologies, cardiovascular diseases, and some cancers. We discuss clinical relevance and potential limitations of data from cohort studies, as well as the need to establish causality and elucidate molecular mechanisms.

Gastric cancer is a challenging public health concern worldwide and remains a leading cause of cancer-related mortality. The primary risk factor implicated in gastric cancer development is infection with Helicobacter pylori. H. pylori induces chronic inflammation affecting the gastric epithelium, which can lead to DNA damage and promotion of precancerous lesions. Disease manifestations associated with H. pylori are attributed to virulence factors with multiple activities and its capacity to subvert host immunity. One of the most significant H. pylori virulence determinants is the cagPAI gene cluster, which encodes a type IV secretion system and the CagA toxin. This secretion system allows H. pylori to inject the CagA oncoprotein into host cells, causing multiple cellular perturbations. Despite the high prevalence of H. pylori infection, only a small percentage of affected individuals develop significant clinical outcomes, while most remain asymptomatic. Therefore, understanding how H. pylori triggers carcinogenesis and its immune evasion mechanisms is critical in preventing gastric cancer and miti-gating the burden of this life-threatening disease. This review aims to provide an overview of our current under-standing of H. pylori infection, its association with gastric cancer and other gastric diseases, and how it subverts the host immune system to establish persistent infection.

The ordered Ca3TaGa3Si2O14 and disordered La3Ga5SiO14 crystals of the lantangallium silicate family were grown by the Czochralski method. The independent coefficients of thermal expansion of crystals αc and αa were determined by X-ray powder diffraction based on the analysis of X-ray diffraction spectra measured in the temperature range of 25÷1000°C. It is shown that in the temperature range of 25÷800°C the thermal expansion coefficients are linear. At temperatures above 800°C there is a nonlinear character of the thermal expansion coefficients associated with a decrease in the Ga content in the crystal lattice of the lantangallium silicate family crystals.

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

The microbiota is now recognized as one of the major players in human health and disease, in-cluding cancer. As regards breast cancer (BC), a clear link between microbiota and oncogenesis is still to be confirmed. Yet, part of the bacterial gene mass inside the gut, constituting the so called “estrobolome”, influences the sexual hormonal balance and, since the increased exposure to estrogens is associated with an increased risk, it may impact on the onset, progression, and treatment of hormonal dependent cancers, which account for more than 70% of all BCs. The hormonal dependent BCs are also affected by environmental and dietary endocrine disruptors and phytoestrogens which interact with microbiota in a bidirectional way: on one side disruptors can alter the composition and functions of the estrobolome, on the other the gut microbiota influences the metabolism of endocrine active food components. This review highlights the current evidence about the complex interplay between endocrine disruptors, phytoestrogens, microbiome, and BC, within the frames of a new “oncobiotic” perspective.

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

Endocytosis in mammalian cells is a fundamental cellular machinery that regulates vital physiological processes, such as the absorption of metabolites, release of neurotransmitters, hormonal secretion, cellular defense, and delivery of biomolecules across the plasma membrane. A remarkable characteristic of the endocytic machinery is the sequential assembly of the complex proteins at the plasma membrane followed by transportation of various cargo molecules to different cellular compartments. In all eukaryotic cells, functional characterization of endocytic pathways is based on dynamics of the protein complex modules. To coordinate the assembly and functions of the numerous parts of the endocytic machinery, the endocytic proteins interact significantly within and between the modules. Clathrin dependent and independent endocytosis, caveolar pathway and receptor mediated endocytosis have been attributed in a greater variety of physiological and pathophysiological roles such as, autophagy, metabolism, cell division, apoptosis, cellular defense, and intestinal permeabilization. Notably, any defect or alteration in the endocytic machinery results in the development of pathological consequences associated with human diseases such as cancer, cardiovascular diseases, neurological diseases, and inflammatory diseases. In this review, an in-depth endeavor has made to illustrate the process of endocytosis, and associated mechanisms describing pathological manifestation associated with dysregulated endocytosis machinery.

Why do neurons communicate through spikes? By definition, spikes are all-or-none neural events which occur at continuous times. In other words, spikes are on one side binary, existing or not without further details, and on the other can occur at any asynchronous time, without the need for a centralized clock. This stands in stark contrast to the analog representation of values and the discretized timing classically used in digital processing and at the base of modern-day neural networks. As neural systems almost systematically use this so-called event-based representation in the living world, a better understanding of this phenomenon remains a fundamental challenge in neurobiology in order to better interpret the profusion of recorded data. With the growing need for intelligent embedded systems, it also emerges as a new computing paradigm to enable the efficient operation of a new class of sensors and event-based computers, called neuromorphic, which could enable significant gains in computation time and energy consumption — a major societal issue in the era of the digital economy and global warming. In this review paper, we provide evidence from biology, theory and engineering that the precise timing of spikes plays a crucial role in our understanding of the efficiency of neural networks.

This paper offers insights into the nexus of youth, masculinity and right-wing populism in Australia. Here we make reference to a wide body of international literature on the topic. There is some affinity between disenfranchised (white) working-class young men and the radical right. Survey data were collected for a project on masculinity and the far right in Australia. 203 young men worked primarily in “blue collar” sectors of the Australian labour force. Some survey responses locate them partly or potentially within the field of the populist right-wing, with many expressing anti-government sentiments and the discourse of white male victimhood. The majority were nostalgic for stereotypical masculinity. While right-wing populist movements across the world certainly differ, they often share a discourse promoting traditional gender roles.

In former times, the spinal cord was considered a hard-wired network for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic device whose structures and functions adapt to changing circumstances. While such changes also occur under physiological conditions, the most dramatic alterations take place during or after various pathological events. It is astonishing what mechanisms the musculo-skeletal system has evolved to come to grips with the damages. Many of these changes are maladaptive, but some appear to help adapt to the new conditions. Although myriads of studies, using manifold methods, have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases are still little understood, due to a number of reasons. We will here try to summarize some results and remaining problems in a selection of diseases, in particular spinal muscular atrophy (SMA), amyotrophic laterals sclerosis (ALS), and predominantly spinal cord injury (SCI) with occasional relations to stroke. Especially the changes in SCI (and stroke) depend on the cause, site and extent of the afflicted damage and are therefore multifarious. At the end, we will briefly summarize results indicating that operant, classical and instrumental conditioning can be used to produce plastic changes in healthy people, with potentials for applications to patients with spinal cord injury. In order not to overload the article, we will not delve deeply into sub-cellular processes.

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

heterocycles are particularly common moieties within marine natural products. Specifically, tetrahydrofuranyl rings are present in a variety of compounds which present complex structures and interesting biological activities. Focusing on terpenoids, a high number of tetrahydrofuran-containing metabolites have been isolated during the last decades. They show promising biological activities, making them potential leads for novel antibiotics, antikinetoplastid drugs, amoebicidal substances or anticancer drugs. Thus, they have attracted the attention of the synthetic community, and numerous approaches to their total syntheses have appeared. Here, we offer the reader an overview of marine-derived terpenoids and related compounds, with a special focus on their isolation, structure determination, biological profiles and total syntheses.

Modeling what makes an advertisement persuasive, i.e., eliciting the desired response from consumer, is critical to the study of propaganda, social psychology, and marketing. Despite its importance, computational modeling of per- suasion in computer vision is still in its infancy, primarily due to the lack of benchmark datasets that can provide persuasion-strategy labels associated with ads. Motivated by persuasion literature in social psychology and marketing, we introduce an extensive vocabulary of persuasion strategies and build the first ad image corpus annotated with persuasion strategies. We then formulate the task of persuasion strategy prediction with multi-modal learning, where we design a multi-task attention fusion model that can leverage other ad-understanding tasks to predict persuasion strategies. Further, we conduct a real-world case study on 1600 advertising campaigns of 30 Fortune-500 companies where we use our model’s predictions to analyze which strategies work with different demographics (age and gender). The dataset also provides image segmentation masks, which labels persuasion strategies in the corresponding ad images on the test split. We publicly release our code and dataset: https://midas-research.github.io/persuasion-advertisements/

Hearing loss in infancy leads to preventable speech, language, and cognitive developmental delay [1, 2]. Sensorineural hearing loss (SNHL) is caused by damages, problems, or issues related to the inner ear such as the cochlea with or without the auditory nerve; cranial nerve VIII, involvement. There are three anatomic areas which include the outer ear: composed of the auricle and external auditory canal and the middle ear: which includes the tympanic membrane, ossicles, and the middle ear space, the inner ear: composed of the cochlea, semi-circular canals, and internal auditory canals. The unique anatomical shape of the auricle catches the incoming sound waves to send them down the external auditory canal. Hearing risk assessment should be part of all health visits while regular hearing screening checks are done for all children from 4 to 21 years [1, 2]. Assessment of hearing loss includes history, physical examination and specific hearing assessment tests.

Studies suggest that elevated postnatal blood lead levels (BLLs) are negatively associated with child growth. This study aimed to investigate associations of childhood BLLs at age one-year and growth outcomes at age six-years (n=661) in a cohort of children in Allada, Benin. The growth outcomes studied are weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ) and BMI-for-age Z-score (BMIZ), head circumference (HC), underweight, stunting, and wasting. Multivariable regression models examined associations between blood lead levels, growth outcomes with adjustment for potential confounders. The geometric mean BLLs was 59.3 μg/L and 82% of children had BLLs &gt;35 μg/L at one year. After adjusting for confounding factors, no association was found between BLLs quartiles and HAZ, WAZ, BMIZ, and height and weight growth velocities. However, boys in the highest quartile had 1.02 cm lower HC (95% CI: [-1.81, -0. 24]) as compared to those in the lowest quartile with a dose-response trend across quartiles (Ptrend =0.02). Furthermore, an increased risk of being stunted was observed in children in the highest quartile of exposure compared to the first (OR: 2.43; 95% CI: [1.11 – 5.33]) with a dose-response trend (Ptrend =0.03). Blood lead was found to be associated with an increased risk of childhood stunting and lower head circumference in a resource-limited setting.

The Internet of Things (IoT) has become one of the most attractive domains nowadays. It works by creating a special network between physical devices such as vehicles, home equipment, and other items. In recent days, the common technologies of communication such as Wi-Fi and 2G/3G/4G cellular are insufficient for the IoT networks because they are designed to serve appliances with immense processing capabilities such as laptops and PCs. Moreover, most of these technologies are centralized and use an existing infrastructure. Currently, the new communication technologies such as Z-Wave, 6LowPAN, and Thread are dedicated to the IoT and have been developed to meet its requirements. These technologies can handle many factors such as range, data requirements, security, power demands, and battery life. Nevertheless, the security issues in IoT systems have major concerns and matters because vulnerabilities in such systems may result in fatal catastrophes. In this paper, an enhanced IoT security framework for authentication and authorization is proposed and implemented to protect the IoT protocols from different types of attacks such as man-in-the-middle attack, reply attack, and brute force attack. The proposed framework combines an enhanced token authentication that has identity verification capabilities and a new sender verification mechanism on the IoT device side based on time stamp, which in turn can mitigate the need for local identity verification methods in IoT devices. The proposed IoT security framework is tested using security analysis with different types of attacks compared with previous related frameworks. The analysis shows the high capability of the proposed framework to protect IoT networks against many types of attacks compared with current available security frameworks. Finally, the proposed framework is developed using Windows application to simulate the framework phases, check its validity through the real network, and calculate the payload time is adds.

Early disease detection in livestock allows for target treatment decreasing antibiotics use and allow advancements in precision veterinary medicine. MicroRNA (miRNA) -driven signaling cascades play a crucial role in the context of farm animal disease diagnostics and prediction, and their proper understanding remains a challenge. In livestock farm animals, only a small number of miRNAs have been fully validated with respect to disease conditions and physiological or behavioral traits. Low abundance of miRNAs in blood and bodily fluids, along with a small number of nucleotides, makes detection and discrimination tedious and challenging task in. miRNAs usually are homologous, owing to which detection specificity becomes next to impossible when screening for multiple miRNAs in the same analyte sample. Hence, a concurrent, multiplexing, approach becomes crucial for the development of on-farm point-of-care based detection systems. Comprehensive screening methods demand broad dynamic range and enhanced specificity. For on-farm handheld platform development, the ability to screen for multiple varieties of miRNA is essential. In this review paper, I provide an overview of the recent developments of miRNA sensing and the current bottlenecks in the realization of the sensors for detecting miRNAS as target analyte for various livestock disease detection applications. Due to the nascent stages of this research, the possibilities of exploiting miRNAs as a biomarker opens up ways to move from reactive to predictive possibilities in diseases detection in the modern digital livestock farming.

Euglenoids are a common component of primary producers in high acidic and organic shallow freshwater systems. They are free-living photosynthetic motile flagellates exhibiting rapid responses to various external stimuli including chemical pollution. The unique combination of diverse physiological processes of Euglena such as photosynthesis, movement, and orientation offers a range of sensitive criteria that respond to aquatic pollutants. This has led to the development of several acute and chronic assay methods to monitor the adverse impacts of potent toxicants in aquatic ecosystems. Euglenoids also reflect the consequences of physical stress factors such as UV radiation. This review summarizes the ecotoxicity studies using euglenoid flagellates as model species and their potential to contribute toward rapid screening of ecological impacts of pollution in the aquatic environment. Factors determining the reliability of Euglena tests are outlined.

Sustainable and Responsible Design (SRD) harnesses design’s potential to address eco-social problems and in doing so challenge the status quo of design education by reframing the social and ecological consequences, boundaries and agencies of design. This critical and transdisciplinary approach frays the edges of traditional design disciplines with embedded and reflexive modes of learning. We describe characteristics of SRD education and present theories of learning to empower students in this complex terrain. The learning associated with SRD education is ecologically engaged, participative, critical, expansive and designerly. We recount case studies of our own experiences advancing sustainable and responsible undergraduate design education in the UK. We identify path constraints such as disciplinary fragility, appropriation, and power dynamics in the design school. The push for a revision of priorities generates tensions where there is often greenwashing rhetoric of sustainability and inclusivity. We describe strategies and tactics to address these tensions. We highlight the agency we have as educators and designers and argue that design education can only meaningfully participate in response to the challenges presented by climate change, other types of ecocide, and social problems when educators make substantive commitments to supporting sustainability literacies and design approaches that serve the interests of diverse stakeholders.

This material presents the results of a comparative analysis of the fungal diversity in the world system of microbial culture collections on one side with a variety of known fungal producers on the other side. The main VKM databases used are Fungal DC and Metabolites of Fungi, the central point of analysis - the fungal ability to synthesize promising metabolites for applied use. It indicates that the option of obtaining new promising strains from the collection funds is still underestimated by the scientific community. In particular it is shown that not more than 3% of the total fungal species fund contained in culture collections are used practically. The database Fungal DC developed in VKM is available on-line in www.vkm.ru and www.mycobank.org. It is possible their use will considerably expand the range of studied strains and lead to the acquisition of new scientifically significant data.

Parkinson’s disease (PD) is an aging-related and the second most common neurodegenerative disease after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigro-striatal DA neurons. Two main histopathological hallmarks exist in PD: cytosolic inclusion bodies termed Lewy bodies that mainly consist of α-synuclein protein, the oligomers of which produced by misfolding are regarded to be neurotoxic, causing DA cell death; and black pigments termed neuromelanin (NM) that are contained in DA neurons and markedly decrease in PD. Synthesis of human NM is regarded to be similar to that of melanin in melanocytes; Melanin synthesis in skin is via DOPAquinone (DQ) by tyrosinase, whereas NM synthesis in DA neurons is via DAquinone (DAQ) by tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). DA in cytoplasm is highly reactive and is assumed to be oxidized spontaneously or by an unidentified tyrosinase to DAQ and then synthesized to NM. Intracellular NM accumulation above a specific threshold was reported to be associated to DA neuron death and PD phenotypes. This review reports recent progress in biosynthesis and pathophysiology of NM in PD.

This study determines the threshold for the computational rate of actuator motor controllers for unmanned underwater vehicles necessary to accurately follow discontinuous square wave commands. Motors must track challenging square-wave inputs, and identification of key computational rates permit application of deterministic artificial intelligence (D.A.I.) to achieve tracking to a machine-precision degree of accuracy in direct comparison to other state-of-art approaches. All modeling approaches are validated in MATLAB simulations where the motor process is discretized at varying step-sizes (inversely proportional to computational rate). At a large step-size (fast computational rate), discrete D.A.I. shows a mean error more than three times larger than that of a ubiquitous model-following approach. Yet, at a smaller step size (slower computational rate), the mean error decreases by a factor of 10, only three percent larger than that of continuous D.A.I. Hence, the performance of discrete D.A.I. is critically affected by the sampling period for discretization of the system equations and computational rate. Discrete D.A.I. should be avoided when small step-size discretization is unavailable. In fact, continuous D.A.I. has surpassed all modeling approaches which makes it the safest and most viable solution to future commercial applications in unmanned underwater vehicles.

Deep learning techniques, such as convolutional neural networks (CNN), generative adversarial networks (GAN), and graph neural networks (GNN), have over the past decade changed the ac-curacy of prediction in many diverse fields. In recent years, the application of deep learning tech-niques in computer vision tasks in pathology demonstrated extraordinary potential in assisting clinicians, automating diagnosis, and reducing costs for patients. Formerly unknown pathologi-cal evidence, such as morphological features related to specific biomarkers, copy number varia-tions, and other molecular features, were also able to be captured by deep learning models. In this paper, we review popular deep learning methods and some recent publications about their appli-cations in pathology.

New setting is introduced to study resolving number and chromatic number alongside dominating number. Different types of procedures including set, optimal set, and optimal number alongside study on the family of neutrosophic hypergraphs are proposed in this way, some results are obtained. General classes of neutrosophic hypergraphs are used to obtains these numbers and the representatives of the colors, dominating sets and resolving sets. Using colors to assign to the vertices of neutrosophic hypergraphs and characterizing resolving sets and dominating sets are applied. Some questions and problems are posed concerning ways to do further studies on this topic. Using different ways of study on neutrosophic hypergraphs to get new results about numbers and sets in the way that some numbers get understandable perspective. Family of neutrosophic hypergraphs are studied to investigate about the notions, dimension and coloring alongside domination in neutrosophic hypergraphs. In this way, sets of representatives of colors, resolving sets and dominating sets have key role. Optimal sets and optimal numbers have key points to get new results but in some cases, there are usages of sets and numbers instead of optimal ones. Simultaneously, three notions are applied into neutrosophic hypergraphs to get sensible results about their structures. Basic familiarities with neutrosophic hypergraphs theory and hypergraph theory are proposed for this article.