Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that develops as a consequence of different factors such as oxidative stress and accumulation of the protein amyloid β (Aβ) in the brain, resulting in apoptosis of neuronal cells. The search for a treatment for this disorder is essential as current medications are limited to alleviating symptoms and palliative effects. The aim of this study is to investigate the effects of mint extracts on selected mechanisms implicated in the development of AD. To enable a thorough investigation of mechanisms, including effects on -secretase (the enzyme the leads to the formation of A), on Aβ aggregation, and on oxidative stress and apoptosis pathways, a neuronal cell model, SH-SY5Y cells was selected. Six Mentha taxa were investigated for their in vitro β-secretase (BACE) and Aβ-aggregation inhibition activities. Also, their neuroprotective effects on H2O2-induced oxidative stress and apoptosis in SH-SY5Y cells were evaluated through caspase activity. Real-time PCR and Western blot analysis were carried out for the two most promising extracts to determine their effects on signalling pathways in SH-SY5Y cells. All mint extracts had strong BACE inhibition activity. M. requienii extracts showed excellent inhibition of Aβ-aggregation, while other extracts showed moderate inhibition. M. diemenica and M. requienii extracts lowered caspase activity. Exposure of SH-SY5Y cells to M. diemenica extracts resulted in a decrease in the expression of pro-apoptotic protein, Bax, and an elevation in the anti-apoptotic protein, Bcl-xL, potentially mediated by down-regulation of ASK1-JNK pathway. These results indicate that mint extracts could prevent the formation of Aβ and also could prevent their aggregation if they had already formed. M. diemenica and M. requienii extracts have potential to suppress apoptosis at the cellular level. Hence, mint extracts could provide a source of efficacious compounds for a therapeutic approach for AD.

The need to understand the process by which particles, including solar wind and coronal ions as well as pickup ions, are accelerated to high energies (ultimately to become anomalous cosmic rays) motivate a multi-fluid shock wave model which includes kinetic effects (e.g. ion acceleration) in an electromagnetically self-consistent framework. Particle reflection at the cross-shock potential leads to ion acceleration in the motional electric field and thus anisotropic heating and pressure in the shock layer, with important consequences for the multi-fluid dynamics. This motivates development of a multi-fluid model of solar wind electrons and ions treated as fluid, coupled self-consistently with a small population of kinetically treated ions (e.g. pickup ions.) Consideration of both the time dependent and steady state regimes, indicate that such a multi-fluid approach is necessary for resolving the, Debye scale, particle reflecting cross-shock potential and subsequent dynamics. To study charge separation effects in narrow, supersonic wave layers we consider a reduction of the system to the steady state for cold ions and hot electrons and find two types of solitary waves inherent to the reduced two-fluid system in this limiting case.

Burrowing crabs are considered to be the ecosystem engineers in mangrove ecosystems because they have impact on the ecosystem functioning through bio-geochemical transformations. This process depends on the size and shape of burrows. The present study analysed architecture of burrows, constructed by crabs in a restored mangrove habitat. Fourteen crab species were found to construct the burrows of 13 different shapes with predominance of ‘I’,’J’,’L’. The burrow shape was diverse in Metopograpsus messor, followed by Austruca occidentalis, Gelasimus vocans, and A. annulipes. The burrow structural complexity was higher during summer in Avicennia or open zone. Sesarmids were larger in size than fiddlers, making the burrows of wider opening. Fiddlers were relatively smaller in size and they constructed complex burrows at vertical position, making longer and deeper burrows, in contrast to sesarmids, which formed simple burrows at horizontal position, digging shorter and shallower burrows. The sesarmids have smaller burrows without branching in mangrove zones, whereas the fiddler crabs (except Austruca variegata) have larger burrows with or without branching in open and Avicennia zones. The fiddler crabs especially Austruca occidentalis and A.annulipes have separate openings and passage for exit and entry as an adaptation against predators. The present work identified Austruca occidentalis and A. annulipes as the most potent bio-turbating crab species for restored mangrove habitats due to their efficiency in soil excavation and large sized burrows.

A review of the surface ablation of hominin teeth by attrition, abrasion and erosive wear. The occurrence of these lesions is explored in a sample of South African fossil australopithecine dentitions revealing excessive wear. Interpretation of the nature of the dietary components causing such wear in the absence of carious erosion provides insight into the ecology of the Plio-pleistocene epoch (1-2 million years ago). Fossil teeth inform much of the living past by their retained evidence after death. Tooth wear is the ultimate forensic evidence of lives lived.

The kipping handstand push-up (kHSPU) is an exercise performed by many thousands of CrossFit participants. The safety of kHSPUs has been questioned because of vertical impacts upon the head. Here, we measured the axial loads placed upon the head during kHSPUs and sought to identify other factors that may place participants at risk of injury. 16 volunteers from a single gym performed 3 sets of up to 7 kHSPUs with their head and one hand contacting force platforms. Forces were recorded continuously and video recording were made while performing the exercises. The force profiles showed distinct landing and kipping peaks. Participants landed with more force than during their normal headstand, but less than their body weight. The force on the head was greatest during the "kip," and was usually more than body weight. Participants who reported pain following kHSPUs moved their head into extension during the exercises. Forces to the head during kHSPUs were below forces proposed for damage to the young male cervical spine, but overlapped those proposed for female cervical spines. While kipping handstand push-ups may be safe for young and previously uninjured male athletes, they may be unsafe for females and for those with previous injury or other compromising factors.

This contribution is an attempt to reconstruct the favorable atmosphere that prevailed in Lau-sanne in 1986-87 and provided the backdrop of our invention of two-dimensional ion cyclotron resonance mass spectroscopy (2D ICR-MS). To avoid a self-centered histoire d’ancien combattant, we shall try to emphasize the context, the contributions of key players within our nascent research group at UNIL and the established group of Tino Gäumann at EPFL, the role of external speakers, and the open atmosphere that was not yet polluted by bibliometrics, obsessive concern with im-pact factors, and top-down management of research. We shall also explain why the idea of 2D ICR-MS has been ignored for many years and still has a limited impact: different scientific cul-tures in the ICR and NMR communities, different concerns with fundamental vs. applied research, different status of theory and numerical simulations, different levels of commitment of instrument manufacturers, not to mention many theoretical problems that appear to be at least as challenging in ICR as in NMR.

The total, soluble and insoluble oxalate contents of fresh and wok-fried fat hen (Chenopodium album) leaves were extracted and measured using HPLC chromatography. The total oxalate content of the raw leaves was 1112.4 mg/100 g dry matter (DM), and the levels were significantly reduced by boiling (682.8 mg/100 g DM) or cooking the leaves in a wok (883.6 mg/100 g DM). The percentages of soluble oxalate contents in the total oxalates of the raw and boiled leaves were similar (mean 75%), while the proportion of soluble oxalate content in the wok-fried leaves were reduced to 53.4% of the total, giving a significant increase in the insoluble oxalate content of the wok-fried leaves. The percentage of insoluble calcium in the total calcium was significantly reduced (P < 0.05) when the leaves were boiled but the insoluble oxalate content significantly increased (67.2%) in the wok-fried leaves when compared to the content of the original raw leaves. Processing the cooked leaves into pesto or extracting the juice gave final products that contained significantly reduced total and soluble oxalate contents. The addition of calcium chloride to the juice made a very small reduction in the soluble oxalate content in the juice.

Current VAT rules for cross-border e-commerce companies in the EU are not sustainable, because they are extremely complex and often opaque, due to the lack of tax harmonization. The aim of the research is to explore, using a qualitative method, what kind of harmonization would make the current legislation more uniform, simpler, more transparent, and easier to understand, without conflicting with the rules of any Member State. To this end, the aspects of the new platform regulation introduced on 1 July 2021 and its potential for expansion are assessed through information from possible sales models. The research suggests that the rules on platforms do not cover all possible sales models, which in our view imposes an unnecessary extra administrative burden on some businesses and makes their tax activities less transparent. In the light of the results of the research, we propose that the current EU platform regulation should be extended to cover B2B, B2C transactions and services. As a result of this suggested harmonization, a simpler, more transparent, uniform and sustainable tax system would contribute to the whitening of the economy, generating additional tax revenue for Member States.

: The objective of this work is to elucidate the role of partnerships and the number of partners necessary for lead user innovation outcomes. Lead user theory identifies these users as being ahead of market trends and experiencing significant benefits from innovating. So far, most lead user research has concentrated on firms and not individual lead users’ perspective. Data were obtained using a quantitative design during which 321 respondents participated. The SPSS software was used to analyze the data and determine significance. These findings indicate a connection between number of partners and lead user innovation success. This demonstrates that number of partners is significant in determining the success or failure of an innovation. This study provides empirical evidence that the number of partners is an essential factor that influences the success of innovation, and establishes the absolute numbers for achievement of successful innovation. Future studies must investigate the possible implications of integrating the partner variables with other characteristics of the lead user.

Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide, accounting for approximately 25% of deaths among pregnant women. We previously reported that pregnancy serum facilitates HEV replication in vitro. However, the differences in host cells with HEV infection induced by pregnancy serum and fetal bovine serum (FBS) are unclear. In this study, differentially expressed proteins were identified in HEV-infected hepatoma cells (HepG2) supplemented with different sera by using isobaric tags for relative and absolute quantitation. Proteomic analysis indicated that HEV infection significantly induced 1014 differentially expressed proteins in HEV-infected HepG2 cells when supplemented with FBS compared with pregnancy serum. Further validation by Western blot confirmed that filamin A, heat-shock proteins 70 and 90, Cytochrome c, and Thioredoxin were associated with HEV infection. This comparative analysis provides an important basis to further investigate HEV pathogenesis in pregnant women and HEV replication.

Purpose: The purpose of this study is to further explore how e-loyalty and E-marketing influences E-trust and satisfy the demand by offering fresh perspectives based on research as well as emphasis on the factors influencing the E-trust such as culture as a mediator. This study not only contributed theoretically but also presented practical implementations. Design/methodology/approach: Online survey was used to obtain data by focusing the Hospitality sector (Hotel Industry) and verifying the conceptual framework. Data was collected in multiple time lags. Findings: Findings showed that the E-trust influenced by E-loyalty and E-Marketing. E-trust comes from the previous experiences, e-loyalty and e-marketing. Further, some trends such as culture influenced the e-trust. Research limitation/implications: The present study is quite suitable for those Researchers interested in learning more about the effects of E-loyalty and E-marketing on user E-trust and how to mitigate cultural influences can benefit from the current study. This research also has implications for those who wish to improve market allure and survival in digital world. This study focused on the hospitality sector (Hotel Industry) in China; however, the sector and geography could be altered to suit the needs of the study's participants. Practical implications: The present study delivers the practical guidelines which are quiet suitable for understanding the formation of E-loyalty, E-marketing, and E-trust through which specific E-marketing strategy can be designed to deal with the consumer’s E-loyalty and their expectations as per their Cultural perspective. At some particular regions/countries, cultural trends are more important than practical market. This research study practically showed that how culture changed the consumer set of mind. Originality/value: The relationship between E-loyalty, E-marketing, E-trust, specifically with the cultural influence in digital market has been the subject of few research.

The sustainability of agriculture depends as much on the natural resources required for production as it does on the stakeholders that manage those resources. It is thus essential to understand the variables that influence the decision-making process of agricultural stakeholders to design educational programs, interventions, and policies geared towards their specific needs, a required step to enhance agricultural sustainability. We examined the perceptions, experiences, and priorities that influence management decisions of five major groups of agricultural stakeholders (conventional small grain producers, organic small grain producers, organic vegetable producers, extension agents and agro-industry crop consultants, and researchers) across the Montana, United States. Results revealed that while stakeholder groups have distinct perceptions, experiences, and priorities, there were similarities across groups. Specifically, organic vegetable and organic small grain producers showed similar responses that were, in turn, divergent of conventional producers, researchers, and crop consultants. Conventional small grain producers and researchers showed overlapping response patterns while crop consultants formed an isolated group. Our results reinforce the need for agricultural education and programs that address unique and shared experiences, priorities, and concerns of multiple stakeholder groups. This study endorses the call for a paradigm shift from the traditional top-down agricultural extension model to one that accounts for participants’ socio-ecological contexts to facilitate the adoption of sustainable agricultural systems that support environmental and human wellbeing.

This paper focuses on the physical attributes of land that intrinsically limit land use and possibly affect land values. In particular, we investigate if the slope of a land does decrease its price and investigate the role of land slope in forming more reliable constant-quality land price indices and aggregate house price indices. We find that, while land slopes do decrease the land price per unit, they have a small effect on the quality-adjusted land price indices in selected neighborhoods in Auckland, New Zealand, where sloped terrain is common.

This paper assesses the use the Global Sustainable Tourism Criteria (GSTC) indicators for monitoring tourism along a mountainous route. The study was carried out along a mountain route in the Drakensberg Mountains of South Africa. A survey was carried out among tourism businesses, local communities and local government officials located along the Maluti Route, which passes though the eastern part of the Free State Province of South Africa. This study constitutes the first assessment in which the GSTC indicators are applied in the assessment of the sustainability of route tourism in South Africa. The study first evaluated the importance of each indicator by considering the level of application in tourism business organisations before examining the perceptions of local community members and local government officials regarding the applicability of the indicators in the assessment of tourism sustainability. The results suggest that there is a general appreciation of tourism sustainability among tourism business operators although shortcomings were evident on environmental and socio-economic indicators. In conclusion, the paper suggests ways through which tourism sustainability could be enhanced among different players along the Maluti Route.

Activation of the N-methyl D-aspartate receptor (NMDAR) results in increased sensitivity of spinal cord and brain pathways that process sensory information, particularly that which relates pain. The NMDAR shows increased activity in fibromyalgia and hence modulation of the NMDAR is a target for therapeutic intervention. A literature review of interventions impacting on the NMDAR shows a number of drugs to be active on the NMDAR mechanism in fibromyalgia patients, with variable clinical effects. Low-dose intravenous ketamine and oral memantine both show clinically useful benefit in fibromyalgia. However, consideration of side-effects, logistics and cost need to be factored into management decisions regarding use of these drugs in this clinical setting. Overall benefits with current NMDAR antagonists appear modest and there is a need for better strategy trials to clarify optimal dose schedules and to delineate potential longer –term adverse events. Further investigation of the role of the NMDAR in fibromyalgia and the effect of other molecules that modulate this receptor appear important to enhance treatment targets in fibromyalgia.

Households and businesses are generating unprecedented levels of electrical and electronic wastes (e-waste), fueled by modernisation and rapid obsolescence. While the challenges imposed by e-waste are similar everywhere in the world, disparities in progress to deal with it exists; with developing nations such as South Africa lagging. The increase in e-waste generation increases the need to formulate strategies to manage it. This paper presents an overview of e-waste management on a global and South African scenarios with a specific case for Cathode Ray Tube (CRT) waste management practices in South Africa. CRTs present the biggest problem for recyclers and policy makers because they contain hazardous elements such as lead and antimony. Common disposal practices have been either landfilling or incineration. The research into the South African practices with regards to CRT waste management showed that there is still more to be done to effectively manage this waste stream. This is despite clear waste regulatory frameworks in the country. However, recent developments have placed e-waste as a priority waste stream, which should lead to intensified efforts in dealing with it. Overall, these efforts should aim to maximise diversion from landfilling and to create value-addition opportunities, leading to social and environmental benefits.

In every economy, Stock markets are part of the key elements the build it up. A few decades ago, there has been a significant change in Ghana stock market returns (GSE). Our study examines the statistical and economic significance of investor sentiment, based on weather conditions/changes, on stock market returns. OLS models, assisted by unit root tests were employed in analyzing the data obtained from the Ghana stock exchange platform from 2000 to 2017. From our literature review, we discovered that investors’ perceptions play a central role in finalizing the direction of stock market returns. Regarding our empirical results, we tested whether weather variations influence the investment decisions of investors; we discovered that temperature and cloud cover significantly influences stock market returns. This is because of mood changes is associated with weather conditions variations. However, sunshine per our regression coefficient shows a statistically insignificant impact on investors’ investment choices. Precipitation to a large extend influence stock market activities further affecting its results negatively as our regression results depicted. We concluded stock brokerage firms, companies, and investors (foreign/local) must incorporate weather changes/effects when strategizing about their investment outcomes.

The development of biofuels and biodiesel industry specifically, has resulted in the generation of large amounts of glycerol as a surplus. The conversion of glycerol, into chemicals with indus-trial interest, through anaerobic fermentation using E. coli as a biocatalyst is an attractive alter-native to improve economic performance in the biodiesel industry, for example through the bi-otransformation of residual glycerol into ethanol. For 2019, the size of the global ethanol market was valued at $ 89.1 billion US dollar. Biodiesel can be produced from several materials like rapeseed, palm, soya, corn, palm kernel, frying oil or olive-pomace oil (OPO). The last, can be extracted from alperujo, byproduct of olive oil process. However, olive-pomace oil converting into biodiesel is not enough established to achieve a global olive-oil/biodiesel derived process with minimized waste generation. Traditionally biodiesel production process produces an equivalent of 10% by mass of glycerol as a waste or by-product. This work explores the conver-sion of residual glycerol into chemicals like ethanol and hydrogen with a focus on projecting raw material potential availability from OPO, contributing to the promotion of the use of biofu-els and biodegradable compounds.

Venous thromboembolism (VTE) is a prevalent medical condition with high morbidity, mortality, and associated cost. Anticoagulation remains the main treatment for VTE, though the decision on when, how, and for how long to administer anticoagulants is increasingly complex. This review highlights the different phases of VTE management, special circumstances for consideration such as antiphospholipid syndrome, coronary artery disease, cancer associated thrombus and COVID, and future anticoagulation options. Anticoagulation management will continue to be a complex decision, applying evidence-based medicine to individual patients with the hope to maximize effectiveness while minimizing risks.

Faba bean (Vicia faba L.) is a partially outcrossing species requiring an isolation distance to maintain genetic purity when more than one variety is grown in field conditions. This information is crucial for seed growers and faba bean breeders. A study was conducted at the University of Sydney’s Plant Breeding Institute, Narrabri over two years to examine the extent of natural outcrossing using a creamy white flower characteristic as a morphological marker, which is controlled by a single recessive gene. The white flowered genotype (IX225c) was grown in paired rows of 150 m length in four directions from a central 480 m2 plot of the normal flowered genotype PBA Warda. A beehive was placed in the central plot at flowering time and natural pollination was allowed. At maturity, seed samples were taken from the white flowered genotype at designated intervals along each axis and 100 seeds from each sample were grown in the glasshouse/birdcage to the 4-5 leaf stage and the proportion of plants displaying stipule spot pigmentation (normal flower colour and spotted stipule are linked) was used to determine the percentage of outcrossing. Maximum outcrossing of 2.28% occurred where both genotypes were grown side by side (0 m) and the degree of outcrossing decreased as the distance along each axis from the central plot increased. At 6 m distance the outcrossing was less than 1%, however on occasion it increased to 1% beyond a distance of 100 m, indicating the volatile and unpredictable nature of bee flights. Distance had the major effect on outcrossing, but direction and its interaction had no effect. The results suggest that to limit outcrossing to below 0.5%, a distance of more than 150 m between plots of different faba beans cultivars would be required. It also indicated that Australian faba bean genotypes are mostly self-fertile and a relatively narrow isolation distance will ensure self-fertilization in seed production and breeding programs.

Researchers’ attention has been turned on Health expenditure, Carbon emissions, and economic growth as they play a focal role in the current debate on environmental protection and sustainable development. Our paper endeavors to investigate the impact of economic growth and CO2 emissions on Health expenditure for two main countries in Asia (China and India) using a dynamic panel data model estimated employing the Generalized Method of Moments (GMM) for the period 1960–2019. Our empirical results show that there is a significant relationship between health expenditure, CO2 emissions, and economic growth. The empirical evidence indicates a significant positive impact of CO2 emissions on health expenditure whiles economic growth has a negative impact on health expenditure for both countries for the period under study. The population growth rate has transposed effect on India's health spending; on the other hand, its impact on China’s health spending is significantly positive. The strong observable correlation between health expenditure and economic growth is crucial for economic development.

All RNA viruses deliver their genomes into target host cells through processes distinct from normal trafficking of cellular RNA transcripts. The delivery of viral RNA into most cells hence triggers innate antiviral defenses that recognize viral RNA as foreign. In turn, viruses have evolved mechanisms to subvert these defenses, allowing them to thrive in target cells. Therefore, drugs activating defense to exogenous RNA could serve as broad-spectrum antiviral drugs. Here we show that transcriptional signatures associated with cellular responses to the delivery of a non-viral exogenous RNA sequence into human cells predict small molecules with broad-spectrum antiviral activity. In particular, transcriptional responses to the delivery of Cas9 mRNA into human hematopoietic stem and progenitor cells (HSPCs) highly matches those triggered by small molecules with broad-spectrum antiviral activity such as emetine, homoharringtonine, pyrvinium pamoate and anisomycin, indicating that these drugs are potentially active against other RNA viruses. Furthermore, these drugs have been approved for other indications and could thereby be repurposed to novel viruses. We propose that the antiviral activity of these drugs to SARS-CoV-2 should therefore be determined as they have been shown as active against other coronaviruses including SARS-CoV-1 and MERS-CoV. Indeed, two of these drugs- emetine and homoharringtonine- were independently shown to inhibit SARS-CoV-2 as this article was in preparation. These drugs could also be explored as potential adjuvants to COVID-19 vaccines in development due to their potential effect on the innate antiviral defenses that could bolster adaptive immunity when delivered alongside vaccine antigens.

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

This review asks some hard questions about what the enigmatic graphoglyptid trace fossils are, documents some of their early fossil record from the Ediacaran-Cambrian transition and explores the idea that they may not have been fossils at all. Most researchers have considered the Graphoglyptida to have had a microbial-farming mode of life similar to that proposed for the fractal Ediacaran Rangeomorpha. This begs the question “What are the Graphoglyptida if not the Rangeomorpha persevering” and if so then “What if…?”. This provocative idea has at its roots some fundamental questions about how to distinguish burrows sensu-stricto from the external molds of endobenthic sediment displacive organisms.

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

There is a paucity of data on the progression of track cycling sprinters, and the evolution of training and performance over a training cycle. Following prior research showing relationships between sprint cycling power and endurance cycling power, we compared these relations over a 3-month period. Our hypothesis is large improvements in power would come from training either for sprint power or sprint capacity, and this would be reflected in the data. A total of publicly available 25 datasets. These data were plotted against the line of best fit for 30-s and 2-min power to assess if training towards the line led to better 30-s power. We observe the best performances came from riders who start below the 30-s vs 2-min power line of best fit, with greater capacity and ability to ride fast over a sprint series, and progressing towards focusing on specific power in the final block leading into a competition. These results support the hypothesis of combined capacity and power training based on rider-specific relationship to the line of best fit between these measures versus a strictly maximal power training focus.

Several pathotypes of enteric E. coli have been identified. The group represented by Shiga toxin-producing E. coli (STEC) is of particular interest. Raw milk and raw milk products are significant sources of STEC infection in humans; therefore, identifying pathogens at the herd level is crucial for public health. Most national surveillance programs focus solely on raw milk and raw milk cheeses that are ready for retail sale, neglecting the possibility of evaluating the source of contamination directly at the beginning of the dairy chain. In order to assess the viability of new molecular methodologies applied to raw milk filters enabling the identification of the presence of STEC serotypes in milk production and apply the same methods to identify the presence of these pathogens in calf feces we analyzed, through a commercial real-time PCR assay, a total of 290 samples coming from 18 different dairy herds; 88 bulk tank milk (BTM), 104 raw milk filters (RMF) and 98 calves’ feces samples. In total 3.4% of BTM, 41.4% of RMF and 73.4% of calves’ feces tested positive for stx presence, supporting our hypothesis that BTM is not a suitable matrix to assess the STEC presence at herd level, underestimating it. Our conclusion is that the surveillance program needs critical and extensive improvements such as RMF and calves’ feces analysis implementation in order to be more efficient in detecting and preventing STEC infections. The epidemiology of these infections and the characteristics of the pathogen clearly show how a One Health approach will be pivotal to improve our capabilities to control the spread of these infections.

Members of the DUF34 (domain of unknown function 34) family, also known as the NIF3 protein superfamily, are ubiquitous across superkingdoms. Proteins of this family have been widely annotated as “GTP cyclohydrolase I type 2” through electronic propagation based on one study. Here, the annotation status of this protein family was examined through comprehensive literature review and integrative bioinformatic analyses that revealed varied pleiotropic associations and phenotypes. This analysis combined with functional complementation studies strongly challenges the current annotation and suggests that DUF34 family members may serve as metal ion insertases, chaperones, or metallocofactor maturases. This general molecular function could explain how DUF34 subgroups participate in highly diversified pathways such as cell differentiation, metal ion homeostasis, pathogen virulence, redox and universal stress responses.

In recent years, many libraries and archives have started digitizing their collections thus making maps by Indigenous peoples more easily available for scholars to study. While a number of these maps were discussed by G. Malcolm Lewis in the History of Cartography series (volume 2, book 3, Chapter 4: 1984), more have since been found and disseminated. These maps are critical in understanding the historic and current land tenure of Indigenous groups. Further, Indigenous claims to land can be seen in their connections via toponymy. European concepts of territory and political boundaries did not coincide with First Nation/American Indian views resulting in the mistaken view that Natives did not have formal concepts of their territories. Further, Tribes/First Nations with cross-border territory have special jurisdictional problems. This paper will illustrate how many Native residents were very spatially cognizant of their own lands, as well as neighboring nations’ lands, overlaps between groups, hunting territories, populations, and trade networks. Currently, the Sinixt First Nation provides a perfect example of how an Aboriginal people are inputting and using a GIS representation of their territory with proper toponymy and use areas.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (&gt;1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

Generating long-lived mucosal and systemic antibodies through respiratory immunization with protective antigens encapsulated in nanoscale biodegradable particles could potentially decrease or eliminate the incidence of many infectious diseases but requires incorporation of a suitable mucosal immunostimulant. We previously found that respiratory immunization with a model protein antigen (LPS-free OVA) encapsulated in PLGA 50:50 nanoparticles (~380 nm diameter) surface modified with complement peptide-derived immunostimulant 02 (CPDI-02; formerly EP67) through 2kDa PEG linkers increases mucosal and systemic OVA-specific memory T-cells with long-lived surface phenotypes in young, naïve female C57BL/6 mice. Here, we determined if respiratory immunization with LPS-free OVA encapsulated in similar PLGA 50:50 microparticles (~1 μm diameter) surface modified with CPDI-02 (CPDI-02-MP) increases long-term OVA-specific mucosal and systemic antibodies. We found that, compared to MP surface modified with inactive, scrambled scCPDI-02 (scCPDI-02-MP), intranasal administration of CPDI-02-MP in 50 μL sterile PBS greatly increased titers of short-term (14 days post-immunization) and long-term (90 days post-immunization) antibodies against encapsulated LPS-free OVA in nasal lavage fluids, bronchoalveolar lavage fluids, and sera of young, naïve female C57BL/6 mice. Thus, surface modification of biodegradable microparticles with CPDI-02 is likely to increase long-term mucosal and systemic antibodies against encapsulated protein antigen after respiratory and possibly other routes of mucosal immunization.

Cellular automata (CA) models have emerged as a valuable tool in corrosion management. This manuscript provides an overview of the application of cellular automata models in corrosion research, highlighting their benefits and contributions to understanding the complex nature of corrosion processes. Cellular automata models offer a computational approach to simulate corrosion behavior at the microscale, capturing the intricate interactions between electrochemical reactions, material properties, and environmental factors generating a new vision of predictive maintenance. It discusses the key features of cellular automata, such as the grid-based representation of the material surface, the definition of state variables, and the rules governing cell-state transitions. The ability to model local interactions and emergent global behavior makes cellular automata particularly suitable for simulating corrosion processes. Finally, cellular automata models offer a powerful and versatile approach to studying corrosion processes, expanding models that can continue to enhance our understanding of corrosion and contribute to the development of effective corrosion prevention and control strategies.

Oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) mediates the degradation of Membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1), throughout the interaction of its protein binding motif (PBM) with the Discs-large homologous regions 1 (PDZ1) domain of MAG1-1. Generic variation in the E6 gene that translates to changes in the protein’s amino acidic sequence modifies the interaction of E6 with the cellular protein MAGI-1. MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells, where it interacts with a variety of proteins regulating signaling pathways. MAGI-1 is a multidomain protein containing two WW (rsp-domain-9), one guanylate kinase-like, and six PDZ domains. PDZ domains played an important role in the function of MAGI-1 and served as targets for several viral proteins including the HPV-16 E6. The aim of this work was to evaluate, with an in silico approach, employing molecular dynamics simulation and protein-protein docking, the interaction of the intragenic variants E-G350 (L83V), E-C188/G350 (E29Q/L83V), E-A176/G350 (D25N/L83V), E6-AAa (Q14H/H78Y/83V) y E6-AAc (Q14H/I27RH78Y/L83V) and E6-reference of HPV-16 with MAGI-1. We found that variants E-G350, E-C188/G350, E-A176/G350, AAa and AAc increase their affinity to our two models of MAGI-1 compared to E6-reference.

The rapid growth of the global wearable technologies market is projected to reach $61.30 billion by 2030 which reflects a shift towards personalised health monitoring embedded in everyday activities. This paper explores the potential of embroidered interdigitated transducer (IDT)-based sensors for non-invasive, continuous monitoring of human biomarkers, particularly glucose levels, in human sweat. The study employs innovative embroidery techniques to create flexible fabric-based sensors with gold-coated IDTs. Experimental results demonstrate the sensor’s capability to detect water droplets and glucose concentrations, showcasing promising applications for health monitoring. The embroidered IDT-based sensors offer a unique approach for seamless integration into clothing, paving the way for personalised, continuous health data capture.

In 2020, students of Pakistan had to adapt to the online environment for the very first time. This study aims to analyze the perceptions of medical, dental, and allied health students about online education in Pakistan. A descriptive, cross-sectional study was done to assess the level of acceptance of undergraduate students. A pre-validated questionnaire regarding demographics, past-experience of e-learning, advantages disadvantages of e-learning, and general perception of students towards e-learning was distributed. Descriptive statistics were computed for demographics, Mann-Witney-U test was used to compare the differences of perceptions between pre-clinical year and clinical years students. Kruskal-Wallis test was applied to compare the results of three specialties of students. Chi-square was used to compare overall category-wise positive and negative responses of students. 1200 students participated in the study. The major advantage identified by all students was the ‘comfortable environment’ in which they studied online. The major disadvantage selected by preclinical year students was ‘anxiety due to social isolation’ and that chosen by clinical year students was ‘lack of patient interaction’. Overall, 72% of students had a negative perception of e-learning. Student-teacher training, student counselling sessions, and innovative techniques need to be introduced to enhance student engagement and reduce pandemic stress.

Changes in agricultural policy may have rapid impact even on landscapes which have taken millennia to form. Here we explore the potential of UK leaving the EU as a catalyst for profound changes in pastoral landscapes in Wales. Impending change of the trading regime governing agricultural produce, concurrent to public pressure to use agricultural subsidies for environmental goals, may lead to unforeseen consequences for Welsh natural environment. We employ a combination of change demand modelling and ‘story and simulation approach’ to predict the effect of five hypothetical scenarios on land use and land use change in Wales by 2030. We show that the most extreme trade scenario would result in a near-uniform distribution of broadleaf woodland across most of Wales. Abandonment of marginal and low productivity grazing would likely give way to afforestation, initiating a return to forested landscapes not seen in Wales for several thousands of years.

Semisolid casting can provide excellent castings, but the nature of the pore-forming mechanisms has not been properly clarified. In the current communication, it was suggested that hydrogen precipitated during slurry making might have a decisive role in the formation of both gas and shrinkage porosity. Intensive stirring at the end of the slurry making process may act as a degassing step. Without the intense stirring, structures of primary slurry particles form around the hydrogen pores, strongly affecting pore formation and feeding during the intensification stage.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

Small hydro-power systems seem to be the best solution for energy generation through the use of pump as turbine (PAT) due to its low cost and lesser environmental hazards associated with it. Recently, PAT applications are gaining global attention in energy generation but its operation is not fully understood. The performance and flow behavior is affected by several operational conditions. This study seeks to investigate the effects of rotational speed on flow behavior and performance of a PAT. Rotational speed is an important physical parameter that affects the operation of a PAT. A selected centrifugal pump model of four blades and splitters was used for the study. Numerical simulations were carried out using k-ε turbulence model to solve the three-dimensional (3D) equations in both pump and PAT modes. The outcomes were then validated using experimental results in the pump mode to obtain overview flow physiognomies. The results predicted that the efficiency increases as the rotational speed increases in the pump mode whereas in turbine mode, higher rotational speed cannot convert hydraulic energy into mechanical energy. Thus, a rotational speed of 1500 rpm performed the highest efficiency of 69.8% at QBEP among the other rotational speeds selected. Moreover, the head performance in the turbine mode increases as the flow rate increases. This research provides useful information which will help improve PAT performance as well as selecting PAT for small hydro-power site.

This paper aims to research whether there is link between FDI inflows and Economic growth in the Republic of Seychelles Island. The ordinary least square results obtained shows that in the impact of FDI inflows on economic growth is low. Small Island Developing States attracts less FDI inflow because they are limited to few resources that attracts overseas firms which results in retarded development. The research lighted that impact of foreign direct investment on host countries does not only depend on the quality and quantity of the FDI inflows but some other variables such as the internal policies and the management skills, market structures, economic trends among others.

This paper reports on the optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation systems for cattle farming in rural areas of Bangladesh. Bangladesh is a lower middle-income country with declining rates of poverty among its 160 million people due to persistent economic growth in conjunction with balanced agricultural improvements. Most of the rural households adopt a mixed farming system by cultivating crops and simultaneously rearing livestock. Among the animals raised, cattle are considered as the most valuable asset for the small/medium-scale farmers in terms of their meat and milk production. Currently, along with the major health issue, the COVID-19 pandemic is hindering the world’s economic growth and has thrust millions into unemployment; Bangladesh is also in this loop. However, natural disasters such as COVID-19 pandemic and floods, largely constrain rural smallholder cattle farmers from climbing out of their poverty. In particular, small and medium-scale cattle farmers face many issues that obstruct them from taking advantage of market opportunities and imposing a greater burden on their families and incomes. An appropriate measure can give a way to make those cattle farmers’ businesses both profitable and sustainable. Optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation system for cattle farming is a new and forward-looking approach for sustainable development of the livestock sector. In this study, we design and optimize a thin-film coating assisted hybrid (photovoltaic-battery-generator) power system by using the Hybrid Optimization of Multiple Energy Resources (HOMER, Version 3.14.0) simulation tool. An analysis of the results has suggested that the off-grid hybrid system is more feasible for small and medium-scale cattle farming systems with long-term sustainability to overcome the significant challenges faced by smallholder cattle farmers in Bangladesh.

The adverse relationship between viral hepatitis and pregnancy in developing countries was seen as a reflection of retrospective biased hospital-based data collection by the West. However, the discovery of HEV from an epidemic of non-A, non-B hepatitis in Kashmir and documenting increased incidence and severity of hepatitis E in pregnancy from a house-to-house survey unmasked the unholy alliance. Among the family of HEV’s, genotype (gt)-1, with a unique ORF4-encoded protein enhancing viral polymerase activity and viral replication, is the sole HEV that shows this adverse relationship. The epidemics caused by HEV-gt1 and not by HEV-gt2 show adverse relationship with pregnancy. The pathogenesis of the unholy alliance is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the mother including: infection, replication and damage to the maternal-foetal interface by HEV-gt1; vertical transmission of HEV to foetus causing severe foetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the mother promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of ALF. Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are 4 main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans by undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

Irregular female migration to Europe is a growing phenomenon, as more and more women are fleeing their countries of origin due to gender inequality and violence. During the migration process, women experience physical, psychological and social problems that affect their sex lives. The aim of our study is to describe and understand how irregular migrant wom-en living in humanitarian reception centers experience their sexuality at different stages of the migration process. This qualitative phenomenological study collected data through a sixteen in-depth interviews with irregular migrant women between January and February 2023. Data anal-ysis was carried out using ATLAS-ti 23.0 software, from which three themes were extracted: 1) The sexual reality of sub-Saharan women, 2) In search of a better life: take the risk or surrender, and 3) The migrant sexual revolution. The sexual reality of sub-Saharan women is subject to a complex normative order. The migratory process has severe consequences on migrant women's sex life. The sexual needs of irregular migrant women admitted to humanitarian reception cen-ters undergo a process of change that must be understood by healthcare providers in order to make improvements to care provision.

This review summarizes the most recent developments of research on protozoan parasite infections ac-quired through food and drinking water and is aimed at gathering updated knowledge on the risk factors, illnesses caused, and measures for prevention. Reports included dated from 2019 to the present and regarded recent outbreaks and cases of severe infec-tions, prevalence in different population segments and food handlers, and occurrence in food and drinking water. Cryptosporidium spp., Entamoeba histolytica, Giardia intestinalis, Trypanosoma cruzi and Toxoplasma gondii were the microorganisms most frequently involved in large outbreaks and/or severe infections, while Cyclospora cayetanensis was most frequently involved in single case reports. Cystoisospora belli was implied in severe infections in immunocompromised patients, while Blastocystis homi-nis, Sarcocystis spp., Dientamoeba fragilis, Endolimax nana and Pentatrichomonas hominis appeared to be less relevant for number of symptomatic infections and pathogenic potential. A progressive improvement in surveillance of protozoan infections and infection sources was highlighted, especially in developed countries. The apparent increase in cases was concomitant with the implementa-tion of reporting systems and the application of molecular diagnostic methods that represent valuable in-struments for establishing epidemiological links and preventing or limiting outbreaks. The pathogenic role and sources of infection should be better elucidated for some species.

As customer demand for green products increases in the digital economic era, this study analyses the green innovation of the e-tailer and supplier in drop shipping models. Moreover, drop shipping e-tailers and suppliers with a drop shipping option need to make choices regarding whether to provide green or normal products to the market. When a supplier with a drop shipping option produces green products, more fees may be invested on the production of green products than on normal products. The drop shipping e-tailers and suppliers with a drop shipping option can also choose to sell normal products at a low cost, as before. This study designs four models of drop shipping e-teilers and suppliers with a drop shipping option under different choices, analyzes their operational process in drop shipping models, and investigates five theorems. The optimal pricings decisions and green degree of drop shipping e-tailers and suppliers with a drop shipping option were evaluated in this study. The impacts of the green innovation factor, green elasticity coefficient, manufacturing and distribution costs on the drop shipping e-tailers and suppliers with a drop shipping option, and the effect of other environmental parameters on the green degree of green products are also analyzed through computer simulation. The findings of the simulation analysis provide valuable guidance for e-tailers and suppliers with green innovation in drop shipping models and offer important academic and practical implications for e-commerce and the digital economy.

Whistler mode waves play a major role in regulating the lifetime of trapped electrons in the Earth's radiation belts. Specifically, whistler mode hiss waves are one of the mechanisms that maintains the slot region between the inner and outer radiation belts. The generation mechanism of hiss is a topic still under debate with at least three prominent theories present in the literature. Lightning generated whistlers in their ducted or non-ducted modes, are considered to be one of the possible sources of hiss. We present a study of new observations from the Radio Receiver Instrument (RRI) on the Enhanced Polar Outflow Probe (ePOP: currently known as SWARM-E). RRI consists of two orthogonal dipole antennas, which enables polarization measurements, when the satellite boresight is parallel to the geomagnetic field. Here we present 75 passes of ePOP - RRI from 2014 - 2018, in which lightning whistlers and hiss waves were observed. In more than 50% of those passes hiss is found to co-exist with the lightning whistlers. Moreover, the whistler observations are correlated with observations of wave power at the lower-hybrid resonance. The observations and a whistler mode ray-tracing study suggest that multiple-hop lightning induced whistlers can be a source of hiss and plasma instabilities in the magnetosphere.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Bangladesh's railway system mostly uses typical manual railway crossing technique or boom gates through its 2,955.53 km rail route all over the country. The accidents are frequently happening in the railway crossings due to not having obstacle detectable and quickly operating gate systems, and also for fewer safety measures in the railway crossing. Currently, there are very few automatic railway crossing systems (without obstacle detectors) available, however, all of them are dependent on the national power grid without a backup plan for any emergency cases. Bangladesh is still running a bit behind in the power generation of its consumption, hence it is not possible to have a continuous power supply at all times all over the countryside. We aim to design and develop a smart railway crossing system with an obstacle detector to prevent common types of accidents in the railway crossing points. We design to use two infrared (IR) sensors to operate the railway crossing systems which will be controlled by the Arduino Uno. This newly designed level crossing system will be run with the help of sustainable renewable energy which is cost-effective, eco-friendly, and apply under the national green energy policy towards achieving sustainable development in Bangladesh as a part of the global sustainable goal to face climate change challenges. We have summarized the simulated results of several renewable energy sources including a hybrid system and optimized the Levelized Cost of Energy (LCOE), and the payback periods.

Eucalyptus, a therapeutic plant mentioned in the ancient Algerian pharmacopeia, specifically two species belonging to the Myrtaceae family - E. radiata and E. cinerea, were investigated in this study for their antibacterial, antioxidant, and anti-inflammatory properties. The study used aqueous extracts (AE) obtained from these plants, and the extraction yields were found to be dif-ferent. The in vitro antibacterial activity was evaluated using a disc diffusion assay against three typical bacterial strains. The results showed that E. radiata EAq was effective against all three strains, while E. cinerea EAq was only effective against E. coli. Both extracts displayed significant antioxidant activity compared to BHT. The anti-inflammatory impact was evaluated using a pro-tein (BSA) inhibition denaturation test. The E. radiata extract was found to inhibit inflammation by 75% at a concentration of 250 g/ml, significantly higher than the placebo. Ellagic acid, a pri-mary phytochemical found in the extracts, demonstrated noteworthy toxic and pharmacokinetic characteristics and a maximum binding energy of -7.53 kcal/mol for its anti-TyrRS activity in sili-co. The study suggests that the extracts and their primary phytochemicals could enhance the effi-cacy of antibiotics, antioxidants, and non-steroidal anti-inflammatory drugs (NSAIDs). As phar-maceutical engineering experts, we believe this research contributes to developing natural-based drugs with potential therapeutic benefits.

The frequent occurrence of rib fractures in slaughtered lambs results in significant economic loss to producers and processors in South Australia and raises concerns about the welfare of the animals. The prevalence of rib fractures became evident through the Enhanced Abattoir Surveillance (EAS) program introduced in 2007. The present study aimed to investigate the association between rib fracture prevalence in lambs at slaughter and their nutrition and management on the farm of origin. The slaughter of 30,055 lambs from 60 farms was monitored at a South Australian abattoir in November 2016. Rib fracture prevalence was 4% (range 0 - 18% per consignment), with all consignments of more than 240 lambs having at least one with fractured ribs. Traceback investigation on 56 of the 60 farms suggests that rib fractures most probably occur during routine husbandry procedures and, based on soil mineral analysis, are associated with calcium inadequacy. There was substantial variation between lines of lambs from different farms, and factors contributing to the differences included line size, region, and soil characteristics, including available calcium. There is a need to modify sheep husbandry and management practices to improve sheep welfare and reduce the cost of rib fractures to the sheep industry.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

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

There have been beaching events of the marine alga pelagic sargassum in coastal regions of the Caribbean Sea, West African countries, and the north-northeast region of Brazil since 2011. Its presence has caused environmental and socioeconomic impacts while several studies were conducted in order to understand the causes of this phenomenon, as well as alternatives to mitigate its impacts. The objective of this research was to evaluate pelagic sargassum biomass as a raw material for the manufacture of medium-density multilayer particleboards. These are composed of 30% sargassum particles in their inner layer and 70% sugarcane bagasse particles on their outer layers which are bonded with castor oil-based polyurethane resin. A physical and chemical characterization was carried out in order to evaluate sargassum particles while physical and mechanical tests were carried out in order to evaluate the panels. Results were subsequently compared with indications from NBR 14810-2:2018 and ISO 16893:2016 standards. A life cycle assessment based on ISO 14040:2006 and 14044:2006 was carried out as to complement the feasibility study of these panels and to compare their different manufacturing processes. The multilayer panels met the minimum requirements for physical and mechanical properties established by regulations, indicating that the Sargassum spp. biomass can be used as filling. The life cycle assessment study indicates that sargassum panels produced in the Belém-PA-Brazil region present lower environmental impacts in four of seven evaluated categories when compared to conventional panels. As such, they constitute an alternative way to mitigate environmental impacts generated by beaching events.

Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SNPs) in DPP9 and loss of function (LoF) variants have not been explored. Human genomic databases including The Cancer Genome Atlas (TCGA) were interrogated to identify DPP9 LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that DPP9 and DPP8 are intolerant to LoF variants. DPP9 LoF variants were most often associated with uterine carcinoma. Two DPP9 intronic SNPs that have been associated with lung fibrosis and COVID-19 were not associated with liver fibrosis or cancer. All four DPP4-like genes were overexpressed in liver tumours and their joint high expression was associated with poor survival in HCC. Increased DPP9 expression was associated with obesity in HCC patients.. High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 were associated with very poor survival in HCC. Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. This comprehensive data mining suggests that DPP9 is essential for human survival and the DPP4 protease family is important in cancer pathogenesis.

The Eurasian grapevine (Vitis vinifera L.) is the most widely grown horticultural crop in the world and is important for the economy of many countries. In the wine production chain, grape varieties play an important role as they directly influence the authenticity and classification of the product. Identifying the different grape varieties is therefore fundamental for quality control and inspection activities, as well as for regulating production. Currently, ampelography and molecular analysis are the main approaches to identifying grape varieties. However, both methods have limitations. Ampelography is subjective and prone to errors and is experiencing enormous difficulties as ampelographers are increasingly scarce. On the other hand, molecular analyses are very demanding in terms of cost and time. In this scenario, Deep Learning (DL) and Machine Learning (ML) methods have emerged as a classification alternative to deal with the scarcity of ampelographs and avoid molecular analyses. In this study, the most recent and current methods for identifying grapevine varieties using DL classification-based approaches are presented through a systematic literature review. The classification pipeline of the 31 studies found in the literature was described, highlighting its pros and cons. Most of the studies used DL-based models trained with leaf images acquired in a controlled environment at a maximum distance of 1.2 metres to classify grape varieties. In addition, there is a large gap between practical applications and the datasets used: a great lack of varieties, limited data acquired in the field and a lack of tests on plants under adverse conditions. Potential directions for improving this area of research were also presented.

Through the half-unit circle area computation using the integration of the corresponding curve power series representation, we deduce a slow converging positive infinite series to $\pi$. However, by studying the remainder of that series we establish sufficiently close inequalities with equivalent lower and upper bound terms allowing us to estimate, more precisely, how the series approaches $\pi$. We use the obtained inequalities to compute up to four-digit denominator, what are in this sense, the best rational numbers that can replace $\pi$. It turns out that the well-known convergents of the continued fraction of $\pi$, $22/7$ and $355/113$ called, respectively, Yuel\"{u} and Mil\"{u} in China are the only ones found. Thus we apply a similar process to find rational estimations to $\pi+e$ where $e$ is taken as the power series of the exponential function evaluated at $1$. For rational numbers with denominators less than $2000$, the convergent $920/157$ of the continued fraction of $\pi+e$ turns out to be the only rational number of this type.

Under one-health perspective and the worldwide antimicrobial resistance concern, we investigate extraintestinal pathogenic Escherichia coli (ExPEC), uropathogenic E. coli (UPEC), and multidrug resistant (MDR) E. coli from 197 isolates recovered from healthy dogs in Spain between 2013 and 2017. Ninety-one (46.2%) isolates were classified as ExPEC and/or UPEC including 50 clones, among which (i) four clones were dominant (B2-CH14-180-ST127, B2-CH52-14-ST141, B2-CH103-9-ST372 and F-CH4-58-ST64815) and (ii) 15 had been shown to be displayed by previously published isolates causing extraintestinal infections in humans. Twenty-eight (14.2%) isolates were classified as MDR, associated with B1, D and E phylogroups and included 24 clones, of which eight had also been identified among human isolates causing infections. We selected 23 ST372 strains, 21 healthy dogs faecal isolates and two human clinical isolates for whole genome sequencing and built a SNP-tree with these 23 genomes and 174 genomes (128 from canine strains and 46 from human strains) obtained from public databases. The analysis of these 197 genomes allowed to identify six clusters. Cluster 1 comprised 74.6% of the strain genomes that were mostly composed of canine strain genomes (P &lt; 0.00001). Clusters 4 and 6 also included canine strain genomes, while clusters 2, 3 and 5 were significantly associated with human strain genomes. All these findings suggest that dogs are reservoirs of ExPEC, UPEC and MDR E. coli isolates with zoonotic potential.

Bioactive surface coatings have retained the attention of researchers and physicians due to their versatility and range of applications in orthopedics, particularly in infection prevention. Antibacterial metal nanoparticles (mNPs) are a promising therapeutic, with vast application opportunities on orthopedic implants. The current research aimed to construct a polyelectrolyte multilayer on a highly porous titanium implant using alternating thin film coatings of chitosan and alginate via the layer-by-layer (LbL) self-assembly technique, along with the incorporation of silver nanoparticles (AgNPs) or titanium dioxide nanoparticles (TiO2NPs), for antibacterial and osteoconductive activity. These mNPs were characterized for their physicochemical properties using quartz crystal microgravimetry with dissipation system, nanoparticle tracking analysis, scanning electron microscopy, and atomic force microscopy. Their cytotoxicity and osteogenic differentiation capabilities were assessed by AlamarBlue and alkaline phosphatase (ALP) activity assays, respectively. The antibiofilm efficacy of the mNPs tested against Staphylococcus aureus. The LbL polyelectrolyte coating was successfully applied to the porous titanium substrate. A dose-dependent relationship between nanoparticle concentration and ALP as well as antibacterial effects was observed. TiO2NP samples were also less cytotoxic than AgNP counterparts, although similarly antimicrobial. Together, these data serve as a proof-of-concept for a novel coating approach for orthopedic implants with antimicrobial and osteoconductive properties.

Woodland strawberry (Fragaria vesca L.) is an underutilized plant species, appreciated by consumers for its qualitative features. Utilizing technical means of production, such as plant biostimulants, that can increase crop productivity and quality could be highly important in woodland strawberry cultivation. The scope of the present study was to appraise the influence of two biostimulants (Trichoderma atroviride and plant protein hydrolysate) - used either alone or combined - on plant performance and economic profitability of two woodland strawberry genotypes (‘Alpine’ and ‘Regina delle Valli’). Overall, data showed that ‘Alpine’ had the highest productive performances, whereas ‘Regina delle Valli’ revealed the highest fruit qualitative traits. T. atroviride inoculation and V-PH application significantly boosted plant marketable yield (+20.5% for T. atroviride and +12.9% for V-PH), total sugars (+1.9% for Trichoderma and +1.4% for V-PH) and anthocyanins (+14.1% for T. atroviride and +9.8% for V-PH) compared to non-treated plants. Plants supplied with both biostimulants had higher marketable yield (+34.8%), mean fruit weight (+6.0%), fruit dry matter (+13.8%), total sugars (+3.5%), ascorbic acid (+12.7%), flavonoid (+26.3%) and anthocyanins (+29.9%) compared to non-treated plants. Furthermore, our study revealed that the highest fruit polyphenols concentration was recorded in both genotypes treated with the combination of biostimulants and in ‘Regina delle Valli’ sprayed with V-PH, whereas the highest antioxidant activity was found in ‘Regina delle Valli’ fruit when plants were supplied with both biostimulants. Our study pointed out that the application of microbial and non-microbial biostimulants, especially in combination, might be an useful strategy for improving performances of underutilized species and, therefore, encourage its cultivation, valorisation and economic profitability (+10195.3 €/ha when plants were exposed to both biostimulants).

Coronavirus disease 2019 (COVID-19) displays clinical heterogeneity, but little information is available for patients with mild or very early disease. We aimed to characterize biomarkers that are useful in discriminating the hospitalization risk in a COVID-19 cohort from Northern Italy during the first pandemic wave. We enrolled and followed for four weeks 76 symptomatic SARS-CoV-2 positive patients and age/sex-matched healthy controls. Patients with mild disease were discharged (n.42), and the remaining were hospitalized (n.34). Blood was collected before any anti-inflammatory/immunosuppressive therapy and assessed for soluble C5b-9/C5a, H3-neutrophil extracellular traps (NET), calprotectin, DNase plasma levels by ELISA, and a panel of pro-inflammatory cytokines by ELLA. Calprotectin and NET levels discriminate between hospitalized and non-hospitalized patients, while DNase negatively correlates with NET levels; there are positive correlations between calprotectin and both NET and neopterin levels. Neopterin levels increase in patients at the beginning of the disease and more in hospitalized than non-hospitalized ones. C5a and sC5b-9, and other acute phase proteins correlate with neopterin, calprotectin, and DNase. Both NET and neopterin levels negatively correlate with platelet count. We show that calprotectin, NET, and neopterin are important proinflammatory parameters potentially useful in discriminating between COVID-19 patients at risk for hospitalization.

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.

Paratuberculosis, or Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis affecting both domestic and wild ruminants. The agent was also found in wild mammals such as wild boar (Sus scrofa), however, the role of wild mammals in the epidemiology of MAP is unclear. During the research period, 941 free-ranging wild boar (S. scrofa) legally hunted in two locations in the Centre-eastern region of Portugal were examined. Ninety-seven wild boar exhibited one or more gross lesions and were tested for the presence of Mycobacterium avium subsp. paratuberculosis using acid-fast staining, mycobacterial culture, poly-merase chain reaction (PCR), and histopathological examination. Forty-five animals (46.4%, 95% CI: 36.5-56.3%) were identified as infected, as indicated by positive results in culture and/or PCR. The findings revealed that the most significant risk factor was being a juvenile compared to year-lings and adults (OR = 10.2, 95% CI: 2.2-48.0). Based on our results, 37.9% (n = 11) of the infected animals were considered suitable for human consumption. Our findings offer novel insights into mycobacterial infections in wild boar populations in Portugal and suggest that wild boar could be a source of human infection if zoonotic potential is considered.

The growing attention for plug-in electric vehicles, and the associated high-performance demands, have initiated a development trend towards highly efficient and compact on-board battery chargers. These isolated ac-dc converters are most commonly realized using two conversion stages, combining a non-isolated power factor correction (PFC) rectifier with an isolated dc-dc converter. This, however, involves two loss stages and a relatively high component count, limiting the achievable efficiency and power density and resulting in high costs. In this paper a single-stage converter approach is analyzed to realize a single-phase ac-dc converter, combining all functionalities into one conversion stage and thus enabling a cost-effective efficiency and power density increase. The converter topology consists of a quasi-lossless synchronous rectifier followed by an isolated dual active bridge (DAB) dc-dc converter, putting a small filter capacitor in between. To show the performance potential of this bidirectional, isolated ac-dc converter, a comprehensive design procedure and multi-objective optimization with respect to efficiency and power density is presented, using detailed loss and volume models. The models and procedures are verified by a 3.7 kW hardware demonstrator, interfacing a 400 V dc-bus with the single-phase 230 V, 50 Hz utility grid. Measurement results indicate a state-of-the-art efficiency of 96.1% and power density of 2.2 kW/dm³, confirming the competitiveness of the investigated single-stage DAB ac-dc converter.

The criteria of “Distinctness, Uniformity and Stability” as well as a high "overall quality index” are used to register the Italian modern varieties to the national register. Differently, local conservation varieties can be certified under different EU Directives having, as overall objective, the preservation of biodiversity and the containment of genetic erosion. In recent years, products derived from an-cient grains are perceived to be healthier and more sustainable by consumer, especially in Italy, with consequent higher market prices. Ancient tetraploid wheat varieties registered in the national reg-ister of conservation varieties are 28, 24 of which are Sicilian. They are supposed to have a wide genetic variability compared to modern ones, making them vulnerable of fraud because they are difficult to trace. It is therefore important to have tools able to discriminate the autochthonous Si-cilian varieties. This can be done by gluten proteins composition, which also gives information on the technological properties of derived products. Fifty-one accessions belonging to 22 ancient va-rieties of Sicilian tetraploid (mostly durum) wheat were analyzed. Although a wide intra-accession and intra-varietal variability was assessed, the gliadin pattern of bulks of seeds belonging to each variety was discriminatory. Moreover, differences in technological attitudes were found between landraces. This paves the way to use gluten protein patterns for traceability allowing local farmers and producers to valorize their products and assure consumers about the transparency of the entire supply chain.

Nanotechnology has become a popular topic in agricultural and animal research, generating sig-nificant global interest. Nanoparticles (NPs)-enabled agriculture and animal husbandry (AHs) products have three main principles: crop production, protection, and nutrient enrichment. Re-search on this topic has grown exponentially in recent years, with an increasing number of peer-reviewed literature and patents on NPs-enabled agriculture and AH products. This study examines and collects data on the various applications of NPs-enabled agricultural products for crop production, protection, and livestock improvement from the core nanotechnological database. The search returned several types of NPs and products used in agriculture and AH, countries that utilize these products at a commercial level, and analysis of these data by phyton, R-statistical software. Our findings show remarkable growth of nanotechnology in agriculture, AH, and re-search fields for future sustainability goals in the era of climate change

Volatile organic compounds (VOCs) released from plants have been correlated with disease-status. Analysis of VOCs using GC-MS is time-consuming, laboratory-based, and requires specialist training. Electronic nose devices (E-nose) provide a portable alternative. Three different E-nose devices were compared to assess how accurately they could detect Mango Twig Tip Dieback and Panama disease in banana. The devices were initially trained on known volatiles, then pure cultures of Pantoea sp., Staphylococcus sp., and Fusarium odoratissimum, and finally, on infected and healthy mango leaves and field-collected, infected banana pseudo-stems. The experiments were repeated three times with six replicates for each host-pathogen pair. The variation between healthy and infected host materials was evaluated by principal component and linear discriminant analysis, cross-validation and chemometric data analysis. GC-MS analysis was conducted contemporaneously and identified an 80% similarity between healthy and infected plant material. The portable C 320 was 100% successful in discriminating known volatiles but had a low capability in differentiating healthy and infected plant substrates. The advanced devices (PEN 3 / MSEM 160) successfully detected healthy and diseased samples with a high variance. The results suggest that E-nose devices are more sensitive and accurate in detecting changes of VOCs between healthy and infected plants compared to headspace GC-MS.

This paper addresses the conceptual exploration of various issues that form an integral part of the ethical dimensions surrounding the use of artificial intelligence (AI) in the field of marketing. We critically review some of the main ethical challenges AI poses to humanity: privacy, data security, bias, transparency, and accountability. Therefore, we will discuss the delicate balance between exploiting the transformation potential of AI for personally designed marketing strategies and ethical imperatives to safeguard the rights of consumers to retain trust. Then, the present regulatory landscape responding to these ethical challenges will be assessed by building on effective regulation, like the GDPR, existing proposed legislative frameworks, and industry guidelines. To underscore the role of an ongoing dialogue between marketers, technologists, ethicists, and regulators for developing a responsible AI ecosystem in marketing. Further, strategic recommendations for implementing company-based ethical AI marketing practices. The further strong guidelines provide enhancement transparency to consumers and investment in research to remove biases from algorithms. It also underscores principal scopes of further research and development, focusing on the need for new-age solutions to guide the ethical quagmires that AI-led marketing throws up. We suggest that integration should be done proactively and collaboratively. Thus, if attention is paid more to ethics and multidisciplinary dialogue, only such hyperbolic promises can be realized by AI-driven marketing. There are such promises through which AI-driven marketing will meet business goals and be huge at societies' values.

Isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) was obtained 95% yield by 2-methyl-6-nitrobenzoic anhydride (MNBA)/4-dimethylaminopyridine (DMAP)-catalyzed reaction at room temperature for 190 minutes in dichloromethane. The structure of isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) was established by NMR, FTIR, and the high resolution of mass spectroscopies. In vitro sun protection factor evaluation exhibited value of 37.10 ± 0.03 which indicates that isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) as a sunscreen agent with high protection.

The Universe has a gravitational horizon with a radius R_h = c/H coincident with that of the Hubble sphere. This surface separates null geodesics approaching us from those receding, and as free-falling observers within the Friedmann-Lemaitre-Robertson-Walker spacetime, we see it retreating at proper speed c, giving rise to the eponymously named cosmological model R_h = ct. As of today, this cosmology has passed over 20 observational tests, often better than LCDM. The gravitational radius R_h therefore appears to be highly relevant to cosmological theory, and in this paper we begin to explore its impact on fundamental physics. We calculate the binding energy of a mass m within the horizon and demonstrate that it is equal to mc². This energy is stored when the particle is at rest near the observer, transitioning to a purely kinetic form equal to the particle's escape energy when it approaches R_h. In other words, a particle's gravitational coupling to that portion of the Universe with which it is causally connected appears to be the origin of rest-mass energy.

The purpose of this study is to find out the e-reputation management of the hotel industry, as well as the social media channels used as the tools of hotel e-reputation building. This study used a qualitative approach by analyzing the in-depth interviews with hotel marketing communication practitioners of 15 hotel companies in Bandung City. The findings identified that e-reputation is considered a crucial factor in determining hotel performance due to the change of customers’ behaviors today and identified also three types of e-reputation management activities implemented by hotel companies, such as online activities, offline activities, and online/offline activities. The results of this study have implications for the hospitality industry, as a reference for formulating their marketing strategies.

Does cell clustering influence intrinsic and acquired multi-drug resistance (MDR) differently? To address this question, we studied cultured monolayers (representing individual cells) and cultured spheroids (representing clusters) formed by drug-naïve (intrinsic MDR) and drug-exposed (acquired MDR) lines of ovarian cancer A2780 cells by cytometry of reaction rate constant (CRRC). MDR efflux was characterized by accurate and robust “cell number vs. MDR efflux rate constant (kMDR)” histograms. Both drug-naïve and drug-exposed monolayer cells presented unimodal histograms; the histogram of drug-exposed cells was shifted towards higher kMDR value suggesting greater MDR activity. Spheroids of drug-naïve cells presented a bimodal histogram indicating the presence of two subpopulations with different MDR activity. In contrast, spheroids of drug-exposed cells presented a unimodal histogram qualitatively similar to that of the monolayers of drug-exposed cells but with a moderate shift towards greater MDR activity. The observed greater effect of cell clustering on intrinsic than on acquired MDR can help guide the development of new therapeutic strategies targeting clusters of circulating tumor cells.

A drug repositioning effort supported the possible use of the anti-HIV drug etravirine as a treatment for Friedreich Ataxia (FRDA). Etravirine increases frataxin protein and corrects the biochemical defects in cells derived from FRDA patients. Because of these findings, and since etravirine displays a favorable safety profile, we conducted this pilot open-label phase 2 clinical trial assessing the safety and potential efficacy of etravirine in FRDA patients. Thirty-five patients were stratified into 3 severity groups and randomized to etravirine 200 mg/day or 400 mg/day. They were treated for 4 months. Efficacy endpoints were represented by changes in peak oxygen uptake and workload as measured by incremental exercise test, SARA score, cardiac measures, measures of QoL and disability. Data were collected 4 months before the start of the treatment (T-4), at the start (T0), at the end (T4) and 4 months after the termination of the treatment (T+4). Etravirine was well tolerated. Etravirine completely stopped the progression of the SARA score during the 4-months treatment period, compared to the 4 months pre and post treatment. It increased peak workload, while the improvement of peak oxygen uptake was not statistically significant. No changes in the cardiac measures were observed. Health and QoL measures showed a worsening at the suspension of the drug. In this open trial etravirine significantly improved neurological function and was generally safe and reasonably tolerated. This suggests that etravirine represents a potential therapeutic agent in FRDA deserving testing in a randomized placebo controlled clinical trial.

Lightning has received a lot of attention in scientific literature during the recent decade, not only because it is an impressive atmospheric phenomenon but also its associations with severe storms that cause unprecedented damages to agriculture, electric power networks, property, and life. This study assessed the Spatio-temporal characteristics of lightning occurrence with elevation in Uganda using lightning flash and elevation datasets for a period of fifteen years (1998-2013). Datasets used in this study included daily lightning flashes as captured by Lightning Imaging Sensor (LIS) aboard on Tropical Rainfall Measurement Mission (TRMM) satellite and elevation data in form of Digital Elevation Model (DEM) obtained from the Shuttle Radar Topography Mission (SRTM). Spatio-temporal results indicated that ~80% of areas with an elevation that ranges from 800-1200 m above mean sea level (masl) in Uganda had severe lightning occurrences and ~20% of areas with an elevation greater than 1200 m (masl) had severe lightning occurrences. The country received an enhanced number of lighting events with the highest number in 1999. Subsequently, a reduced trend was observed from 2002 to 2007 followed by an increment in the number of lightning events in (2010, 2011, 2012, and 2013). The intensity of the events decreased gradually though two peaks were observed, (1998-2001) and (2010-2013). Furthermore, results indicate escalations in the frequency and duration of lightning events from 60 times in 1998 to approximately 200 times in 2013 and from 1000 microseconds in 1998 to more than 2000 microseconds in 2013. Generally, the country experienced an enhanced increase in lighting occurrences over the study period which therefore calls for urgent actions to combat the root cause and also provide effective measures to reduce the impacts of lightning strikes.

Pretreatment of cells with proteolysis inhibitors diminished intensity and changed shape of DNICs specific EPR signal in a treatment time-dependent manner. The level of DNIC formation was significantly influenced by the presence of protein degradation products. Interestingly, formation of HMWDNICs depended on the availability of LMWDNICs. The extent of glutathione involvement in the in vivo formation of DNICs is minor yet noticeable, aligning with our prior research findings.

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p&lt;0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).

Dried blood spot (DBS) testing on confetti is one of the most common methods used to collect and extract DNA from field samples for molecular epidemiology of malaria studies. Here, we investigated whether ethanol or other solutions used to clean scissors are a source of sample contamination. DBS were prepared from 3 drops of blood from two Plasmodium falciparum cultures spotted on confetti, and 3 solutions (water, ethanol and DNase) were used to clean scissors between spots during DNA extraction. For each cleaning solution, two blank confetti were used as negative controls. Samples were analyzed by PCR-based genotyping of merozoite surface proteins 1 & 2 (msp-1 and msp-2), and P. falciparum chloroquine resistance transporter (Pfcrt). A total of 15 samples were analyzed. Based on msp-1 and msp-2 amplification, P. falciparum was detected on blank confetti when scissors were washed with ethanol. Based on Pfcrt amplification, DNA of P. falciparum was detected on blank confetti when scissors were cleaned with ethanol or water. No P. falciparum genes were detected on blank confetti when scissors were cleaned with DNase. Scissors cleaned with DNase prevented cross-contamination between samples during processing of dried blood spots, whereas ethanol (which is commonly used) fails to avert cross-contamination.

The aim of this study was to identify factors, that influence satisfaction and dissatisfaction in the use of public e-procurement. The use of IT solutions promotes sustainable development. Hence, there is a need to conduct research that will allow for the best possible adjustment of e-procurement solutions in order to implement them as widely as possible in business practice. This study used a quantitative exploratory survey-based approach. The obtained research results were analyzed using statistical methods, including factor analysis PCA. Factor analysis identified three main satisfaction factors and two dissatisfaction factors in e-procurement use, highlighting the importance of support, intuitiveness, and security in user satisfaction. This study contributes to the existing literature by providing a nuanced understanding of the factors influencing user satisfaction and dissatisfaction within e-procurement systems, specifically highlighting the role of intuitive design and technical support. It offers a unique perspective by integrating these insights with the specific requirements of public procurement, thereby filling a gap in research on enhancing user experience in the context of sustainable purchasing practices.

E-commerce is a rapidly evolving global trend that is having a significant impact on consumer behavior and business strategies. Despite its growing impact, e-commerce adoption by Moroccan firms remains low and research on this topic in this context is scarce. This study aims to fill this gap by investigating the main determinants influencing e-commerce adoption by Moroccan firms. We use logit, probit, and conditional mixed process-probit models to identify the critical factors driving e-commerce adoption. Our results reveal five key findings. First, newer firms that are more open to innovation and change are more likely to adopt e-commerce. Second, firms with a higher proportion of highly educated employees are more likely to adopt e-commerce. Third, the digital skills of new employees do not directly influence the likelihood of e-commerce adoption. Fourth, being listed on digital platforms increases the likelihood of e-commerce adoption. Finally, there is a positive relationship between firms engaged in innovation activities and e-commerce adoption. These findings highlight the need for additional investment in promoting modern organizational practices, reskilling workers, and implementing advanced technologies to facilitate effective e-commerce integration among Moroccan SMEs. By addressing these challenges, Moroccan firms can harness the full potential of e-commerce and contribute to the country’s economic growth and digital transformation.

Toxins present in cigarette and e-cigarette smoke constitute a significant cause of illnesses and are known to have fatal health impacts. Specific mechanisms by which toxins present in smoke impair cell repair are still being researched and are of prime interest for developing more effective treatments. Current literature suggests toxins present in cigarette smoke and aerosolized e-vapor trigger abnormal intercellular responses, damage mitochondrial function, and consequently disrupt the homeostasis of the organelle’s biochemical processes by increasing reactive oxidative species. Increased oxidative stress sets off a cascade of molecular events, disrupting optimal mitochondrial morphology and homeostasis. Furthermore, smoking-induced oxidative stress may also amalgamate with other health factors to contribute to various pathophysiological processes. An increasing number of studies show that toxins may affect mitochondria even though exposure to secondhand or thirdhand smoke. This review assesses the impact of toxins present in tobacco smoke and e-vapor on mitochondrial health, networking, and critical structural processes including mitochondria fission, fusion, hyperfusion, fragmentation, and mitophagy. The efforts are focused on discussing current evidence linking toxins present in first, second, and thirdhand smoke to mitochondrial dysfunction

Multi-sensor data fusion of E-tongue and E-nose can provide a more comprehensive and more accurate analysis results. However, it also brings some redundant information, it is a hot issue to reduce the feature dimension for pattern recognition. In this paper, the taste-olfactory data fusion based on E-tongue and E-nose combined with Support Vector Machine (SVM) was used to classify five different beers. First, the taste and olfactory feature information were obtained based on E-tongue and E-nose. Second, the original feature data of single system were fused, then Principal Component Analysis (PCA) was applied to extract principal components, Genetic Algorithm-Partial Least Squares (GA-PLS) was used to select the characteristic variables, 20 subsets were generated with those variables based on the best Variable Importance of Projection (VIP) score. Finally, the classification models based on SVM were established, also c and g of SVM were calculated by Grid Search (GS), Genetic Algorithm (GA), and Particle Swarm Optimization (PSO), the classification results of all subsets were obtained. The results showed that the classification accuracy using data fusion was much higher over single E-tongue and single E-nose, and the variable selection method by VIP had the best classification performance in #12 subset coupled with GA-SVM.

Intertidal seagrass plays a vital role in estimating the overall health and dynamics of coastal environments due to its interaction with tidal changes. However, most seagrass habitats around the globe have been in steady decline due to human impacts, disturbing the already delicate balance in environmental conditions that sustain seagrass. Miniaturization of multi-spectral sensors has facilitated very high resolution mapping of seagrass meadows, which significantly improve the potential for ecologists to monitor changes. In this study, two analytical approaches used for classifying intertidal seagrass habitats are compared: Object-based Image Analysis (OBIA) and Fully Convolutional Neural Networks (FCNNs). Both methods produce pixel-wise classifications in order to create segmented maps, however FCNNs are an emerging set of algorithms within Deep Learning with sparse application towards seagrass mapping. Conversely, OBIA has been a prominent solution within this field, with many studies leveraging in-situ data and multiscale segmentation to create habitat maps. This work demonstrates the utility of FCNNs in a semi-supervised setting to map seagrass and other coastal features from an optical drone survey conducted at Budle Bay, Northumberland, England. Semi-supervision is also an emerging field within Deep Learning that has practical benefits of achieving state of the art results using only subsets of labelled data. This is especially beneficial for remote sensing applications where in-situ data is an expensive commodity. For our results, we show that FCNNs have comparable performance with standard OBIA method used by ecologists, while also noting an increase in performance for mapping ecological features that are sparsely labelled across the study site.

Introduction: Left atrial hypertension is one of the pathophysiologies of heart failure with preserved ejection fraction. We hypothesized that left atrial pressure response (LAPR) to incremental pacing is higher in patients with atrial fibrillation (AF) and can predict left ventricular diastolic dysfunction. Methods: Patients requiring left atrial access as a part of a therapeutic procedure for AF (n=204, AF group) or supraventricular tachycardia (n=34, control group) were analyzed (male n=183, 54±12 years old). LAPR was measured during incremental pacing. Results: Baseline left atrial pressure and LAPR at all pacing rates were not different between the AF and control groups. They were higher in patients with a high E/e’ (≥ 8) than in those with a low E/e’ (&lt; 8). LAPR at a pacing interval of 400ms and E/e' were positively correlated (r=0.373, p&lt;0.001). Body mass index and a high E/e' were independent predictors of pacing-induced left atrial hypertension. Conclusions: The LAPR to incremental pacing was constant regardless of AF. The non-invasive echocardiographic marker E/e' reflected pacing-induced left atrial hypertension.

In contemporary narratives, the rural and regional identities of a place, as judged by its inhabitants’ sense of belonging, continue to be important points that need to be (re)considered when discussing places as instruments for local development. This paper pushes forward these debated and explores the construction of rural and regional identity in Romania with the help of a case study that focuses on two rural communities situated on opposite sides of the river Mureș. Based on participant and ethnographic observation and making use of a qualitative analysis, this paper highlights the most significant features of the local cultural identities expressed by the two sets of people, which often coincide with the most important characteristics attributed to the regions separated by the river Mureș. The results of this study underline the dividing role of a river in the preservation of rural and regional identity. They also demonstrate that rural identity construction along the river has generated both rural development opportunities and various risks.

In Bangladesh, climate change is a major concern because of its geophysical location and climate dependent agriculture. As sessile organisms, crops plants have to face difficulties often in this environmentally vulnerable country. Therefore, this study examines the seasonal trend of two climatic parameters viz. temperature (maximum and minimum) and rainfall over a period of 1983 to 2013. Besides, this study provides insight into the relationship between climatic parameters and crop yield of two major crops viz. rice and wheat during 1997-2013. To assess the relationship of climatic parameters with time and yield using Pearson correlation analysis, time series data used at an aggregate level. SPSS software utilized for this analysis. The cropping seasons such as rice growing seasons Aus (summer rice), Aman (autumn rice) and Boro (winter rice) exhibited a significant increase in maximum and minimum temperature. Rainfall found to have a decreasing trend for all the seasons. This study also revealed that the climatic parameters had significant effects on rice yield, but these results varied among three rice crops. Maximum temperature had positive effects on all rice yields, especially on Aus and Aman. Minimum temperature had a negative effect on Aman rice yield but a positive effect on Aus rice yield. Wheat yield negatively associated with temperature. Rainfall exhibited negative relation with both rice and wheat yield.

There has been debate recently on how the population in traditional mining areas of Central and Eastern Europe face precarity and marginalization. A spatial approach was employed in a Romanian context using available statistical data on a south Carpathian area (i.e Gorj County), surveys and in-depth interviews with residents in one of the rural communities of Gorj. Our findings highlight that a large number of rural localities in this county are technically, economically, and socially underdeveloped. Many inhabitants face a lack of financial resources and employment opportunities, which has led to the emigration of young people to larger Romanian cities or to other countries. We conclude that in order to avoid a much deeper social and spatial marginalization of local inhabitants, an integrated strategy is needed to target economic and social development, investment in infrastructure and public services, the promotion of employment and training opportunities, and to better integrate local culture and traditions into tourism.

The E-learning system has achieved great development after the pandemic. In this work, we proposed three artificial intelligence-based enhancements to our linguistic interactive E-learning system from different aspects. Compared with the original phonetic transcription exam system, our enhancements include an MFCC+CNN-based disordered speech classification module, a Transformer-based Grapheme-to-Phoneme converter, and a Tacotron2-based IPA-to-Speech speech synthesis system. This work not only provides a better experience for the users of this system but also explores the utilization of artificial intelligence technologies in the E-learning field and linguistic field.

The ceramic sherds from approximately 20 samples of lead-glazed tableware, recovered from diverse archaeological sites, including three repurposed storage pits transformed into dumpsters within the medieval city of Santarém (13th-14th century), underwent a meticulous examination. This investigation utilized techniques such as micro-Raman, ground state diffuse reflectance absorption, and X-ray fluorescence spectroscopies, in addition to X-ray diffraction and stereomicroscopy. A parallel study was conducted on contemporaneous European ceramics (glazed sherds) sourced from archaeological sites dating back to the 13th-15th centuries in Saintonge (France), Ardenne, Zomergem, and Bruges (Belgium), as well as Surrey-Hampshire, Kingston, and Cheam (England). The colour of the ceramic bodies is predominantly white or whitish, with a few exhibiting a vivid red hue. Ceramic sherds with a light paste composition were likely crafted using kaolin clays as raw materials. Analyses of fabric, mineralogical, and elemental composition of the sherds suggest that the majority of Santarém's glazed ceramics were locally or regionally produced, potentially derived from a Pliocene kaolin-rich sand formation. However, this conclusion is not supported by the absence of discovered lead glaze kilns or workshops in Santarém for the late Middle Ages. A distinctive feature from the European workshop ceramics lies in the quartz temper content and fabric.

Bacteria’s ability to withstand the detrimental effects of antimicrobials may take the form of resistance or tolerance with the minimum inhibitory concentration (MIC), the mutant prevention concentration (MPC), and the mutant selection window as salient concepts. Isolates exposed for 30 days to different concentrations of selected antibiotics, biocides, and heavy metals, singly and in combination, were additionally exposed to very high (15 × MIC) concentrations of ampicillin., and their tolerance was calculated the time to kill 99.9% of the isolate population (MDK99.9). These values were increased by 30 to 50% in test isolates compared to the untreated control. BAC 10-exposed isolates had the highest tolerance increase, and the tolerance appeared to originate from two sources, i.e., stochastic persistence and genetic-induced persistence, involving multiple genes using diverse mechanisms. The mutant selection window of the isolates to ampicillin, amoxicillin, and oxytetracycline also slightly increased compared to the control, indicating the amplification of persister cells during the 30-day exposure. These findings indicate that bacterial exposure to sub-inhibitory concentrations of environmental chemical stressors may not always result in the development of antimicrobial resistance but could initiate this process by selecting for persisters that could evolve into resistant isolates.

Knowledge is not merely the characteristic of certain pieces of information being deemed true and justifiable, but rather a process. Within an axiomatic system, the set of information that reaches the status of knowledge forms a universe that provides an interpretation of the reality one aims to describe. Language exchanges information through communication and the process of justification (exchange of information), if it consistently justifies a particular piece of information, it elevates it to knowledge. In this paper, we provide a framework for knowledge within an axiomatic model where we define the fundamental elements of communication and grammar. As a result, the structure dictates that knowledge, to be considered as such, must be investigateable by anyone who utilizes it in its entirety, both in form and content. Ultimately, the development of knowledge processing, referred to as \emph{knowmatics}, represents a clear evolution of the computer science that processes information (subset of knowledge).

The appearance of bubbles and foam can influence the likeability of a wine even before its consumption. Since foams are essential to visual and taste attributes of sparkling wines, it is of great importance to understand which compounds affect bubbles and foam characteristics. The aim of this work was to investigate the effect of interactions among proteins, amino acids, and phenols on the characteristics of foam in sparkling wines by using synchronous fluorescence spectroscopy techniques. Results has shown that several compounds present in sparkling wines influence foam quality differently, and importantly, highlighted how the interaction of those compounds might result in different effects on foam parameters. Amongst the results, mannoproteins were found to be most likely to promote foam and collar stability, while phenols were likely to increase the ratio of small bubbles and collar height in the foam matrix. In summary, this work contributes to a better understanding of the effect of wine compounds on foam quality as well as the effect of the interactions between those compounds.

To improve efficacy and safety of sunscreen emulsions, UV‐filter skin permeation could be kept as low as possible by reducing UV‐filter content or changing emulsion composition. In this work, different lipid phase ratio (12, 14 and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro by suitable methodologies: spreadability, viscosity, pH, occlusion factor, BMTZ release, sun protection factor (SPF). Sensory attributes were assessed by trained panelists in three different phases: before/during pick‐up, rub‐in, after application. Raising the lipid phase ratio led to an increase of viscosity and to a corresponding drop of spreadability while the incorporation of BMTZ‐loaded NLC determined a decrease of occlusion factor and an increase of SPF. No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by lipid phase ratio. These results suggest that lipid phase ratio and BMTZ incorporation into NLC could contribute to determine technological and sensory properties of O/W emulsions.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early le-sions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions under necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis use its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease

The distribution of zakat, which is still carried out directly through mosques or zakat amil bodies, can hinder the payment process due to inaccurate calculations and difficulties in finding zakat amil institutions. In the digital era, information technology is very important in the management of zakat, alms, and infaq. Therefore, a zakat information management system was created. The e-Zakat program, developed using the waterfall method, plays an important role in five main aspects of zakat management: muzaki and mustahiq data collection, zakat collection, zakat distribution, mustahiq development, and reporting. The use of information technology in this program is expected to increase efficiency, accountability, transparency, as well as the reach of zakat and muzaki involvement.

The majority of E-commerce transactions reveal private information such as customers' identities, order contents, and payment information during the transaction. Other personal information such as health conditions, religion, and even ethnicity may be also deduced. Even when deploying electronic cryptocurrencies such as Bitcoin, anonymity cannot be fully guaranteed. Also, many anonymous payment schemes suffer from possible double spending circumstances. E-commerce privacy is basically a difficult problem as it involves parties with concurring interests. Three major e-commerce requirements are highly difficult to resolve: anonymous purchase, anonymous delivery, and anonymous payment. This work presents a possible e-commerce system addressing all three anonymity requirements for electronic-items business on open networks. The system offers anonymous entities authentication mechanisms up to completing a fair anonymous e-commerce transaction. The system is based on deploying a physically clone-resistant hardware token for each relevant involved party. The tokens are made clone-resistant by accommodating a Secret Unknown Cipher (SUC) in each hardware-token as a digital PUF-like identity. A set of novel generic system-setups for units, protocols and e-commerce schemes is introduced. The proposed anonymization is basically attained by virtually-replacing relevant e-commerce entities by low-cost, unique and clone-resistant tokens/units using SUCs. The units act as trustable anonymous, authenticated and non-replaceable entities monitored by their acting users.

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

The theory of water transport in trees, according to which the main driving force of water movement is the suction created by the evaporation of water by the meniscus (the curved surface of the capillary liquid column) on the evaporating elements, supported from below by root pressure, is flawed. The capillary effect in nature is around one meter. In the case of open-air gaps, the leaf cannot suck in the water against gravity because, in this case, the plant would not be sucking in water, but air through the open-air gap. If not, how do trees transport water? When evaporation occurs, there is no suction towards the canopy, but pressure is due to a reduction in the cross-section of the water pipe caused by heat loss through evaporation. At night, when evaporation stops, a thermal equilibration process is triggered, which restores the original cross-section of the pipe. This generates suction and draws water from the soil. As the hydrostatic pressure in the pipe is high for tall trees, the pipe is cut off. To prove my theory, I have given several examples. Water transport is not based on physical mechanical laws alone. There may be complex physiological, biochemical, and biophysical processes behind the operation of the pipe system.

Inappropriate expression of histone deacetylase (HDAC6) and deregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway are common aberrations observed in cancers. LASSBio-2208, was previously described as a dual inhibitor in the nanomolar range of HDAC6 and PI3Kα, being three times more potent in inhibiting HDAC-6. In this paper we described the cytotoxic and antiproliferative potency of LASSBio-2208 on different tumour cell lines, its possible synergism effect in association with PI3K and HDAC-6 inhibitors, and its DMPK in vitro profile. Our studies have demonstrated that LASSBio-2208 has moderate cytotoxic potency on MCF-7 (IC50 = 23 µM), CCRF-CEM (IC50 = 8.54 µM) and MOLT-4 (IC50 = 7.15 µM), with no cytotoxic effect on hPBMC. In addition, it has a good antiproliferative effect on MCF-7 cells (IC50 = 5.44 µM), low absorption by PAMPA-GIT and low permeation through the blood-brain barrier by PAMPA-BBB, exhibiting high metabolic stability in rat plasma. Moreover, LASSBio-2208 exhibited synergism when combined with getadolisib and tubastatin A, using the concentration corresponding to their CC50 values on MOLT-4 and CCRF-CEM cells.