Complex systems exhibit critical thresholds at which they transition among alternative phases. Complex systems theory has been applied to analyze disease progression, distinguishing three stages along progression: (i) a normal non-infected state, (ii) a pre-disease state in which the host is infected and responds; therapeutic interventions could still be effective, (iii) an irreversible state, where the system is seriously threatened. The Dynamical Network Biomarker (DNB) theory sought for early-warnings of the transition from health to disease. Such DNBs might range from individual genes to complex structures in transcriptional regulatory or protein-protein interaction networks. Here we revisit transcriptomic data obtained during infection of tobacco plants with tobacco etch potyvirus to identify DNBs signaling the transition from mild/reversible to severe/irreversible disease. We identified genes showing a sudden transition in expression along disease. Some of these genes cluster in modules that show the properties of DNBs. These modules contain both genes known to be involved in response to pathogens (e.g., ADH2, CYP19, ERF1, KAB1, LAP1, MBF1C, PR1, or TPS5) and other genes not previously related to biotic stress responses (e.g., ABCI6, BBX21, NAP1, OSM34, or ZPN1).

The tobacco epidemic is one of the leading public health threats the world has ever faced and public health policy that seeks to limit the problem may not only have to target the price of tobacco but also the initiation stage in a smoker’s life – the adolescent stage. This research contributes to the health economics literature by using a Bayesian hierarchical logistic model, estimated using Hamiltonian Monte Carlo (HMC) methods to empirically identify what drives the intentions to quit smoking among adolescent smokers in Zambia. Results suggest that among the junior secondary school-going adolescent smokers in Zambia, about 63% have plans to quit smoking. We find socio-demographic characteristics and several tobacco-smoking-related factors as the main drivers of adolescent smokers’ plans to quit smoking. Most importantly, we provide insights that could be useful to help adolescent smokers realize their quitting plans.

With the COVID-19 pandemic continuing and the resulting economic burden increasingly apparent, the Indonesian government began to prepare a "new normal" phase and make peace with COVID-19. From this new decision arises the question of the readiness of businesses and the industrial sector to resume operations amid COVID-19. This article aims to provide concise and precise information about the preparations that can be made by businesses to operate safely amid COVID-19 based on existing scientific studies and literatures. From the literature visits it can be concluded that transmission and danger of a COVID-19 pandemic can be prevented through: creation of infectious disease prevention and response plan, implementing basic infection prevention measures, policies and procedures for proper identification and isolation of sick people, applying flexibilities in policies, and protections in the workplace.

While the angiotensin converting enzyme 2 (ACE2) protein is defined as the primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, the viral serine molecule might be mobilized by the host's transmembrane protease serine subtype 2 (TMPRSS2) enzyme from the viral spike (S) protein and hijack the host’s N-acetyl-D-galactosamine (GalNAc) metabolism. The resulting hybrid, serologically A-like/Tn (T-nouvelle) structure potentially acts as a host–pathogen functional molecular bridge. In humans, this intermediate structure will hypothetically be replaced by ABO(H) blood group-specific, mucin-type structures, in the case of infection hybrid epitopes, implicating the phenotypically glycosidic accommodation of plasma proteins. The virus may, by mimicking the synthetic pathways of the ABO(H) blood groups, bind to the cell surfaces of the blood group O(H) by formation of a hybrid H-type antigen as the potential precursor of hybrid non-O blood groups, which does not affect the highly anti-glycan aggressive anti-A and anti-B isoagglutinin activities, exerted by the germline-encoded nonimmune immunoglobulin M (IgM). In the non-O blood groups, which have developed from the H-type antigen, these IgM activities are downregulated by phenotypic glycosylation, while adaptive immunoglobulins might arise in response to the hybrid A and B blood group structures, bonds between autologous carbohydrates and foreign peptides, suggesting the exertion of autoreactivity. The non-O blood groups thus become a preferred target for the virus, whereas blood group O(H) individuals, lacking the A/B phenotype-determining enzymes and binding the virus alone by hybrid H-type antigen formation, have the least molecular contact with the virus and maintain the critical anti-A and anti-B isoagglutinin activities, exerted by the ancestral IgM, which is considered the humoral spearhead of innate immunity.

It has been a long time since the world has experienced a pandemic with such a rapid devastating impact as the current COVID-19 pandemic. The causative agent, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is further unusual in that it appears capable of infecting many different mammal species. As a significant proportion of people worldwide are infected with SARS-CoV-2 and may spread the infection unknowingly before symptoms occur or without any symptoms ever occurring, there is a non-negligible risk of humans spreading SARS-CoV-2 to wildlife, in particular mammals. Because of SARS-CoV-2’s evolutionary origins in bats and reports of humans transmitting the virus to pets and zoo animals, regulations for prevention of human-to-animal transmission have so far focused mostly on these animal groups. Here, we summarize recent studies and reports that show that a wide range of distantly related mammals are likely susceptible to SARS-CoV-2 and that susceptibility or resistance to the virus is in general not predictable, or only to some extent, by phylogenetic proximity to known susceptible or resistant hosts. In the absence of solid evidence on the SARS-CoV-2 susceptibility/resistance for each of the >5,500 mammal species, we argue that sanitary precautions should be taken when interacting with any mammal species in the wild. Preventing human-to-wildlife SARS-CoV-2 transmission is important for protecting these (sometimes endangered) animals from disease, but also to avoid establishment of novel SARS-CoV-2 reservoirs in wild animals. The risk of repeated re-infection of humans from such a wildlife reservoir could severely hamper SARS-CoV-2 control efforts. For wildlife fieldworkers interacting directly or indirectly with mammals, we recommend sanitary precautions such as physical distancing, wearing face masks and gloves, and frequent decontamination, which are very similar to regulations currently imposed to prevent transmission among humans.

Relationships between the Farey sequence and the Riemann hypothesis other than the Franel-Landau theorem are discussed. Whether a function similar to Chebyshev’s second function is square-root close to a line having a slope different from 1 is discussed. The nontrivial zeros of the Riemann zeta function can be used to approximate many functions in analytic number theory. For example, it could be said that the nontrival zeta function zeros and the Möbius function generate in essence the same function - the Mertens function. A different approach is to start with a sequence that is analogous to the nontrivial zeros of the zeta function and follow the same procedure with both this sequence and the nontrivial zeros of the zeta function to generate in essence the same function. A procedure for generating such a function is given.

The present grievous situation of the tuberculosis disease can be improved by efficient case management and timely follow-up evaluations. With the advent of digital technology this can be achieved by quick summarization of the patient-centric data. The aim of our study was to assess the effectiveness of the ODK Scan paper-to-digital system during testing period of three months. A sequential, explanatory mixed-method research approach was employed to elucidate technology use. Training, smartphones, application and 3G enabled SIMs were provided to the four field workers. At the beginning, baseline measures of the data management aspects were recorded and compared with endline measures to see the impact of ODK Scan. Additionally, at the end, users’ feedback was collected regarding app usability, user interface design and workflow changes. 122 patients’ records were retrieved from the server and analysed for quality. It was found that ODK Scan recognized 99.2% of multiple choice bubble responses and 79.4% of numerical digit responses correctly. However, the overall quality of the digital data was decreased in comparison to manually entered data. Using ODK Scan, a significant time reduction is observed in data aggregation and data transfer activities, however, data verification and form filling activities took more time. Interviews revealed that field workers saw value in using ODK Scan, however, they were more concerned about the time consuming aspects of the use of ODK Scan. Therefore, it is concluded that minimal disturbance in the existing workflow, continuous feedback and value additions are the important considerations for the implementing organization to ensure technology adoption and workflow improvements.

Background: Access to rehabilitation is crucial for the realization of the right to health and a proper concern of global health. Yet, reliable information to guide rehabilitation service planning is unavailable in many countries in part due to the lack of appropriate indicators. To ensure universal health coverage and meet the central imperative of “leaving no one behind” countries must be able to assess key aspects of rehabilitation policy and provision and monitor how they have discharged their human rights responsibilities towards those most disadvantaged, including people with disability. This article describes the process of developing an expert guided indicator framework to assess governments’ efforts and progress in strengthening rehabilitation in line with the Convention on the Rights of Persons with Disabilities. Methods: A systems methodology - concept mapping - was used to capture, aggregate and confirm the knowledge of diverse stakeholders on measures thought to be useful for monitoring the implementation of the Convention with respect to health related rehabilitation. 56 individuals generated a list of 107 indicators through online brainstorming which were subsequently sorted by 37 experts from the original panel into non overlapping categories. 41 participants rated the indicators for importance and feasibility. Multivariate statistical techniques where used to explore patterns and themes in the data and create the indicators’ organizing framework which was verified and interpreted by participants. Results: A concept map of 11 clusters of indicators emerged from the analysis grouped into three broader themes: Governance and Leadership (3 clusters); Service Delivery, Financing and Oversight (6 clusters); and Human Resources (2 clusters). The RESYST was comprehensive and well aligned with the Convention. On average, there was a moderately positive correlation between importance and feasibility of the indicators (r=.58) with experts prioritizing the indicators contained in the clusters of the Governance and Leadership domain. Two of the most important indicators arose from the Service Delivery, Financing and Oversight domain and reflect the need to monitor unmet needs and barriers in access to rehabilitation. In total, 59 indicators achieved above average score for importance and comprised the two–tiered priority set of indicators. Conclusion: Concept mapping was successful in generating a shared model that enables a system’s view of the most critical legal, policy and programmatic factors that must be addressed when assessing country efforts to reform, upscale and improve rehabilitation services. The RESYST provides a data driven basis for the development of standardized data collection tools to facilitate comparative analysis of rehabilitation systems.

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

During the COVID-19 outbreak, most university courses have been offered on online platforms. A sudden shift from face-to-face classroom learning to online formats could influence the learning effectiveness of classes. This study aims to investigate differences in the learning effectiveness of online and face-to-face lecture courses. It also explores factors that impact the effectiveness of online instruction. These factors include interactions among learners, interactions between learners and the instructor, the quality of online platforms, learners’ ability to use devices and follow instructions, and learners’ situational challenges. The study participants were 261 university students at King Mongkut’s University of Technology Thonburi in Bangkok, Thailand. All participants were enrolled in at least one lecture course, such as history, humans and the environment, the environment and development, or general philosophy, during the 2019 academic year. A questionnaire was distributed to participants after they completed these courses in May 2020. Paired simple t-test analyses were used to compare the effectiveness of online and face-to-face classes, and a multiple regression analysis was used to identify factors that impact the learning effectiveness of online classes. The results show that online classes are less effective than face-to-face courses. The multiple regression analysis also revealed that the effectiveness of online learning was significantly impacted by learners’ ability to interact with classmates during class, their ability to interact with instructors after the class, the quality of online platforms, and disturbances or distractions in learners’ environments.

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

The separation of sister chromatids during anaphase is the culmination of mitosis and one of the most strikingly beautiful examples of cellular movement. It consists of two distinct processes: Anaphase A, the movement of chromosomes toward spindle poles via shortening of the connecting fibers, and anaphase B, separation of the two poles from one another via spindle elongation. I focus here on anaphase A chromosome-to-pole movement. The chapter begins by summarizing classical observations of chromosome movements, which support the current understanding of anaphase mechanisms. Live cell fluorescence microscopy studies showed that poleward chromosome movement is associated with disassembly, or ‘melting’ of the kinetochore-attached microtubule fibers that link chromosomes to poles. Microtubule-marking techniques established that kinetochore-fiber disassembly often occurs through a ‘pac-man’ mechanism, where tubulin subunits are lost from kinetochore-attached plus ends and the kinetochore appears to consume its microtubule track as it moves poleward. In addition, kinetochore-fiber disassembly in many cells occurs partly through ‘flux’, where the microtubules flow continuously toward the poles and tubulin subunits are lost from minus ends. Molecular mechanistic models for how load-bearing attachments are maintained to disassembling microtubule ends, and how the forces are generated to drive pac-man and flux-based movements, are discussed.

Sustainable food consumption has attracted a widespread attention during last decades by scholars, policy makers and consumers. In line with this, farmers’ markets (FMs) have the potential to encourage sustainable agricultural production and consumption. By reducing the number of actors and distances along the food chain, these alternative food systems foster the reconnection between farmers and consumers and contribute to different social, economic and environmental sustainable goals. This paper provides insights on the role of consumers' sustainability concerns related to their motivation for shopping at FMs. By means of a choice experiment, we analyze the determinants of consumers’ WTP for buying apples at FMs. We are particularly interested in understanding how attitudes towards the three sustainability dimensions are related to consumer preferences in this context. We find that consumer attitudes towards direct contact with producers, contributing to farmers’ income, and environmental benefits can be directly related to product characteristics that are specific to FMs.

GaN ultraviolet photodetector with metal-semiconductor-metal structure is achieved by growing on a periodic trapezoid column-shape patterned sapphire substrate using metalorganic chemical vapor deposition. Under 5-V reverse bias, the photodetector fabricated on such patterned sapphire substrate exhibits a lower dark current, a higher photocurrent, and a 476 % enhancement in the maximum responsivity as compare with those of the photodetector fabricated on conventional flat sapphire substrate. It is also found that the much larger UV-to-visible rejection ratio and the fact that responsivity drops in a smaller cut-off region are observed from photodetector fabricated by using a periodic trapezoid column-shape patterned sapphire substrate. These phenomena may all be attributed to the reduction of threading dislocation density and the improved quality of GaN film, as well as the internal reflection and/or scattering effect on the interface between GaN film and the periodic trapezoid column-shape pattern of the substrate.

The use of Light Amplification by Stimulated Emission of Radiation (i.e., LASERs or lasers) by the U.S. Department of Defense is not new and includes laser weapons guidance, laser-aided measurements, even lasers as weapons (e.g., Airborne Laser). Lasers in support of telecommunications is also not new. The use of laser light in fiber optics shattered thoughts on communications bandwidth and throughput. Even the use of lasers in space is no longer new. Lasers are being used for satellite-to-satellite crosslinking. Laser communication can transmit orders-of-magnitude more data using orders-of-magnitude less power and can do so with minimal risk of exposure to the sending and receiving terminals. What is new is using lasers as the uplink and downlink between the terrestrial segment and the space segment of satellite systems. More so, the use of lasers to transmit and receive data between moving terrestrial segments (e.g., ships at sea, airplanes in flight) and geosynchronous satellites is burgeoning. This manuscript examines the technological maturation of employing lasers as the signal carrier for satellite communications linking terrestrial and space systems. The purpose of the manuscript is to develop key performance parameters (KPPs) to inform U.S. Department of Defense initial capabilities documents (ICDs) for near-future satellite acquisition and development. By appreciating the history and technological challenges of employing lasers rather than traditional radio frequency sources for satellite uplink and downlink signal carrier, this manuscript recommends ways for the U.S. Department of Defense to employ lasers to transmit and receive high bandwidth, large-throughput data from moving platforms that need to retain low probabilities of detection, intercept, and exploitation (e.g., carrier battle group transiting to a hostile area of operations, unmanned aerial vehicle collecting over adversary areas). The manuscript also intends to identify commercial sector early-adopter fields and those fields likely to adapt to laser employment for transmission and receipt.

The population’s mobility in urban areas is a necessary variable in the modeling of risk scenarios caused by atmospheric contamination. The inclusion of this concept makes static models more dynamic while considering people within a city to be an entity with complex mobility processes. We propose a conceptual and methodological tool to make the representation of the social, economic and territorial components, as well as the patterns in the population´s mobility to delimitate risk areas for human health by exposure of contaminants. In the volatile organic compounds (VOC), benzene, ethylbenzene, toluene and xylene (BTEX) are amongst the most dominant substances in fugitive vapor emissions in gas stations (GS). In urban areas, the exposure to BTEX by residential proximity and proximity to other facilities, which cause intra-urban agglomeration, can impact and affect human health. This model seeks to facilitate the focalization, identification and prioritization of risk areas by BTEX environmental contamination. This article goes beyond de conceptual framework. It suggests methodological and instrumental aspects to be applied in other cities. The government agencies must consider these results when establishing rules, permissions and procedures to reduce environmental pollution for managing the risk in a complex urban environment.

Saikosaponin (SS) a is a compound with various pharmacological properties and easily degraded into SSb1 and SSg in acid condition. In present work another two new degradation products of SSa formed under acid hydrolytic condition were detected and isolated by analytical and semi-preparative liquid chromatography technology, furthermore their structures were characterized as hydroxyl-saikosaponin a and SSb2 by spectral analysis, which is not only essential in stability-indicating method development and validation but also could be used as a worst case to assess the analytical method performance of SSa. Moreover their structural transformation pathways were also proposed.

In 1990 the Malaysian Government launched Vision 2020 with the goal of Malaysia becoming a ‘fully developed country’ by the year 2020. In this drive for development the country has been examining many of its key natural assets, exploring how to both preserve them whilst ensuring that they make the maximum possible contribution to national development goals. Endau Rompin is one of these assets, being the second largest National Park in Peninsula Malaysia. The rich tropical rainforest flora and fauna of the Park and its hinterland, however, are threatened by various anthropogenic forces, most notably deforestation and poaching; both of which have taken the Park’s flagship species - the Tiger Panthera tigris jacksoni – towards the brink of local extinction. Malaysia’s statutory East Coast Economic Region Development Council commissioned a study to consider ways of increasing tourism revenues from the Park while at the same time reversing these threats. The key conclusion drawn is that a more holistic, landscape-scale approach should be adopted, with Endau Rompin forming part of a wider strategic economic zone based around sustainable tourism and land management. The proposed expanded zone extends eastwards beyond the confines of the Park, across the coastal plain to the South China Sea, and onwards to the neighbouring Mersing Islands. This expanded zone is referred to as Malaysia’s new ‘Rainforest to Reef Region’.

The concept of a Social License to Operate (SLO) has become increasingly important in the sustainability literature in recent years. Having its origins in the business discourse of the mining industry with respect to limiting opposition to mining projects, the notion of a social contract above and beyond legal requirements has since become applied across a number of different industries. Despite the concepts adoption confusion exists over the practices and outcomes of SLO, and particularly the nature of engagement. Given this situation it is surprising that not more attention to the role of marketing, and social marketing in particular, in operationalizing the concept. The paper discusses the potential of social marketing to contribute to SLO. Economic, political and social relations are complex in SLO and exchange is intricate in such relational environments. A community-based social marketing orientation is proposed as a means to improve exchange relations and enhance engagement. Seven models of SLO related social marketing models are discussed with community-based social marketing and adaptive co-marketing models being regarded as the most positive for the achievement of an SLO. Potential barriers to adoption of these approaches are noted.

The aim of this work is to compare two softwares (MAUD and TOPAS) based on the Rietveld algorithm and to test the concept of tolerance factor using the dissolution at high temperature of yttrium into BaTiO₃. In general, both softwares give up different values of the crystalline parameters however the trends are similar in most cases but the analysis of the strain and crystallite size in the BaTiO₃ crystals suggests that, in this particular case, MAUD offered results more consistent with the expected behavior. Using the crystalline parameters calculated by Rietveld, the tolerance factor values were obtained and these data suggest even better stability in the crystalline structure than that expected using theoretical parameters. Tolerance factor concept also indicates that Ti⁴⁺ should be preferred.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

COVID-19 has affected 212 countries around the world, killing nearly 300,000 and infecting more than 4.4 million by May 14, 2020. Bangladesh, a South Asian low-middle-income economy, has experienced a demographic and epidemiological transition with rapid urbanization and a gradual increase in life expectancy. It is the seventh most populous country in the world and population of the country is expected to be nearly double by 2050. The increasing burden of communicable diseases in Bangladesh can be attributable to rapid urbanization and nearly 50% of all slum dwellers of the country live in Dhaka division. In 2017, National Rapid Response Team of IEDCR investigated 26 incidents of disease outbreak. The joint survey of the Power and Participation Research Centre and BRAC Institute of Governance and Development reveals that per capita daily income of urban slum and rural poor drops by 80% due to present countrywide shutdown enforced by the government to halt the spread of Covid-19. 40%-50% of these population took loans to meet the daily expenses. However, the country has just 127,000 hospital beds, 91,000 of them in government-run hospitals. Researchers say, the country’s economy is economy is losing BDT 33 billion every day from its service and agriculture sectors during the nationwide shutdown.

1) Landsat operational land imager (OLI) data and consequent laboratory measurements were used to predict Chlorophyll-a (Chl-a) concentration and the trophic states for an inland lake within the East Kolkata Wetland, India; 2) The most suitable band ratio was identified by performing Pearson correlation analysis between Chl-a concentrations and possible OLI band and band ratios from the study points; 3) The results showed highest correlation coefficient from the band ratio OLI5/OLI4 with an R value of 0.85. The prediction model was then developed by applying regression analysis between the band ratio OLI5/OLI4 and Chl-a concentration of the study points. The reflectance ratios of the validation points were given as input on the prediction model and the model output was considered as predicted Chl-a values of the validation points to check the efficiency of the prediction model. The regression model between laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points revealed a high correlation with an R² value of 0.78. Trophic State Index (TSI) of the lake was also calculated from laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points. The study presented a high correlation of TSI determined from predicted data with TSI from laboratory reference data (R = 0.88). The TSI values of the lake ranged from 65 to 75 which indicate that the lake is appeared to be eutrophic to hypereutrophic conditions. 4) This empirical study showed that Landsat 8 OLI imagery can be effectively applied to estimate Chl-a levels and trophic states for inland lakes.

Vancomycin is one of the ‘last-line’ classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in 1950s it was widely used after 1980s for the treatment of infections caused by methicillin-resistant Staphylococci as prevalence of such strains were increased. However, currently it is evident that vancomycin resistant Staphylococcusaureusandvancomycin-resistant Enterococci have been developed as a result of various reasons including use of avaparcin, which is an analog of vancomycin, as feed additive in livestock. In present day context, more attention should be paid on prevention of emergence of resistance for the antibiotics in order to keep antibiotics effective. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have in depth understanding on the antibiotic they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discussthe pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects and alternative therapy for vancomycin.

This study sought to investigate steel frames’ performance with dual lateral loader system (Frame bending + bracings of divergent and convergent) in near and far filed to fault. In order to this, four categories of steel frame with dual system with 8, 10 and 12 story are designed with average formation based on existing seismic regulation in 2800 standard of Iran and tenth chapter of national regulations of construction (planning and performing steel construction). Time history non-linear dynamic analysis under the effect of near and far field earthquakes has been done on plan’s models. Then the maximum of floors’ dislocation, floors’ drift, roof dislocation, base shear and energy curves of frames are shown and compared with each other. All non-linear time history analyses have been accomplished using PERFORM 3D software.

Graph coloring is a manifestation of graph partitioning, wherein, a graph is partitioned based on the adjacency of its elements. Partitioning serves potentially as a compartmentalization for any structural problem. Vertex coloring is the heart of the problem which is to find the chromatic number of a graph. The fact that there is no general efficient solution to this problem that may work unequivocally for all graphs opens up the realistic scope for combinatorial optimization algorithms to be invoked. The algorithmic complexity of graph coloring is non-deterministic in polynomial time (NP) and hard. To the best of our knowledge, there is no algorithm as yet that procures an exact solution of the chromatic number comprehensively for any and all graphs within the polynomial (P) time domain. However, several heuristics as well as some approximation algorithms have been attempted to obtain an approximate solution for the same. Here, we present a novel heuristic, namely, the 'trailing path', which returns an approximate solution of the chromatic number within polynomial time, and, with a better accuracy than most existing algorithms. The ‘trailing path’ algorithm is effectively a subtle combination of the search patterns of two existing heuristics (DSATUR and Largest First), and, operates along a trailing path of consecutively connected nodes (and thereby effectively maps to the problem of finding spanning tree(s) of the graph) during the entire course of coloring, where essentially lies both the novelty and the apt of the current approach. The study also suggests that the judicious implementation of randomness is one of the keys towards rendering an improved accuracy in such combinatorial optimization algorithms. Apart from the algorithmic attributes, essential properties of graph partitioning in random and different structured networks have also been surveyed, followed by a comparative study. The study reveals the remarkable stability and absorptive property of chromatic number across a wide array of graphs. Finally, a case study is presented to demonstrate the potential use of graph coloring in protein design – yet another hard problem in structural and evolutionary biology.

HER2/neu positive breast tumors predict a high mortality and comprise 25-30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2 overexpressing breast cancer cell lines (i.e. SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e. MCF7 and MDA-MB-468). FKA at cytotoxic concentrations to breast cancer cell lines also has minimal effect on the growth of non-malignant breast epithelial MCF10 cells. FKA induces G2M arrest in cell cycle progression of HER2 overexpressing breast cancer cell lines through inhibition of Cdc2 and Cdc25C phosphorylation and down-regulation of Myt1 and Wee1expression leading to increased Cdc2 kinase activities. In addition, FKA induces apoptosis in SKBR3 cells by increasing the protein expression of Bim and BAX and decreasing expression of Bcl₂, Bcl_x/L , XIAP and survivin. FKA also down-regulates the protein expression of HER-2 and inhibits AKT phosphorylation. Herceptin plus FKA treatment leads to enhanced growth inhibitory effect on HER-2 overexpressing breast cancer cell lines through down-regulation of Myt1, Wee1, Skp2, Survivin and XIAP. Our results suggest the promise of FKA as a novel apoptosis inducer and G2 checkpoint abrogating agent in combination with Herceptin for treatment of HER2 overexpressing breast cancer.

This paper presents a review of cloud application architectures and its evolution. It reports observations being made during the course of a research project that tackled the problem to transfer cloud applications between different cloud infrastructures. As a side effect we learned a lot about commonalities and differences from plenty of different cloud applications which might be of value for cloud software engineers and architects. Throughout the course of the research project we analyzed industrial cloud standards, performed systematic mapping studies of cloud-native application related research papers, performed action research activities in cloud engineering projects, modeled a cloud application reference model, and performed software and domain specific language engineering activities. Two major (and sometimes overlooked) trends can be identified. First, cloud computing and its related application architecture evolution can be seen as a steady process to optimize resource utilization in cloud computing. Second, this resource utilization improvements resulted over time in an architectural evolution how cloud applications are being build and deployed. A shift from monolithic servce-oriented architectures (SOA), via independently deployable microservices towards so called serverless architectures is observable. Especially serverless architectures are more decentralized and distributed, and make more intentional use of independently provided services. In other words, a decentralizing trend in cloud application architectures is observable that emphasizes decentralized architectures known from former peer-to-peer based approaches. That is astonishing because with the rise of cloud computing (and its centralized service provisioning concept) the research interest in peer-to-peer based approaches (and its decentralizing philosophy) decreased. But this seems to change. Cloud computing could head into future of more decentralized and more meshed services.

Huperzine A is an herbal reversible inhibitor of Acetylcholinesterase (AChE). A molecular docking analysis on Huperzine A molecule has been carried out to understand its structure, conformational flexibility, intermolecular interaction and the binding affinity in the active site of AChE enzyme. Further, the charge density distribution of huperzine A molecule (lifted from the active site of AChE) was determined from the high level quantum chemical calculations coupled with charge density analysis. The binding affinity of Huperzine A towards AChE was calculated from the molecular docking; the lowest docked energy is -8.46 kcal/mol. In the active site, huperzine A molecule interacts with acyl binding pocket-Phe330 of AChE, that is, the bicyclo ring group of huperzine A forms an intermolecular interaction with the oxygen atom of main chain of the amino acid residue Phe330 at the distances 3.02 and 3.25 Å respectively. On the other hand, a gas phase study on huperzine A molecule also performed using HF and DFT (B3LYP) methods with the basis set 6-311G**. The molecular structure, conformation, and the charge density distribution of huperzine A molecule in the gas phase have determined using quantum chemical calculations and the charge density analysis. The comparative studies between the gas phase and the active site forms of huperzine A molecule, explicitly reveals the degree of conformational modification and the charge density redistribution of huperzine A when present in the active site. The dipole moment of the molecule in the active site is 6.85 D, which is slightly higher than its gas phase value (5.91 D). The electrostatic potential (ESP) surface of active site molecule clearly shows the strong electronegative and positive ESP regions of the molecule, which are the expected strong reactive locations of the molecule.

The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydoxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant increases in the level of oxidative damage marker 8-OHdG and cell proliferation activity were observed in breast carcinoma patients in comparison to benign and normal controls, which were accompanied by significant decrease in non enzymatic antioxidants and TAS concentrations. 8-OHdG and cell proliferation level were negatively correlated with non enzymatic antioxidants viz., Vitamin A, Vitamin C, vitamin E level and total antioxidant activity. Altered levels of biomarkers of oxidative stress and cell proliferation activity amongst the malignant, benign and controls suggest a correlation of increased oxidative stress and cell proliferation activity in the progression of disease in breast carcinoma patients. Among the oxidative stress markers and cell proliferation index, decreased level of vitamin A, vitamin C, vitamin E, TAS and increased level of 8-OHdG, cell proliferation index emerged as best predicted biomarkers for subjects with malignancy and benign breast disease.

This article develops duality principles and numerical results for a large class of non-convex variational models. The main results are based on fundamental tools of convex analysis, duality theory and calculus of variations. More specifically the approach is established for a class of non-convex functionals similar as those found in some models in phase transition. Finally, in the last section we present a concerning numerical example and the respective software.

This paper presents an overview of the smart electro-clothing systems (SeCSs) targeted at health monitoring, sports benefits, fitness tracking, and social activities. Technical features of the available SeCSs, covering both textile and electronic components, are thoroughly discussed and their applications in the industry and research purposes have been highlighted. In addition, it also presents the developments in the associated areas of wearable sensor systems and textile-based dry sensors. As it became evident during the literature research, such a review on SeCSs covering all relevant issues has not been presented before. This paper will be particularly helpful for new generation researchers investigating the design, development, function and comforts of the sensor integrated clothing materials.

A novel and highly pathogenic coronavirus (2019-nCoV)-induced pneumonia spread worldwide in a short time. However, studies on the effects of 2019-nCoV on the male reproductive system are limited. The aim of this study is to describe the clinical characteristics of the male reproductive system of COVID-19 patients and to explore the presence of 2019-nCoV in semen. Retrospective, single-center case series of 112 male patients with confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 2 to March 7, 2020. Demographic data, symptoms and signs related to the male reproductive system, throat swabs and semen samples were collected and analyzed. 2019-nCoV RNA measured in throat swab and semen samples. The organ distribution of ACE2 mRNA and protein in human tissue on The Human Protein Atlas portal and investigated immunohistochemistry (IHC) images of the testis. The HPA dataset revealed relatively high levels of ACE2 protein and RNA expression in the testis. A total of 3 severe COVID-19 patients (2.7%) presented with orchidoptosis, while no patients experienced other symptoms or signs related to the male reproductive system. The analysis of 2019-nCoV RNA in semen included 17 patients with fertility needs. Among these patients, 9 (52.9%) remained positive for 2019-nCoV according to throat swab analysis, and 8 (47.1%) became negative. In the semen 2019-nCoV analysis, all 17 patients were negative for the N gene and ORF1ab gene. In view of the potential impairment, long-term follow-up for male COVID-19 patients with fertility needs is of great significance.

Background and objectives: The correlation of cardiac troponin I with early in-hospital outcomes in acute myocardial infarction is not well established. This study aims to assess the role of troponin I in predicting in-hospital outcomes and early left ventricular systolic dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). Patients and methods: In a prospective study, 116 patients (74males and 42 females), with STEMI who had been admitted to the Coronary CareUnit from March 2015 to September 2015 were enrolled. Patients were divided according to the level of troponin I on admission into 3 groups (low, medium and high elevation). Results: The mean age (+ SD) of the patients was 60+11.4 years. The troponin level of 66.2% of males was high compared with 52.4% of females (p=0.002). The incidence of acute pulmonary edema (21.1%), cardiogenic shock (7%) and early left ventricular systolic dysfunction (49.3%) was significantly higher among patients with high troponin level compared with (0%, 0% and 16%, respectively) among patients with low troponin level. All deaths and cardiac arrest were of high troponin level. Conclusions: High admission troponin I in STEMI permits early identification of patients at increased risk of major cardiac complications and death.

Quantifying the landscape pattern change can effectively demonstrate the ecological progresses and the consequences of urbanization. Based on remotely sensed land cover data in 1994, 2000, 2006 and a gradient analysis with landscape metrics at landscape- and class- level, we attempted to characterize the individual and entire landscape patterns of Shanghai metropolitan during the rapid urbanization. We highlighted that a roadscape transect approach that combined the buffer zone method and the transect-based approach was introduced to describe the urban-rural patterns of agricultural, residential, green, industrial, and public facilities land along the railway route. Our results of landscape metrics showed significant spatiotemporal patterns and gradient variations along the transect. The urban growth pattern in two time spans conform to the hypothesis for diffusion–coalescence processes, implying that the railway is adaptive as a gradient element to analyze the landscape patterns with urbanization. As the natural landscape was replaced by urban landscape gradually, the urban fringe expanded radically. The results also showed that the desakota region expanded its extent widely. Satellite towns witnessed the continual transformation from the predominantly rural landscape to peri-urban landscape. Furthermore, the gap between urban and rural areas remained large especially in public service. More reasonable urban plans and land use policies should push to make more of an effort to transition from the urban-rural separation to coordinated urban-rural development. This study is a meaningful trial in demonstrating a new form of urban–rural transects to study the landscape change of large cities from a strategic viewpoint. By combining gradient analysis with landscape metrics, we addressed the process of urbanization both spatially and temporally, and provided a more quantitative approach to urban studies.

The ratio of males to females with ASD is generally quoted as 4:1 though it is believed that there are biases preventing females being diagnosed and that the true ratio is lower. These biases have not been clearly identified or quantified. Starting with a clinical dataset of 1711 children <18 years old four different methods were employed in an inductive study to identify and quantify the biases and calculate the proportion of females missed. A mathematical model was constructed to compare the findings with current published data. The true male to female ratio appears to be 3:4. Eighty per cent of females remain undiagnosed at age 18 which has serious consequences for the mental health of young women.

Here we report a comparative study of the pyhtochemical profile and a biological activity of the two onion extracts, namely A. cepa L. and A. × cornutum (Clementi ex Visiani 1842). Identification of flavonoids and anthocyanins and their individual quantities were determined by high performance liquid chromatography (HPLC). The potency of both extracts to scavenge free radicals was determined by DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical-scavenging activity and oxygen radical absorbance capacity (ORAC) methods. DNA protective role was further tested by single-cell gel electrophoresis (COMET) assay and by Fenton’s reagent causing double strand brakes on pUC19 plasmid. In the presence of both extracts, a significant decrease in the DNA damage was observed, which indicates a protective role of A. cepa and A. × cornutum on the DNA strand brakes. Additionally, cytotoxicity was tested on glioblastoma and breast cancer cell lines. The results showed that both extracts had antiproliferative effect, but the most prominent decrease in cellular growth was observed with glioblastoma cells

Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

This study used double-bounded dichotomous-choice to estimate and analyze the factors affecting households’ willingness to pay (WTP) for water quality improvement. This study notes that households with higher income, living near polluted water source, using tap water instead of natural water, who are handicraft producers, and who have more members are willing to pay more. However, households who rarely hear about environmental pollution issues and who are offered a higher bid are more likely to refuse to pay. Solutions to improve water quality are suggested such as to raise people's awareness through communication channels and social organizations; to increase income associated with environmental protection policies; to construct wastewater treatment plants; to encourage the relocation of production establishments to industrial parks and industrial complexes; to put regulations on collection, payment and sanctions in case of not declaring and paying fees into village conventions; to promulgate circulars, and bylaws to concretize and simplify regulations and policies of the Government, Ministry of Natural Resources and Environment.

Vehicle to vehicle (V2V) and Vehicle to infrastructure (V2I) or briefly V2X communications are the one of hot topics in automotive industry. Therefore, this situation is providing many advantages of connected vehicles and infrastructures which bring to human life. For instance, vehicles and road infrastructures which shares information with each other, provides a neat flow regulation, more ordered traffic flow and therefore jammed traffic dependent accident’s percentage will be decreased. On the other hand, security is the most important issue for these systems because the operation of V2X networks is completely dependent on uninterrupted and accurate information sharing. In the light of these information, in this paper we review security issues and current solution architectures. We also propose some open problems in this lively field.

SARS-CoV2 RNA depended RNA polymerase is an essential enzyme for the survival of the virus in hosts as it helps in the replication of viral RNA. There are no human polymerases that share either sequence or structural homology with viral RNA depended RNA polymerase. These make it a good target for inhibitor discovery, as a specific inhibitor cannot cross-react with the human polymerases. We have used virtual screening, docking, binding energy calculation and simulation to show that valproic acid Co-A, a metabolite from prodrug valproic acid, forms stable interaction with nsP12 of CoV. Our results suggest valproic acid Co-A could be a potential inhibitor of nsP12 of SARS-CoV2.

We consider the financial planning problem of a retiree wishing to enter a retirement village at a future uncertain date. The date of entry is determined by the retiree's utility and bequest maximisation problem within the context of uncertain future health states. In addition, the retiree must choose optimal consumption, investment, bequest and purchase of insurance products prior to her full annuitisation on entry to the retirement village. A hyperbolic absolute risk-aversion (HARA) utility function is used to allow necessary consumption for basic living and medical costs. The retirement village will typically require an initial deposit upon entry. This threshold wealth requirement leads to exercising the replication of an American put option at the uncertain stopping time. From our numerical results, active insurance and annuity markets are shown to be a critical aspect in retirement planning.

In order to overcome the limitation of the traditional adaptive Unscented Kalman Filtering (UKF) algorithm in noise covariance estimation for statement and measurement, we propose a hybrid adaptive UKF algorithm based on combining Maximum a posteriori (MAP) criterion and Maximum likelihood (ML) criterion, in this paper. First, to prevent the actual noise covariance deviating from the true value which can lead to the state estimation error and arouse the filtering divergence, a real-time covariance matrices estimation algorithm based on hybrid MAP and ML is proposed for obtaining the statement and measurement noises covariance, respectively; and then, a balance equation the two kinds of covariance matrix is structured in this proposed to minimize the statement estimation error. Compared with the UFK based MAP and based ML, the proposed algorithm provides better convergence and stability.

We propose a new theory beyond the standard model of elementary-particle physics. Employing the concept of a quantized spacetime, our theory demonstrates that the zero-point energy of the vacuum alone is sufficient to create all the fields, including gravity, the static electromagnetic field, and the weak and strong interactions. No serious undetermined parameters are assumed. Furthermore, the relations between the forces at the quantum-mechanics level is made clear. Using these relations, we quantize Einstein’s gravitational equation and explain the Dark Energy in our universe. Beginning with the zero-point energy of the vacuum, and after quantizing Newtonian gravity, we combine the energies of a static electromagnetic field and gravity in a quantum spacetime. Applying these results to the Einstein gravity equation, we substitute the energy density derived from the zero-point energy in addition to redefining differentials in a quantized spacetime. We thus derive the quantized Einstein gravitational equation without assuming the existence of macroscopic masses. This also explains the existence of the Dark Energy in the universe. For the weak interaction, by considering plane-wave electron and the zero-point energy, we obtain a wavefunction that represents a β collapse. In this process, from a different point of view than Weinberg-Salam theory, we derive the masses of the W and Z bosons and the neutrino, and we calculate the radius of the neutron. For the strong interaction, we previously reported an analytical theory for calculating the mass of a proton by considering a specific linear attractive potential obtained from the zero-point energy, which agrees well with the measurements. In the present study, we calculate the strong interaction between two nucleons, i.e., the mass of the pi-meson. The resulting calculated quantities agree with the measurements, which verifies our proposed theory.

Cyanobacteria are ubiquitous phototrophic bacteria that inhabit diverse environments across the planet. They dominate many eutrophic lakes impacted by excess nitrogen (N) and phosphorus (P) forming dense accumulations of biomass known as cyanobacterial harmful algal blooms or cyanoHABs. Their dominance in eutrophic lakes is attributed to a variety of unique adaptations including N and P concentrating mechanisms, N fixation, colony formation that inhibits predation, vertical movement via gas vesicles, and the production of toxic or otherwise bioactive molecules. While some of these molecules have been explored for their medicinal benefits, others are potent toxins harmful to humans, animals, and other wildlife known as cyanotoxins. In humans these cyanotoxins affect various tissues, including the liver, central and peripheral nervous system, kidneys, and reproductive organs among others. They induce acute effects at low doses in the parts-per-billion range and some are tumor promoters linked to chronic diseases such as liver and colorectal cancer. The occurrence of cyanoHABs and cyanotoxins in lakes presents challenges for maintaining safe recreational aquatic environments and the production of potable drinking water. CyanoHABs are a growing problem in the North American (Laurentian) Great Lakes basin. This review summarizes information on the occurrence of cyanoHABs in the Great Lakes, toxicological effects of cyanotoxins, and appropriate numerical limits on cyanotoxins in finished drinking water.

Since the beginning of 2020, tetracycline (TC), such as minocycline (MINO), has been used to inhibit coronavirus disease 2019 (COVID-19). Traditional Japanese Kampo medicine, such as Saiko-keishi-to (SKT), has recently received a lot of attention for its anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effects. We describe a COVID-19 patient treated with MINO and SKT in anticipation of their anti-SARS-CoV-2 properties. A 90-year-old male patient with Alzheimer’s disease was referred to a medical clinic due to fever, appetite loss, and general malaise. Based on positive SARS-CoV-2 rapid antigen tests, he was diagnosed with COVID-19. He did not have COVID-19 pneumonia, but he had difficulty in eating on his own. As a result, he was referred to a hospital for admission. After admission, he was treated with molnupiravir to avoid aggravation. Seven days after his admission, he was discharged. After his discharge, he was referred to our hospital as an outpatient due to a prolonged mild fever and general malaise. As a precaution, a real-time reverse transcription-polymerase chain reaction (RT-PCR) test was performed, which yielded a positive result. Therefore, the aforementioned symptoms were thought to be caused by prolonged COVID-19. He was treated with MINO and SKT due to the anti-viral properties of these two drugs. The RT-PCR test became negative 7 days after receiving this treatment, and the fever and general malaise subsided.

The critical hypoxia in COVID-19 patients during this pandemic, has taken away many lives all around the globe. The mechanism has been poorly understood and initially, word got around that it was a SARS (Severe Acute Respiratory Syndrome) pneumonia. The atypical images in lung computerized axial tomography (CAT) scans were alarming. This immediately alerted everyone including poor countries to purchase lacking sophisticated ventilator equipment. However, in some countries, even 88% of the patients on ventilators lost their lives. New observations and pathological findings are gradually clarifying the disease. What seems evident is that it is not only one disease but several, with different responses in different countries and different altitudes. The critical hypoxia and «gasping» present in some patients are not totally understood. It was mentioned that it could be like a High-Altitude Pulmonary Edema (HAPE). Hereby, as high-altitude medicine and hypoxia physiology specialists, we compare the pathophysiology with that of high-altitude exposure in order to understand the mechanisms involved. Some differences in lung radiological images along with transmission and viral attack mechanisms are discussed. The oxygen transport triad used at high-altitude can be applied on this pathology in order to propose even the use of erythropoietin (EPO) early in the treatment. The immune system is the most important long-term survival tool, so we suggest a short-term strategy: the use of special Earth open-circuit astronaut-resembling suits with effective outside air filtering re-breathing mechanisms in order to return to work and daily activities, without contamination risk. Thereby, the curve can be flattened without quarantine and the economy could recover.

The application of the sensors optical fiber in the areas of scientific instrumentation and industrial instrumentation is very attractive due to its numerous advantages. In the industry of civil engineering for example, quasi-distributed sensors made with optical fiber are used for reliable strain and temperature measurements. Here, a quasi-distributed sensor in the frequency domain is discussed. The sensor consists of a series of low-finesse Fabry-Perot interferometers where each Fabry-Perot interferometer acts as a local sensor. Fabry-Perot interferometers are formed by pairs of identical low reflective Bragg gratings imprinted in a single mode fiber. All interferometer sensors have different cavity length, provoking the frequency-domain multiplexing. The optical signal represents the superposition of all interference patterns which can be decomposed using the Fourier transform. The frequency spectrum is analyzed and sensor´s properties were defined. Following, a quasi-distributed sensor was numerically simulated. Our sensor simulation considers sensor properties, signal processing, noise system and instrumentation. The numerical results show the behavior of resolution vs. signal-to-noise ratio. From our results, the Fabry-Perot sensor has high resolution and low resolutions. Both resolutions are conceivable because the FDPA algorithm elaborates two evaluations of Bragg wavelength shift

Background: Early identification and prevention of hypoxic ischemic encephalopathy (HIE) may reduce neonatal mortality and morbidity. Objective: We aimed to correlate between urinary Activin-A and MRI (conventional and Diffusion-weighted) and the severity of HIE in full-term neonates. Methods: Forty-five full-term neonates with HIE admitted to NICU and 15 normal neonates were enrolled into the study. The concentration of urinary Activin-A was determined using enzyme immunoassay kits and MRI were done. Correlations between urinary Activin-A and MRI with the degree of HIE were done. Results: Urinary Activin-A levels were significantly higher in neonates with HIE than controls (P<0.001). It was positively correlated with the clinical grading of HIE and a cutoff value of 0.08µg/l on day-1 after birth had a sensitivity of 98.6% and specificity of 97.1% for prediction of HIE. DW-MRI detected HIE with a high sensitivity (85%) compared to the low sensitivity of conventional MRI (35%). An ADC value of ≤ 0.8 was the best sensitivity-specificity cutoff point for detecting severe ischemic injury. DW-MRI imaging was positively correlated with Urinary Activin-A and both of them were positively correlated with the clinical grades of HIE (P < 0.001). Conclusions: DW-MRI imaging is correlated well with urinary Activin-A in full-term neonates with HIE and both of them are correlated with the degree of HIE. Early determination of urinary Activin-A combined with DW-MRI imaging can early detect HIE and its severity in full-term neonates with HIE.

A literature review was conducted to summarize the frequency of the D-allele of the angiotensin-converting enzyme-1 in all countries with available data. Using an ecological study design limited to high income countries, we found that the country-level frequency of the D-allele was associated with increased COVID-19 incidence and mortality.

Coronavirus disease (COVID-19) is a new discovered strain where WHO officially declares the disease as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The incubation period of this disease is between 14 days. Ordinary clinical symptoms that reported around the world include fever, cough, fatigue, diarrhoea and vomiting as well as asymptomatic for certain people. Infection is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.

MEMS (Micro-electromechanical Systems) becomes important increasingly due to the smarter and smaller fuze used in OICW (Objective Individual Combat Weapon). MEMS Safety and Arming (S&A) device is employed in different platforms and regions for small caliber projectile. Therefore, it is necessary to make a parametric study of the MEMS S&A device in different apply environments and explore the main sensitive factors of the MEMS S&A device to provide reference for designs. In this paper, based on the MEMS S&A device designed by our term, theory and finite element models are established, and the centrifugal insurance mechanism of the MEMS S&A device is parametric studied under the different speeds, temperature and thickness of the model by nonlinear dynamic method. By comparing the experimental and predicted results, the established FEM model is verified, and the conclusion is that the temperature and the centrifugal force are the main sensitive factors in the centrifugal insurance mechanism. In summary, we can suggest that the application environment, which the MEMS S&A device is suitable for, is the temperature equal to or slightly greater than normal temperature and the rotating speed higher than35000r/min of small caliber projectile.

We propose the traditional goal of cancer therapists to develop a single drug or drug combination that can, by itself, eliminate all cancer cells within a host has neglected potential treatments that may achieve curative outcomes by strategically combining agents that are individually effective but non-curative. We derive basic principles for such an approach from the eco-evolutionary dynamics of background extinctions in which a “first strike” reduces the size and heterogeneity of the initial population and is followed immediately by demographic and ecological “second strikes” that push the population below an extinction threshold. This proposed strategy appears identical to the empirically-derived curative therapy in childhood Acute Lymphocytic Leukemia.

The purpose of this study was to evaluate the bioactivity and cell response of a well-characterized Nurse´s A-phase (7CaO•P2O5•2SiO2) ceramic and his effect compared to a control (tissue culture polystyrene-TCPS) on the adhesion, viability, proliferation and osteogenic differentiation of ahMSCs in vitro. Cell proliferation (Alamar Blue Assay), Alizarin Red-S (AR-s) staining, alkaline phosphatase (ALP) activity, osteocalcin (OCN) and collagen I (Col I) were evaluated. Also, field emission scanning electron microscopy (FESEM) images were acquired in order to visualise the cells and the topography of the material. The proliferation of cells growing in a direct contact with the material was slower at early stages of the study because of the new environmental conditions. However, the entire surface was colonized after 28 days of culture in growth medium (GM). Osteoblastic differentiation markers were significantly enhanced in cells growing on Nurse´s A phase ceramic and cultured with osteogenic medium (OM), probably due to the role of silica to stimulate the differentiation of ahMSCs. Moreover, calcium nodules were formed under the influence of ceramic material. Therefore, it is predicted that Nurse´s A-phase ceramic would present high biocompatibility and osteoinductive properties being a good candidate to be used as a biomaterial for bone tissue engineering.

Fourteen (14) rack-mounted polycrystalline modules installed on the concrete roof of the solar energy applications laboratory at the Kwame Nkrumah University of Science and Technology (KNUST) in Ghana, a hot humid environment were assessed after 19 years of continuous outdoor expodure. The physical state of the modules was documented using a visual inspection checklist. They were further assessed by current-voltage (I-V) characterization and thermal imaging. The modules were found to be in good physical state, except some bubbles on front side and minor discolouration/corrosion at edge of the cells. Compared with reference values, the performance decline of the modules observed over the exposure period was: nominal power (P_nom), 21% to 35%; short circuit current (I_sc), 5.8% to 11.7%; open circuit voltage (V_oc) 3.6% to 5.6% and 11.9% to 25.7% for fill factor (FF). It is hoped that this study will provide some helpful information to project developers, manufacturers and the research community on the long-term performance of PV modules in Ghana.

Food waste is one of the greatest challenge to sustainability in developed and developing countries. In the former, food waste is concentrated in the final part of the chain. Too Good To Go is a digital platform aimed to prevent food waste, where consumers can buy magic boxes from different outlets containing food products that are approaching their end-of-life. However, the mechanism of the platform enable the outlets to publish their offering much in advance of the pick-up time, raising the question whether the food sold on the platform is effectively a leftover or a planned production. Our empirical study gathers data from over 1200 outlets in Rome on the Too Good To Go platform.

This paper presents a microgrid distributed energy resources (DERs) for a rural standalone system. It is made up of solar photovoltaic (solar PV) system, battery energy storage system (BESS), and wind turbine coupled to permanent magnet synchronous generator (WT-PMSG). The DERs are controlled by maximum power point tracking (MPPT) based proportional intergral (PI) controllers for both maximum power tracking and error feedback compensation. The MPPT uses the perturb and observe (P&O) algorithm for tracking the maximum power point of the DERs. The PI gains are tuned using the Ziegler-Nichol’s method. The developed system was built and simulated in MATLAB/Simulink under two conditions - constant load, and step load changes. The controllers enabled the BESS to charge even during conditions of varying load and other environmental factors such as change of irradiance and wind speed. The reference was tracked very well by the output voltage of the DC grid. This is a useful research for electrifying the rural islanded areas, too far from the grid.

This paper deals with the environmental characterization of a large and densely populated area, with a poor reputation for contamination, considering the contribution of environmental features (air, soil, soil hydraulic and groundwater) and the potential effects on human health. The use of Geographic Information System (GIS) has made possible a georeferenced inventory and, by overlaying environmental information, an operational synthesis of comprehensive environmental conditions. The cumulative effects on environmental features were evaluated, taking into account superposition effects, by means of the spatial multicriteria decision analysis (S-MCDA). The application of the S-MCDA for converging the combination of heterogeneous factors, related to soil, land and water, deeply studied by heterogeneous groups of experts, constitutes the novelty of the paper. The results confirmed an overall higher potential of exposure to contaminants in the environment and higher mortality rates in the study area for some tumours, but hospital admissions for tumours were generally similar to the regional trend. Besides, mortality data may be strictly dependent on the poor socioeconomic conditions, quality of therapy and a lack of welfare in the area relative to the rest of Italy. Finally, as regards the possible relationship between presence of contaminants in the environment and health conditions of the population no definite conclusions can be drawn, although the present study encourages the use of the new proposed methods, that increase the possibilities for studying the combined effect of more environmental factors.

In order to meet the military requirements of the fuze, such as precision strike, efficient mutilates ability and low collateral damages, the microminiaturization is an inevitable trend of secure system. Based on the silicon-based MEMS S&A device designed by our term, the design principles of each module and fabrication process are introduced. The average fracture strength and Young's modulus of the silicon are 726 MPa and 175 GPa from the tensile test, respectively. From Hopkinson impact experiment, we can get the threshold-value judging mechanism being safety under the impact overload of 20526 g, and this value is much more than the standard of the drop overload 12000g; the arming value under the centrifugal overload obtained from theory, simulation and experiment is at the range of 28200 g and 32000 g, it shows that the threshold-value judging mechanism can be arming compared with the value 35951g of design principle. Therefore, the threshold-value judging mechanism can meet the design requirements of overload. Furthermore, the relationship of fracture threshold-values obtained by different theories is found out through parametric design method, as shown in Figure 14, it provides the theory evidence to the follow parametric design.

The seeds of red clover are heteromorphic and two color morphs can be visually recognized, light purple and yellow, resulting from heterozygosity and recessive homozygosity at two loci. Here, we report the responses of seed imbibition, seed germination, and early seedling growth of the two morphs to distilled water, sodium chloride, and complete nutrient solution. The sensitivity of red clover seeds to treatments increased with the stage of development in what seems to be a cumulative process. No differences were found in seed imbibition between morphs or between treatments. In seedling growth, on the contrary, treatments were always effective, but differences between morphs were only observed in seeds that were treated with nutrient solution, whereas in the intermediate stage of seed germination, the effects by treatments were observed together with the appearance of differences between morphs in distilled water and in the treatment by sodium chloride solution. Simultaneously, the superior performance of the yellow morph that was found in germination, which appears to be a trait stable across cultivars of red clover seeds, turned into a superior performance of the light purple morph in seedling growth.

A gold(I) complex with a triphenylphosphine and a monodentate N,N-dimethyldithiocarbamate ligand was synthesized and characterized by Raman spectroscopy and single crystal X-ray diffraction. DFT calculations (Gaussian 09, PBE1PBE/Lanl2dz) were undertaken for a single complex in the gas-phase. The DFT-optimized structure is in good agreement with the crystal structure and the DFT-calculated Raman spectrum also is in excellent agreement with the experimental spectrum. Assignments of the Raman peaks are based on these DFT calculations. Frontier molecular orbitals were calculated and their nature is discussed.

Whereas waste management research has focused on mostly urban municipalities in South Africa, not much is known about the current performance of waste management services from the perspective of community residents in rural municipalities. This study reports on the status and effectiveness of waste management practices from the perspective of community residents in the Umkhanyakude and Zululand Districts in the rural areas of the KwaZulu-Natal province of South Africa. Making use of structured questionnaires, primary data was obtained by interviewing 333 respondents representing households in the study area. Results have revealed several shortfalls in the provision of municipal waste management services, except for solid waste removal from households (66%), and management of landfill sites (41%). The degree of dissatisfaction for waste management services rendered was very high (97.3%). Furthermore, the majority (61.4%) of respondents were not willing to participate in waste segregation due to lack of appropriate knowledge and infrastructure. The study also pinpointed some benefits associated with waste minimization, as well as barriers constraining effective waste recycling. Based on these findings, there is a dire need for transforming current waste management practices toward increased recycling rates by creating more environmental awareness and a supporting infrastructure.

In the paper, by virtue of the Fa`a di Bruno formula, some properties of the Bell polynomials of the second kind, and the inversion formulas of binomial numbers and the Stirling numbers of the first and second kinds, the authors simplify meaningfully and significantly coefficients in two families of ordinary differential equations associated with higher order Frobenius–Euler numbers.

This study uses data from the pilot project "Community Monitoring for Better Health and Education Services Delivery Project'' in Burkina Faso, to model the joint impact of generic essential drugs and nursing staff supplies constraints on access to primary health care in the country. The results show that statistical endogeneity of supply side constraints are present in the standard univariate probit specification of access to care. However, when accounted for, the resulting Trivariate Probit model shows that although shortages of generic essential drugs supply do not seem to constitute a significant barrier to access in Burkina Faso, shortages in nursing staff supply do. In fact, the likelihood of primary care access is reduced by 85.5% among those that reported having experienced a shortage in nursing staff, while paradoxically increasing by 60.3% among those that reported having experienced a shortage in generic essential drugs. A potential explanation for these findings is that overall the health care needs in the three surveyed regions in the country were more linked to primary health care services consumption from nurses, although further research would be important to clearly elucidate the position of health goods such as generic essential drugs.

Many academics are critical of the current publishing system, but it is difficult to create a better alternative. This review relates to the Sciences and Social Sciences, and discusses the primary purpose of academic journals as providing a seal of approval for perceived quality, impact, significance, and importance. The key issues considered include the role of anonymous refereeing, continuous rather than discrete frequency of publications, avoidance of time wasting, and seeking adventure. Here we give recommendations about the organization of journal articles, the roles of associate editors and referees, measuring the time frame for refereeing submitted articles in days and weeks rather than months and years, encouraging open access internet publishing, emphasizing the continuity of publishing online, academic publishing as a continuous dynamic process, and how to improve research after publication. Citations and functions thereof, such as the journal impact factor and h-index, are the benchmark for evaluating the importance and impact of academic journals and published articles. Even in the very top journals, a high proportion of published articles are never cited, not even by the authors themselves. Top journal publications do not guarantee that published articles will make significant contributions, or that they will ever be highly cited. The COVID-19 world should encourage academics worldwide not only to rethink academic teaching, but also to re-evaluate key issues associated with academic journal publishing in the future.

This short note proposes a national Geographic Information System (GIS) - based health infrastructure to deal with epidemics and pandemics. Currently, there is no pan-India health infrastructure available that can compile, update, and report the spread of epidemic diseases. It not only curtails the opportunity of finding the real-time data on the spatial distribution of a disease but prevents one to inquire into the causes of the disease through epidemiological analysis. The proposed infrastructure in this study is a pan-India one and can broadly be divided into two parts, hotspot mapping and accessibility to services. In the first part, hospitals are proposed to act as nodes of data collection, sending data to a national GIS portal. This portal shall have the capabilities of plotting the data using map rendering services such as Google and Bing Maps. This way, hotspots can be visualized in no time, benefitting the government and common citizenry alike. The second part deals with the accessibility of citizenry to a wide range of services, i.e., healthcare services, grocery outlets, emergency services, baby food, and many other essential services of the day to day life. In order to implement this, we propose that the government need to enforce a mandatory submission of locational coordinates of all Goods and Services Tax (GST) enrolled service providers. Once the coordinates are submitted, the government can effectively control the opening and closing of services and inform the citizenry at the same time. The proposed infrastructure is going to help deal with the extraordinary situations during epidemic and pandemics similar to what the world is currently facing in the form of Corona Virus Disease 2019 (COVID-19). Furthermore, the infrastructure can be scaled up or down as per the spread of a disease. The health-GIS platform proposed in this concept paper, shall help India in controlling and managing the epidemic more efficiently.

In this study, we describe quark confinement in terms of linear interaction potentials and solve the problem of the net spin of a proton. The three quarks in a proton are assumed to revolve around a common center, and their masses are determined assuming they are Dirac particles. On the basis of these assumptions, the magnetic moment of a proton can be derived. Moreover, the rotation of the quarks is considered, in which an electrical current induces a magnetic field. Thus, the scalar product of the magnetic moment and field describes the linear interaction potential between the quarks, and the mass of the proton can be obtained. The proton mass predicted by this physical model is consistent with experimental values, and no numerical or fitting calculations are required. Furthermore, using the newly derived spins and angular momentum of the three quarks, we derived the net spin of a proton. Additionally, we predicted the mass of a pi-meson from the same model, which agrees with the experimental values.

Vitamin A and E are important during pregnancy, the neonatal period, and childhood. The objective of this study was to assess whether maternal RRR-a-tocopherol supplementation affects serum and breast milk retinol. Serum was collected at baseline and twenty days later, and breast milk, at baseline, and on days 1, 7, and 20 after delivery. After the baseline serum collection, the supplemented group (n=16) received a single 400 IU of RRR-α-tocopherol. The control group (n=18) was only performed collections. Retinol and alpha tocopherol levels were determined by liquid chromatography. Serum retinol and alpha tocopherol at baseline and 20 days after delivery indicated proper vitamin A (> 20 µg/dL) and E (> 516 μg/dL) statuses in the control and supplemented groups (p > 0.05). Colostrum retinol levels on days 1 and 7 after delivery were significantly higher in the supplemented group (p = 0.018 and p = 0.012, respectively). Maternal vitamin E supplementation increased colostrum retinol by 52.23% and 111.2%, 24 hours and 7 days, respectively. However, retinol in mature milk did not differ between the groups (p > 0.05). In conclusion, the supplementation with 400 IU of RRR-α-tocopherol improved vitamin A bioavailability in breast milk.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Due to the fact that abrasive media can deform flexibly in abrasive flow machining (AFM) making this method easily to polish the complex holes and the curved surface of the hard machining shapes. Although abrasive media dominate the polishing behavior in AFM process, the mechanism of the abrasive media are not easy to understand because of the high viscous gels, therefore, many finishing works need lots of time to design AFM process. Power laws of the abrasive gels is studied here to evaluate the non-Newtonian flow of abrasive gels in complex holes polishing firstly, at the mean time different abrasive gels are utilized to finish the complex holes to follow the results by non-Newtonian flow calculation. Moreover, traditional AFM has difficulty to achieve a uniform roughness of radial distribution in the complex holes polishing because of the non-uniform abrasive forces. So a helical passageway is proposed to create a multiple motion of abrasive medium and to obtain the even surface of the complex holes in AFM process.

Air corridors are an integral part of the advanced air mobility infrastructure. They are the virtual highways in the sky for transportation of people and cargo in the controlled airspace at an altitude of around 1000 ft. to 2000 ft. above the ground level. This paper presents fundamental insights into the design of air corridors with high operational efficiency as well as zero collisions. It begins with the definitions of air cube, skylane or track, intersection, vertiport, gate, and air corridor. Then, a multi-layered air corridor model is proposed. Traffic at intersections is analyzed in detail with examples of vehicles turning in different directions. The concept of capacity of an air corridor is introduced along with the nature of distribution of locations of vehicles in the air corridor and collision probability inside the corridor are discussed. Finally, the results of simulations of traffic flows are presented.

This study aimed to investigate the healing effect of advanced platelet-rich fibrin (A-PRF) clot membranes in the reduction of palatal wounds resulting from free gingival graft (FGG) harvesting, in the re-epithelization rate and in the pain experience after surgery. Twenty-five patients requiring soft tissue augmentation (gingival recession coverage or keratinized gingiva augmentation) participated in this prospective randomized clinical study. After FGG harvesting, the test group (n=14) received A-PRF clot membranes at the palatal wound and the control group (n=11) a gelatin sponge. Epithelialization rate of the palatal wound, wound healing area, correspondent percentage of reduction and post-surgical pain experience were assessed. The follow-up period was 90 days. There was a significantly higher reduction of the palatal wound area in the A-PRF group vs. the control group, at 7 (p<0.001), 14 (p=0.009) and 30 days (p<0.001) follow-up. The maximum difference between groups was attained at 30 days (91.5% for A-PRF vs. 59.0% for the control group). At 14 days a significant difference in the proportion of patients showing total epithelization was found: 64.3% for A-PRF vs. 9.1% for the control group (p=0.012). At 90 days, both groups showed total recovery. Overall, the control group experienced a higher level of pain and discomfort until the 14th day, being significantly higher on the second day (p=0.013). The results suggest that A-PRF membranes haste the healing process by promoting a greater reduction along the recovery period and an apparent less painful postoperative period.

Microaggressions are subtle verbal and non-verbal slights based on group membership, and they are ubiquitous in the lives of racial minorities, women, and LGBTQ individuals (Sue, 2010). The goal of the current paper is to introduce a role-playing based exercise on effective responses to microaggressions. The workshop draws on the prejudice responding workshops of Plous (2000) and Lawson, et al. (2010) but integrates research-based strategies. The activity was tested in two groups of undergraduate students, and the findings suggested that both groups felt more prepared to deal with microaggressions after participating.

Background: Telemedicine (interconsultation between primary and hospital care teams) has been operating in the counties of Central Catalonia Bages, Moianès and Berguedà since 2011 in the specialties of teledermatology, teleulcers, teleeyelids and teleaudiometries. For the period until the end of 2019, a total of 52,198 visits have been recorded. Objective: To analyse the differential costs between telemedicine and usual care in a semi-urban environment. Methodology: A cost-minimization evaluation, including direct and indirect costs from a societal perspective, distinguishing healthcare and user’s costs, within a three-month period. Results: Telemedicine saved € 780,397 over the period analysed. A differential cost favourable to telemedicine of about € 15/visit has been observed, the patient being the largest beneficiary of this saving (by 85%) in terms of shorter waiting times and travel costs. From the healthcare system perspective, moving the time spent in a hospital care consultation to primary care is efficient in terms of the total time devoted per patient. In social terms and in this context, telemedicine is more efficient than usual care. Conclusion: Users’ saving of time in terms of consultation and travel is the main driver of interconsultation between primary and hospital care savings in a semi-urban context. The telemedicine service is also economically favourable for the healthcare system, enabling it to provide a more agile service, which also benefits the healthcare professionals.

One important motivation for the implementation of the Water Framework Directive is the creation of non-market environmental benefits such as improved ecological quality, or greater opportunities for open-access river recreation via microbial pollution remediation. Pollution sources impacting on ecological or recreational water quality can be uncorrelated but non-market benefits arising from riverine improvements are typically conflated within benefit valuation studies. Using stated preference choice experiments, we seek to disaggregate these sources of value for different river users, thereby allowing decision makers to understand the consequences of adopting alternative investment strategies. Our results suggest anglers derive greater value from improvements to the ecological quality of river water, in contrast to swimmers and rowers for whom greater value is gained from improvements to recreational quality. We also find three distinct groups of respondents: a majority preferring ecological over recreational improvements, a substantial minority holding opposing preference orderings and a small proportion expressing relatively low values for either form of river quality enhancement. As such, this research demonstrates that the non-market benefits which may accrue from different types of water quality improvements are nuanced in terms of their potential beneficiaries and, by inference, their overall value and policy implications.

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in the cerebral vasculature. A growing body of epidemiological data shows that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades that evolve before neurodegenerative changes. Gut microbiome alterations also have been observed in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, and inflammatory CNS diseases. Interestingly, only recently has the dog gut microbiome been recognized to more closely resemble in composition and in functional overlap with the human gut microbiome as compared to rodent models. This article aims to review the physiology of the gut-brain axis (GBA), and its involvement with neurodegenerative diseases in dogs and humans. Additionally, we outline the advantages and disadvantages of traditional in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases using dogs.

The traditional herbal medicine, Hochu-ekki-to, has been shown to have preventive effects on viral infection and stress. This study aimed to evaluate the clinical effects of Hochu-ekki-to on two stress-related rat models of polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into control and treatment groups, the latter of which were subjected to stress induced by exposure to adrenocorticotropic hormone (ACTH) or cold temperatures. After these stress inductions, rats were orally treated with dissolved Hochu-ekki-to once per day for 7 days. Rats subjected to the two different stressors exhibited upregulation of steroid hormone receptors (in ovaries) and reproductive hormones (in blood), and consequent stimulation of abnormal follicle development accompanied by elevation of Hsp 90 expression (in ovaries). Treatment with Hochu-ekki-to for 7 days after stress induction increased immune functions, reduced the stress-induced activation of Hsp 90, and normalized the levels of the tested steroid hormone receptors and reproductive hormones. Our findings suggest that stress stimulations may promote the activation of Hsp 90 via the dysregulation of steroid hormone receptors and reproductive hormones, but that post-stress treatment with Hochu-ekki-to improves reproductive and immune functions in the ovaries of stressed rats.

Microbial symbioses exhibit astounding adaptations, yet all symbionts face the problem of how to reliably associate with host offspring every generation. A common strategy is vertical transmission, in which symbionts are directly transmitted from the female to her offspring. The diversity of symbionts and vertical transmission mechanisms is as expansive as the diversity of eukaryotic host taxa that house them. However, there are several common themes among these mechanisms based on the degree to which symbionts associate with the host germline during transmission. In this review, we detail three distinct vertical transmission strategies, starting with associations that are transmitted from host somatic cells to offspring somatic cells, either due to lacking a germline or avoiding it. A second strategy involves somatically-localized symbionts that migrate into the germline during host development. The third strategy we discuss is one in which the symbiont maintains continuous association with the germline throughout development. Unexpectedly, the vast majority of documented vertically inherited symbionts rely on the second strategy: soma-to-germline migration. Given that not all eukaryotes contain a sequestered germline and instead produce offspring from somatic stem cell lineages, this soma-to-germline migration is discussed in the context of multicellular evolution. Lastly, as recent genomics data have revealed an abundance of horizontal gene transfer events from symbiotic and non-symbiotic bacteria to host genomes, we discuss their impact on eukaryotic host evolution.

More than a decade ago, a new mitochondrial Open Reading Frame (mtORF) was discovered in corals of the family Pocilloporidae, which turn out to be an effective barcode gene for these corals. However, its function remains unknown. Recently, this gene revealed the existence of a hybrid Stylophora lineage (RS_LinA) inhabiting in sympatry along the environmental gradient of the Red Sea (18.5°C to 33.9°C) with its parental species (RS_LinB). Furthermore, in RS_LinB, the mtORF uncovered phylogeographic patterns that were strongly correlated with environmental variations. This was similar to the patterns unraveled by hsp70, suggesting that mtORF too might be involved in thermal adaptation. Here we used computational approaches to characterize the mtORF and to identify its potential role. Results showed that this gene encodes a transmembrane protein (0.97<P< 1.00) involved in transport (0.80<P< 0.87), regulation of metabolic processes (0.70<P<0.85), and likely in the cell-surface receptor signaling pathway (0.56<P<0.80). Predicted protein functions differed among Stylophora lineages and interestingly, in RS_LinB only, the protein was intrinsically disordered and displayed domains involved in cellular complexes and stress response (0.0001< P <0.001). These characteristics, exclusive of an endemic lineage adapted to extreme environmental fluctuations, support a role of the mtORF in stress response, speciation and adaptation.

The practice of collecting, treating and management of solid waste prior to disposal has become a necessity in developing and modern societies. Over the years, it is known that most wastes that are disposed have a second hand value. However, the construction cost for conventional Material Recovery Facility(s) (MRFs) has been a major barrier for implementation. These technologies require considerable technical expertise, which is often not available in developing nations to successfully operate the MRFs. Covenant University; a private mission institution through her waste to wealth scheme is focused on managing and processing used materials to reusable products. These include Pet bottles, Paper wastes, Food wastes from cafeteria, plastic food packs, nylon, tin cans and others. Specific areas chosen for the Survey include the residential areas for staff and students and the two cafeterias. The waste generated was characterized based on the waste stream so as to quantify the amount of recyclable waste generated and most occurring. The survey involved the use of structured questionnaires, on-site observations and measurements. The study reveals an average amount of recyclable waste generated per day in the institution as 13.46% pet bottles, 4.03% paper, 55.56% food waste, 12.64% plastic, 9.63% nylon and 4.68% tin cans. The study established that adequate waste characterization is a requirement for effective integrated solid waste management which would boost resource recovery, reuse and recycling.

Neuropsychiatric manifestations of COVID-19 include delirium, general malaise, headache, and psychiatric symptoms. These manifestations are related to the neuroinflammatory response to viral antigens and proinflammatory mediators/immune cells. Tetracyclines, such as minocycline, have antibacterial and anti-inflammatory properties. Saiko-keishi-to, a traditional Japanese Kampo medicine, also has anti-inflammatory properties. Given the anti-inflammatory properties of minocycline and Saiko-keishi-to, we describe two cases of COVID-19 with prolonged headaches and general malaise successfully treated with these medications.

The alkylation of 1,1,2-trimethyl-1H-benzo[e]indole with 2-chloroacetamide, followed by work-up of the reaction mixture with a base and the subsequent treatment of a crude product with acetic acid gives 10a,11,11-trimethyl-10a,11-dihydro-8H-benzo[e]imidazo[1,2-a]indol-9(10H)-one. The structure assignments were based on data from ¹H, ¹³C and ¹⁵N NMR spectroscopy. The optical properties of the obtained compound were studied by UV-vis and fluorescence spectroscopy.

Praeruptorin A(PA), a naturally existing pyranocumarin, is isolated from the dried root of Peucedanum praeruptorum Dunn. So far the anti-cancer effect and molecular mechanism behind Praeruptorin A action in human cervical cancer HeLa cells remain unknown. In the present study, we find that PA reduces cell proliferation and colony formation of human cervical cancer HeLa cells through inducing cell cycle arrest at G0/G1 phase. PA-upregulated p21 and p27 proteins are observed, accompanied with inhibition of cyclin D1 and S-phase kinase-associated protein 2(Skp2) proteins expression. PA could significantly inhibit migration and invasion of human HeLa cells. Meanwhile, PA significantly reduces invasive protein expression of matrix metalloproteinase-2 (MMP-2), and increases protein expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). PA is observed to possess the capacity in suppressing ERK1/2 activation. PD98059 (ERK specific inhibitor) significantly enhances PA-induced downregulation of MMP-2 expression, and upregulation of TIMP-2 expression. Moreover, we found that PA treatment notably inhibits 12-O-tetradecanoylphorbol-13-acetate(TPA)-upregulated ERK1/2 activation, MMP-2 expression, cellular migration and invasion in human HeLa cells. Taken together, these findings are the first to demonstrate the anti-cancer activity of PA, which may act as a promising therapeutic agent for the treatment of human cervical cancer.

Location-Based Services (LBS) have been widely deployed for the connected vehicle (CV) applications such as vehicle navigation,vehicle tracking and location-based augmented reality. The current LBS deployments have limitations in supporting time-critical CV use cases, including vehicle to vehicle (V2V), vehicle to infrastructure (V2I) and vehicle-to-people (V2P) safety applications. The paper presents the new LBS framework based on the publish-subscribe communication paradigm, to enable device-to-device (D2D) connections through use of selected application protocols in the application layer of the TCP/IP layered protocol model. Two publish-subscribe application protocols, Distributed Data Service (DDS) real-time publish and subscribe (DDS-RTPS) and Message Queue Telemetry Transport (MQTT), are introduced to support the LBS D2D applications. A number of test scenarios with Mosquitto MQTT and OpenDDS under 4G-mobile broadband (MBB) services are designed to assess the transmit/receive round-trip time (RTT) and packet-loss rate (PLR) with settings of a publisher to multiple subscribers, to simulate the connections to multiple vehicles. The transmission frequency is set for 10 Hz and the message sizes vary from 100 to 2000 Bytes. The PLRs are defined as the percentages of the delayed messages beyond a delay limit. Static test results with OpenDDS show that for the RTT delay beyond the limit of 100 ms, the total PLRs range between 5.25% and 8.76% for the message size of 50 to 2000 Bytes. Vehicle testing results with Mosquitto show that PLRs for the RTT delays between 200 ms and 1000 ms are 0.63%, 3.58% and 5.77%, for connections with 1, 4 and 10 vehicles, respectively. The results demonstrate the potential of the D2D LBS framework for medium-demanding CV safety applications such as V2P and V2I use cases, taking advantages of the 4G-MBB services and 5G extreme mobile broadband (eMBB) services and mobile devices generally available with all road users.

In this study, diabetogenic effects of long term Ochratoxin A (OTA) administration in rats were investigated and its role in the etiology of diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these purposes. The rats were divided into 3 different study and control groups according to the duration of the OTA administration. Rats received 45 μg OTA daily in their feed for 6, 9 and 24 weeks study groups. Three control groups without any treatment were also used in the same periods. Blood and pancreatic tissue samples were collected during the necropsy at the end of 6, 9 and 24 weeks. Plasma values of insulin, glucagon and glucose in study and control groups were determined. Pancreatic lesions were evaluated by histopathological examination; then insulin and glucagon expression in these lesions were determined by immunohistochemical methods. Statistically significant decrease in insulin levels in contrast to increases in glucagon and glucose levels in blood were observed. Slight degeneration in Langerhans islet cells were observed at the histopathological examination in all OTA treated groups. Immunohistochemistry of pancreatic tissue revealed decreased insulin and increased glucagon expression. This study demonstrated that OTA may cause pancreatic damage in Langerhans islet and predispose rats to DM.

To mitigate the COVID-19 infection, many world governments endorsed the cessation of non-essential activities, such as the school attendance. Thereby, forcing the evolution of the teaching model to the virtual classroom. In the present work we show the application of a modified version of the adapted COVID-19 stress scales (ACSS) which also included teaching anxiety and preparedness, and resilience for academic professionals in Mexico, during the unprecedented transformation of the education system undergone in the COVID-19 quarantine. Most of the studied variables: gender, age, academic degree, household occupants, having a disease, teaching level, teaching mode, work hours, resilience, teaching anxiety and preparedness, and fear of being an asymptomatic patient (FOBAP), showed significant statistical correlation between each other (p<0.050) and to the 6 areas of the ACSS (danger, contamination, social economical, xenophobia, traumatic stress and compulsive checking). Our results further showed that the perceived stress and anxiety, fell into the category of absent to mild with only the danger section of the ACSS falling into the moderate category. Finally, resilience generated throughout the quarantine, seems to be a predictor of the adaptation the academic professional has undergone to cope with stress.

The world has been highly impacted by the COVID-19 as the virus has spread to all continents – about 200 countries in total. The latest update claims about 4,000,000 confirmed cases and about 300,000 confirmed deaths owing to the COVID-19 pandemic. This probably makes the COVID-19 as the most dangerous contagious disease in the era 2000s. Apart from massive publications on this topic, there is no available qualitative analysis that describes the dynamic spreads of the COVID-19 and its impacts on healthcare and the economy. Through the system archetypes analysis, this paper explains that the dynamic spread of the COVID-19 consists of the limits to growth and the success to successful structures. The limits to growth elucidates that more symptomatic and asymptomatic patients owing to infected droplets may be bounded by self-healing and isolated treatments. The success to successful structure explains that once the COVID-19 affects the economy through the lockdown, there will be a limited fund to support the government aids and the aggregate demand. In overall, this paper gives readers simplified holistic insights into understanding the dynamic spread of the COVID-19.

Drug delivery to the brain represents a challenge especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as other statins, has shown potential anticancer properties that are difficult to exploit in the CNS. In the present work the physico-chemical, mucoadhesive and permeability enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with different molecular weight (MW) chitosans (LNCchit) prepared by a novel one-pot technique were characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release and permeability across two nasal mucosa models. Results show that all formulations present adequate particle size (below 220 nm), positive surface charge, narrow droplet size distribution (PDI<0.2) and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties dependent on the MW of the coating chitosan. The results of permeation across RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT permeated after 4h for nanocapsules coated with low MW chitosan, high MW chitosan and control SVT was 13.91 ± 0.78 µg, 9.15 ± 1.23 µg and 1.42 ± 0.21 µg respectively. These results were confirmed by the SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

There is a growing interest in fibers supporting optoelectrical properties for textile and wearable display applications. Solution-processed electroluminescent (EL) material systems can be continuously deposited onto fiber or yarn substrates in a roll-to-roll process, making it easy to scale manufacturing. It is important to have precise control over layer deposition to achieve uniform and reliable light emission from these EL fibers. Slot-die coating offers this control and increases the rate of EL fiber production. Here, we report a highly adaptable, cost-effective 3D printing model for developing slot dies used in automatic coating systems. The resulting slot-die coating system enables rapid, reliable production of alternating current powder-based EL (ACPEL) fibers and can be adapted for many material systems. The benefits of this system over dip-coating for roll-to-roll production of EL fibers are demonstrated in this work.

The ongoing pandemic of the 2019 novel coronavirus disease (COVID-19) raises a global health crisis, which has resulted in 75,778 confirmed cases with 2130 deaths in China and beyond. Atypical symptom renders it challenging to earlier recognize the 2019-nCoV carrier with the potential ability of equivalent transmission. Therefore, it is needed to gain full spectrum of COVID-19. Here we report clustered COVID-19 cases of person-to-person transmission. The symptoms of typical pneumonia are shared by the two familial members, namely son (Patient 1) and father (Patient 2). Unexpectedly, an influenza-like illness (ILI) is also caused in Patient 3 having close contact with Patient 1 at personal dinner party. Combined with clinical and epidemiological study, chest computed tomography (CT) and molecular diagnosis demonstrate that all the three cases tested positive for COVID-19 with distinct symptoms by human-to-human transmission. To the best of knowledge, it closes in part (if not all), a missing gap of clinical repertoires of COVID-19 outbreaks and underlines the possibility that neglection of cryptic/asymptomatic/mild cold-like syndromes gives biased screen in the earlier stage of COVID-19 cases.

One of the most used markers of cancer stem cells in several cancers, including colorectal cancer and breast cancer, is CD44. CD44 is a glycoprotein that traverses the cell membrane and binds to many ligands including hyaluronan resulting in activation of signaling cascades. Several reports have shown conflicting data on the expression of CD44 and that the expression depends on modes of investigations and subtypes of cancers. In addition, the correlation between CD44 expression and drug resistance, immune infiltration, EMT, metastasis and patients prognosis in several cancer types remains unclear. This study investigated CD44 expression in several cancers and explored its relationship with tumorigenesis using various publicly available databases, including The Cancer Genome Atlas, GEPIA, Oncomine, Genomics of Drug Sensitivity in Cancer and Tumor Immune Estimation Resource. Our analysis reveals that CD44 is differentially expressed in different cancers. CD44 expression is significantly associated with cancer patients’ survival in gastric, pancreatic and colorectal cancers. In addition, CD44 expression is closely linked with immune infiltration and immune suppressive features in pancreatic, colon adenocarcinoma and stomach cancer. High CD44 expression was significantly correlated with the expression of drug resistance-, EMT- and metastasis- linked genes. Tumors expressing high CD44 have higher mutation burden and afflict older patients than tumors expressing low CD44. Cell lines expressing high CD44 are more resistant to anti-cancer drugs compared to those expressing low CD44. Protein-protein interaction investigations and functional enrichment analysis showed that CD44 interacts with gene products related to cell-substrate adhesion, migration, platelet activation, and cellular response to stress. KEGG pathway analysis revealed that these genes play key roles in biological adhesion, cell component organization, locomotion, G-α-signaling and the response to stimulus. Overall, this investigation reveals that CD44 play significant roles in tumorigenesis, can be used as a prognostic biomarker in several cancers and can be therapeutically targeted in cancer therapy.

We present and benchmark FilterNet, a flexible deep learning architecture for time series classification tasks, such as activity recognition via multichannel sensor data. It adapts popular CNN and CNN-LSTM motifs which have excelled in activity recognition benchmarks, implementing them in a many-to-many architecture to markedly improve frame-by-frame accuracy, event segmentation accuracy, model size, and computational efficiency. We propose several model variants, evaluate them alongside other published models using the Opportunity benchmark dataset, demonstrate the effect of model ensembling and of altering key parameters, and quantify the quality of the models’ segmentation of discrete events. We also offer recommendations for use and suggest potential model extensions. FilterNet advances the state of the art in all measured accuracy and speed metrics on the benchmarked dataset, and it can be extensively customized for other applications.

The Standard Model (SM) fails to account for either the triplication of fermion families or chiral symmetry breaking in the electroweak sector. Here we show that both phenomena arise from the approach to chaos of quantum theory near the Fermi scale.

Aurora kinase A (AURKA) is a normal cell proliferation-inducing enzyme encoded by AURKA gene, with over-expression observed in different types of malignancies. Hence, the goal is to find potential inhibitors against AURKA. In this study, molecular docking, Standard Precision and Extra Precision methods were employed. After the docking study, the ligands showed an extremely low binding score which suggested very high binding affinity of the ligands. Furthermore, Quantum polarized ligand docking (QPLD) was performed to predict the binding status of the molecules. Based on the binding affinity, the top four compounds were chosen for further analysis. The docked complexes were further analyzed in explicit water conditions using 100 ns molecular dynamics simulations and binding free energy calculation. Then, density functional theory (DFT) calculation was used to calculate the molecular properties of the molecules. Finally, systems biology experiments validated the molecular docking and molecular dynamics simulation studies and indicated that quercetin, kaempferol, luteolin and rutin could inhibit the AURKA. The results show that, these four molecules have high binding affinity to the AURKA and significant interactions (LEU139, GLU211and ALA213) were also identified with the hinge region of Aurora kinase A. Thus, LEU139, GLU211, and ALA213 were identified as the crucial protein mechanisms.

After proving, in a purely categorial way, that the inclusion functor InAlg(Σ) from Alg(Σ), the category of many-sorted Σ-algebras, to PAlg(Σ), the category of many-sorted partial Σ-algebras, has a left adjoint FΣ, the (absolutely) free completion functor, we recall, in connection with the functor FΣ, the generalized recursion theorem of Schmidt, which we will also call the Schmidt construction. Next we define a category Cmpl(Σ), of Σ-completions, and prove that FΣ, labeled with its domain category and the unit of the adjunction of which it is a part, is a weakly initial object in it. Following this we associate to an ordered pair (α,f), where α=(K,γ,α) is a morphism of Σ-completions from F=(C,F,η) to G=(D,G,ρ) and f a homomorphism in D from the partial Σ-algebra A to the partial Σ-algebra B, a homomorphism ΥαG,0(f):Schα(f)B. We then prove that there exists an endofunctor, ΥαG,0, of Mortw(D), the twisted morphism category of D, thus showing the naturalness of the previous construction. Afterwards we prove that, for every Σ-completion G=(D,G,ρ), there exists a functor ΥG from the comma category (Cmpl(Σ)↓G) to End(Mortw(D)), the category of endofunctors of Mortw(D), such that ΥG,0, the object mapping of ΥG, sends a morphism of Σ-completion in Cmpl(Σ) with codomain G, to the endofunctor ΥαG,0.

This article discusses how, in today’s world of disruptive and dramatic social change (DSC), non-sports related coaching, which includes a wide range of services such as life coaching, career coaching, executive coaching, and team coaching, can inadvertently fuel undesirable social dynamics. There is little or no awareness of this risk among coaches and coachees. The global, fast-growing, multi-billion-dollar industry aimed at supporting people and organisations to perform better and increase wellbeing while managing and adapting to change has been developed with limited sociological input. The article is based on 15 years of social constructionist-informed reflective practice by a sociologist-turned-coach, and uses a multi-layered autoethnographic account to argue for a sociologically informed paradigm shift in coaching, as well as relevant sociological knowledge and social and human sciences research methodology in coaches’ education. It presents the rationale and key features of a new coaching approach that places DSC-relevant sociological concepts at the heart of the coaching process, helps people develop psycho-sociological awareness, and uses a learning-to-develop through research design. A new definition of coaching to address DSC is derived. Coaching practitioners will find DSC-relevant sociological concepts, critical reflections, coaching questions, and procedures to expand coaching effectiveness. Interdisciplinary research topics combining coaching sociology and coaching psychology are suggested.

The Betz limit sets a theoretical upper limit for the power production by turbines expressed as a maximum power coefficient of 16/27. Betz’s theory is accurate and it is based on the calculation of kinetic energy.

Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. COVID-19 mRNA vaccines would not escape this rule. Unfortunately, the degree of inflammation produced by these vaccines is variable, probably depending on the genetic background and previous immune experiences, which through epigenetic modifications, could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V).

Pain is a major problem in sick newborn infants, especially for those needing intensive care. Pharmacological pain relief is the most commonly used but may be ineffective, have side effects, including long-term neurodevelopmental sequelae. The effectiveness and safety of alternative analgesic methods are ambiguous. The objective is to review the effectiveness and safety of non-pharmacological methods of pain relief in newborn infants and to identify those that are the most effective. PubMed and Google Scholar were searched using the terms: ‘infant’, ‘premature’, ‘pain’, ‘acupuncture’, ‘skin to skin contact’, ‘sucrose’ ‘massage’, ‘musical therapy’ and ‘breastfeeding’. We included 24 studies assessing different methods of non-pharmacological analgesic techniques. Most resulted in some degree of analgesia but many were ineffective and some were even detrimental. Sucrose, for example, was often ineffective but more effective than music therapy, massage, breast milk (for extremely premature infants) or non-invasive electrical stimulation acupuncture. There were also conflicting results for acupuncture, skin to skin care and musical therapy. Most non-pharmacological methods of analgesia provide some modicum of relief for preterm infants but none are completely effective and there is no clearly superior method. Study is also required to assess potential long-term consequences of any of these methods.

More than half a century has passed since the discovery of the genetic code, but its origin is still one of the greatest mysteries in life science, although a plenty of theories have been proposed so far, as none can explain satisfactorily why the genetic code evolved in such a way, especially in the context of the biochemical system, a relation of part to whole. Here, a new hypothesis is proposed, according to which ATP is at the origin of the genetic code by its coevolution with the pristine biochemical system of the protocell. This hypothesis shows how primitive life with its genetic code emerged through a series of processes from energy flow to information communication mediated by ATP. First, ATP is the only energetic product of photosynthesis, and is at the energetic heart of the extant biochemical systems. Second, ATP serves as not only an energy carrier but also an informatization molecule, as ATP could energetically elongate chains of both polynucleotides and polypeptides, thus providing a bridge between these molecules and eventually mediating biochemical innovation in the protocell from energy transformation to informatization, a process for creating and managing information. Informatization was inevitably coupled with structuralization (processes for organizing or incorporating cellular structures), cyclizing polynucleotides and polypeptides into a feedback loop of reciprocal causation. The triplet codon might be only for stereochemical handling of amino acids through, e.g., Watson–Crick pairing interactions. It is only the evolutionary completion of the genetic code from RNA to DNA that, contrary to the central dogma, marked the dawn of cellular life, when Darwinian evolution began to operate. The ATP hypothesis sheds light on the origin of life, together with the formation of both photosynthetic and biochemical systems, which remains largely unknown thus far.