Recently, the medical image processing is extensively used in several areas. In earlier detection and treatment of these diseases is very helpful to find out the abnormality issues in that image. Here there are number of methods available for segmentation to detect the lung nodule of computer tomography (CT) image. The main result of this paper, the earlier detection of lung nodules using Pre-processing techniques of top-hat transform, median and adaptive bilateral filter was compared both filtering methods and proved the adaptive bilateral filter is suitable method for CT images. The proposed segmentation technique uses novel strip method and the image is split into number of strips 3, 4, 5 and 6. A marker- watershed method based on PSO and Fuzzy C-mean Clustering method was proposed method. Firstly, the input image was reduced noise reduction and smoothing and the filter image is using strips method and then the image is segmented by marker watershed method. Secondly, the enhanced PSO technique was used to locate the better accurate value of the clustering centers of Fuzzy C-mean Clustering. Final stage, with the accurate value of centers and the enhanced target function and the small region of the segmented object was clustered by Fuzzy C-mean. In segmentation algorithm presented in this paper gives 95% of accuracy rate to detect lung nodules when strip count is 5.

When present in specific amounts in the air, the colorless, odorless, and tasteless gases monoxide and carbon dioxide may either replace oxygen in red blood cells (CO) or increase the respiratory rate causing cardiac arrhythmias (CO2), leading to death. Commercial sensors take around 8 h to detect levels of CO (50 PPM), causing moderate poisoning. SnO2 presents controlled interactions with the atmosphere using conductance and vacancy adjustments to capture electrical properties. However, the selectivity of gas detection by SnO2 can still be improved, thus also increasing the application possibilities. The present study aimed to optimize the sensing of CO and CO2 in SnO2 using palladium functionalization. The vapor-liquid-solid method synthesized a network of SnO2 nanobelts decorated with palladium nanoparticles. The sensitivity of the sensors for CO and CO2 were evaluated, characterizing parameters such as response time, a wide range of CO and CO2 concentrations, and temperature. In the seventh measurement cycle, the sensor response for different concentrations of gases in consecutive cycles showed a sensitivity of up to 125% for CO in 60 s. Furthermore, we observed increased sensor sensitivity with material doping with nanoparticles from 130 ppm to 1360 ppm in 30 seconds to CO. Conclusion: The results provide a better understanding of the sensitivity of SnO2 in palladium-decorated nanoparticles, offering insights for detecting low CO concentrations quickly. The behavior of these doped nanosensors showed us the importance of considering them as a practical possibility for detecting these gases of importance to human health.

Members of the insect ATP binding cassette transporter subfamily C2 (ABCC2) in several moth species are known as receptors for the Cry1Ac insecticidal protein from Bacillus thuringiensis (Bt). Mutations that abolish the functional domains of ABCC2 are known to cause resistance to Cry1Ac, although the reported levels of resistance vary widely depending on insect species. In this study, the function of the ABCC2 gene as putative Cry1Ac receptor in Helicoverpa zea, a major pest of over 300 crops, was evaluated using CRISPR/Cas9 to progressively eliminate different functional ABCC2 domains. Results from bioassays with edited insect lines support that muta-tions in ABCC2 was associated with Cry1Ac resistance ratios (RR) ranging from 7.3- to 39.8-fold. No significant differences in susceptibility to Cry1Ac were detected between H. zea with partial or complete ABCC2 knockout, although highest levels of tolerance were observed when knocking out half of ABCC2. Based on >500-1,000-fold RRs reported in similar studies for closely related moth species, the low RRs observed in H. zea knockouts support that ABCC2 is not a major Cry1Ac receptor in this insect.

Selecting drought-tolerant and more water-efficient wheat genotypes is a research priority, spe-cifically in regions with irregular rainfall or areas where climate change is expected to result in reduced water availability. The objective of this work was to use high-throughput measurements with morphophysiological traits to characterize wheat genotypes in relation to water stress. Field experiments were conducted from May to September 2018 and 2019, using a sprinkler bar irriga-tion system to control water availability to eighteen wheat genotypes: BRS 254; BRS 264; CPAC 01019; CPAC 01047; CPAC 07258; CPAC 08318; CPAC 9110; BRS 394 (irrigated biotypes) and Aliança; BR 18_Terena; BRS 404; MGS Brilhante; PF 020037; PF 020062; PF 120337; PF 100368; PF 080492; TBIO Sintonia (rainfed biotypes). The water regimes varied from 22 to 100% of the crop evapotranspiration replacement. Water stress negatively affected gas exchange, vegetation indices and grain yield. High throughput variables TCARI, NDVI, OSAVI, SAVI, PRI, NDRE and GNDVI had higher correlation with yield and morphophysiological measurements. The drought re-sistance index indicated that genotypes Aliança BRS 254, BRS 404, CPAC 01019, PF 020062, and PF 080492 were more drought tolerant.

Water is an essential commodity to sustain life. The condition of water in Tiruchirappalli was measured using different Physicochemical parameters like Temperature, pH, TDS, Total Solids, Salinity, Total Hardness, and Electrical Conductivity. Water samples were collected from different places in Tiruchirappalli city, Tamil Nadu. Water samples were examined by different chemical methods. According to the results, Thiruvarambur-1 showed comparatively higher results in the case of every parameter compared to other sampling stations. Obtained results were further interpreted using statistical tools. Considering ECs as a principal component for the regression and correlation analysis with other parameters significant correlation was found. A strong correlation was observed between ECs and TDS, Total Hardness, Turbidity, and Salinity.

Recently, microfluidics deformability cytometry has emerged as a powerful tool for high throughput mechanical phenotyping of large populations of cells. These methods characterize cells by their mechanical fingerprints through exerting hydrodynamic forces and monitoring the resulting deformation. These devices have shown great promise for label free cytometry, yet there is a critical need to improve their accuracy and reconcile any discrepancies with other methods, such as atomic force microscopy. In this study, we employ computational fluid dynamics simulations and uncover how the elasticity of frequently used carrier fluids such as methyl-cellulose dissolved in phosphate-buffered saline is significantly influential to the resulting cellular deformation. We conducted CFD simulations that are conventionally used within the deformability cytometry field, which neglect fluid elasticity. Subsequently, we incorporated a more comprehensive model that simulates the viscoelastic nature of the carrier fluid. A comparison of the predicted stresses between these two approaches underscores the significance of the emerging elastic stresses in addition to the well-recognized viscous stresses along the channel. Furthermore, we utilize a two-phase flow model to predict the deformation of a promyelocyte (i.e. HL-60 cell type) within a hydrodynamic constriction channel. The obtained results highlight a substantial impact of the elasticity of carrier fluid on cellular deformation and raise questions about the accuracy of mechanical property estimates derived by neglecting elastic stresses.

The study of coherent vortices remains an urgent field of singular optics of vortex beams. In this paper, coherent properties of partially coherent vortex Bessel—Gaussian optical beams propagating through a uniform medium (free space) or a turbulent atmosphere are examined theoretically. The consideration is based on analytical solution of the equation for the transverse second-order mutual coherence function of the field of a partially coherent optical radiation in a turbulent atmosphere. For the partially coherent Bessel—Gaussian beam, the second-order mutual coherence function of the source field is taken as a Gaussian Shell-model. In this approximation, we analyze the behavior of the coherence degree and the integral coherence scale of these beams as a function of the propagation pathlength, propagation conditions, and beam parameters, such as the radius of the Gauss factor of the beam, parameter of the Bessel factor of the beam, topological charge, and correlation width of the source field of partially coherent radiation. In addition, the integral coherence scale of the partially coherent vortex Bessel—Gaussian beam is compared with that of the partially coherent Gaussian beam. It is found that as a partially coherent vortex Bessel—Gaussian beam propagates through a turbulent atmosphere, there appear not two (as might be expected: one due to atmospheric turbulence and another due to partial coherence of the source field), but only one ring dislocation of the coherence degree (due to the simultaneous effect of both these factors on the optical radiation). In addition, it is shown that the dislocation of the coherence degree that affects significantly the beam coherence level is formed only for beams, for which the coherence width of the source field is larger than the diameter of the first Fresnel zone.

All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval >21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

Psoralens have been used in the treatment of several skin diseases such as psoriasis and atopic eczema through PUVA (psoralen + UVA), cutaneous T-cell lymphoma through ECP (extracorporeal photochemotherapy), and recently, the treatment of solid tumors through X-PACT (x-ray psoralen activated cancer therapy). Ingesting psoralens and exposing the molecules to UVA light allows for the flat-planar psoralens to intercalate or slide in-between base pairs and then to form photo-adducts with the DNA backbone which can stop or slow DNA replication. The intrinsic ability of psoralens to bind with DNA and their therapeutic effectiveness contribute to the increased interest in the study of these molecules. Several studies measuring psoralen-DNA binding capabilities have used a variety of spectroscopic techniques and different experimental conditions. In this study, spectrofluorometry was used to measure the DNA-binding capabilities of three different psoralen derivatives (6E, AMT and 8-MOP) under identical experimental conditions. The binding constants were 0.325x106 M-1 for 8-MOP, 0.516x106 M-1 for AMT, and 7.30x106 M-1 for 6E. This direct comparison of the three different psoralens demonstrated the impact of their molecular structure on the DNA-binding capacity. 6E’s significantly greater binding constant makes it the stronger candidate for further studies looking into potential applications for cancer treatment.

Policing is considered a high-stress occupation due to the demanding nature of the job. Addressing police stress requires a detailed understanding of how psychosocial risk factors influence various aspects of their well-being. Moreover, an analysis of the direct effects of work conditions and the mediating effects of cognitive appraisals is also warranted. Using the Demands-Resources-Individual Effects (DRIVE) model of work-related stress [19], this study investigated the direct effects of work conditions on well-being and also examined the intermediate role of perceived job stress and job satisfaction in the relationship between work conditions and well-being. Five hundred and seventy-eight police officers from the Jamaica Constabulary Force (J.C.F.) completed the questionnaire. Data were analyzed using hierarchical regressions and the Hayes Process tool for mediation analysis. Both perceived job stress and satisfaction mediated the relationship between work conditions and general physical health. Perceived job stress was an indirect pathway through which work conditions influenced psychological distress, whereas job satisfaction was not a significant mediator. In contrast, job satisfaction mediated the relationship between work conditions and positive well-being, but perceived job stress did not. These findings provide significant evidence for periodically monitoring and auditing perceptions of stress and job satisfaction as they are likely precursors to subsequent health problems.

Shared micromobility has gained significant attention in the field of transportation engineering in recent years as an environmentally friendly, convenient, and easily accessible transportation mode. Like other medium-sized cities, Birmingham, Alabama implemented a shared micromobility pilot program in 2021 that captured the attention of local travelers. This study examined shared e-scooter usage and associated travel patterns in Birmingham using 2021-2022 field data. From these data, ArcGIS maps were used to showcase trip origins and destinations. To gain a further understanding of e-scooter travel patterns in the study area, zip code and block group densities were calculated. Additionally, a negative binomial regression model was constructed to identify determinants of shared e-scooter trips. The analysis results showed that the usage of shared e-scooters was the highest during the nighttime, on weekends, and in the fall season. Furthermore, the research findings indicated that shared e-scooters experienced their highest utilization rates in areas with a higher proportion of educated and higher-income individuals. These findings suggest that travelers’ mode choice related to the use of micromobility modes is influenced by environmental and demographic factors. Overall, this case study offers valuable contributions to the understanding of the role of shared e-scooters in Birmingham's transportation landscape and can guide transportation authorities in other medium-sized cities in their efforts to plan for micromobility options.

A recent study has suggested that the age profiles for deaths due to COVID-19 variants differs between variants and shows male/female specificity. This study demonstrates the age and sex dependency is common among human pathogens. The often-reported higher susceptibility to infections among the young and elderly is true in general but does not apply to individual pathogens. Even among different types of pneumonia there are subtle differences in the age profile. The gender ratio between pathogens likewise shows wide variation from as low as 10% female admissions for leptospirosis to around 90% for gonococcal admissions. The observed age/sex variation observed for mortality due to COVID-19 variants is an expression of a far wider phenomenon with implications to the age/sex response to vaccines. We propose that such differences are likely to be controlled by small noncoding RNAs which act as potent regulators of gene expression leading to altered cell morphology, metabolism, immune function, and response to vaccines.

This paper focuses on the relationship between Mental Health and the Landscape. It aims to find out how people respond to Biophilic inspired landscape design in a healthcare setting. The focal point is not to cure diseases but to help them deal with the physiological, psychological, and psycho-social imbalance and provide a healing environment for the overall well-being of an individual. For this study, a Multispecialty Hospital was selected where an Indoor Healing Garden is used as a retrofitting tool to reduce stress and thus reconnect humans with nature. A multi-method approach is being used for this study. Initially, a questionnaire was conducted for the targeted users categorized into three types – patients, staff, and visitors to know their longing for the landscape. Based on this data and available literature, an evidence-based design was proposed. This conceptual design model is then shown to the targeted user and the response is recorded. The data has then collaborated with similar studies done earlier and design elements are highlighted which helps in creating a restorative environment by reducing stress and increasing recovery rate and thus approaching sustainable development.

Spondyloptosis is a condition where there is complete dislocation of L5 over sacrum. It is a form of spinal dislocation in which one spinal segment is lodged in the anterior or posterior space of another or advanced spondylolisthesis [1]. Treatment is usually spinal fusion depending on the level of lesion [2]. This clinical case is of a 15 year old male with a history of fall from auto-rickshaw followed by a blunt trauma from a heavy iron rod falling over his abdomen. There was no history of loss of consciousness, but the patient had an excruciating pain over back immediately after the incident. Patient is now paraplegic with loss of sensation below L5 along with loss bladder and bowel control since the time of injury. The T1 weighted MRI of spine revealed grade 5 anterior lysthesis of L5 over S1 level with complete spinal cord transaction. The patient was operated to restore the vertebral alignment with pedicle screws and rods. After 3 months, patient is now treated for neuro-musculoskeletal , genitourinary and genitointestinal function with biofeedback, pelvic floor exercises and timed voiding [3]. When a patient has issues with urine retention, Valsalva manoeuvres, Crede's method, suprapubic tapping, and anal stretching are employed to help them void more effortlessly [4].

Systematic results of lattice dynamical calculation are reported for the novel (SiC)m/(GeC)n superlattices (SLs) by exploiting a modified-linear chain model (M-LCM) and a realistic rigid-ion- model (RIM). By employing the bond polarizability method in the framework of M-LCM, we have simulated Raman intensities for the graded (SiC)10-D/(Si0.5Ge0.5C)D/(GeC)10-D/(Si0.5Ge0.5C)D SLs by carefully integrating interfacial layer thickness D (≡ 0, 1, 2, 3 monolayers (MLs)). The variation of D has initiated considerable up (down) shifts of GeC-, (SiC)-like Raman peaks in the middle of the optical phonon frequency region. With D = 3 MLs, the maximum energy shift (by ~ 47 cm-1) of SiC-like modes has caused substantial changes in the Raman intensity profiles linked to the localization of atomic displacements at the interfacial transition regions. This effect can be considered as a vital tool for authenticating the interfacial structures in technologically important SLs. By using a RIM, we have reported SL phonon dispersions along the growth [001] as well as in the plane [100], [110] perpendicular to the growth. Our simulations of phonons in the acoustic mode region have not only confirmed the formation of minigaps at the zone center and zone edges but also provided evidence of anti-crossing and phonon confinement. Besides examining angular dependence of zone-center optical modes, we have also discussed phonon folding, confinement and anisotropic behavior in (SiC)m/(GeC)n SLs.

According to data from the U.S FDA, the likelihood of a new drug progressing from Phase I clinical trials to market approval is only 8% (DiMasi et al., 2016). Furthermore, a significant attrition rate of 35% occurs during Phase II studies due to the failure to demonstrate clinical efficacy (Arrowsmith, 2011). These statistics underscore the urgent need to reassess the current research and development (R&D) paradigm. To address this challenge, a promising approach called reverse translational pharmacology (RTP) has emerged, aiming to enhance the predictive value of preclinical models used in biomedical research by leveraging animal models that spontaneously develop analogous diseases to humans (Schneider et al., 2018). The rationale behind RTP is that knowledge gained from clinical trials in canines can subsequently inform and guide human clinical trials, leading to improved outcomes for both species. Additionally, this approach capitalizes on the opportunity to stimulate veterinary drug development by leveraging pharmacokinetic (PK), efficacy, and safety data obtained from human clinical studies (Schneider et al., 2018). The application of reverse translational pharmacology holds immense potential for expediting drug development and advancing medical knowledge. By employing animal models that naturally develop diseases akin to those found in humans, researchers can enhance the predictive capacity of preclinical models, thereby mitigating the high attrition rates encountered in later stages of clinical trials. Moreover, the exchange of knowledge and data between human and veterinary medicine engenders a synergistic relationship, fostering progress in both domains (Schneider et al., 2018). As this innovative approach gains momentum, fostering collaborations between basic and clinician scientists, pharmaceutical companies, and veterinary professionals becomes increasingly imperative. By sharing resources, expertise, and findings, we can pave the way for groundbreaking discoveries and the development of safe and efficacious treatments for diverse diseases. Embracing reverse translational pharmacology offers an avenue to redefine the R&D paradigm, bringing us closer to a future where a higher proportion of drugs successfully traverse the arduous path from the laboratory to market approval, ultimately benefiting patients across species. In this brief commentary, we highlight four examples of diseases where reverse translational modeling has been used to support pharmaceutical research, including some applications developed in our research laboratory (SMART Pharmacology) at the Iowa State University College of Veterinary Medicine. In doing so, this report also seeks to provide a brief overview of the heuristic value of computational approaches in comparative research. To further illustrate the value of these in silico approaches, we deliberately chose to employ some features of ChatGPT to produce the present summary (OpenAI. (2023). GPT-3.5 [ChatGPT]. Retrieved from https://openai.com).

This paper discusses about the quantum energy levels of muonic hydrogen considering only Coulomb interaction. The computational analysis in this paper will help the reader get a good understanding of how different a muonic hydrogen is from its electronic counterparts. Energy eigenvalues are calculated by numerical method and the probability density distribution of muon around the nucleus is plotted for different quantum states using special functions. The code is written in python. A comparative study of emission spectra between the muonic hydrogen and hydrogen has also been discussed.

Since 2020 COVID-19 has caused serious mortality around the world. Given the ambiguity in es-tablishing COVID-19 as the direct cause of death we first investigate the effects of age and sex upon all-cause mortality during 2020 and 2021 in England and Wales. Since infectious agents have their own unique age profile for death, we explore several methods to adjust single year of age deaths in England and Wales during 2019 (the pre-COVID-19 base year) to a pathogen-neutral single year of age baseline. This adjusted base year is then used to confirm the widely reported higher deaths in males for most ages above 43 years in both 2020 and 2021. During 2020 (+ COVID-19 but no vac-cination) both male and female population-adjusted deaths were significantly increased above age 35. A significant reduction in all-cause mortality among both males and females aged 75+ could be demonstrated in 2021 during widespread COVID–19 vaccination, however, below age 75 deaths progressively increased. This finding arises from a mix of vaccination and year of age profiles of deaths for the different SARS-CoV-2 variants. In addition, specific effects for age around puberty were demonstrated where females had higher deaths rather than males. There is evidence that year-of-birth cohorts may also be involved, indicating that immune priming to specific pathogen outbreaks in the past may lead to lower deaths for some birth cohorts. To specifically identify the age profile for the COVID-19 variants in 2020 to 2023, we employ the proportion of total deaths at each age which are potentially due to or ‘with’ COVID-19. The original Wuhan strain, and the Alpha variant show somewhat limited divergence in the age profile with the Alpha variant shifted to a moderately higher proportion of deaths below age 84. The Delta variant specifically targeted persons below age 65. The Omicron variants showed significantly lower proportion of overall mortality, with markedly higher relative proportion of deaths above age 65 steeply increasing with age to a maximum around 100 years of age. A similar age profile for the variants can be seen in the age-banded deaths in US states – although slightly obscured by using age bands rather than single year of age. However, the US data shows that higher male deaths are greatly dependent on age and the COVID-variant. Deaths determined as ‘due to’ COVID-19 (as opposed to ‘involving’ COVID-19) in England and Wales were especially over-estimated in 2021 relative to the change in all-cause mortality. This arose as a by-product of an increase in COVID-19 testing capacity in late 2020. Potential structure-function mechanisms for the year of age specificity of SARS-CoV-2 var-iants are discussed. The question is posed as to whether vaccines based on different variants carry the specific age profile through into the vaccine.

In the paper, we explore the notion of global digital citizenship, particularly with respect to museums and cultural heritage organizations. In this perspectives study, we explore current examples of how museums can adapt to the tenets of global digital citizenship necessary to navigate and participate in increasingly interconnected digital worlds and culture, and to collectively address global challenges.

All vaccines exhibit both specific and non-specific effects. The specific effects are measured by the efficacy against the target pathogen, while the non-specific effects can be detected by the change in all-cause mortality . All-cause mortality data (gender, age band, vaccination history, month of death) between January 2021 and May 2022 was compiled by the Office for National Statistics. COVID–19 vaccination gave good protection on many occasions but less so for younger ages. Each gender and age group shows its own unique vaccination benefit/disbenefit time profile. Individuals are free to make vaccination decisions. For example, women aged 18-39 show a cohort who do not progress beyond the first or second dose. The all-cause mortality outcomes for the Omicron variant showed a very poor response to vaccination with 70% of sex/age/vaccination stage/month combinations increasing all-cause mortality, probably due to unfavorable antigenic distance between the first-generation vaccines and this variant, and additional non-specific effects. The all-cause mortality outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated, and virus vector appear better than the mRNA vaccines in this specific respect. The latter are seemingly more likely to increase all-cause mortality especially in younger age groups. An extensive discussion/literature review is included to provide potential explanations for the observed unexpected vaccine effects.

The evaluation of the possibility of obtaining dihaploids by the method of anther culture in vitro to accelerate selection for resistance to prolonged flooding of seeded rice with water was carried out. The object of research is rice hybrids F2 of the Rice Breeding and Seed Production Laboratory of the “Donskoy” ASC, obtained as a result of interbreeding the best economically valuable varieties with samples bearing genes of resistance to prolonged flooding with water. Basic nutrient medium with an optimal composition of nutrition elements and growth hormones stimulating callo- and morphogenesis were used. For the induction of callus formation, 12604 anthers were planted, according to 26 hybrid combinations represented by 68 plants, as a result, 716 neoplasms were obtained, including 586 non–morphogenic callus, 130 regenerating plants. Cultivation of anthers revealed large genotypic differences in the samples. According to the responsiveness to neoplasms, 60% of the panicles showed a positive result, the rest did not give callus. The most responsive to the formation of callus were hybrid combinations: 5009/2 – 84 pcs., 5010/2 – 94 pcs., 4565/3 – 85 pcs., 4641/2 – 69 pcs. They also showed the ability to morphogenesis. Androgenic plants were obtained by 14 hybrid combinations, their share was 1.03% of the total number of inoculated anthers. 30 green regenerative lines from four rice hybrids were obtained, differing in visual morphological assessment: 5009/2 - 5 pcs., 5010/2 – 5 pcs., 4565/3 – 2 pcs., 4641/2 – 18 pcs. The isolated lines are characterized by good responsiveness in the culture of anthers in vitro, carry genes for resistance to prolonged flooding, and can be used in rice breeding programs using DG technologies.

Ovarian cancers are curable by surgical resection when discovered early enough. Unfortunately, most ovarian cancers are diagnosed in the later stages. One strategy to identify early ovarian tumors is to screen women who have the highest risk scores. This mini review summarizes the accuracy of different methods used to assess the risk of developing ovarian cancer, including family history, BRCA genetic tests, and polygenic risk scores. The accuracy of these is compared to the maximum theoretical accuracy, revealing a substantial gap. We suggest that this gap, or missing heritability, could be caused by epistatic interactions between genes. An alternative approach to computing genetic risk scores, using chromosomal-scale length variation should incorporate epistatic interactions. Future research in this area should focus on this and other alternative methods of characterizing genomes.

The article presents the results of a morpho-physiological assessment of rice samples by the strength of growth, as well as an assessment of the degree of development of the conducting system of the flag leaves of rice plants. The resistance of varieties to flooding is very relevant in the fight against weeds due to the deep layer of water that weeds cannot overcome. Currently, there are no zoned varieties in Russia that would meet these requirements. Therefore, the problem of creating such rice varieties is urgent, as it will reduce production costs, reduce grain losses during harvesting, improve the quality of the products obtained, and also reduce the pesticide load on the ecosystem. As a result of research, a number of studied samples revealed the potential to quickly lengthen the first leaves, overcome a large layer of water and accumulate vegetative mass. As a result of the evaluation of the conducting system of the flag leaf of rice plants, it was found that in plants with the flood resistance gene Sub1A, which stops growth under water, the conductive beams were smaller in comparison with other fast-growing samples with the AG, Sk genes. Consequently, fast-growing samples have bigger sizes of the conducting system as a resistance mechanism.

Nitrogen fertilization ensures the proper growth of trees. The aim of the study was to evaluate the impact of differentiated nitrogen fertilization on selected parameters. It was assumed that such analysis is an indirect picture of the needs of cherries grown in herbicide fallow. The content of minerals in two layers of the soil, in leaves, and its influence of tree growth, and the content of chlorophyll in leaves were assessed. The experiments were carried out in three different cherry orchards. Three levels of fertilization were applied in each orchard: 0 kg, 60 kg and with 120 kg N ha- 1. As expected the fertilization resulted in an increase in the content of nitrate and ammonium forms of nitrogen in the soil, however, their content was also dependent on precipitation and temperature. Additionally a high nitrogen fertilization increased the content of phosphorus and potassium and decreased the magnesium in the topsoil layer. High nitrogen fertilization caused the decrease of content of phosphorus and potassium in the leaves. The level of calcium and magnesium in leaves increased with fertilization of 60 kg N ha–1 but decreased with the dose to 120 kg N ha–1. The use of nitrogen fertilization increased the vegetative growth of trees measured by leaf area and trunk cross-sectional area. However, the chlorophyll content was not dependent on the amount of nitrogen fertilization.

This paper responds to the research question, “can urban farming help Nepali cities become more sustainable”? Especially after the Covid-19 pandemic, urban residents have begun to realize that food transported from long distances could not always be reliable. Urban farming can help produce fresh food locally and avoid long-distance transportation, and refrigeration. This practice also helps reduce greenhouse gases through plant carbon use efficiency (CUE). Urban farming not only helps city-dwellers towards achieving self-reliance in food production but also in vegetation carbon dynamics (VCD) while supporting the circular economy. Urban farming consists of edible landscapes, which can also be an aesthetic public space. As urban lands command higher prices than agricultural land, urban farming usually happens on residential yards, roofs, balconies, community gardens, and dedicated areas in public parks. Rainwater harvesting, and redirecting can help irrigate urban farms which can be part of rain gardens. The national census of 2021 (CBS 2022, p5) identifies that 66 percent of Nepal’s population live in urban areas. However, the World Bank (2018), shows that only 21 of Nepal’s population was projected to live in urban areas in 2021. It is not debatable that the urbanization process in Nepal is on the rise. Thus, urban agriculture can play an important role to supplement the residents’ food needs. Many cities in Nepal have already successfully adapted to urban farming where residents grow food on their building site, balconies, and rooftop often growing plants on pots, vases, and other types of containers. The UN-Habitat, with the support of European Union and local agencies, has published a rooftop farming training manual (2014) showing the feasibility of urban farming in Nepal.The paper discusses how Public Private Partnership (PPP) can promote urban agriculture and make the process more effective and attractive to urban farming households. It also analyzes how a PPP approach also facilitates the use of better technology, advisory support, and use of research extension activities. This paper draws on literature review, secondary data (e.g., from National Census Nepal 2021) and authors’ professional experiences related to best practices in the areas to analyze the benefits and challenges related to urban farming in Arizona, USA. The paper will provide recommendations for Nepali cities to maximize the benefit provided by urban farming. It is expected to be useful to Nepali policy makers, and government agencies, and nonprofit organizations which promote sustainability, and organic farming.

This paper looks at key elements of global culture that are driving a new paradigm shift in museums causing them to question their raison d'être, their design and physical space, recognizing the need to accommodate visitor interaction and participation, and to reprioritize institutional outcomes and goals reexamining their priorities. As heritage sharing in online spaces reaches across national, political, and social boundaries on platforms and networks, this has been driven by museum engagement with Internet life during the pandemic. Museum relationships and interactions with communities both local and global, continue to challenge core values and precepts, leading to radical changes in how museums define their roles and responsibilities. In this new cultural landscape, museums are responding to human digital identity in a tidal wave of human interactions on the Internet, from social media to online sharing of images and videos. This is revealing shared perspectives on cultural conflict as being tied to freedom of expression of one’s heritage embedded in digital identity.

The term STODS (Surgical Temporary Ocular Discomfort Syndrome) has been coined to describe the ocular surface perturbations induced by surgery. As one of the most important refractive elements of the eye, Guided Ocular Surface and Lid Disease (GOLD) optimization is fundamental to success in achieving refractive outcomes and mitigating STODS. Effective GOLD optimization and the prevention/treatment of STODS, requires an understanding of the molecular, cellular and anatomic factors that influence ocular surface microenviroment and the associated perturbations induced by surgical intervention. By reviewing the current understanding of STODS etiologies, we will attempt to outline a rationale for a tailored GOLD optimization depending on the ocular surgical insult. With a bench to bedside approach, we will highlight clinical examples of effective GOLD perioperative optimization can mitigate STODS deleterious effect on preoperative imaging and postoperative healing.

Low-lying coastal communities are often threatened by compound flooding (CF), which can be determined through the joint occurrence of storm surges, rainfall and river discharge either successively or in close succession. The trivariate distribution can demonstrate the risk of the compound phenomenon more realistically rather than considering each contributing factor independently or in a pairwise dependency. Recently vine copula has been recognized as the highly flexible approach to constructing a higher dimensional joint density framework. In such construction, parametric class copula with parametric univariate marginal distributions is often involved. Such incorporation can lack flexibility due to parametric functions with prior distribution assumptions about their univariate marginal and/or copula joint density. This study introduces the vine copula approach in a nonparametric setting by introducing Bernstein and Beta kernel copula density in establishing trivariate flood dependence. The proposed model is applied to 46 years of flood characteristics collected on the west coast of Canada. The univariate flood marginal distribution is modelled using nonparametric kernel density estimation (KDE). The 2-D Bernstein estimator and Beta kernel copulas estimator are tested independently in capturing pairwise dependencies to establish D-vine structure in a stage-wise nesting approach in three alternative ways, each by permutating the location of the conditioning variable. The best-fitted vine structure is selected using goodness-of-fit (GOF) test statistics. The performance of the nonparametric vine approach is also compared with the vine constructed in the parametric and semiparametric fitting procedure. Investigation reveals that the D-vine constructed using Bernstein copula with normal KDE marginals nonparametrically performed well in capturing dependence of the compound events. Finally, the derived nonparametric model is used in the estimation of trivariate OR- and AND-joint return periods, further employed in estimating failure probability (FP) statistics. The trivariate return periods for the AND-joint case are higher than for the OR-joint case for the same flood combination. Also, the trivariate flood hazard results in a high-value FP than bivariate and univariate events. Ignoring the trivariate dependence could result in the underestimation of FP

The interaction between oceanographic, meteorological, and hydrological factors can result in an extreme flooding scenario in the low-lying coastal area, called compound flooding (CF) events. For instance, rainfall and storm surge (or high river discharge) can be driven by the same meteorological, tropical or extra-tropical cyclones, resulting in a CF phenomenon. The trivariate distributional framework can significantly explain compound events' statistical behaviour reducing the associated high-impact flood risk. Resolving heterogenous dependency of the multidimensional CF events by incorporating traditional 3-D symmetric or fully nested Archimedean copula is quite complex. The main challenge is to preserve all lower-level dependencies. An approach based on decomposing the full multivariate density into simple local building blocks via conditional independence called vine or pair-copulas is a much more comprehensive way of approximating the trivariate flood dependence structure. In this study, a parametric vine copula of a drawable (D-vine) structure is introduced in the trivariate modelling of flooding events with 46 years of observations of the west Coast of Canada. This trivariate framework searches dependency by combining the joint impact of annual maximum 24-hr rainfall and the highest storm surge and river discharge observed within the time ±1 day of the highest rainfall event. The D-vine structures are constructed in three alternative ways by permutation of the conditioning variables. The most appropriate D-vine structure is selected using the fitness test statistics and estimating trivariate joint and conditional joint return periods. The investigation confirms that the D-vine copula can effectively define the compound phenomenon's dependency. The failure probability (FP) method is also adopted in assessing the trivariate hydrologic risk. It is observed that hydrologic events defined in the trivariate case produce higher FP than in the bivariate (or univariate) case. It is also concluded that hydrologic risk increases (i) with an increase in the service design life of the hydraulic facilities and (ii) with a decrease in return periods.

Trends in excess winter mortality (EWM) were investigated from the winter of 1900/01 to 2019/20. During the 1918-1919 Spanish flu epidemic a maximum EWM of 100% was observed in both Denmark and the USA. During the Spanish flu epidemic in the USA 70% of excess winter deaths were coded to influenza. EWM steadily declined from the Spanish flu peak to a minimum around the 1970’s to 1980’s. There is evidence that this decline was accompanied by a shift in deaths away from the winter, and that the EWM calculation shifted from a maximum around April to June in the early 1900’s to around March since 1967. EWM has a good correlation with the number of estimated influenza deaths, but in this context influenza pandemics after the Spanish flu only had an EWM equivalent to that for seasonal influenza. Using data from 1980 onward the effect of influenza vaccination on EWM was examined using a large international data set. No effect of increasing influenza vaccination could be discerned; however, there are multiple competing forces influencing EWM which will obscure any underlying trend, e.g., increasing age at death, multimorbidity, dementia, polypharmacy, diabetes, and obesity – all of which either interfere with vaccine effectiveness or are risk factors for influenza death. After adjusting the trend in EWM in the USA influenza vaccination can be seen to be masking higher winter deaths among a high morbidity US population. Winter deaths are clearly the outcome of a complex system of competing long-term trends.

In perennial fruit crops, bearing can be influenced by various factors, including environmental conditions, germplasm, rootstocks, and cultivation methods. Cherries, one of the most important and popular fruit species from the temperate climate zone, achieve high prices on the market. New agricultural technologies and environmental factors force a change in the approach to cherry cultivation. Old-type cherry orchards with their high demand for water, nutrients and manual work are replaced by orchards of self-pollinating cherry cultivars grown on dwarf rootstocks. These changes make it necessary to search for ways to regulate fruiting, in particular to thin buds, flower and fruit. In view of environmental regulations and consumer pressure, thinning methods are being sought that either do not involve the use of chemicals or that use eco-friendly chemical agents. This review examines recent progress in understanding the effect of thinning methods on the physiology, tree growth and fruit quality of cherries, discusses horticultural practices aimed to ensure regular cropping and their influence on fruit quality, and provides suggestions for future research.

Museums increasingly recognize the need to address advances in digital culture which impact the expectations and needs of their audiences. Museum collections of real objects need to be presented both on their own premises and digitally online, especially as social media becomes more and more influential in people’s everyday lives. We investigate these challenges magnified by advances in digital and computational media and culture looking particularly at recent and relevant reports on changes in the ways museums interact with the public. We find that the Covid-19 pandemic has accelerated many of the changes driving museum transformation. We believe that museums must be more prepared than ever to adapt to unabated technological advances set in the midst of cultural and social revolution, now intrinsic to the digital landscape in which museums are inevitably connected and participating across the global digital ecosystem where they inevitably find themselves entrenched.

Viruses are obligate intracellular parasites that are dependent on host factors for their replication. One such host protein, p97 or the valosin-containing protein (VCP), is a highly conserved AAA ATPase that facilitates replication of diverse RNA- and DNA-containing viruses. The wide range of cellular functions attributed to this ATPase is consistent with its participation in multiple steps of the virus life cycle from entry and uncoating to viral egress. Studies of VCP/p97 interactions with viruses will provide important information about host processes and cell biology, but also viral strategies that take advantage of these host functions. The critical role of p97 in viral replication might be exploited as a target for development of pan-antiviral drugs that exceed the capability of virus-specific vaccines or therapeutics.

Two welcome extensions of evolutionary thinking have come to prominence over the last thirty years: the so-called “extended evolutionary synthesis” (EES) and debate about biological kinds and individuals. These two agendas have, however, remained orthogonal to one another. The EES has mostly restricted itself to widening the explanations of adaptation offered by the preceding “modern evolutionary synthesis” by including additional mechanisms of inheritance and variation; while discussion of biological kinds has turned toward philosophical questions of essential vs. contingent properties of life forms and realist vs. epistemological approaches to categorization and classification. Here we attempt to broaden the explanatory scope of evolutionary theory by linking these two agendas. We expand on the mechanistic orientation of the EES, using new understandings of networked systems of components in order to engage the distinct intellectual challenge of the origination of historical kinds. With this phrase we designate a subset of natural kinds that acquires, through evolutionary processes, a quasi-independent lineage-history. Such kinds emerge in both biology and culture, and we enlarge the limited number of historical kinds that have thus far been recognized in evolutionary biology in a series of paradigmatic exemplars, from genes and cell types to rituals and music. For each exemplar we discern specific mechanisms by which it arose and persists; comparing these, we suggest a general unity in the ways in which diverse historical kinds originate.

Preclinical animal studies provide valuable opportunities to better understand human diseases and contribute to major advances in medicine. This review provides a comprehensive overview of ocular parameters in humans and selected animals, with a focus on the ocular surface, detailing species differences in ocular surface anatomy, physiology, tear film dynamics and tear film composition. We describe major pitfalls that tremendously limit the translational potential of traditional laboratory animals (ie., rabbits, mice and rats) in ophthalmic research, and highlight the benefits of integrating companion dogs with clinical analogues to human diseases into preclinical pharmacology studies. This One Health approach can help accelerate and improve the framework in which ophthalmic research is translated to the human clinic. Studies can be conducted in canine subjects with naturally occurring or non-invasively induced ocular surface disorders (eg., dry eye disease, conjunctivitis), reviewed herein, and tear fluid can be easily retrieved from canine eyes for various bioanalytical purposes. In this review, we discuss common tear collection methods, including capillary tubes and Schirmer tear strips, and provide guidelines for tear sampling and extraction to improve the reliability of analyte quantification (drugs, proteins, others).

We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID- 19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients and with monoclonal antibodies against the viral S-protein. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.

Herpesviruses usurp cellular stress responses to avoid immune detection while simultaneously promoting viral replication and spread. The unfolded protein response (UPR) is an evolutionarily conserved stress response that is activated when the protein load in the ER saturates its chaperone folding capacity causing an accrual of misfolded proteins. Through translational and transcriptional reprogramming, the UPR aims to restore protein homeostasis; however, if this fails the cell undergoes apoptosis. It is commonly thought that many enveloped viruses, including herpesviruses, may activate the UPR due to saturation of the ER with nascent glycoproteins and thus these viruses may have evolved mechanisms to evade the potentially negative effects of UPR signaling. Over the past fifteen years there has been considerable effort to provide evidence that different viruses may reprogram the UPR to promote viral replication. Here we provide an overview of the molecular events of UPR activation, signaling and transcriptional outputs, and highlight key findings that demonstrate that the UPR is an important cellular stress response that herpesviruses have hijacked to facilitate persistent infection.

In our recently proposed theory of quantum gravity, a black hole arises from the spontaneous localisation of an entangled state of a large number of atoms of space-time-matter [STM]. Prior to localisation, the non-commutative curvature of an STM atom is described by the spectral action of non-commutative geometry. By using the techniques of statistical thermodynamics from trace dynamics, we show that the gravitational entropy of a Schwarzschild black hole results from the microstates of the entangled STM atoms and is given (subject to certain assumptions) by the classical Euclidean gravitational action. This action, in turn, equals the Bekenstein-Hawking entropy (Area/$4{L_P}^2$) of the black hole. We argue that spontaneous localisation is related to black-hole evaporation through the fluctuation-dissipation theorem.

We investigate the flow structure and dynamics of moderate-Rayleigh-number ($Ra$) thermal convection in a two-dimensional inclined porous layer. Direct numerical simulations (DNS) confirm the emergence of $\mathit{O}(1)$ aspect-ratio large-scale convective rolls, with one `natural' roll rotating in the counterclockwise direction and one `antinatural' roll rotating in the clockwise direction. As the inclination angle $\phi$ is increased, the background mean shear flow intensifies the natural-roll motion, while suppressing the antinatural-roll motion. Moreover, our DNS reveal---for the first time in single-species porous medium convection---the existence of \emph{spatially-localized} convective states at large $\phi$, which we suggest are enabled by subcritical instability of the base state at sufficiently large inclination angles. To better understand the physics of inclined porous medium convection at different $\phi$, we numerically compute steady convective solutions using Newton iteration and then perform secondary stability analysis of these nonlinear states using Floquet theory. Our analysis indicates that the inclination of the porous layer stabilizes the boundary layers of the natural roll, but intensifies the boundary-layer instability of the antinatural roll. These results facilitate physical understanding of the large-scale cellular flows observed in the DNS at different values of $\phi$.

Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons serving as an axon guidance molecule. In the immune system, Sema4A regulates immune cell activation and function granting a fine tuning of immune response. Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal and breast cancers. Cancers have been associated with abnormal angiogenesis. The function of Sema4A in angiogenesis and cancer is not defined. Recent studies have demonstrated Sema4A expression and function in endothelial cells. However, the results of these studies are controversial as they report either pro – or anti-angiogenic Sema4A effects depending on the experimental settings. In this mini-review, we discuss these findings as well as our data on Sema4A regulation of inflammation and angiogenesis, which both are important pathologic processes underlining tumorigenesis and tumor metastasis. Understanding the role of Sema4A in those processes may guide the development of improved therapeutic treatments for cancer.

The presence of wireless communication grows undeniably more prevalent each year. Since the introduction of the IEEE 802.11 standard for Wireless Local Area Networks (WLAN) in 1997, technologies have progressed to provide wireless accessibility to industries and consumers with growing ease and convenience. As the usage of personal devices, such as phones and watches, that connect to the Internet through Wi-Fi increases, wireless attacks on users are becoming more critical. This paper provides a novel attack model to offer an organized and comprehensive view of the possible attacks on WiFi latest security standards. All exiting attacks will be investigated, with emphasis on more recent attacks, such as the KRACK and PMKID Dictionary attacks. This paper will then analyze the technology offered in the new Wi-Fi Protected Access III (WPA3) security scheme and provide a comprehensive security analysis and discussion to determine whether it has addressed the vulnerabilities of its predecessor. An interesting finding of this paper is that WPA3 still lacks to address all the issues existed in WPA2 and explore other mitigations for future research.

Encapsulation of antioxidant polyphenols leads to increase solubility and bioavailability of these micronutrients in solution. The encapsulation of antioxidant resveratrol, genistein and curcumin by folic acid-chitosan nanocapsules was studied in aqueous solution, using multiple spectroscopic methods, TEM images. Structural analysis showed that polyphenol bindings are via hydrophilic, hydrophobic and H-bonding contacts with resveratrol forming more stable conjugates. As chitosan size increased, the binding efficacy and stability of polyphenol-polymer adducts were increased. Polyphenol binding induced major alterations of chitosan morphology. Chitosan nanoparticles are capable of delivery of polyphenols in vitro.

The mitochondrial network is a dynamic organization within eukaryotic cells that participates in a variety of essential cellular processes, such as ATP synthesis, central metabolism, apoptosis and inflammation. The mitochondrial network is balanced between rates of fusion and fission that respond to pathophysiologic signals to coordinate appropriate mitochondrial processes. Mitochondrial fusion and fission are regulated by proteins that either reside or translocate to the inner or outer mitochondrial membranes or are soluble in the inter-membrane space. Mitochondrial fission and fusion are performed by GTPases on the outer and inner mitochondrial membranes with the assistance of other mitochondrial proteins. Due to the essential nature of mitochondrial function for cellular homeostasis regulation of mitochondrial dynamics is under strict control. Some of the mechanisms used to regulate the function of these proteins are post-translational proteolysis and/or turnover and this review will discuss these mechanisms required for correct mitochondrial network organization.

In small-scale hydropower scheme, the most important component is electro-mechanical equipment. Since cost contribution of this component is high because hydrokinetic projects require negligible civil works. Turbine and alternator contribute major fraction of the hydrokinetic projects. Thus, there is a requirement to estimates the electromechanical equipment cost for the hydrokinetic hydropower scheme. The present paper investigates design parameters of the hydrokinetic turbines and intends to develop cost correlation which depends on most critical parameters of hydropower sites such as velocity and power capacity. In this present work, three zero head turbines are considered including straight blade Darrieus, two Stage Savonius, and Gorlov Helical. The size and cost of major components have been calculated based on material, manufacturing, research and design, and assembly costs. Based on cost and site parameters, cost correlation has been developed. The obtained cost has been validated with available zero head turbines in the market and installed projects. A techno-economic analysis has been carried out to select economical hydrokinetic turbine for river and canal application.

In this work, we derive the spectral efficiency, secrecy outage probability, and bit error rate of a communication system assisted by a large intelligent surface (LIS). We consider a single-antenna user and an array of antennas at the transmitter side and the possibility of a direct link between transmitter and receiver. Additionally, there is a single-antenna eavesdropper with a direct link to the transmitter, which is modeled as a Nakagami-m distributed fading coefficient. The channels from transmitter to the LIS and from the LIS to the user may or may not have the line-of-sight (LoS) and are modeled by the Nakagami- m distribution. Moreover, we assume that the LIS elements perform non-ideal phase cancellation leading to a residual phase error that assumes a Von Mises distribution. We show that the resulting channel can be accurately approximated by a Gamma distribution whose parameters are analytically estimated using the moments of the equivalent signal-to-noise ratio. We also provide an upper bound for the error probability for M-QAM modulations. With the derived formulas, we analyze the effect of the strength of the LoS link by varying the Nakagami parameter, m.

Large intelligent surfaces (LIS) promises not only to improve the signal to noise ratio, and spectral efficiency but also to reduce the energy consumption during the transmission. We consider a base station equipped with an antenna array using the maximum ratio transmission (MRT), and a large reflector array sending signals to a single user. Each subchannel is affected by the Rayleigh flat fading, and the reflecting elements perform non-perfect phase correction which introduces a Von Mises distributed phase error. Based on the central limit theorem (CLT), we conclude that the overall channel has an equivalent Gamma fading whose parameters are derived from the moments of the channel fading between the antenna array and LIS, and also from the LIS to the single user. Assuming that the equivalent channel can be modeled as a Gamma distribution, we propose very accurate closed-form expressions for the bit error probability and a very tight upper bound. For the case where the LIS is not able to perform perfect phase cancellation, that is, under phase errors, it is possible to analyze the system performance considering the analytical approximations and the simulated results obtained using the well known Monte Carlo method. The analytical expressions for the parameters of the Gamma distribution are very difficult to be obtained due to the complexity of the nonlinear transformations of random variables with non-zero mean and correlated terms. Even with perfect phase cancellation, all the fading coefficients are complex due to the link between the user and the base station that is not neglected in this paper.

Previous studies showed that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related imino adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in tumor cells and may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, we synthesized and evaluated for their antiproliferative activity in four tumor cell lines (RD, HCT116, HeLa, A549) and ability of inhibiting P-gp-mediated MDR some ten diversely substituted 1-Ph-DHPIQ derivatives bearing at position 2 carboxylate groups (COOH, COOEt), nitriles (CN) and Mannich bases (e.g., morpholinomethyl derivatives). Lipophilicity parametrization and molecular docking calculations improved the understanding of the structure-activity relationships in cytotoxicity and P-gp inhibition of the investigated 1-Ph-DHPIQs, which led us to disclose a novel Mannich base HCl salt (8b’), which proved to be cytotoxic to all the tested tumor cell lines in the low micromolar range (IC50 < 20 M) and to inhibit in-vitro the efflux pumps P-gp and MRP1 responsible for MDR, with IC50s of 0.45 and 12.1 M, respectively.

Ganoderma lucidum, commonly known as the "Lingzhi" or "Reishi" mushroom, has long been recognized for its potential health benefits, and medicinal properties in traditional Chinese medicine. In recent years, the emerging field of nanotechnology has opened up new possibilities in order to use the remarkable properties of G. Lucidum at the nanoscale. The unique combination of bioactive compounds present in G. Lucidum, such as triterpenoids, polysaccharides, and peptides, has inspired interest in leveraging their therapeutic potential through nanotechnological approaches. Various nanomaterials, including nanoparticles, nanofibers, and nanocomposites, have been employed to encapsulate and deliver these bioactive components to target cells or tissues, enhancing stability, controlled release, and consequently their bioavailability. Nanotechnology-based strategies have been investigated for the efficient extraction and purification of bioactive compounds from G. Lucidum. The use of nanoscale materials has facilitated the extraction process, enhancing the yield and purity of the active components. Additionally, nanocarriers and nanoformulations have been developed to protect these sensitive bioactive compounds from degradation, ensuring their stability during storage and transportation. The use of G. Lucidum-based nanomaterials has shown promising results in several biomedical applications. Nanoparticles loaded with bioactive compounds derived from G. Lucidum have exhibited potent anticancer activity by targeting cancer cells, inducing apoptosis, and inhibiting tumor growth. Additionally, nanotechnology-based formulations have demonstrated immunomodulatory effects, promoting the activation of immune cells and enhancing the body's defense mechanisms. GL, combined with the potential of nanotechnology, presents an exciting frontier in the development of novel therapeutic and biomedical applications. The utilization of nanomaterials for extraction, delivery, and integration of bioactive compounds from G. Lucidum has shown immense potential for improving drug delivery, tissue engineering, and disease treatment. Further research and development in this interdisciplinary field are warranted to fully exploit the synergistic benefits offered by G. Lucidum, and nanotechnology, ultimately leading to innovative solutions for human health and well-being.

Phosphorus (P) deficiency is a major constraint limiting sustainable rice cultivation in sub-Saharan Africa—partly due to the deeply weathered soils that have low pH and contain high P-fixing Fe and Al oxides. Soil texture also affects P availability and use efficiency. In this study, we evaluated the combined effect of soil texture (sand, clay loam, and clay) and P treatments (P-dipping and two other P fertilizer levels) on growth of NERICA 4 rice in the initial growth stages. In a factorial experiment, we measured the interaction effects of soil texture and P treatments on shoot parameters and root morphology. Both treatments had significant interaction effects on all measured parameters, except shoot biomass, and affected the photosynthetic rate, with the highest mean values obtained under clay loam soil texture and P-dipping treatment, respectively. The treatments also affected rice root morphology. In a striking contrast, whereas mean root length under clay was significantly higher than that under clay loam texture, mean shoot P uptake under clay loam soil was significantly higher than that under clay soil texture. The interactive effect of soil texture and P-dipping influenced NERICA 4 shoot and root physiological and morphological characteristics under clay loam soil texture.

Stock bubbles are characterized by unpredictable price surges and subsequent declines, causing significant losses for investors. The study aimed to detect mildly explosive patterns in S&P 500-listed stocks in real-time using the GSADF test. This study focused on the length, the normality of the stock bubble episode and compared the effectiveness of SADF and GSADF tests in bubble detection, consistently finding GSADF's superiority. The duration of breakouts exhibited non-normality, suggesting unusually long bubble durations.

In order to improve the charge collection efficiency, we simulated and experimentally tested the doping structure of the electron multiplication layer in EBCMOS. In this paper, we simulate the charge collection efficiency of EBCMOS under different doping methods by modeling the collisional scattering of electrons with solid atoms in semiconductor materials and combining the transport trajectories of electrons in the electron multiplication layer, the simulation results indicate that using a layered doping structure to reduce the thickness of the index heavily doped layer can effectively optimize the electric field distribution in the electron multiplier layer and reduce the recombination rate of electrons. The optimized doping structure has a significant effect on improving charge collection efficiency. Based on the simulation results, doped samples were prepared and tested. The test results showed that the charge collection efficiency obtained under the condition of a P-type silicon substrate thickness of 7μm and an index heavily doped layer thickness of 1μm was 72.65%, reducing the thickness of the index heavily doped layer to 0.1μm, the charge collection efficiency obtained can reach 86.27%, which proves that reducing the thickness of the index heavily doped layer can effectively improve the charge collection efficiency of EBCMOS devices.

A mild, efficient, and photocatalytic synthesis of 6-phosphorylated phenanthridines via tandem radical addition/cyclization/aromatization of 2-isocyanobiphenyls with diarylphosphine oxides is reported. The method features operational simplicity, metal-free conditions, using low-cost rose Bengal as catalyst and sustainable air as terminal oxidant at room temperature, and providing the desired products in moderate to good yields.

This article analyzes and compares the integration of two different maximum power point tracking (MPPT) control methods, which are tested under partial shading and fast ramp conditions. These MPPT methods are designed by Improved Particle Swarm Optimization (IPSO) and a combination technique between Neural Network and Perturb & Observe method (NN_P&O). These two methods are implemented and simulated for photovoltaic systems (PV), where various system responses, such as: voltage and power are obtained. The MPPT techniques were simulated using Matlab/Simulink environment. A comparison of the performance of IPSO and NN_P&O algorithms is carried out to confirm the best accomplishment of the two methods in terms of speed, accuracy and simplicity.

The circuitry of the summarized "floating" differential stages (FDS) based on complementary field-effect transistors with a control p-n junction (CJFET), intended for use in low-noise analog microcircuits, for example, operational amplifiers. The results of modeling the flow characteristics of one of the CJFET FDSs in the LTSpice XVII environment at low temperatures (down to -197 ⁰С) and exposure to a neutron flux in the range of 1e13 ÷ 1e15 n / cm² are presented.

The lipid composition of biomembranes influence the properties of the lipid bilayer as well as that of the proteins. In this study, the lipidome and the lipid/protein ratio of membranes from High FiveTM insect cells overexpressing mouse P-glycoprotein was characterized. This provides a better understanding of the lipid environment in which P-glycoprotein is embedded, and thus of its functional and structural properties. The relative abundance of the distinct phospholipid classes and their acyl chain composition was characterized. A mass ratio of 0.57 +/- 0.11 phospholipids to protein was obtained. Phosphatidylethanolamines are the most abundant phospholipids, followed by phosphatidylcholines. Membranes are also enriched in negatively charged lipids (phosphatidylserines, phosphatidylinositols and phosphatidylglycerols), and contain small amounts of sphingomyelins, ceramides and monoglycosilatedceramides. The most abundant acyl chains are monounsaturated, with significant amounts of saturated chains. The characterization of the phospholipids by HPLC-MS allowed identification of the combination of acyl chains, with palmitoyl-oleoyl being the most representative for all major phospholipid classes except for phosphatidylserines, which are mostly saturated. A mixture of POPE:POPC:POPS in the ratio 45:35:20 is proposed for the preparation of simple representative model membranes. The adequacy of the model membranes was further evaluated by characterizing their surface potential and fluidity.

The influence of the type and amount of oxygen (O), nitrogen (N), and/or phosphorus (P) heteroatoms on the surface of carbon nanotube (CNT) on stability and catalytic activity in the oxygen reduction reaction (ORR) was investigated in alkaline media. It is shown that the functionalization of CNT leads to the growth of the electrochemically active surface and to an increase in the activity in ORR. At the same time, a decrease in stability is observed after the functionalization of CNT under accelerated corrosion testing in an alkaline media. These results are most significant on CNT after functionalization in HNO3 due to the formation of a large number of structural defects. However, the subsequent doping by N and / or P atoms provides a further activity increase and enhances the corrosion stability of CNT. Thus, as shown by the studies of characteristic parameters (SEAS, E1/2, corrosion stability), CNT doped with N and NP are a promising catalytic system that can be recommended for use as fuel cell cathodes. An important condition for effective doping is the synthesis of carboxyl and carbonyl oxygen containing group on the surface of CNT.

Incidental P losses from non-point sources may contribute to eutrophication and to decreased soil fertility. These incidents have been related to heavy rainfall on freshly fertilized agricultural soils and little is known about such incidents on more natural soils or in forests. The aim of this work is to determine if incidents of high P leaching also occur in spruce forests, and if such incidents are of significance in P cycling. We found a peak in the mineral soil solution showing that single events of high P leaching occur. The orthophosphate concentration in the Bf-horizon of the 80-year old spruce forest peaked in the autumn of the second year of a continuous monitoring. The concentration increased by more than 85 times compared to the highest concentration obtained earlier during the sampling. The amount leached during this 6 months peak is 10 times higher than the average annual leaching. This P leaching might be due to a combination of high P deposition/through-fall and a high anion exchange with dissolved-organic-carbon and Cl-. We suggest that single events of high sub-surface P leaching may contribute to the overall P leaching, and might increase with the global warming as more DOC is expected to be released to the soil solution.

P-glycoprotein (P-gp), a membrane-bound transporter, can eliminate xenobiotics by transporting them out of the cells or blood-brain barrier (BBB) at the expense of ATP hydrolysis. Thus, P-gp mediated efflux plays a pivotal role in altering the absorption and disposition of a wide range of substrates. Nevertheless, the mechanism of P-gp substrate efflux is rather complex since it can take place through active transport and passive permeability in addition to multiple P-gp substrate binding sites. A nonlinear quantitative structure-activity relationship (QSAR) model was developed in this study using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to explore the perplexing relationships between descriptors and efflux ratio. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 50, r² = 0.96, q²_CV = 0.94, RMSE = 0.10, s = 0.10) and test set (n = 13, q² = 0.80–0.87, RMSE = 0.21, s = 0.22). When subjected to a variety of statistical validations, the developed HSVR model consistently met the most stringent criteria. A mock test also asserted the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.

Rocas Atoll is a unique environment in the Equatorial Atlantic Ocean, hosting a large number of endemic species and studies on the chemical diversity emerging from this biota are rather scarce. Therefore, the present work aims to assess the metabolomic diversity and pharmacological potential of the microbiota from Rocas Atoll. A total of 76 bacteria were isolated and cultured in liquid culture media to obtain crude extracts. About one third (34%) of these extracts were considered cytotoxic against human colon adenocarcinoma HCT-116 cell line. 16S rRNA gene sequencing analysis revealed that the bacteria producing cytotoxic extracts are mainly from the Actinobacteria phylum, including Streptomyces, Salinispora, Nocardiopsis and Brevibacterium genera, and in a smaller proportion from Firmicutes phylum (Bacillus). The search in the GNPS spectral library unveiled a high chemodiversity being produced by these bacteria, including rifamycins, antimycins, desferrioxamines, ferrioxamines, surfactins, surugamides, staurosporine and saliniketals, along with several unidentified compounds. Using an original approach, molecular network successfully highlighted groups of compounds responsible for the cytotoxicity of crude extracts. DEREPLICATOR+, a recently developed in silico tool (GNPS), allowed the identification of derivatives of the macrolide novonestimycin, as the cytotoxic compounds into the extracts produced by Streptomyces BRB-298 and BRB-302. Overall, these results highlighted the pharmacological potential of bacteria from this singular Atoll.

Abstract：Objective: To compare the effects of fermentation on the chemical composition of Gastrodia Tuder Halimasch Powder, and to provide a basis for the processing, processing and clinical application of this medicinal material. Methods: UHPLC-Q-Orbitrap HRMS was used to identify compound structure by comparing excimer ions, characteristic fragment ions and reference substances, and referring to relevant literature and database search. The main differential components were screened by orthogonal partial least squares-discriminant analysis (OPLS-DA), and the differential components were quantitatively studied by high performance liquid chromatography, and the differences in the types and contents of chemical components before and after fermentation were compared. Results: A total of 77 compounds were identified or preliminarily derived after fermentation, including 21 terpenes, 18 organic acids, 9 flavonoids, 7 nucleosides, 6 amides, 4 amino acids, 2 pyrrolidone derivatives, 2 sterols, 2 alkaloids and 6 others.Through high performance liquid chromatography, it was found that the content of daidzein genistein and ergosterol was significantly increased after fermentation, and a new component ergosterol was produced. Compared with Gastrodia Tuder Halimasch Powder before fermentation, the content of genistin and other components was significantly reduced, and there may be a process of genistin conversion to genistein.Conclusion: The fermentation process will have a certain influence on the types and contents of the chemical components of Gastrodia Tuder Halimasch Powder, and ergosterol, genistein and .daidzein may be the main pharmacodynamic components, which can provide a useful reference for the clinical rational application, quality control and mechanism of action of Gastrodia Tuder Halimasch Powder.

In this paper, the stabilization and high efficiency of an unstable Second Harmonic Generation (SHG) of a Nd : YVO4 laser with a KTP intracavity is carried out by using a passive Q-switching crystal and a parametric modulation method (harmonic modulation) is shown. The harmonic modulation was defined as um(t) = Amsin(2π fmt), with modulation amplitude as Am(Vpp), and modulation frequency as fm(Hz), applied to the pumping of the Nd : YVO4 -KTP laser to control the amplitude and frequency of the emission, thus stabilizing the dynamic states of this laser. The promising application of this green light source is materialized when such light is necessary for high-density optics, such as in the treatment materials industry or in some aesthetic applications.

In the early decades of the 19th century, the deaf population in the eastern US and Canada was distributed across a vast area. After the 1817 founding of the American School for the Deaf (ASD) in Hartford, CT and the subsequent establishment of schools for the deaf in New York City (NYSD), Philadelphia, and many other US states, hundreds of deaf students called these schools home for several years. After leaving school, the early American Deaf community faced a challenge: How would the community maintain its social and linguistic ties across a vast geographical area once community members had dispersed to their hometowns? In this paper we analyze the attendance registries of two large gatherings of deaf individuals in Hartford in the years 1850 and 1854. These were among the largest and earliest known gatherings of deaf adults. The demographic data included in these registries open a window onto the evolving American Deaf community of the mid-19th century. Our analyses of the attendees’ school affiliations, ages, and marital status show that the signing community that had taken root among students at schools in Hartford and New York persisted among the adult graduates of those schools in towns across the northeastern US. We compare the places of residence of ASD and NYSD alumni in 1850 and 1854 to their hometowns when they first enrolled at school. Our comparisons suggest the mid-19th-century signing community had become more urban; it was centered to a greater extent in populous cities such as New York, Boston, and Hartford than had been true when the attendees had enrolled in school. We consider how the geography of deafness in the 19th century might inform our understanding of the sources of regional variation in ASL. We also consider how early cross-regional interactions may have inhibited such regional variation.

Kaposi sarcoma is the most common neoplasm associated with Human Immunodeficiency Virus (HIV) infection. Most patients with a confirmed diagnosis experienced limited disease progression. We describe the case of a 49-year-old African American male with a rare presentation of disseminated Kaposi sarcoma as determined by multi-organ work-up. The patient’s cutaneous manifestations involved several hyperpigmented skin lesions, but the worsening of his respiratory symptoms coupled with unexplained weight loss led providers to develop a high suspicion for disseminated disease progression. This case highlights the need to increase awareness of atypical Kaposi sarcoma presentation.

Keywords: Academic Trends; Energy Consumption; Higher Education Institutions; Systematic Literature Review; Scholarly output; University buildings

Background: Maternal mortality remains dire in Nigeria, claiming 40,000 lives yearly due to pregnancy complications. Factors like limited healthcare access, poverty, and early marriage worsen the crisis. Despite efforts to improve skilled birth attendance, Nigeria struggles to meet MDG targets, underscoring the urgent need for more effective interventions. Objectives: The objective of the study is to assess and understand the knowledge of community members regarding the risk factors influencing maternal mortality in the Ede South Local Government Area of Osun State, Nigeria. Methodology: A descriptive cross-sectional study was conducted. The study methodology involves employing the Leslie Kish formula to select 185 participants from the Ede South Local Government Area in Osun State, Nigeria. The selection process involved the use of a systematic sampling technique to ensure a representative sample based on population demographics and characteristics, ensuring a balanced and accurate selection process. Quantitative data was collected through a self-administered questionnaire and analysed using SPSS version 21. Results: The study encompassed 185 participants. 64.9% females with a mean age of 27.3 + 8.3 years. Among them, 60.5% were single, 46.6% being students, 55.7% held a BSc degree, 64.9% were Yoruba and 61.1% identified as Christian. 91.4% were aware about maternal mortality, 74.6% recognized maternal deaths in reproductive-aged women. Participants identified that maternal deaths mostly occur during labour (91.4%). Direct causes, such as bleeding (88.1%), unsafe abortion (88.6%), infection (49.2%), and hypertension (64.9%), were recognized. Results indicated substantial awareness concerning specific risk factors: lack of education (98.9%), poverty (91.6%), poor health care services in facilities (94.0%), alcohol consumption (87.6%) and poor transportation (78.4%). Conclusion: Findings revealed good awareness of maternal deaths and critical factors such as ANC impact and direct causes of maternal mortality like bleeding and unsafe abortion. However, gaps persisted in SDG awareness, suggesting the need for targeted interventions to enhance overall understanding and address identified knowledge gaps.

Tropical sea surface temperature (SST) variability, mainly driven by the El Niño–Southern Oscillation (ENSO), influences the atmospheric circulation and hence the transport of heat and chemical species in both the troposphere and stratosphere. This paper uses Met Office, ERA5 and MERRA2 reanalysis data to examine the impact of SST variability on the dynamics of the polar stratosphere and ozone layer over the period 1980 to 2020. Particular attention is paid to studying the differences in the influence of different types of ENSO (East Pacific (EP) and Central Pacific (CP)) for the El Niño and La Niña phases. It is shown that during the EP El Niño, the zonal wind weakens more strongly and changes direction more often than during the EP El Niño, and the CP El Niño leads to a more rapid decay of the polar vortex (PV), an increase in stratospheric air temperature and an increase in the concentration and total column ozone than during EP El Niño. For the CP La Niña, the PV is more stable, which often leads to a significant decrease in Arctic ozone. During EP La Niña, powerful sudden stratospheric warmings are often observed, which lead to the destruction of PV and an increase in column ozone.

The benefits of multi-robot systems are substantial, bringing gains in efficiency, quality, and cost, and are useful in a wide range of environments from warehouse automation, to agriculture, and even extend in part to entertainment. In multi-robot system research, the main focus is on ensuring efficient coordination in the operation of the robots, both in task allocation and navigation. However, much of this research seldom strays from theoretical bounds; there are many reasons for this, with the most prominent and impactful being resource limitations. This is especially true for research in areas such as multi-robot path planning (MRPP) and navigation coordination. This is a large issue in practice as many approaches are not designed with meaningful real-world implications in mind and are not scalable to large multi-robot systems. This survey aims to look into the coordination and path-planning issues and challenges faced when working with multi-robot systems, especially those using a prioritised planning approach and identify key areas which are not well-explored and the scope of applying existing MRPP approaches to real-world settings.

The effectiveness of a recently proposed methodology in the identification of damage in planar, multi-storey, Reinforced Concrete (RC) moment-frames, which develop a plastic-yield mechanism on their beams, is showcased here via the examining of a group of such existing multi-storey frames with three or more unequal spans. According to the methodology, the diagram of the instantaneous Eigen-Frequencies of the frame in the nonlinear regime is drawn as a function of the inelastic seismic roof displacement by performing a sequence of pushover and instantaneous modal analyses with gradually increasing target displacement. Using this key-diagram, the locations of severe seismic damage in an existing moment-frame can be evaluated if the instantaneous fundamental eigen-frequency of the damaged frame, at an analysis step within the nonlinear area, is known in advance by “the monitoring and the identification of frequencies” using a local network of uniaxial accelerometers. This is a hybrid technique because both procedures, the instrumental Monitoring of the structure and the Pushover analysis on the frame (M and P technique), are combined. Moreover, the damage image of the planar multi-storey moment-frame is illustrated, and the lateral stiffness matrix of the damaged frame is calculated with high accuracy.

Most patients with classic Hodgkin lymphoma (cHL) are cured with combination chemotherapy, but approximately 10-20% will relapse and another 5-10% will have primary refractory disease. The treatment landscape of relapsed/refractory (R/R) cHL has evolved significantly over the past decade following the approval of brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, and the PD-1 inhibitors, nivolumab and pembrolizumab. These agents have significantly expanded options for salvage therapy prior to autologous hematopoietic cell transplantation (AHCT), post-transplant maintenance, and treatment of relapse after AHCT, which have led to improved survival in the modern era. In this review, we highlight our approach to management of R/R cHL in 2023 with a focus on choosing first salvage therapy, post-transplant maintenance, and treatment of relapse after AHCT. We also discuss management of older adults and transplant-ineligible patients who require a separate approach. Finally, we review novel immunotherapy approaches in clinical trials, including combinations of PD-1 inhibitors with other immune-activating agents as well as novel antibody-drug conjugates, bispecific antibodies, and cellular immunotherapies. Ongoing studies assessing biomarkers of response to immunotherapy and dynamic biomarkers such as circulating tumor DNA may further inform treatment decisions and enable a more personalized approach in the future.

It is generally believed that the universe emerged from the Big Bang, before which space and time did not exist. However, Penrose proposed his theory of conformal cyclic cosmology, in which an aeon existed preceding this universe. Based on the cosmological principle, the universe is homogeneous and isotropic, expanding without center, but recently more and more deviations have been observed. By studying the fundamental particles and reactions of nature, we initiated a model that the Big Bang is the result of the collapse of a neutrino star within a black hole. We therefore re-analyze the cosmic microwave background (CMB) and find that the Center of the universe where the Big Bang occurred was at 0.66 ^+0.03 _-0.01 times the radius of the surface of last scattering away from the Local Supercluster (LS) and at Galactic coordinates (l, b) = (286^o +/- 10^o, -43^{o +7} _-6). If we look from the LS to the Center, the universe is spinning clockwise. Our findings are supported by Penrose’s conformal cyclic cosmology, low-variance circle sets in the CMB, and many other independent observational evidence of cosmic inhomogeneities, spatial anisotropies, and time variations.

Kinases play an important role in regulating various intracellular signaling pathways that control cell proliferation, differentiation, survival and other cellular processes and their deregulation causes more than 400 diseases. Consequently, macrocyclization can be considered a noteworthy approach to develop new therapeutic agents for human diseases. Macrocyclization has emerged as an effective drug discovery strategy over the past decade to improve target selectivity and potency of small molecules. Small compounds with linear structures upon macrocyclization can lead to changes in their physicochemical and biological properties by firmly reducing conformational flexibility. A number of distinct protein kinases exhibit similar binding sites. Comparison of protein binding site provides crucial insights for the drug discovery and development. Binding site similarities are helpful to understand polypharmacology, identifying potential off-targets and repurposing of known drugs. In this review, we focused on comparing binding sites of those kinases for which macrocyclic inhibitors are available/studied so far. Furthermore, we calculated the volume of binding site pocket for each targeted kinase and then compared it with the binding site pocket of the kinase for which only acyclic inhibitors were designed till date. Our review and analysis of several explored kinases might be useful to target new protein kinases for macrocyclic drug discovery.

The term ‘Hallmarks of Cancer’ was coined by Hanahan and Weinberg in their influential reviews and they described genome instability as a property of cells enabling cancer development [1, 2]. Accurate DNA replication of genomes is central to diminish genome instability. Here, the understanding of the initiation of DNA synthesis in origins of DNA replication to start leading strand synthesis and the initiation of Okazaki fragment on the lagging strand are crucial to control genome instability. Recent findings have provided new insights into the mechanism of the remodelling of the prime initiation enzyme, DNA polymerase α-primase, during primer synthesis, how the enzyme complex achieves lagging strand synthesis, and how it is linked to replication forks to achieve optimal initiation of Okazaki fragments. Moreover, the central roles of RNA primer synthesis by Pol-prim in multiple genome stability pathways such as replication fork restart and protection of DNA against degradation by exonucleases during double-strand break repair is discussed.

There are unsolved problems related to inflation, gravity, dark matter, dark energy, missing antimatter, and the birth of the universe. Some of them can be better answered by assuming the existence of aether and hypoatoms. Both were created during the inflation in the very early universe. While aether forms vacuum, hypoatoms, composed of both matter and antimatter and believed to be neutrinos, form all observable matter. In vacuum, aether exists between the particle-antiparticle dark matter form and the dark energy form in a dynamic equilibrium: A + A-bar = gamma + gamma. The same reaction stabilizes hypoatoms and generates a 3-dimensional sink flow of aether that causes gravity. Based on the hypoatom structure, the singularity does not exist inside a black hole; the core of the black hole is a hypoatom star or neutrino star. By gaining enough mass, ca. 3 X 10²² M_sun, to exceed neutrino degeneracy pressure, the black hole collapses or annihilates into the singularity, thus turning itself into a white hole or a Big Bang. The universe is anisotropic. Its center, or where the Big Bang happened, is at 0.66^+0.03_-0.01 times the radius of the observable universe at Galactic coordinates (l, b) = (286⁺¹⁰_-10, -43⁺⁷_-6). If we look from the Local Group to the center of the universe, the universe is rotating clockwise.

There are various biomaterials in nature, but none fulfills all the requirements. Cellulose, eco-friendly material-based biopolymers, have been advanced biomedicine to satisfy most market demand and circumvent many ecological concerns. This review aims to present an overview of the state of the art in cellulose's knowledge and technical biomedical applications. It included an extensive bibliography of recent research findings for fundamental and applied investigations. The chemical structure of cellulose allows modifications and simple conjugation with several materials, including nanoparticles, without tedious efforts. Cellulose-based materials were used for biomedicine applications such as antibacterial agents, antifouling, wound healing, drug delivery, tissue engineering, and bone regeneration. They advanced the applications to be cheap, biocompatible, biodegradable, easy for shaping and processing into different forms, with suitable chemical, mechanical and physical properties.

Aquatic animals have unique physiological mechanisms to absorb and retain minerals from their diets and water. Research and development in the area of mineral nutrition of farmed fish and crustaceans have been relatively slow and major gaps exist in the knowledge of trace element requirements, physiological functions and bioavailability from feed ingredients. Quantitative dietary requirements have been reported for three macroelements (calcium, phosphorus and magnesium) and six trace minerals (zinc, iron, copper, manganese, iodine and selenium) for selected fish species. Mineral deficiency signs in fish include reduced bone mineralization, anorexia, lens cataracts (zinc), skeletal deformities (phosphorus, magnesium, zinc), fin erosion (copper, zinc), nephrocalcinosis (magnesium deficiency, selenium toxicity), thyroid hyperplasia (iodine), muscular dystrophy (selenium) and hypochromic microcytic anaemia (iron). An excessive intake of minerals from either diet or gill uptake causes toxicity and therefore a fine balance between mineral deficiency and toxicity is vital for aquatic organisms to maintain their homeostasis either through increased absorption or excretion. Release of minerals from uneaten or undigested feed and from urinary excretion can cause eutrophication of natural waters, which requires additional consideration in feed formulation. The current knowledge in mineral nutrition of fish is briefly reviewed.

Approximately 240 million people are chronically infected with hepatitis B virus (HBV), despite four decades of an effective HBV vaccine. During chronic infection, HBV forms two distinct templates responsible for viral gene transcription: (1) episomal covalently closed circular (ccc)DNA and (2) host-genome integrated viral templates. Multiple ubiquitous and liver-specific transcription factors are recruited onto these templates and modulate viral gene transcription. This review details the latest developments in antivirals that inhibit HBV gene transcription, and their impact on the stability of viral transcripts. Notably, nuclear receptor agonists exhibit potent inhibition of viral gene transcription from cccDNA, small molecule inhibitors repress HBV X protein-mediated transcription from cccDNA and small interfering RNAs and single-stranded oligonucleotides result in transcript degradation from both cccDNA and integrant templates. These antivirals mediate their effects by reducing viral transcripts abundance, eventually leading to loss of surface antigen expression, and can potentially be added to the arsenal of drugs with demonstrable anti-HBV activity. Thus, these candidates deserve special attention for future repurposing or further development as anti-HBV therapeutics.

A growing body of evidence continues to demonstrate the vital roles that zinc and its transporters play on human health. The solute carrier (SLC) 30 and 39 families, with ten and fourteen members, respectively, control zinc transport in cells. TMEM163, a recently characterized zinc transporter, has similar characteristics in both structure and function to the SLC30 family. This review examines recent data that reveal TMEM163 to be a zinc efflux transporter and a new member of the cation diffusion facilitator (CDF) family of mammalian zinc transporter (ZNT) proteins. It also discusses reports that implicate TMEM163 in various human diseases.

The universal Debye – Mayer – Kelly hybrid model was proposed for the description of the heat capacity from 0 K to the melting points of substance within the experimental uncertainty for the first time. To describe the heat capacity, the in-house software on the base of commercial one DELPHI-7 was used with a 95% confidence level. To demonstrate the perfect suitability of this model, a thermodynamic analysis of the heat capacities of the fourth group elements, and some compounds of the A^IIIB^V and A^IIB^VI phases was carried out. It produced good agreement within the experimental uncertainty. There is no a similar model description in literature.The Similarity Method is a convenient and effective tool for critical analysis of the heat capacities of isostructural phases, which was used as an example for diamond-like compounds. Phases with the same sum of the atomic numbers of elements (Z), such as diamond and B_0.5 N_{0.5 (cub)} (Z = 6); pure silicon (Si) and Al_0.5 P_0.5 (Z=14); pure germanium (Ge) and Ga_0.5 As_0.5 (Z = 32)); pure grey tin (alpha-Sn) and In_0.5 Sb_0.5, and Cd_0.5 Te_0.5 (Z = 50) have the same heat capacity experimental values in the solid state. The proposed models can be used to both different binary and multicomponent phases. It helps to standardize the physicochemical constants.

Low levels of physical activity (PA) and sedentarism are associated with the onset of different pathologies and health problems. Regular physical activity has been linked with being beneficial to the health of the general population. Within this framework of analysis, the aim of the present study is to analyse the existing association between the time spent doing physical activity and the expressed motives for doing so, from which the first innovative aspect of the paper emerges: the use of the time spent doing PA as a study variable of the phenomenon. The data analysed come from the latest special Eurobarometer survey about the sport and physical activity done in Europe. Using an exploratory factorial analysis and a structural equations model, we were able to find a six-dimensional factorial model that explains the reasons for doing PA, demonstrating that there is no relationship between the reasons for and time spent doing PA. Therefore, motivation is not a variable that explains the time spent doing PA and another type of variable must be used to explain the phenomenon if PA is to be incentivised.

Background: Inappropriate use of antibiotics has been reported to contribute to the emergence and increase of antimicrobial resistance (AMR) in the world. Antibiotics are prescription-only medicines to be dispensed to a person with a legal prescription inscribed by a qualified medical practitioner. Enforcing the dispensing of antibiotics with prescription is a way to promote the rational use of antibiotics and preventing the development and spread of AMR. It is, therefore, the responsibility of a pharmacist to dispense or supervise the dispensing of antibiotics in pharmacies and ensure its rational use. This study aimed to assess pharmacists’ knowledge, attitude and practice regarding the dispensing of antibiotics without prescription in Tanzania. Methods: An online semi-structured questionnaire was designed, tested and shared with licensed pharmacists in Tanzania through an invitation link sent in their official WhatsApp groups. A list of names, contacts and emails of licensed pharmacists obtained from the Pharmacy Council was used to directly contact and request pharmacist to fill the questionnaire, in case the pharmacist contact was not on WhatsApp, a text SMS invitation was sent. Study data were collected and managed using REDCap electronic data capture tools hosted at Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. Data were then downloaded and exported into Statistical Package for Social Sciences (SPSS) version 20 for data analysis; Chi-square test was used to test association for categorical data, where a p-value of less than 0.05 was considered statistically significant. Results: More than 75% of pharmacists had excellent knowledge about the legal requirements for dispensing antibiotics and of the AMR challenge. Of the interviewed pharmacists, seventy-four percent admitted to dispensing antibiotics without prescription in their daily practice. The main reasons for administering antibiotics without prescription were the profitability nature of pharmacy business, a failure of the patient to get a prescription and lack of stringent regulatory authorities. Penicillins, macrolides and floroquinolones were the classes of antibiotics mostly dispensed without a prescription. Conclusion: The study shows that the dispensing of antibiotics without prescription is a common practice in Tanzania. The regulatory authorities should make regular inspections in pharmacies to detect this malpractice. The community should be trained on the importance of taking laboratory tests before getting medications for their sickness by a qualified medical practitioner.

The past few years have brought substantial progress toward understanding how human cytomegalovirus (HCMV) enters the remarkably wide spectrum of cell types and tissues that the virus infects. Neuropilin-2 and platelet-derived growth factor receptor alpha (PDGFRa) were identified as receptors, respectively, for the trimeric and pentameric glycoprotein H/glycoprotein L (gH/gL) complexes that in large part govern HCMV cell tropism, while CD90 and CD147 were also found to play roles during entry. X-ray crystal structures for the proximal viral fusogen, glycoprotein B (gB), and for the pentameric gH/gL complex (pentamer) have been solved. A novel virion gH complex consisting of gH bound to UL116 instead of gL was described, and findings supporting the existence of a stable complex between gH/gL and gB were reported. Additional work indicates that the pentamer promotes a mode of cell-associated spread that resists antibody neutralization, as opposed to the trimeric gH/gL complex (trimer), which appears to be broadly required for the infectivity of cell-free virions. Finally, viral factors such as UL148 and US16 were identified that can influence the incorporation of the alternative gH/gL complexes into virions. We will review these advances and their implications for understanding HCMV entry and cell tropism.

Utility perceived by individuals is believed to be different from the utility experienced by that individual. System dynamicists implicitly categorize this phenomenon as a form of bounded rationality and traditionally employ a simple smoothing function to capture it. We challenge this generalization by testing it against an alternative formulation of utility perception that is suggested by modern theories of behavioral economics. In particular, the traditional smoothing formulation is compared with the peak-end rule in a simple theoretical model as well as in a medium-size model of electronic health record implementation. Experimentation with the models reveals that the way utility perception is formulated is important and might affect behavior and policy implications of system dynamics models.

The transmission of light is one of the key optical processes in the terrestrial environment (the atmosphere and underlying surfaces). The dependence of light transmittance on the illumination/observation conditions and optical properties of the atmosphere–underlying system can be studied using the integro-differential radiative transfer equation. However, for numerous applications a set of analytical equations is needed to describe the transmitted light intensity and flux. In this paper, we describe various analytical techniques to study light transmittance through light scattering and absorbing media. A physical significance and improved mathematical accuracy of approximations are provided using the analytical models for the diffusion exponent, average cosine of the light field, spherical and plane albedos. The accuracy of various approximations is studied using exact radiative transfer calculations with various scattering phase functions, single-scattering albedos, observational conditions, and optical depths.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

Despite great interest in how dynamic fluctuations in psychological states such as mood, social safety, energy, present-focused attention, and burnout impact stress, well-being, and health, most studies examining these constructs use retrospective assessments. Here, we discuss how ecological momentary assessments (EMAs) address methodological issues associated with retrospective reports, able to reveal dynamic associations between psychological states at small timescales that are often missed in stress and health research. In addition to helping researchers characterize daily and within-day fluctuations and temporal dynamics between different health-relevant processes, EMAs can elucidate mechanisms through which interventions reduce stress and enhance well-being. EMAs can also be used to identify changes that precede critical health events, which can in turn be used to inform the delivery of ecological momentary interventions (EMIs of just-in-time interventions) that prevent such events from occurring. To enable this work, this narrative review provides examples of scales and single-item questions used in EMA studies, makes concrete recommendations for researchers seeking to employ EMAs in their research, and discusses limitations of EMA methods. In doing so, we aim to encourage the use of these methods in research given that, when used carefully, EMA methods are well-poised to greatly advance our understanding of how intrapersonal dynamics affect stress levels, well-being, and human health.

Minirhizotron tubes were installed to monitor root growth dynamics of mature Shiraz grapevines in a rootstock trial established in the hot climate Riverina region of New South Wales, Australia. The vertical root distribution and seasonal root growth dynamics of Shiraz on own-roots and Shiraz grafted on the rootstocks Ramsey, 140 Ruggeri and Schwarzmann was studied for five seasons across a seven-year period to a depth of 60 cm. New root production was significantly influenced by genotype, soil depth, season, growth stage and year. Soil moisture and soil tem-perature were monitored at 10, 30 and 60 cm in the last two seasons. Soil moisture at 30 cm and soil temperature at all three depths were significant predictors of root growth. New root numbers were significantly higher in 140 Ruggeri than the other rootstocks. To the depth studied, 140 Ruggeri roots were evenly distributed from the topsoil down, whereas the majority of roots of Schwarzmann and Shiraz were located at intermediate depths in the 10-40 cm ad 20-40 cm zones respectively, while Ramsey roots were found at 20 cm or below. Depending on genotype, root growth occurred across several phenological stages but tended to peak at flowering. In some years we observed root growth in early and late winter at rates exceeding that of autumn, and this was associated with warmer temperatures during this period. Overall, seasonal rooting dynamics were responsive to abiotic factors but dominated by genotype.

Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phos-phatidylcholine, cholesterol and monosialogangliosides (NL) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that NL will preserve SH-SY5Y neuroblastoma cell viability following hypoxic injury and will reduce injury in mice following middle cerebral artery occlusion (MCAO). Neuroblastoma were exposed to 20-hour physoxic (5% oxygen) or hypoxic (1% oxygen) condition without or with NL (100 or 300 µg/mL). Viability was measured using calcein-AM fluorescence and SH-SY5Y gene expression of antioxidant proteins heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and superoxide dismutase 1 (SOD1) were measured by quantitative polymerase chain reaction. C57BL/6J mice were treated with saline (N=8) or NL (10000 ug/mL, N=7) while undergoing 60-minute MCAO followed by reperfusion. Day 2 post-injury neurologic impairment score and infarction size were compared. Neuroblastoma showed reduced viability following hypoxia that was reversed by NL. NL increased gene expression of HO-1, NQO1 and SOD1 versus controls. NL-treated mice showed reduced neurologic impairment and brain infarct size (18.8±2% versus 27.3±2.3%, p=0.017) versus controls. NL reduced stroke injury in mice subjected to MCAO likely through induction of an antioxidant stress response. NL is a candidate novel agent for stroke.

The human oral microbiome refers to an ecological community of symbiotic and pathogenic microorganisms found in the oral cavity. The oral cavity is a suitable environment that provides various kinds of biological niches such as teeth, tongue, and oral mucosa. The oral cavity is the gateway between the external environment and the human body, maintaining oral homeostasis, protecting the mouth, and preventing disease. On the flip side, the oral microbiome plays an important role in triggering, development, and progression of oral and systemic diseases. Currently, disease diagnosis through the analysis of the human oral microbiome has been realized with the recent development of innovative detection technology, and is overwhelmingly promising compared to the previous era. It has been found that patients with oral diseases and systemic diseases have variations in the oral microbiome compared to normal subjects. This narrative review provides insight into the pathophysiological role that oral microbiome plays in influencing oral and systemic diseases, and updates the knowledge related to the oral microbiome over the past 30 years. A wide range of updates was provided with the latest knowledge of the oral microbiome to help researchers and clinicians in both academic and clinical aspects. The microbial community information can be utilized in non-invasive diagnosis and help develop a new paradigm in precision medicine, which will benefit human health in the era of post-metagenomics.

Price markups and firm Tobin’s Q ratios are widely believed to have been increasing in the past several decades. Various models for the calculation of price markups have been developed, but each have methodological drawbacks and some results are poorly reflective of the near past wider macroeconomic experience. This paper defines an approach for the definition and measurement of markup pricing using the measure of Economic Rent and The Capital Asset Pricing Model. The results show limited markup pricing for The UK’s FTSE 100 companies (2018-2023), but that that certain Real Estate, Technology/Media and Financial Services/Equity Investment firms have enjoyed higher price markup levels. An analysis of the business models of these firms is used to qualitatively propose explanations for such markups. Finally, this work offers a formal proof that that expected price markup is equal to Tobin’s Q and finds that the empiric market level of markup is near equivalent to the market Tobin’s Q; differences between the markup and Tobin’s Q at the level of the firm are equally assessed.

The Hubble parameter H(z), as a function of redshift, is modified by the presence of a new term originated from the extrinsic curvature in an embedded space-time. Assuming an asymptotic expansion factor $a\sim 0$ or, equivalently $z\rightarrow \infty$, it is obtained a nearly resemblance of the present model ($\beta$-model) with quintessence $w$CDM model with $H(z)\sim H_{wCDM}(z)$ at background level. In conjunction with $\Lambda$CDM, we test the models using a pack of recent datasets like that of the ``Gold 2018'' growth data, the best-fit Planck2018/$\Lambda$CDM parameters on the Cosmic Microwave Background (CMB), the Baryon Acoustic Oscillations (BAO) measurements, the Pantheon Supernovae type Ia and the Hubble parameter data with redshift ranging from $0.01 < z < 2.3$. Performing the Akaike Information Criterion (AIC) to ascertain the statistical viability of the model from Jeffreys' scale, we apply a joint likelihood analysis to the data with the Markov Chain Monte Carlo (MCMC) method. We find that the present model is in very good agreement with observations with a close statistical equivalence with the $\Lambda$CDM and $w$CDM cosmologies at 1-$\sigma$ level. We also show that a mild alleviation of the $\sigma$ tension between the growth amplitude factor and the matter content $(\sigma_8$-$\Omega_m)$ of the observations from CMB and Large Scale Structure (LSS) probes. A comparison of the aforementioned full pack of data in MCMC chains is made with the resulting MCMC from Pantheon SNIa+$H(z)$ in order to analyse the sensitivity of the models and how they respond to a cosmography analysis on the evolution of $H(z)$ and the deceleration parameter $q(z)$. In this sense, we find that only the $\beta$-model can be unaffected to the variations of the previous datasets due to its several minima in the likelihood (degeneracies) of the related parameters with an overall percentage relative difference only up to 4$\%$.

Only a handful of microbial mosquito larval pathogens have been described to date. Sampling of several natural enzootic infections of mosquito larvae in southwestern Florida indicated the presence of microbial pathogens capable of extensive larval mortality. Microscopic analysis of one sample site revealed extensive apparent growth of a Pythium-like microbe on mosquito lar-vae, with highest infection observed on the siphon and head regions. Structures consistent with sporangia were seen on infected insects after lactophenol blue staining, and higher resolution scanning electron micrographs (SEM) showed sporangia and encysted zoospores targeting the head and siphon regions. The isolate was single colony purified and molecular identification targeting the ITS and COX1 loci coupled to phylogenetic reconstruction indicated that the isolate belonged to the Pythium genus, but was distinct from its closest characterized species, P. angusta-tum. Morphological features were characterized, with the isolate showing rapid growth on all mycological media tested and relatively high thermotolerance, capable of robust growth at 37oC, and hence was designated, P. thermoculicivorax. Sampling from a second series of natural infec-tions of mosquito larvae resulted in the molecular identification of three Trichoderma isolates, one with high similarity to T. strigosum, and the other two clustering with, but distinct from, T. asperellum. These data highlight the occurrence of natural enzootic infections of mosquito larvae, potentially as a resource for the identification of new mosquito pathogens.

With end-to-end encryption for video streaming services becoming more popular, network administrators face new challenges in preserving network performance and user experience. Video ads may cause traffic congestion and poor Quality of Experience. Because of the natural variation in user interests and network situations, traditional algorithms for increasing QoE may face limitations. To solve this problem, we suggest a novel method that uses user facial emotion recognition to deduce QoE and study the effect of ads. We use open-access Face Emotion Recognition (FER) datasets and extract facial emotion information from actual observers to train machine learning models. Participants were requested to watch ad videos and provide feedback, which will be used for comparison, training, testing, and validation of our suggested technique. Our tests show that our approach beats the ITU-T P.1203 standard in terms of accuracy by 37.1%. Our method provides a hopeful answer to the problem of increasing user engagement and experience in video streaming services.

(1) Background: The typical transporter protein, P-glycoprotein (P-gp), has been proven to be associated with multidrug resistance (MDR). Pyxinol and 24S-Pyxinol amino acid ester derivatives had been demonstrated to be promising P-gp inhibitors for reversal of tumor MDR in KBV cells, however, their roles in MDR reversal in other tumor-resistant cells are still unclear. (2) Methods: In the present study, we synthesized 40 amino acid ester derivatives of Pyxinol and 24S-Pyxinol. The MDR reversal effects of these derivatives were evaluated in A549/Tax, MCF-7/ADR, and HCT-8/VCR cells using the CCK-8 assay. Subsequently, western blot assay, intracellular Rhodamine123 (Rh123) accumulation assay and P-gp ATPase activity assay were utilized to investigate the effects of active compound on P-gp. Molecular docking was used to predict the possible binding patterns of active compound to P-gp. Moreover, based on UPLC-Q/TOF-MS cellular metabolomics technology to identify endogenous differential metabolites and metabolic pathways associated with tumor MDR effects of the active compound. (3) Results: The results of the CCK-8 assay showed that compounds 8, 14, 16, 17, 18, 23, 25, 34, 36, 37 exhibited strong MDR reversal effect in A549/Tax, MCF-7/ADR and HCT-8/VCR cells, which were screened by reversal fold (RF) greater than 5. Among them, 10 μM of derivative 37 (new compound) showed the outstanding activity (RF: 15.31) in reversing MDR in A549/Tax cells. Compound 37 could act as a substrate for P-gp and inhibit the efflux function of P-gp by competitively binding to the binding site of antitumor drugs. Meanwhile, the molecular docking results confirmed that compound 37 was identified to under-go high-affinity binding to the drug binding site of P-gp. In addition, 14 endogenous differential metabolites and 6 metabolic pathways involved closely associated with the reversal of tumor MDR effects of compound 37 were identified. (4) Conclusions: Overall, a new candidate compound 37 (24S-3-L-threonyl-Pyxinol) could be provided for reversing tumor MDR by this study.

A vivid debate is ongoing in the scientific community about statistical malpractice and the related publication bias. No general consensus exists on the consequences and this is reflected in heterogeneous rules defined by scientific journals on the use and reporting of statistical inference. This paper aims at discussing how the debate is perceived by the agricultural economics community and implications for our roles as researchers, contributors to the scientific publication process, and teachers. We start by summarizing the current state of the p-value debate and the replication crisis, and commonly applied statistical practices in our community. This is followed by motivation, design, results and discussion of a survey on statistical knowledge and practice among the researchers in the agricultural economics community in Austria, Germany and Switzerland. We conclude that beyond short-term measures like changing rules of reporting in publications, a cultural change regarding empirical scientific practices is needed that stretches across all our roles in the scientific process. Acceptance of scientific work should largely be based on the theoretical and methodological rigor and where the perceived relevance arises from the questions asked, the methodology employed, and the data used but not from the results generated. Revised and clear journal guidelines, the creation of resources for teaching and research, and public recognition of good practice are suggested measures to move forward.

We investigate the effect of geopolitical risk on the returns of the Information Technology, Communication Services, and Consumer Staples sector firms within the S&P 500 index. We use the event study methodology and perform more than 17,000 regressions to provide empirical evidence at the sector level that geopolitical risk leads to different responses across these 3 sectors. The response of the Information Technology sector is negative for all event windows under study, except the one spanning 10 days prior to the geopolitical event and 10 days after. The Communication Services sector has positive returns as a result of geopolitical events for all event windows, except the one from the geopolitical event date and 5 days after. The Consumer Staples sector shows a negative impact on geopolitical risk for all event windows except the one from the geopolitical event date and 5 days after, demonstrating a negative correlation to the Communication Services sector.

Following legalization, cannabis has quickly become an important horticultural crop in Canada and increasingly so in other parts of the world. However, due to previous legal restrictions on cannabis research there are limited scientific data on the relationship between nitrogen (N), phosphorus (P), and potassium (K) supply (collectively: NPK) and the crop yield and quality. This study examined the response of a high delta-9-tetrahydrocannabinol (THC) Cannabis sativa cultivar grown in deep-water culture with different nutrient solution treatments varying in their concentrations (mg L^-1) of N (70, 120, 180, 250, 290), P (20, 40, 60, 80, 100) and K (60, 120, 200, 280, 340) according to a central composite design. Results demonstrated that inflorescence yield responded quadratically to N and P, with the optimal concentrations predicted to be 194 and 59 mg L^-1, respectively. Inflorescence yield did not respond to K in the tested range. These results can provide guidance to cultivators when formulating nutrient solutions for soilless cannabis production and demonstrates the utility of surface response design for efficient multi-nutrient optimization.

A series of Si-bearing MgAl₂O₄-spinels were synthesized at 1500-1650 °C and 3–6 GPa. These spinels had SiO₂ contents up to ~1.03 wt%, and showed a substitution mechanism of Si⁴⁺ + Mg²⁺ = 2Al³⁺. Unpolarized Raman spectra were collected from polished single grains, and displayed a set of well-defined Raman peaks at ~610, 823, 856 and 968 cm^-1 which had not been observed before. Aided with the Raman features of natural Si-free MgAl₂O₄-spinel, synthetic Si-free MgAl₂O₄-spinel, natural low quartz, synthetic coesite, synthetic stishovite and synthetic forsterite, we infer that these Raman peaks should belong to the SiO₄ groups. The relations between the Raman intensities and SiO₂ contents of the Si-bearing MgAl₂O₄-spinels suggest that at some P-T conditions some Si must adopt the M-site. Unlike the SiO₄ groups with very intense Raman signals, the SiO₆ groups are largely Raman-inactive. We have further found that the Si cations primarily appear on the T-site at P-T conditions ≤ ~3–4 GPa and 1500 °C, but attain a random distribution between the T-site and M-site at P-T conditions ≥ ~5–6 GPa and 1630–1650 °C. This Si-disordering process observed for the Si-bearing MgAl₂O₄-spinels hints that similar Si-disordering might happen to the (Mg,Fe)₂SiO₄-spinels (ringwoodite), the major phase in the lower part of the mantle transition zone of the Earth and the index mineral for the very strong shock stage experienced by extraterrestrial materials. The likely consequences have been explored.

Flood events and their associated damages have escalated significantly in the last few decades. To add to the gruesome situation, many reports and studies warn that flood risk would aggravate significantly in future periods due to significant alterations in the climate patterns and socio-economic dynamics. Floodplain mapping is looked upon as a viable option to tackle this global issue as it provides both quantitative and qualitative information on flood dynamics. Moreover, with the increasing availability of global data and enhancement in computational simulations, it has become easier to simlate flooding patterns at large scales. This study deter-mines the usability of publicly available datasets in capturing flood hazards over Canada. Run-off data set from the North American Regional Reanalysis (NARR), along with a few other rele-vant inputs are fed to CaMa-Flood, a robust global hydrodynamic model to generate flooding patterns for 1 in 100 and 1 in 200-yr return period events over Canada . The simulated maps are compared and validated with the existing maps of a few flood-prone regions in Canada, thereby establishing their performance over both regional and country-scale. Later, the simulated flood-plain maps are used in conjunction with property related information at 34 cities (within the top 100 populous cities in Canada) to determine the degree of exposure due to flooding in 1991, 2001, and 2011. The results indicate that around 80 percent of inundated spots belong to high and very-high hazard classes in a 200-yr event, which is roughly 4 percent more than simulated for 100-yr event. NARR derived floodplain maps perform very well while compared over the six flood-prone regions. While analyzing the exposure of properties to flooding, we notice an in-crease in the number during the last three decades, with the maximum rise observed in Toronto, followed by Montreal, and Edmonton. To disseminate the extensive flood-related information, a web-based public tool, Flood Map Viewer (http://www.floodmapviewer.com/) is developed. The development of the tool was motivated by the commitment of the Canadian government to provide $63 M over the next three years for the completion of flood maps for higher-risk areas. The study reaches out to demonstrate how publicly available datasets can be utilized with a lesser degree of uncertainty in representing flooding patterns over large regions. The flood re-lated information derived from the study can be used along with vulnerability for quantifying flood risk, which will help in developing appropriate pathways for resilience building for long-term sustainable benefits.

The purpose of this study was to explore the role of moral distress on physician burnout during COVID-19. Physicians in the US were interviewed between February and March 2021; 479 responded to our survey. Results indicated that moral distress was a key mediator in explaining the relationship between perceived organizational support, medical specialization, emotional labor, and coping on burnout. There was no support for increased burnout among female physicians, and contracting COVID-19 likewise did not play a role in burnout. Our findings suggest that physician burnout can be mitigated by increasing perceived organizational support; likewise, physicians who engaged in deep emotional labor and problem-focused coping tended to fare better when it came to feelings of moral distress and subsequent burnout.

Cannabis has developed into a multi-billion dollar industry that relies on clonal propagation of elite genetics with desirable agronomic and chemical phenotypes. While the goal of clonal propagation is to produce genetically uniform plants, somatic mutations can accumulate during growth and compromise long-term genetic fidelity. Cryopreservation is a process in which tissues are stored at cryogenic temperatures, halting cell division and metabolic processes to facilitate high fidelity germplasm preservation. In this study, a series of experiments were conducted to optimize various stages of cryopreservation and develop a protocol for long-term germplasm storage of Cannabis sativa. The resulting protocol uses a standard vitrification procedure to cryopreserve nodal explants from in vitro shoots as follows: Nodes were cultured for 17 hours in a pre-culture solution (PCS), followed by a 20 minute treatment in a loading solution (LS), and a 60 minute incubation in plant vitrification solution 2 (PVS2). The nodes were then flash frozen in liquid nitrogen, re-warmed in an unloading solution at 40°C, and cultured on basal MS culture medium in the dark for 5 days followed by transfer to standard culture conditions. This protocol was tested across 13 genotypes to assess the genotypic variability. The protocol was successful across all 13 genotypes, but significant variation was observed in tissue survival (43.3-80%) and regrowth of shoots (26.7-66.7%). Plants grown from cryopreserved samples were morphologically and chemically similar to control plants for most major traits, but some differences were observed in the minor cannabinoid and terpene profiles. While further improvements are likely possible, this study provides a functional cryopreservation system that works across multiple commercial genotypes for long-term germplasm preservation.