This paper presents an exact solution to the Timoshenko beam theory (TBT) for first-order analysis, second-order analysis, and stability. The TBT covers cases associated with small deflections based on shear deformation considerations, whereas the Euler–Bernoulli beam theory (EBBT) neglects shear deformations. Thus, the Euler–Bernoulli beam is a special case of the Timoshenko beam. The moment-curvature relationship is one of the governing equations of the EBBT, and closed-form expressions of efforts and deformations are available in the literature. However, neither an equivalent to the moment-curvature relationship of EBBT nor closed-form expressions of efforts and deformations can be found in the TBT. In this paper, a moment-shear force-curvature relationship, the equivalent in TBT of the moment-curvature relationship of EBBT, was presented. Based on this relationship, first-order and second-order analyses were conducted, and closed-form expressions of efforts and deformations were derived for various load cases. Furthermore, beam stability was analyzed and buckling loads were calculated. Finally, first-order and second-order element stiffness matrices were determined.

1) Background: Bipolar or manic-depressive disorder is a malign mental disease that frequently faces social stigma. Educational and thinking models are needed to increase people’s awareness and understanding of the disorder. The arts have potential to achieve this goal. 2) Methods: This paper builds on the recent use of heavy metal music as a thinking and education model. It emphasizes the artistic component of heavy metal and its potential to characterize the symptomatology during the episodes of (hypo)mania and depression and the recurrence of these episodes. Heavy metal music has diversified into subgenres that become allegorical to both the symptoms of episodes and the recurrence of bipolar cycles. 3) Results: Examples of songs are given that mirror distinct facets of the disorder. 4) Conclusion: Although the links drawn between art (music) and science (psychiatry) are inherently subjective, such connections might be used to trigger a learning process, facilitate judgment and decision-making, and induce affective reactions and memory formation in the listener. The approach may facilitate collaborative efforts and serve healthcare professionals and educators as a communication tool to aid the public’s comprehension of the disease and an associated social paradox: On one hand, bipolar disorder incurs substantial costs to society. On the other hand, it benefits from the creative artistic and scientific endeavors of bipolar individuals from which cultural and political gains may ensue.

This paper deals with the techno-economic study of the hybrid renewable energy system based on energy storage aspect under the form of hydrogen and methane. Indeed, with the intermittency of the renewable energy sources such as photovoltaic and wind energy, several problems of produced energy injection to the power system network can be encountered due to the shortage or the excess of these sources. This situation appeals the use of systems that ensure the stability of network based on the storage of energy surplus into gas using electrolyzer systems, which will be used afterward to cover the eventual shortage. In the present paper, the study of performance of each pathway of methane and hydrogen storage has been performed by the treatment of multiple scenarios via different architecture case studies in an Algerian location. Whereas, the energy produced by the photovoltaic system, the wind energy and the gas micro turbine sources are considered similar in each case. The modeling and simulation of the studied system operation under optimization criteria has been performed in this work, where the main aim is to define the appropriate configuration taking into account the different with low costs of investment, maintenance operation and immediate reactivity with a big storage capacity.

For the past several decades, abdominal prenatal ultrasonography has been the most significant technology in obstetrics with a long-established application. However, the frequency, exposure time, thermal and cavitation exposure indices, and increased acoustic output of the ultrasonic waves may be harmful to the embryo/fetus and might increase susceptibility to Autism Spectrum Disorder (ASD). The increase in the prevalence of ASD is associated with an affluent ethnicity, high socioeconomic status, and high parental education where prenatal ultrasonography is readily available and affordable. Enhanced biophysical adverse effects may link the analogous increase in prenatal ultrasonography and autism, and prenatal ultrasonography may emerge as a risk factor for autism. Radiography usage provides historical evidence for this fact: the predominant past opinion was that exposure to X-rays during pregnancy caused no significant risk to a fetus. However, the association between X-ray exposure and childhood leukemia was only established 40 years after X-ray use began. This review focuses on excessive PUS usage and ASD development. Public Abstract Advancements in medical technology over the past several decades have made prenatal ultrasound more frequently accessible to expecting mothers during their pregnancy, especially for the affluent. A parallel development in health care is the increase in autism diagnoses (Autism Spectrum Disorder, or ASD) in children of affluent families. There is a general lack of studies of the impact of prenatal ultrasound on fetuses, especially around varying attributes such as frequency, duration of exposure, and thermal and cavitation indices. There is also a historical precedent set, where exposing fetuses to X-rays was not found to be harmful until it was linked to the development of childhood leukemia decades later. This paper seeks to establish a need to further study these attributes of prenatal ultrasound overuse and their possible impact on a developing fetus, with a special focus on the occurrence of Autism.

Noise reduction in medical images is a perplexing undertaking for the researchers in digital image processing. Noise generates maximum critical disturbances as well as touches the medical images quality, ultrasound images in the field of biomedical imaging. The image is normally considered as gathering of data and existence of noises degradation the image quality. It ought to be vital to reestablish the original image noises for accomplishing maximum data from images. Medical images are debased through noise through its transmission and procurement. Image with noise reduce the image contrast and resolution, thereby decreasing the diagnostic values of the medical image. This paper mainly focuses on Gaussian noise, Pepper noise, Uniform noise, Salt and Speckle noise. Different filtering techniques can be adapted for noise declining to improve the visual quality as well as reorganization of images. Here four types of noises have been undertaken and applied on medical images. Besides numerous filtering methods like Gaussian, median, mean and Weiner applied for noise reduction as well as estimate the performance of filter through the parameters like mean square error (MSE), peak signal to noise ratio (PSNR), Average difference value (AD) and Maximum difference value (MD) to diminish the noises without corrupting the medical image data.

Malaysia implemented a movement control order (MCO) to curb the spread of the SARS-CoV-2 virus in March 2020. Despite healthcare services remaining operational, rising COVID-19 infections and MCO restrictions have forced healthcare professionals to seek a compromise between service capacity and standard operating procedure compliance. A cross-sectional survey was conducted among public and private sector doctors, dentists and pharmacists to determine how lockdown measures impacted healthcare services. Responses from 413 doctors, 193 dentists, and 163 pharmacists were analysed. Pharmacy services remained mostly unaffected throughout the MCO. In contrast, operational capacities for surgical and dental services were severely affected during the MCO. All service sectors reported restricting patients or accompanying individuals at the workplace, reductions in staffing capacity, and shortened patient contact time at various degrees. Many pharmacy and medical participants reported supplying extended medication supplies to patients. Adoption of virtual healthcare services was generally poor. All private service sectors suffered financial losses ranging between 59 to 75%. Periodic assessments of the healthcare system throughout the pandemic are required to identify which patients have their treatment compromised so that healthcare managers and policy makers can plan and implement appropriate interventions that help alleviate pressure within the health system.

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

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

In the paper, the authors consider the generating functions of the Hermite polynomials and their squares, present explicit formulas for higher order derivatives of the generating functions of the Hermite polynomials and their squares, which can be viewed as ordinary differential equations or derivative polynomials, find differential equations that the generating functions of the Hermite polynomials and their squares satisfy, and derive explicit formulas and recurrence relations for the Hermite polynomials and their squares.

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

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

We monitored the water quality and hydrological conditions of a horizontal subsurface constructed wetland (HSSF-CW) in Beijing, China, for 2 years. We simulated the area rate constant and the temperature coefficient with the first-order kinetic model. We examined the relationships between the nitrogen (N) removal rate, N load, seasonal variations in the N removal rate, and environmental factors, such as the area rate constant, temperature, and dissolved oxygen (DO). The effluent ammonia (NH₄⁺-N) and nitrate (NO₃⁻-N) concentrations were significantly lower than the influent concentrations (p<0.01, n=38). The NO₃⁻-N load was significantly correlated with the removal rate (R²=0.9566, p<0.01), but the NH^₄+-N load was not correlated with the removal rate (R²=0.0187, p>0.01). The area rate constants of NO₃⁻-N and NH₄⁺-N at 20 °C were 27.01±26.49 and 16.63±10.58 m∙yr⁻¹, respectively. The temperature coefficients for NO₃⁻-N and NH₄⁺-N were estimated at 1.0042 and 0.9604, respectively. The area rate constants for NO₃⁻-N and NH₄⁺-N were not correlated with temperature (p>0.01). The NO₃⁻-N area rate constant was correlated with the corresponding load (R²=0.9625, p<0.01). The NH₄⁺-N area rate was correlated with DO (R²=0.6922, p<0.01), suggesting that the factors that influenced the N removal rate in this wetland met Liebig's law of the minimum.

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

POH (Peri Orbital Hyperpigmentation) represents a minor clinical entity that attracts immense aesthetic damages and it generates social integration difficulties. This review focuses on the etiopathogenic causes of this entity, differentiating and reclassifying this defect as having, on the one hand, genetic causes of melanic hyperproduction – for Fitzpatrick cutaneous phototypes IV and V – and, on the other hand, both genetic and acquired vascular causes, in individuals with light-coloured skin phototypes. Hence, there is a big difference in the field of pathogenic treatment, for the two entities. In addition, this study notes the direct relationship between skin aging and POH, especially for aquired vascular causes. In this reasoning, other aesthetic deficiencies of the skin in the palpebral area should be also considered, like: blepharochalasis, wrinkles, the anatomical causes of the lower eyelid shading, symmetrical or asymmetric suborbital oedema. All of these issues will complicate the therapeutic decision and subsidiary, the pharmaceutical advice. In this context, the review shows the guidelines for a honest councelling of the patients, pointing the efficiency limit for the topical pharmaceutical medication (depigmentants, exfoliants) versus the necessity of minimally invasive or/ and surgical treatments (in blefarochalasis).

In the field of nasal delivery, one of the most fascinating applications is the delivery of drugs directly to the central nervous system bypassing the blood brain barrier. This approach would provide a series of benefits, such as dose lowering and direct targeting of potent drugs, ultimately reducing their systemic side effects. Recently, clinical trials have explored the nasal administration of insulin for the treatment of Alzheimer’s disease, with promising results. The use of nanomedicines could provide further options for making nose-to-brain delivery reality. In particular, apart from the selection of devices able to deposit the formulation in the upper part of the nose, surface modification of these nanomedicines appears the key strategy to optimize the delivery of drugs from the nasal cavity to the brain. In this review, nanomedicines delivery approaches based on surface electrostatic charges, mucoadhesive polymers, as well as chemical moieties targeting nasal epithelium, will be discussed and critically evaluated for nose-to-brain delivery.

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

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

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

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

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

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

This paper presents an approach to the Euler-Bernoulli beam theory (EBBT) using the finite difference method (FDM). The EBBT covers the case of small deflections, and shear deformations are not considered. The FDM is an approximate method for solving problems described with differential equations. The FDM does not involve solving differential equations; equations are formulated with values at selected points of the structure. Generally, the finite difference approximations are derived based on fourth-order polynomial hypothesis (FOPH) and second-order polynomial hypothesis (SOPH) for the deflection curve; the FOPH is made for the fourth and third derivative of the deflection curve while the SOPH is made for its second and first derivative. In addition, the boundary conditions and not the governing equations are applied at the beam’s ends. In this paper, the FOPH was made for all of the derivatives of the deflection curve, and additional points were introduced at the beam’s ends and positions of discontinuity (concentrated loads or moments, supports, hinges, springs, etc.). The introduction of additional points allowed us to apply the governing equations at the beam’s ends and to satisfy the boundary and continuity conditions. Moreover, grid points with variable spacing were also considered, the grid being uniform within beam segments. First-order analysis, second-order analysis, and vibration analysis of structures were conducted with this model. Furthermore, tapered beams were analyzed (element stiffness matrix, second-order analysis). Finally, a direct time integration method (DTIM) was presented. The FDM-based DTIM enabled the analysis of forced vibration of structures, with damping taken into account. The results obtained in this paper showed good agreement with those of other studies, and the accuracy was increased through a grid refinement. Especially in the first-order analysis of uniform beams, the results were exact for uniformly distributed and concentrated loads regardless of the grid. Further research will be needed to investigate polynomial refinements (higher-order polynomials such as fifth-order, sixth-order…) of the deflection curve; the polynomial refinements aimed to increase the accuracy, whereby non-centered finite difference approximations at beam’s ends and positions of discontinuity would be used.

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

Background: CCL11 (eotaxin) is a chemokine with an important role in allergic conditions. Recent evidence indicates that CCL11 plays a role in brain disorders as well. Aims: This paper reviews the associations between CCL11 and aging, neurodegenerative, neuroinflammatory and neuropsychiatric disorders.Methods: Electronic databases were searched for original articles examining CCL11 in neuropsychiatric disorders.Results: CCL11 is rapidly transported from the blood to the brain through the brain-blood barrier. Age-related increases in CCL11 are associated with cognitive impairments in executive functions, episodic and semantic memory and, therefore, this chemokine was described as an “endogenous cognition deteriorating chemokine” (ECDC) or “accelerated brain-aging chemokine” (ABAC). In schizophrenia, increased CCL11 is not only associated with impairments in cognitive functions, but also with key symptoms including formal thought disorders. Some patients with mood disorders and premenstrual syndrome show increased plasma CCL11 levels. In diseases of old age, CCL11 is associated with lowered neurogenesis and neurodegenerative processes and, as a consequence, increased CCL11 increases risk towards Alzheimer's Disease. Polymorphisms in the CCL11 gene are associated with stroke. Increased CCL11 also plays a role in neuroinflammatory disease including multiple sclerosis. In animal models, neutralization of CCL11 may protect against nigrostriatal neurodegeneration. Increased production of CCL11 may be attenuated by glucocorticoids, minocycline, resveratrol and anti-CCL11 antibodies.Conclusion: Increased CCL11 production during inflammatory conditions may play a role in human disease including age-related cognitive decline, schizophrenia, mood disorders and neurodegenerative disorders. Increased CCL11 production is a new drug target in the treatment and prevention of those disorders.

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

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

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

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

Why are pieces of spaghetti generally broken into three to ten segments instead of two as one thinks? How can one obtain the desired number of fracture segments? For these problems, in this paper a strand of spaghetti is considered an elastic rod, and the finite-element software ABAQUS is used to simulate the detailed fracture dynamics of the elastic rod. By changing the size (length and diameter) of the rod, the relevant data on the fracture limit curvature and the number of fractured segments of the elastic rod are obtained. The ABAQUS simulation results confirm the scientific judgment of B. Audoly and S. Neukirch (Fragmentation of rods by cascading cracks: Why spaghetti does not break in half. Phys Rev Lett 95: 095505). Using dimensional analysis to fit the finite-element data, two relations of the elastic rod fracture dynamics are obtained: (1) the relationship between the fracture limit curvature and the diameter, and (2) the relationship between the number of fracture segments and the diameter-length ratio. Results reveal that when the length is constant, the larger the diameter (the smaller the diameter-length ratio D/L), the smaller the limit curvature; and the larger the diameter-length ratio D/L, the fewer the number of fractured segments. The relevant formulations can be used to obtain the desired number of broken segments of spaghetti by changing the diameter-to-length ratio.

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

The present study aims to develop an efficient numerical method for computing the diffraction and radiation of water waves with horizontal long cylindrical structures, such as floating breakwaters. A higher-order scheme is used to discretize geometry of the structure as well as the relevant physical quantities. As the kernel of this method, Wehausen’s free-surface Green function is calculated by a newly-developed Gauss-Kronrod adaptive quadrature algorithm after elimination of its Cauchy-type singularities. To improve computational efficiency, a Chebyshev approximation approach is applied to a fast calculation of the Green function that needs evaluation thousands of times. In addition, OpenMP parallel technique is used to the formation of influence coefficient matrix, which significantly reduces CPU time. Finally, computations are performed on wave exciting forces and hydrodynamic coefficients for the long cylindrical structures, either floating or submerged. Comparison with other numerical and analytical methods demonstrates good performance of the present method.

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

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

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

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

This study presents an exact solution to the free vibration analysis of a uniform Timoshenko beam, with a harmonic vibration being assumed. The Timoshenko beam theory covers cases associated with small deflections based on shear deformation and rotary inertia considerations. In this paper, a moment-shear force-circular frequency-curvature relationship was presented. The complete study was based on this relationship and closed-form expressions of efforts and deformations were derived. The free vibration response of single-span systems and spring-mass systems was analyzed; closed-form formulations of matrices expressing the boundary conditions were presented and the natural frequencies were determined by solving the eigenvalue problem. Systems with intermediate mass, spring, or spring-mass system were also analyzed. Furthermore, first-order dynamic stiffness matrices in local coordinates were derived. Finally, a second-order analysis of beams resting on an elastic Winkler foundation was conducted. The results obtained in this paper were in good agreement with those of other studies.

This paper presents an approach to the Timoshenko beam theory (TBT) using the finite difference method (FDM). The Timoshenko beam theory covers cases associated with small deflections based on shear deformation and rotary inertia considerations. The FDM is an approximate method for solving problems described with differential equations. It does not involve solving differential equations; equations are formulated with values at selected points of the structure. In addition, the boundary conditions and not the governing equations are applied at the beam’s ends. The model developed in this paper consisted of formulating differential equations with finite differences and introducing additional points at the beam’s ends and at positions of discontinuity (concentrated loads or moments, supports, hinges, springs, brutal change of stiffness, spring-mass system, etc.). The introduction of additional points allowed us to apply the governing equations at the beam’s ends. Moreover, grid points with variable spacing were considered, the grid being uniform within beam segments. First-order, second-order, and vibration analyses of structures were conducted with this model. Furthermore, tapered beams were analyzed (element stiffness matrix, second-order analysis, vibration analysis). Finally, a direct time integration method (DTIM) was presented; the FDM-based DTIM enabled the analysis of forced vibration of structures, with damping taken into account. The results obtained in this paper showed good agreement with those of other studies, and the accuracy was increased through a grid refinement. Especially in the first-order analysis of uniform beams, the results were exact for uniformly distributed and concentrated loads regardless of the grid.

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

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

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

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

This study aims to explore the link between public investment and private investment in South Africa, using time series data spanning 40 years (1980–2020). Private investment is subdivided into credit to private sector (CPS) and foreign direct investment (FDI). Several econometric methodologies were used in the study, including the unit root test, cointegration test, and Error Correction Method (ECM). The Phillips-Perron (PP) test results point out that all the variables are stationary at levels with the exception of public investment (PI) which is stationary at first difference. The co-integration test reveals that the variables have a long-run equilibrium relationship. According to the findings of the ECM, public investment has a negative relationship with private investment (as measured by credit to private sector and foreign direct investment). The conclusion implies that in South Africa, public investment crowds out private investment. Other results revealed that, RGDP crowds in credit to private sector while crowding out foreign direct investment. Finally, the ECM findings show that government consumption expenditure crowds out credit to private sector and foreign direct investment. The residuals are homoskedastic and show no serial correlation, indicating that the model is adequate, according to the test for adequacy.

The prevalence of internet gaming disorders (IGD) is considerably high among youth, especially with social isolation imposed by the ongoing COVID-19 pandemic. IGD adversely affects mental health, quality of life, and academic performance. The Internet Gaming Disorder Scale (IGDS9-SF) is designed to detect IGD according to DSM-IV diagnostic criteria. However, inconsistent results are reported on its capacity to diagnose IGD evenly across different cultures. To ensure the suitability of the IGDS9-SF as a global measure of IGD, this study examined the psychometric properties of the IGDS9-SF in a sample of Sri Lankan university students (N = 322, mean age =17.2 ± 0.6, range = 16-18 years, 56.5% males) and evaluated its measurement invariance across samples from Sri Lanka, Turkey, Australia, and the USA. Among Sri Lankan students, a unidimensional structure expressed good fit, invariance across different groups (e.g., gender, ethnicity, and income), adequate criterion validity (strong correlation with motives of internet gaming, daily gaming duration, and sleep quality), and good reliability (alpha = 0.81). Males and online multiplayers expressed higher IGD levels, greater time spent gaming, and more endorsement of gaming motives (e.g., Social and Coping) than females and offline players. Across countries, the IGDS9-SF was invariant at the configural, metric, and scalar levels, albeit strict invariance was not maintained. The lowest and highest IGD levels were reported among Turkish and American respondents, respectively. In conclusion, the IGDS9-SF can be reliably used to measure IGD among Sri Lankan youth. Because the scale holds scalar invariance across countries, its scores can be used to compare IGD levels in the studied countries.

In this paper, we consider a fourth-order suspension bridge equation with nonlinear damping term |u_t|^m-2u_t and source term |u|^p-2u. We give necessary and sufficient condition for global existence and energy decay results without considering the relation between m and p. Moreover, when p>m, we give sufficient condition for finite time blow-up of solutions. The lower bound of the blow-up time T_max is also established. It worth to mention that our obtained results extend the recent results of Wang (J. Math. Anal. Appl., 2014) to the nonlinear damping case.

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

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic still persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the Spike surface protein of the virus are regularly observed in the new variants, potentializing the emergence of novel viruses with different tropism from the current ones, which may change the severity and symptoms of the disease. Growing evidence has shown that mutations are being selected in favor of variants that are more capable of evading the action of neutralizing antibodies. In this context, the most important factor guiding the evolution of SARS-CoV-2 is its interaction with the host’s immune system. Thus, as current vaccines cannot block the transmission of the virus, measures complementary to vaccination, such as the use of masks, hand hygiene, and keeping environments ventilated remain essential to delay the emergence of new variants. Importantly, in addition to the involvement of the immune system in the evolution of the virus, we highlight several chemical parameters that influence the molecular interactions between viruses and host cells during invasion and are also critical tools making novel variants more transmissible. In this review, we dissect the impacts of the Spike mutations on biological parameters such as (1) increase of Spike binding affinity to hACE2; (2) bound time for the receptor to be cleaved by the proteases; (3) how mutations associate with increase of RBD up-conformation state in the Spike ectodomain; (4) expansion of uncleaved Spike protein in the virion particles; (5) increment of Spike concentration per virion particles; and (6) evasion of the immune system. These factors play key roles in the fast spreading of SARS-CoV-2 variants of concern, including the Omicron.

In the paper, the authors establish two identities, which can be regarded as nonlinear differential equations, for the generating function of Eulerian polynomials, find two identities for the Stirling numbers of the second kind, and present two identities for Eulerian polynomials and higher order Eulerian polynomials, pose two open problems about summability of two finite sums involving the Stirling numbers of the second kind. Some of these conclusions meaningfully and significantly simplify several known results.

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

This study presents a prediction model based on Logistic Growth Curve to evaluate the effectiveness of Movement Control Order (MCO) on COVID-19 pandemic spread. The evaluation assesses and predicts the growth models. The estimated model is a forecast-based model that depended on partial data from the COVID-19 cases in Malaysia. The model is then studied together with the effectiveness of the three phases of MCO implemented in Malaysia. Evidence from this study suggests that results of the LGC prediction model match with the progress and effectiveness of the MCO to flatten the curve, thus helped to control the spike in number of active COVID-19 cases and spread of COVID-19 infection growth.

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

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

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

A critical discussion on the computation of the dispersion diagram in periodic one-dimensional guiding structures is carried out. In particular, an analysis is presented of the pros and cons of combined methods that make use of full-wave simulations done with commercial software packages with further analytical post-processing based on simplifications brought by an equivalent circuit model of the structure. Some of the most common methods reported in the literature are reviewed and their advantanges and limitations highlighted. Our discussion is complemented with several selected numerical examples in order to discuss the most relevant aspects that a potential user of these methods should be aware of. Special attention is paid to the relevant role played by the high-order coupling between the two halves of a symmetric unit cell of the periodic structure.

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

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

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

Indonesia is an interesting case study for students of sustainable development and sustainable energy due to its ability to connect the multiple “worlds” it has become part of. Indonesia is an important bridge to Muslim countries, the voice of the Global South in the G20 and a main pillar of the 134-country-strong G77. Indonesia’s development trajectory is also key to the achievement of the Paris Climate Agreement as well as of the 2030 Agenda. Students can learn from how Indo-nesia address contradictions that would have been unsurmountable for other countries. Indone-sia’s energy transition offers helpful lessons, because of its aspiration to become a developed country by 2045. This goal is only possible when a country is able to effectively address barriers and caveats to sustainable energy. It is interesting how Indonesia focuses on silver linings and come up with pragmatic solutions to energy-related issues. This is followed by the “teaching guide,” which provides recommendations how the lessons from Indonesia can be embedded into a learning experience. The “learning activation approach” is introduced, which encourages stu-dents to systematically reflect on the complexity of selected contexts and understand this com-plexity by looking at the technical issues and processes that allow decision-making.

Autism spectrum disorder (ASD) refers to the diverse range of neurodevelopmental disorders accompanying impairments in social interaction, difficulties in communication, and stereotyped or repetitive behaviors. Unlike the older term, autism, the newer term, ASD, better reflects the broad range of autistic symptoms and denotes a single diagnostic category of autism accompanied by numerous conditions. The pineal hormone melatonin is a well-known neuroprotectant and circadian entrainer. This hormone crosses the placenta and enters the fetal circulation, then conveys photoperiodic information to the fetus during pregnancy. These actions enable normal sleep patterns and circadian rhythms, followed by normal neurodevelopment. Melatonin also reduces oxidative stress, which is harmful to the central nervous system. Therefore, melatonin acts as a neuroprotectant and circadian entrainer, and may reduce the risk of neurodevelopmental disorders such as ASD.

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

The most popular schemes of digital potentiometers (DP) and digital-to-analog converters (DAC) are considered. DP and DAC use how elements of parameter adjustment of active RC-filters. The circuits of the DAC on the Kelvin-Varley divider, the Kelvin divider based on the R-2R matrix, and the architecture of the DAC with a segmented circuit are shown. The internal structure of DP an Analog Devices and Intersil company is shown, and also the DP switching circuits in a tunable low-pass filter and a band-pass filter, a programmable inverting amplifier and a voltage regulator are presented.

Autism Spectrum Disorders (ASD) are neurodevelopmental disturbances affecting social skills, whose incidence worldwide is dramatically increasing. Together with the rise of ASD prevalence, several immune conditions are following the same trend, including Atopic Dermatitis (AD), with a possible clinical relationship with ASD. To date, their pathogenesis is still unknown, but several studies highlighted the relevance of gene-environment interactions to the onset of both disorders. Among potential contributing factors, microRNAs (miRNAs), small molecules capable of controlling gene expression and targeting mRNA transcripts, might represent one of the major circulating link, unraveling the connections between neurodevelopmental and immune conditions. We conducted a systematic literature review, under the PRISMA guidelines, trying to define the panel of common miRNAs involved in both ASD and AD. The review retrieved articles published until December 13, 2018, in PubMed, ScienceDirect, PsycARTICLES and Google Scholar. We found a handful works dealing with miRNAs in ASD and AD, with the most overlapping dysregulated miRNAs being miR-146 and miR-155. Two possible compounds are abnormally regulated in both ASD and AD subjects, possibly cross-contributing to the interactions between the two disorders, setting the basis to investigate more precisely the possible link between ASD and AD from another, not just clinical, perspective.

Signal-to-noise ratio (SNR) is an important index to evaluate radiation performance and image quality of optical imaging systems under low illumination background. Under the nighttime lighting condition, the illumination of remote sensing objects is low and varies greatly, usually ranging from several lux to tens of thousands of lux. Nighttime light remote sensing imaging requires high sensitivity and large dynamic range of detectors. Luojia 1-01 is the first professional nighttime light remote sensing satellite in the world. In this paper, we took the nighttime light remote sensing camera carried on the satellite as research object, proposed an in-orbit SNR test method based on time series images to overcome the problem of low spatial resolution. We first analyzed the process of luminous flux transmission between objects and satellite and established a radiative transfer model. By combining the parameters of large relative aperture optical system and high sensitivity CMOS device, we established SNR model and specially analyzed the effect of exposure time and quantization bits on SNR. Finally we used the proposed in-orbit test method to calculate SNR of lighting images acquired by satellite. And the measured result is in good agreement with the model predicted data. Under the condition of 10lx illumination, the SNR of typical objects can reach 27.02dB, which is much better than the requirement of 20dB for engineering application.

Chivalry is a concept that is both familiar and distant to many Japanese. There is no other social class in the world that resembles knights as much as the samurai in Japan. However, why is it that there is such a gap between knights and warriors, even though they are both warriors with the same social status and honor? This paper reviews the legal debates on the deposed sovereigns’ rights have emerged since 20th century. Among them, the right to appoint knights by heads of deposed royal families is one of the focal points. The author begins with a comprehensive review of legal debates on the subject. Six principles on the appointment are extracted from the review. Then, a comparison between chivalry and Bushido, the Japanese Samurai code, was carried out.

Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.

Peer-to-peer (P2P) energy trading is a new data-driven business model currently being trialed within the energy sector. Introducing P2P transactions to an essential service such as energy could have far-reaching implications for individuals and the grid. This paper raises considerations and questions from social, economic/markets and regulatory points of view, that should be understood and addressed by societies and policymakers. It does this by considering under what circumstances it is reasonable to conceptualize P2P energy trading as part of the sharing economy, and drawing parallels to the sharing economy experience in other sectors. In order to reap the full societal benefits, while avoiding considerable risks to infrastructure and individuals, a policy approach promoting dialogue and innovation is necessary. We suggest the regulatory sandbox is the most appropriate tool to achieve this and would help avoid the breakdown of trust between policymakers and platform companies observed in other sectors.

The capacity and the mechanism of the adsorption of aqueous barium (Ba), cobalt (Co), strontium (Sr) and zinc (Zn) by Ecuadorian (NatAllo) and synthetic (SynAllo-1 and SynAllo-2) allophanes were studied as a function of contact time, pH and metal ion concentration using kinetic and equilibrium experiments. The mineralogy, nano-structure and chemical composition of the allophanes were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy and specific surface area analyses. The evolution of adsorption fitted to a pseudo-first-order reaction kinetics, where equilibrium between aqueous metal ions and allophane was reached within < 10 min. The metal ion removal efficiencies varied from 0.7 to 99.7 % at pH 4.0 to 8.5. At equilibrium, the adsorption behavior is better described by the Langmuir model than by the Dubinin-Radushkevich model, yielding sorption capacities of 10.6, 17.2 and 38.6 mg/g for Ba^(2+), 12.4, 19.3 and 29.0 mg/g for HCoO_2^-, 7.2, 15.9 and 34.4 mg/g for Sr^(2+) and 20.9, 26.9 and 36.9 mg/g for Zn^(2+), respectively, by NatAllo, SynAllo-2 and SynAllo-1. The uptake mechanism is based on a physical adsorption process. Allophane holds great potential to remove aqueous metal ions and could be used instead of zeolites, montmorillonite, carbonates and phosphates for wastewater treatment.

The magnetic properties of RCo3B2 compounds, with heavy rare earths, are investigated by using magnetic measurements and electronic structure calculations. The cobalt sublattice magnetizations are very small and antiparallel oriented to rare earths moments. Contributions of cobalt moments to the Curie constants were also shown. The cobalt magnetic behavior has been analyzed in spin fluctuations model. The presence of short-range order above the Curie temperatures in RCo3B2 compounds with R=Tb, Dy, and Ho has been attributed to reminiscent R5d-Co3d interactions.

Glaucoma is a disease associated with retina of eye. Presently, millions of human being is suffering from this disease. Early detection of these diseases can save the people from blindness. Therefore, various methods have been developed for its detection. In this paper, we have studied the reported methods and summarized their performance in terms of accuracy of detection.

Materials design for processing and application requires fundamental understanding of their properties based interatomic interaction. The use of the novel concept of total bond order density (TBOD) as a single quantum mechanical metric to characterize the internal cohesion of a crystal and correlate with the calculated physical properties is particularly appealing. This requires detailed first-principles calculation of the electronic structure, interatomic bonding and related properties. In this article, we use this new concept and apply it to chalcogenide crystals based on data obtained from 25 crystals: Ag₂S, Ag₂Se, Ag₂Te, As₂S₃, As₂Se₃, As₂Te₃, As₄Se₄, Cu₂S, Cu₂Se, Cu₂Te, Cu₄GeS₄, Cu₂SnS₃, Cu₂SnSe₃, GeS₂, GeSe₂, Ge₄Se₉, Sb₂S₃, Sb₂Se₃, Sb₂Te₃, SnS, SnSe, CdSe, CdTe, ZnSe, and ZnTe. Together with the calculated optical and mechanical properties, we demonstrate the efficacy of using this novel approach for materials design that could facilitate the exploration and development of new chalcogenide crystals and glasses. Moreover, the TBOD and its partial components (PBOD) could be the key descriptors in machine learning protocol for broader scale design when a large database is available.

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

I deal with perception and action (e.g. movements) using results from Synergetics, a comprehensive mathematical theory of the selforganized formation ("emergence“) of spatial, temporal, or functional structures in complex systems. I illustrate basic concepts such as order parameters (ops), enslavement, complexity reduction, circular causality first by examples of well known collective, spontaneous modes of human behavior such as rhythmic clapping of hands etc., and then by face recognition. The role played by ops depends on context. In the case of face (or pattern) recognition an op represents the concept of an individual face (action of mind) and it enslaves the action (firing rates) of neurons (body). This insight allows me to interpret syndroms as order parameters playing their mind/body double role. I present criteria for the identification of ops and discuss their general properties including error correction and "remedy“ of deficiencies. Contact is made with a recent paper by Sabine Koch on embodied aesthetics. My approach includes the saturation of attention at various time scales (ambiguous figures/fashion). Adopting a psychological perspective, I discuss some ingredients of beauty such as proportionality and symmetry, but also the importance of irregularities.

In the paper, by virtue of the Faà di Bruno formula, some properties of the Bell polynomials of the second kind, and an inversion formula for the Stirling numbers of the first and second kinds, the authors establish meaningfully and significantly two identities which simplify coefficients in a family of ordinary differential equations associated with higher order Bernoulli numbers of the second kind.

In software development, developers received bug reports that describe the software bug. Developers find the cause of bug through reviewing the code and reproducing the abnormal behavior that can be considered as tedious and time-consuming processes. The developers need an automated system that incorporates large domain knowledge and recommends a solution for those bugs to ease on developers rather than spending more manual efforts to fixing the bugs or waiting on Q&A websites for other users to reply to them. Stack Overflow is a popular question-answer site that is focusing on programming issues, thus we can benefit knowledge available in this rich platform. This paper, presents a survey covering the methods in the field of mining software repositories. We propose an architecture to build a recommender System using the learning to rank approach. Deep learning is used to construct a model that solve the problem of learning to rank using stack overflow data. Text mining techniques were invested to extract, evaluate and recommend the answers that have the best relevance with the solution of this bug report.

Background: Post-traumatic stress disorder (PTSD) is a common debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested for these patients. Deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. 2) Methods: We review the neurocircuitry and up to date clinical concepts that may be of relevance for the implementation of DBS in posttraumatic stress disorder (PTSD). 3) Results: The role of DBS in treatment-refractory PTSD patients has been investigated relying on both preclinical and clinical studies. 4) Conclusions: DBS for PTSD is in its preliminary phases and likely to provide hope to patients with medical refractory PTSD following the results of randomized controlled studies.

This paper first discusses a fractional-order Liu system of order as low as 2.7 and shows its chaotic characteristics by carrying out numerical simulations such as Lyapunov exponents, bifurcation diagrams and phase portraits. Then, by using the topological horseshoe theory and computer-assisted proof, the existence of chaos in the system is verified theoretically. Finally, the fractional-order system is implemented on a Field Programmable Gate Array (FPGA) and the results obtained show that the fractional-order Liu system is indeed chaotic.

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

In light of the latest trends in global installed capacities, the importance of variable renewable energy sources (VRES) to future energy supply systems is evident. Despite this, the inherent intermittency of VRES remains an obstacle to their widespread adoption. Green hydrogen is often suggested as an energy carrier that can account for this in a sustainable manner. In the analysis, a robust European energy system in the context of 2050 and with 100% VRES energy supply is designed through an iterative minimal cost-optimization approach that ensures robust security of supply over 38 weather-year scenarios (1980-2017). The impact of spatial VRES variability is factored in by defining exclusive VRES groups within each optimization region and, from this, it can be seen that higher numbers of groups in each region offer cheap electricity generation locations to the optimizer and thus decrease the total annual cost of the system. Beyond this, the robust system design and impact of inter-annual variability is identified by iteratively combining the installed capacities of different system designs obtained by applying 38 historical weather years. The robust system design outlined here has significantly lower capacities in comparison to the maximum regional capacities obtained in the first round of optimization.

Permanent magnet synchronous motor (PMSM) AC servo system shows the characteristics of uncertainty, time-varying and non-linearity, which makes it difficult for traditional PID control to achieve ideal control effect. Fuzzy control has strong adaptability to the problems of parameter variation, non-linearity and model inaccuracy of the controlled object. Vector control strategy is used to study its control principle and the realization of SVPWM. Because the motor object has certain fractional order characteristics, the fuzzy parameter self-tuning PIλ control is chosen as the position regulator of servo motor. It combines the accuracy of fractional order PI control and the adaptability of fuzzy control. A simulation model of PMSM three-closed-loop system is built in MATLAB/Simulink environment. The results show that the control method is effective and can satisfy the trajectory tracking of servo control.

Despite the successes earned in cataloguing and finding the role of the most of molecular components in living matter, the “biochemical and molecular” perspective, popular in biology, medicine and genetics, is unable to give account for crucial topics as the faculty of living systems to “feel”, to “perceive” what a given stimulus implies (means, indeed) for their survival. Condensed matter physics too, if bounded to a local, short-range, and perturbative approach, fails dramatically. This is also due to the role commonly assigned to water – actually the main constituent of living matter – deemed for long time to be merely chemical (as “solvent” or a reactant/product). Nonetheless, today many evidences show how living matter can be right conceived as a super-structured coherent water-based matrix, suggesting that the characterization of bio(electro)chemical and physical processes undertaken at molecular level in living matter, would let us unable to answer a question like this: what allows an amoeba, moreover without any neurons, to “know” to get closer to a nutrient or escape away from a toxin? I propose that to pursue such a fundamental inquiry it’s necessary an essentially relational approach, that is: to consider the living being at its grounding as the outcome of a physical history of relationships where symmetry-breakings, dissipation and coherence yield the emergence of the living state of matter, conceivable only as a time-dependent open process, and not as a portraited “body”. The effective tools to build up such an approach may be retrieved in far-from-equilibrium thermodynamics (TD), symmetry-breakings and gauge-fields theory, science of complexity, within the framework of a Quantum Field Theory. Indeed, within a field-view of matter, and of water especially, as it has been developed by a Quantum Electrodynamic (QED) description of condensed matter, it’s possible to give account for a physical basis too such an epistemologically elusive, though crucial, feature of living systems (i.e.: perception and meaning). The emerging landscape allows some important meditations about adaptation, evolution, ecodynamics, and about different conceptions of complexity and “information” in living realm. Furthermore, some neuroscientific themes like consciousness, qualia and their links to artificial intelligence could be supplied with due insights.

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

In this paper, a novel voltage control strategy of stand-alone operation brushless doubly fed induction generator for variable speed constant frequency wind energy conversion systems was presented and discussed particularly. Based on the model of the generator power system, the proposed direct flux control strategy employs a nonlinear reduced-order generalized integrator based resonant sliding-mode control scheme to directly calculate and regulated the output value of converter which control winding stator required so as to eliminate the instantaneous errors of power winding stator flux, and no involving any synchronous rotating coordinate transformations. The stability, robustness and convergence capability of the proposed control strategy were described and analyzed. Owing to no extra current control loops involved, therefore simplifying the system configuration design and enhancing the transient performance. Constant converter switching frequency was achieved by using space vector pulse width modulation, which reduce the harmonic of generator terminal voltage. In addition, experimental results prove the feasibility and validity of the proposed scheme, and excellent steady and dynamic state performance is achieved.

All life on Earth uses three integrated molecular systems in which genetic information contained in DNA base sequences is transmitted to ribosomes by RNA and a genetic code, then translated into the amino acid sequences of structural and catalytic proteins. Therefore, the most important point for understanding the origin of life is to determine how such systems could emerge from random processes on the early Earth. In this review, two alternatives are compared: the RNA world hypothesis and the [GADV]-protein world hypothesis. [GADV] refers to four amino acids, Gly [G], Ala [A], Asp [D] and Val [V] that are conserved in the amino acid sequences of many common proteins. Here I will argue that the origins of the three primary processes required for life to begin can be better explained by the GADV hypothesis than the RNA world hypothesis. The GADV hypothesis also incorporates a conversion process by which random polymers can evolve into proteins with ordered sequences.

The voluminous daily output of autism research has become increasingly disconnected, existing largely within highly specific subspecialty areas, and lacking cross-disciplinary linkages of context, theory, and findings to inform a unified body of knowledge. Robust syntheses of published research across the fields of psychiatry, cellular and molecular biology, neurology, endocrinology, immunology, behavioral and social sciences, and pedagogy may help clarify and extend current knowledge by guiding more efficient future research efforts investigating underlying causes, developmental divergences, novel treatments, and specific, sensitive biological markers in autism. This synthesis of interdisciplinary research indicates the hypothalamic-pituitary-adrenal (HPA) stress axis may be at the center of an interaction among sex steroids, immune function, signaling protein transcriptions, neurogenesis, and dysregulation of brain structures sending or receiving projections from the HPA stress axis. These interaction manifest observably as a range of sexually dimorphic behaviors and functional limitations often falling within the current diagnostic features of Autism Spectrum Disorder (ASD). The pathogenicity of endocrine dysregulation may serve as a valuable model for developing a cohesive theory of ASD by explaining how the HPA and connected brain areas respond to extreme conditions of dysregulated endocrine signaling to cause symptoms associated with autism.

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

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

Autism Spectrum Disorder (ASD) is a neuro-developmental disorder that limits social interactions, cognitive skills, and abilities. Since ASD can last during an affected person's entire life cycle, the diagnosis at the early onset can yield a significant positive impact. The current medical diagnostic systems (e.g., DSM-5/ICD-10) are somewhat subjective; rely purely on the behavioral observation of symptoms, and hence, some individuals often go misdiagnosed or late-diagnosed. Therefore, researchers have focused on developing data-driven automated diagnosis systems with less screening time, low cost, and improved accuracy while significantly reducing professional intervention. Human Activity Analysis (HAA) is considered one of the most promising niches in computer vision research. This paper aims to analyze its potentialities in the automated detection of autism by tracking the exclusive characteristics of autistic individuals such as repetitive behavior, atypical walking style, and unusual visual saliency. This review provides a detailed inspection of HAA-based autism detection literature published in 2011 on-wards depicting core approaches, challenges, probable solutions, available resources, and scopes of future exploration in this arena. According to our study, deep learning outperforms machine learning in ASD detection with a classification accuracy of 76\% to 95\% on different datasets comprise of video, image, or skeleton data that recorded participants performing a large number of actions. However, machine learning provides satisfactory results on datasets with a small number of action classes and has a range of 60\% to 93\% accuracy among numerous studies. We hope this extensive review will provide a comprehensive guideline for researchers in this field.

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

This paper discusses the concept of fractional derivative with complex order from the application point of view. It is shown that a fractional derivative is hermitian, if and only if the order is real. The hermitian part of complex order derivatives behave like allpass filters with almost logarithmic phase.

1) Background: Keloids occur after the failure during the wound-healing process, persist the inflammation and are refractory to various treatments. The pathogenesis of keloids is still unclear. We previously analyzed the gene expression profiles in keloid tissue using microarray and Northern blot analysis and found that HtrA1 was markedly upregulated in the keloid lesions. HtrA1 is a member of the HtrA family of serine protease, has been suggested to play a role in the pathogenesis of various diseases including age-related macular degeneration and osteoarthritis by modulating proteins in extracellular matrix or cell surface. We focused on HtrA1, analyzed the localization and the role in keloid pathogenesis. 2) Methods: Twenty seven keloid patients and seven unrelated patients were enrolled in this study. We performed in situ hybridization analysis, immunohistochemical analysis, western blot analysis and cell proliferation assay. 3) Results: First, the fibroblast-like cells expressed HtrA1 higher in the active keloid lesions than in the surrounding lesions in situ hybridization. Second, the proportion of HtrA1-positive cells in keloid was higher than that of in normal skin significantly in immunohistochemical analysis. Third, HtrA1 protein was up-regulated, relative to normal skin tissue samples in western blot analysis. Finally, silencing of HtrA1 gene expression suppressed the cell proliferation significantly. 4) Conclusion: HtrA1 was highly expressed in keloid tissues and the suppression of HtrA1 gene inhibited the proliferation of keloid-derived fibroblasts. HtrA1 may promote keloid development through accelerating cell proliferation and remodeling keloid-specific extracellular matrix or cell surface molecules. HtrA1 is suggested to have an important role in keloid pathogenesis.

Since January, the disease caused by the Sars Cov-2 virus has spread and following pandemic. In a few months, the virus is seriously affecting the health systems of the various countries of the world and placing people in difficult psychological conditions. Few scientific resources on mental health have been published but still no one has proposed an action plan to cope the future psychological problems.This manuscript provides a plan to easily frame the priorities of mental health area related to COVID-19 to be taken into consideration which should be disseminated and that should be known by all health professionals and also by the major administrators of public health.

Endometrial Cancer (EC) is the sixth most commonly occurring cancer in women with 380 000 cases in 2018. Sadly, EC morbidity and mortality are continuously increasing, therefore the medical society have a substantial need for an accurate and inexpensive diagnostic test for EC early detection and a prognostic tool for treatment planning and evaluation. Considering experience with different types of cancers C-reactive protein (CRP) appears to be a promising diagnostic and prognostic factor. Aiming to investigate its potential and in view of EC authors, this paper reviewed the following databases for metanalysis, randomized controlled trials and review articles published up to June 2020: Pubmed, Scopus, Google scholar and ClinicalKey. Studies indicate CRP >3.33 mg/l correlate with EC incidence with HR = 2.29 (p<0.05). Moreover, High-sensitivity CRP assay allows to detect CRP in very low concentrations and distinguish patients with endometriosis, soft tissue sarcomas and possibly EC. Preoperational and postoperational CRP, as well as its dynamic change are independent prognostic factors for EC and are more reliable if analyzed together. However, CRP-to-albumin ratio as well as Glasgow Prognostic Scale have greater prognostic value that CRP alone. Additionally, CRP is possibly a mediator of carcinogenesis and cancer progression through activation of inter alia FcgRs/MAPK/ERK, FcgRs/IL-6/AKT/STAT3 and FcgRs/NF-κB/NLRP3 pathways.

Background: Hereditary hematologic disorders (HHDs) originate from genetic factors that cause disruptions of blood homeostasis. The Thalassemia Unit, Najaf province, Iraq, keeps all medical records of all patients with HHD from the Najaf province. Objectives: We aimed to conduct an epidemiological study to obtain a comprehensive epidemiological picture with regard to sex distribution, and effects of blood groups and consanguinity. Patients and Methods: All registered HHD patients (until May 2019) in the Thalassemia Unit (1122 patients, aged 0.5-65 years old) were included in the study. Results: The prevalence of HHD in Najaf city is 75.6 per 100,000 population. The number of patients registered as new patients is increasing over the years. There are significantly more male than female HHD patients (Male=54.37%, Female=45.63%, p=0.023). The top 3 prevalent HHD are Major thalassemia (33.15%), intermediate thalassemia (31.91%), and Thalassemia+Sickle (12.65%). The highest percentage of patients were in the center of Najaf (56.42%) followed by Kufa, Mishkhab, Haidariah, Manathera, and Abbasiya. The distribution of blood groups and Rh factors of HHD patients in the Najaf population was not significantly different from that in the normal population. The consanguinity rate observed in our patients' parents (78.24%) was significantly higher (p<0.0001) as compared with the consanguinity rate in the population (45.8%). Conclusions: During the last few years, there was an increase in HHD cases in Najaf city and, therefore, there is an urgent need to increase awareness about the effects of consanguinity marriages on HHD in order to limit the incidence of HHD.

Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric problem with a few core symptoms: weaknesses in social behavior, verbal impairments, repetitive behavior and restricted interests. Beyond the core symptoms, autism has strong association with other disorders such as intellectual disability, epilepsy, schizophrenia among many others. This paper outlines a theory of ASD with capacity to connect heterogeneous ‘core’ symptoms, medical and psychiatric comorbidities as well as other etiological theories of autism in a unifying cognitive framework rooted in neuroscience and genetics. Cognition is embedded into an ever-developing structure modified by experiences, including the outcomes of environment influencing behaviors. We introduce the hypothesis that autism is caused by deficits in component-based cognition and the internal learning reinforcing machinery. Specifically, we outline our Cartesian Factor forming autoencoder like model that supports cognition by breaking combinatorial explosion and discuss the cognitive and neural processes behind our model. The high dimensionality of sensory information poses serious problems, since the brain can handle only 7±2 relevant variables at a time making processes, such as the extraction and encoding of the relevant variables and their efficient manipulation critical. These processes are influenced by previous experiences and the internal reward system. In addition, large delays of distributed information processing should be counteracted by learned predictive models to synchronize sensory, proprioceptive, and cognitive signals and have timely and accurate model-based actions. Impairments in any of these aspects may disrupt learning and execution. Combinations of small impairments may allow the solving of low complexity tasks but may become visible if learned variables and the related metric are improper and imprecise, respectively, especially if their number is large. We claim that social interactions are amongst the most challenging cognitive tasks in terms of the number of variables involved. In turn, they are highly susceptible to combinations of small impairments. We consider impairments as the basic colors of autism, whereas the combinations of diverse impairments make the palette of autism. In turn, social processes can be spoiled in many ways and can lead to diverse comorbidities.

Estimation of core and surface temperature is one of the crucial functionalities of the lithium-ion Battery Management System (BMS) towards providing effective thermal management, fault detection and operational safety. While, it is impractical to measure core temperature using physical sensors, implementing a complex estimation strategy in on-board low-cost BMS is challenging due to high computational cost and the cost of implementation. Typically, a temperature estimation scheme consists of a heat generation model and a heat transfer model. Several researchers have already proposed ranges of thermal models having different levels of accuracy and complexity. Broadly, there are first-order and second-order heat capacitor-resistor-based thermal models of lithium-ion batteries (LIBs) for core and surface temperature estimation. This paper deals with a detailed comparative study between these two models using extensive laboratory test data and simulation study to access suitability in online prediction and onboard BMS. The aim is to guide whether it’s worth investing towards developing a second-order model instead of a first-order model with respect to prediction accuracy considering modelling complexity, experiments required and the computational cost. Both the thermal models along with the parameter estimation scheme are modelled and simulated using MATLAB/Simulink environment. Models are validated using laboratory test data of a cylindrical 18650 LIB cell. Further, a Kalman Filter with appropriate process and measurement noise levels are used to estimate the core temperature in terms of measured surface and ambient temperatures. Results from the first-order model and second-order models are analyzed for comparison purposes.

Transdermal alcohol biosensors have the ability to detect the alcohol that emanates from the bloodstream and diffuses through the skin. However, they have suffered from long-term fouling of the sensor element and drift in the resulting sensor readings over time. Here, we report a disposable cartridge platform that solves the problem of sensor fouling, and an enzymatic detection pathway that minimizes baseline drift for sensitive detection. Laboratory characterization of the enzymatic alcohol sensor demonstrates a linear sensor range of between 0 and 50 mM. Further, we show continuous transdermal alcohol data recorded with a human subject over 48 hours.

In the paper, the author introduces the notions "multi-order logarithmic numbers" and "multi-order logarithmic polynomials", establishes an explicit formula, an identity, and two recurrence relations by virtue of the Faa di Bruno formula and two identities of the Bell polynomials of the second kind in terms of the Stirling numbers of the first and second kinds, and constructs some determinantal inequalities, product inequalities, logarithmic convexity for multi-order logarithmic numbers and polynomials by virtue of some properties of completely monotonic functions.

This paper investigates the effects of Inter-generational co-residence on health care market, and labor market outcomes, to see whether or not living under the same roof with at least one parent matters in health care market, and labor market behaviors in post-Affordable-Care Act (ACA) USA. The adopted analytical strategy involves not only looking at the gender differences in co-residence, and its effects on outcomes in the two markets, but also accounting for co-residence endogeneity following the recent literature. Unlike the recent literature that relies on instrumental variables methods, this study adopts a switching regression approach, defining inter-generational co-residence as an endogenous selection process using a binary probit equation, and modeled jointly with the extensive margins and intensive margins in the two markets. This novel approach results in a recursive trivariate probit model for each market, and estimated using penalized maximum likelihood methods. The results suggest that ACA by reorganizing the US health care market, seems to have reduced significantly disparities in health care access among males and females based on race, region of residence, place of birth, and citizenship. However not only do we observe significant differences in inter-generational co-residence status between males and females, we also find significant inequalities in the effects of co-residence on health care market, and labor market outcomes. In fact, co-residence is found to increase health care expenditure by 56.7% among females, while this figure increases to 74.2% among males. In addition co-residing individuals, while spending 69.7% more on health care annually are 1.22 times more likely to access health care, but 31% less likely to use health care intensively during the year. In the labor market, co-residence is found to reduce significantly hours of weekly labor supplied by 41% for females, and 55.6% for males. Furthermore co-residing individuals, while not significantly different in their likelihood of labor force participation, are 1.52 times less likely to work full time once they decide to participate, and also spend about 55.4% less time working in the labor market in post-ACA USA.

Using analytic approach we study the effect of HPA axis secretions to the emotional variation of bipolar II disorder patient. Modified Duffing – Van der Pol oscillator was used to model the emotional variation, that was solved analytically using multiple scale perturbation to obtain an asymptotic solution. The solution was graphed to understand the effect of the variation of the cortisol to the oscillator. It was observed that the increase or decrease of the HPA hormone from the basal level in the body system, affects the mood variation of bipolar II disorder patients.

Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together. Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.

Using a nonclassical symmetry of nonlinear reaction-diffusion equations, some exact multi-dimensional time-dependent solutions are constructed for a fourth-order Allen-Cahn-Hilliard equation. This models a phase field that gives a phenomenological description of a two-phase system near the critical temperature. Solutions are given for the changing phase of a cylindrical or spherical inclusion, allowing for a 'mushy zone' with mixed state that is controlled by imposing a pure state at the boundary. The diffusion coefficients for transport of one phase through the mixture, depend on the phase field value, since the physical structure of the mixture depends on the relative proportions of the two phases. A source term promotes stability of both of the pure phases but this tendency may be controlled or even reversed through the boundary conditions.