Background: The question of whether children are less likely to pass on SARS-CoV-2 is important for planning society’s response to the pandemic. A document available on the Charité hospital website has not been formally published but is frequently referred to as supporting the notion that viral loads are similar in children and adults. Methods: The summary data from this document was extracted and used to produce summary statistics for three age groups: younger children (ages up to 11), older children (ages 12 to 19) and adults (ages 20 and above). Viral loads between the two children’s groups and the adult group were compared using Welch’s t test, which only requires group means and standard deviations and which is robust against moderate departures from normality. Findings: Viral loads were significantly lower than in adults for both younger children (p=0.04) and older children (p=0.04). Overall, viral loads were lower in children than adults (p=0.005). Interpretation: For both younger and older children, on average those with detectable SARS-CoV-2 have significantly lower viral loads than adults. Funding: No funding was received for this analysis.

Hearing impairment is an immensely diagnosed genetic cause, 5% of the total world population effects with different kind of congenital hearing loss (HL). In third-world countries or countries where consanguineous marriages are more common the frequency rate of genetic disorders are at its zenith. Approximately, the incidence of hearing afflictions is ostensibly 7-8:1000 individuals whereas it is estimated that about 466 million peoples suffer with significant HL, and of theses deaf cases 34 million are children’s up to March, 2020. Several genes and colossal numbers of pathogenic variants cause hearing impairment, which aided in next-generation with recessive, dominant or X-linked inheritance traits. This review highlights on syndromic and non-syndromic HL (SHL and NSHL), and categorized as conductive, sensorineural and mixed HL, which having autosomal dominant and recessive, and X-linked or mitochondrial mode of inheritance. Many hundred genes involved in HL are reported, and their mutation spectrum becomes very wide. Mapping of pathogenic genes in consanguinity family is facilitated to understand the disease history. Review presents the bases of HL and also focused on various genetic factors that cause deafness like the basics of genetic inheritance, and classic and well-characterized inherited factors of it. It also overviews the application of linkage analysis, SNPs genotyping and whole exome sequencing methods, in mapping and identification of new locus, causative genes and their variants in families inherited with HL. Conclusively, this review supports researchers in understanding the location of chromosome, the causative genes and specific locus which causing deafness in humans.

External quantum efficiency of industrial-grade green InGaN light-emitting diodes (LEDs) has been measured in a wide range of operating currents at various temperatures from 13 K to 300 K. Unlike blue LEDs, the efficiency as a function of current is found to have a multi-peak character, which could not be fitted by a simple ABC-model. This observation correlated with splitting of LED emission spectra into two peaks at certain currents. The characterization data are interpreted in terms of non-uniformity of the LED active region, which is tentatively attributed to extended defects like V-pits. We suggest a new approach to evaluation of temperature-dependent light extraction and internal quantum efficiencies taking into account the active region non-uniformity. As a result, the temperature dependence of light extraction and internal quantum efficiencies have been evaluated in the temperature range mentioned above and compared with those of blue LEDs.

This article presents answers to the questions on superresolution and structured illumination microscopy as raised in the editorial of a recent publication [K. Prakash et al. arXiv, 2102.13649, 2021]. The answers are based on my personal views on superresolution in light microscopy, supported by reasoning. Discussed are the definition of superresolution, Abbe’s resolution limit and the classification of superresolution methods into non-linear-, prior-knowledge- and near-field-based superresolution. A further focus is put on capabilities and technical aspects of present and future structured illumination microscopy (SIM) methods.

Over the past decade, the credit quality of loan portfolios across most countries in the world remained relatively stable until the financial crises hit the global economy in 2007–2008. In this paper I discuss, the relationship between non-performing loans and economic landscape. Since 2008, nonperforming loans have been an increasingly hot topic in the international scene, due to their important and rising volume and their impact on the economy as a whole, on the banking system and on its credit supply. Since then, average bank asset quality deteriorated sharply due to the global economic recession. Yet the deterioration of loan performance was very uneven across countries. I am interested in explaining these differences in bank asset quality across countries and over time. In this paper, I therefore study the empirical determinants of non-performing loan (NPL) ratios using a data set for EU countries covering the past decade. The paper assumes that the spatial organization of banking systems and the geographical distribution of comercial banks branches, ATMs and GDP growth are major factors influencing the effectiveness in credit system. The aim of this paper is to construct a continuous and quantifiable model, which will demonstrate a role of economic condition, technology, competition, policy, business climate in Financial Stability. Main hypotheses suggests, that GDP growth, interest rate, new business, FDI, ATMs and geographical distribution of branches have an influences on NPL (non-performing loans).

Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.

The present paper aims to increase knowlodge of the methods of resistance estimating of concrete in situ by means of non-destructive tests used to integrate the quantitative results from cylindrical specimens (core). The results of experimental investigations carried out on concrete conglomerate samples of a school building are shown. The experimental campaign then will be presented like a case study, conducted on a series of concrete beams and pillars of an existing building. The distructive tests on cores were conducted at the Civil Structures Laboratory of the Engineering Department of the University of Campania "Luigi Vanvitelli". The expression obtained through the calibration procedure of the values of non-destructive tests with those provided by the core drills allowed to estimate the average values of the compressive strength of the concrete. It is highlighted how this result was achieved with a very limited core number provided that they are extracted in selected points and that there was a proportionality link with the resistances obtained from non distructive tests.

With a large number of annotated non-coding RNAs (ncRNAs), repetitive sequences are found to constitute functional components (termed as repetitive elements) in ncRNAs that perform specific biological functions. Bioinformatics analysis is a powerful tool for improving our understanding of the role of repetitive elements in ncRNAs. This chapter summarizes recent findings that reveal the role of repetitive elements in ncRNAs. Furthermore, relevant bioinformatics approaches are systematically reviewed, which promises to provide valuable resources for studying the functional impact of repetitive elements on ncRNAs.

This paper focuses on evaluating airline service quality from the perspective of passengers view. Until now a lot of researches has performed in airline service quality evaluation in the world but a little research has been conducted in Iran, yet. In this research a framework for measuring airline service quality in Iran is proposed. After reviewing airline service quality criteria, SSQAI model was selected because of its comprehensiveness in covering airline service quality dimensions. SSQAI questionnaire items were redesigned to adopt with Iranian airlines requirements and environmental circumstances in the Iran's economic and cultural context. This study includes fuzzy decision-making theory, considering the possible fuzzy subjective judgment of the evaluators during airline service quality evaluation. Fuzzy TOPSIS have been applied for ranking airlines service quality performances. Three major Iranian airlines which have the most passenger transfer volumes in domestic and foreign flights, were chosen for evaluation in this research. Results demonstrated Mahan airline has got the best service quality performance rank in gaining passengers' satisfaction with delivery of high quality services to its passengers, among the three major Iranian airlines. IranAir and Aseman airlines placed in the second and third rank, respectively, according to passenger's evaluation.Statistical analysis have been used in analyzing passenger responses. Due to abnormality of data, Non-parametric tests were applied. To demonstrate airline ranks in every criterion separately, Friedman test was performed. Variance analysis and Tukey test were applied to study the influence of increasing in age and educational level of passengers' on degree of their satisfaction from airline's service quality. Results showed that age has not significant relation with passenger satisfaction of airlines, however increasing in educational level demonstrated a negative impact on passengers' satisfaction from airline's service quality.

This paper proposes a game-theoretic framework for quantifying effects of strategic bidding behavior of load aggregators (LAs) on wholesale electricity market equilibrium. The independent system operator (ISO) employs double-sided auction design to settle transactions in the wholesale electricity market. Generating companies (GENCOs) and LAs submit their bids to the ISO in the economic model of supply function equilibrium. Under the smart grid paradigm, a LA participates in the electricity market on behalf of end-consumers to minimize their total payment for purchasing electricity. In this paper, bi-level programming (BLP) method is employed to determine optimal bidding strategy of self-interested market participants. In the upper level, the profit of intended market participant is maximized and in the lower level, the ISO clears the market via a bid-based security constrained economic dispatch (SCED). Also, competition of GENCOs and LAs is modeled as a non-cooperative game. To examine the effects of strategic bidding behavior of LAs on market equilibrium, the proposed model is applied to the IEEE 9-bus and the IEEE 30-bus test systems. According to numerical results, to allow the LAs to behave strategically along with the GENCOs makes the former better off and the latter worse off, while the net effect of this on total social welfare turns out to be case-contingent.

Laws and regulations make powerful contribution in addressing multitudes of public health concerns. We examined the Public Health Act (PHA) in Malawi to understand its relevance to the ever-growing and changing threats posed by infectious and non-infectious diseases. The current Public Health Act of Malawi came into effect in 1948 to protect and preserve public health. The Act has undergone several amendments, the last one being in 1975. It draws much of its inspiration and standards from the 19th century British laws on insanitary housing, poor ventilation, and drainage. Such laws are silent on emerging major public health concerns including non-communicable diseases (NCDs) such as cardiovascular diseases and diabetes as well as road traffic injuries. This makes the Act outdated and ill equipped to address the 21st century public health concerns. Although supplementary legislation such as the HIV/AIDS Act and Mental Treatment Act have recently been enacted, they are yet to be consolidated into the Public Health Act. Consequently, existing policies and strategic plans that are meant to address gaps in public health and ensure coordinated effort lack support of laws and regulations. The Act also places great emphasis on mandatory vaccinations, quarantine and isolation against smallpox, a disease that has long been eradicated. Furthermore, although the Public Health Act outlines powers, duties and penalties, it fails to reinforce acceptable behaviour due to the insignificant penalties for noncompliance. There is a need for immediate and prompt revision and restructuring of the Public Health Act based on scientific evidence. Such laws require adequate consultation and interaction with key experts and stakeholders from a wide range of disciplines.

Ongoing COVID-19 Pandemic has resulted into massive damage to various platforms of global economy which has caused disruption to human livelihood. Natural Language Processing has been extensively used in different organizations to categorize sentiments, perform recommendation, summarizing information and topic modelling. This research aims to understand the non-medical impact of COVID-19 on global economy by leveraging the natural language processing methodology. This methodology comprises of text classification which includes topic modelling on unstructured COVID-19 media articles dataset provided by Anacode. Like other Natural Language Processing algorithms, Latent Dirichlet allocation (LDA) and Non-negative matrix factorization (NMF) has been proposed to classify the media articles dataset in order to analyze COVID-19 pandemic impacts in the different sectors of global economy. Model Accuracy was examined based on the coherence and perplexity score which came out to be 0.51 and -10.90 using LDA algorithm. Both the LDA and NMF algorithm identified similar prevalent topics that was impacted by COVID-19 pandemic in multiple sectors of economy. Through intertopic distance map visualization produced by LDA algorithm, it can be reciprocated that general industries which includes children schooling, parental care, and family gatherings had the major impact followed by business sector and the financial industry.

Remote sensing image registration plays an important role in military and civilian fields, such as natural disaster damage assessment, military damage assessment and ground targets identification, etc. However, due to the ground relief variations and imaging viewpoint changes, non-rigid geometric distortion occurs between remote sensing images with different viewpoint, which further increases the difficulty of remote sensing image registration. To address the problem, we propose a multi-viewpoint remote sensing image registration method which contains the following contributions. (i) A multiple features based finite mixture model is constructed for dealing with different types of image features. (ii) Three features are combined and substituted into the mixture model to form a feature complementation, i.e., the Euclidean distance and shape context are used to measure the similarity of geometric structure, and the SIFT (scale-invariant feature transform) distance which is endowed with the intensity information is used to measure the scale space extrema. (iii) To prevent the ill-posed problem, a geometric constraint term is introduced into the L2E-based energy function for better behaving the non-rigid transformation. We evaluated the performances of the proposed method by three series of remote sensing images obtained from the unmanned aerial vehicle (UAV) and Google Earth, and compared with five state-of-the-art methods where our method shows the best alignments in most cases.

Forest community connections are crucial to ensure forest stewardship and sustainability. We explored the potential of mushrooming to enable such connections in contexts where these connections have been historically broken, alienating local people from forests. Taking the case of the recent devolution of a community forest (baldios) in central Portugal to the local population, we present a five-year pilot project to rework mycology from a mushroom-centered approach to a mushroom-in-baldios approach. Mushrooms were used as an entry-point to connect the forest ecology with the challenges of governance and community building. The devised activities provided an opportunity for people inside and outside the local community to adventure into the woods and find out more about their socio-ecological history, develop communal and convivial relationships and engage in the responsible gathering of wild mushrooms. However, the hosting of mushroomers to know, value and engage with the community forest recovery has constantly working against the enclosure of mushrooms to provide marketable forms of leisure. The outcome of these activities depends on the relationships established between mushrooms, mycologists, local administrators, commoners and poachers, all operating within a framework that favors the eradication of resources instead of long-term relationships that sustain places.

According to the operation conditions of time unlimited passive containment heat removal system (TUPAC), a separate effect experiment facility was established to investigate the heat transfer performance of steam condensation in presence of non-condensable gas. The effect of wall subcooling temperature, total pressure and mass fraction of the air on heat transfer process was analyzed. The heat transfer model was also developed. The results showed that the heat transfer coefficient decreased with the rising of subcooling temperature, the decreasing of the total pressure and air mass fraction. It was revealed that Dehbi’s correlation predicted the heat transfer coefficient conservatively, especially in the low pressure and low temperature region. The novel correlation was fitted by the data obtained in the following range: 0.20~0.45 MPa in pressure, 20% ~ 80% in mass fraction, 15°C ~ 45°C in temperature. The discrepancy of the correlation and experiment data was with ±20%.

The remaining capacity can only be measured with offline method. This brings great challenge for the online prediction of Li-ion battery’s RUL. A novel online prediction method for Li-ion battery’s RUL was proposed, which is based on multiple health indicators (HIs) and can be derived from the batteries’ historical operation data. Firstly, four indirect HIs were built according to the battery’s operation current, voltage and temperature data respectively. On that basis, a generalized regression neural network (GRNN) was developed to estimate the battery’s remaining capacity, and the non-linear autoregressive approach (NAR) was utilized to predict the battery’s RUL based on the estimated capacity value. Furthermore, to reduce the interference, twice wavelet denoising were performed with different thresholds. A case study is conducted with a NASA battery dataset to demonstrate the effectiveness of the method. The result shows that the proposed method can obtain Li-ion batteries’ RUL effectively.

Preconception lifestyle modification and reducing several known risk factors may have an influence on the future pregnancy outcome. The aim of the study was to analyse health behaviour and personal values, as well as to assess the relationship of these factors in women without children, in pregnant ones and in women who had already delivered babies. The questionnaire survey included Health Behaviour Inventory (HBI), Personal Value List (PVL) and the sociodemographic data and was conducted in 538 women. These women were divided into 3 groups: women who recently delivered (n = 235), pregnant women (n = 121) and childless women (n = 182). Pregnant women demonstrated a significantly higher level of declared health behaviours and also they rated higher subscales values "positive mental attitude" and "health practices" in comparison to women who recently delivered and to childless women. In all tested groups the highest rated personal value was "a successful family life", while the most appreciated symbol of happiness was "love and friendship". Our results suggest that the system of values and the perception of happiness symbols may influence women's health behaviours. Positioning “health” in the hierarchy of personal values as the most important one may facilitate introduction of healthy behaviours. This in turn could reduce several adverse pregnancy outcomes that are potentially modifiable with changing preconception health attitudes. Our results also identify several unanswered questions and highlights areas where new research is needed.

Bacterial infections occur when wound healing fails to reach the final stage of healing, usually hindered by the presence of different pathogens. Different topical antimicrobial agents are used to inhibit bacterial growth due to antibiotic failure in reaching the infected site accompanied very often by an increased drug resistance and other side effects. In this review, we focus on antimicrobial peptides (AMPs), especially those with a high potential of efficacy against multidrug-resistant and biofilm-forming bacteria and fungi present in wound infections. Currently, different AMPs undergo preclinical and clinical phase to combat infection-related diseases. AMP dendrimers (AMPDs) have been mentioned as potent microbial agents. Various AMP delivery strategies, such as polymers, scaffolds, films and wound dressings, organic and inorganic nanoparticles, to combat infection and modulate the healing rate have been discussed as well. New technologies such as CRISPR-Cas are taken into consideration as potential future tools for AMP delivery in skin therapy.

To understand great disparities in disease outcomes between CIVID-19 patients, we explore infection and host responses in kinetics. From existing data, we deduced a model that the lungs are damaged by rapidly rising flow resistance as a result of retaining white blood cells in lung tissues. The retention of white blood cells is initially triggered by viral infection but aggravated by injuries caused by low temperature. Lungs are initially damaged by fluid leakage, rapidly followed by extruding blood into alveolar spaces. The step of blood extruding is predicted to take place in a very short time. Our simulations show that as little as 0.1% retention of white blood cells in the lungs can lead to their failure in 5 to 10 days. The small degrees of imbalance implies that this imbalance could be corrected by a large number of factors that are known to reduce flow resistance. The model implies that the top priority is maintaining blood micro-circulation and preserving organ functions in the entire disease course, especially after the virus has spread the whole lungs. From exploring a large number of hypothetical infection modes, we propose preventive, mitigating and treatment strategies for ultimately ending the pandemic. The first strategy is avoiding exposures that could result in widespread damages to lungs and taking post exposure mitigating measures that would reduce disease severity. The second strategy is reducing death rate and disability rate from the current levels to one tenth for infected patients by using multiple factors health optimization method. The double reduction strategies are expected to generate a series of chain reactions that favor mitigating or ending the pandemic. Some reactions include a big reduction of the amount of viral discharges from infected patients into the air, the avoidance of panic, chronic stress and emotional distress, and cross-infections which are expected in quarantines. The double reductions would have a final effect of ending the pandemic.

The coronavirus disease caused by SARS-CoV-2 (known as COVID 19) is highly contagious and has spread rapidly over 200 countries over last three months. WHO suggested urgent escalation in testing, isolation and contact tracing, as the "backbone" of managing the pandemic. Globally, the detection of SARS-CoV-2 in patients are done by RT-PCR and blood antibody-based testing. In addition to the existing processes, flow-cytometry could be used as a high-throughput and efficient diagnostic method for detection of COVID 19. The suspected COVID 19 samples can be analyzed using ‘Indirect flow cytometry’, with the specific primary antibody and fluorescent tagged secondary antibodies. The fluorescence signal can distinguish the infected v/s non-infected samples. In the present article, we have summarized the applications of Flow virometry to study various viruses and have proposed possible application in the detection of COVID 19.

The paper demonstrates the analysis of Corona Virus Disease based on a CNN probabilistic model. It involves a technique for classification and prediction by recognizing typical and diagnostically most important CT images features relating to Corona Virus. The main contributions of the research include predicting the probability of recurrences in no recurrence (first time detection) cases at applying our proposed Convolution neural network structure. The Study is validated on 2002 chest X-ray images with 60 confirmed positive covid19 cases and (650 bacterial – 412 viral -880 normal) x-ray images. The proposed CNN compared with traditional classifiers with proposed CHFS feature extraction model. The experimental study has done with real data demonstrates the feasibility and potential of the proposed approach for the said cause. The result of proposed CNN structure has been successfully done to achieve 98.20% accuracy of covid19 potential cases with comparable of traditional classifiers.

Since coffee has been shown to influence positively the metabolism of subjects with metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control but improved fed hyperinsulinemia and HOMA-IR, and plasma adiponectin levels. The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating and intrahepatocellular alanine transaminase activity, assessed by hyperpolarized-¹³C NMR spectroscopy, were reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

This article puts forward the bi-matrix games with crisp parametric payoffs based on interval value function approach. We conclude that the equilibrium solution of the game model can converted into optimal solutions of the pair of the non-linear optimization problem. Finally, experiment results show the efficiency of the model.

Water soluble polymers have gained an increasing interest in enhanced oil recovery (EOR) processes, especially as polymer flooding. Despite the fact that the flow of polymer in porous medium has been a research subject for many decades with numerous publications, there are still some research areas that need progress. The prediction of polymer injectivity remains elusive. Polymers with similar shear viscosity might have different in-situ rheological behaviors and may be exposed to different extent of mechanical degradation. Hence, determining polymer in-situ rheological behavior is of great significance for defining its utility. In this study, an investigation of rheological properties and mechanical degradation of different HPAM (partially hydrolyzed polyacrylamide) polymers was performed using Bentheimer sandstone outcrop cores. Results show that, HPAM in-situ rheology is different from bulk rheology measured in rheometer. Specifically, shear thickening behavior occurs at high rates, and near-Newtonian behavior is measured at low rates in porous media. This deviates strongly from measurements in the rheometer. Polymer molecular weight and concentration influence its viscoelasticity and subsequently its flow characteristics in porous media. Exposure to mechanical degradation by flow at high rate through porous media leads to significant reduction in shear thickening and thereby improved injectivity. More importantly, the degraded polymer maintained in-situ viscosity at low flow rates indicating that improved injectivity can be achieved without compromising viscosity at reservoir flow rates. This is explained by reduction in viscoelasticity. Mechanical degradation also leads to reduced residual resistance factor (RRF), especially for high polymer concentrations. For some of the polymer injections, successive degradation (increased degradation with transport length in porous media) was observed. The results presented here may be used to optimize polymer injectivity.

The Urban Heat Island (UHI) is one of the more serious consequences of urbanization resulting in impacts on thermal comfort levels, heat stress, and even mortality. For Municipal Beirut, implementation of “cool” surface materials and green spaces have been recommended to counterbalance the UHI. This paper builds on previous findings on the topic of non-constructible parcels within the district of Bachoura in Municipal Beirut and examines the possibility of implementing “cool” surface or paving materials and urban vegetation which can improve thermal conditions especially during the summer period and with the viewto project the positive findings of this case study to the entire Municipal Beirut area. A numerical analysis using ENVI-met 4.0 investigates the thermal performance of these non-constructibles further to implementation of high reflective surfaces and urban vegetation within a broad neighborhood scale in Bachoura. Results show reductions in ambient temperatures up to 1K on a summer day.. Within the framework of an integrated approach to planning, this form of urban acupuncture aims for substantial UHI reduction. Energy performance of buildings further to implementation of these mitigation measures is also recommended for future studies and to validate the findings in this paper.

Small non-coding RNAs (sRNAs) are ubiquitously found in the three domains of life playing large-scale roles in gene regulation, transposable element silencing, and defense against foreign elements. While a substantial body of experimental work has been done to uncover function of sRNAs in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are still poorly understood. Recently, high throughput studies using RNA-sequencing revealed that sRNAs are broadly expressed in the Archaea, comprising thousands of transcripts within the transcriptome during non-challenged and stressed conditions. Antisense sRNAs, which overlap a portion of a gene on the opposite strand (cis-acting), are the most abundantly expressed non-coding RNAs and they can be classified based on their binding patterns to mRNAs (3’ UTR, 5’ UTR, CDS-binding). These antisense sRNAs target many genes and pathways, suggesting extensive roles in gene regulation. Intergenic sRNAs are less abundantly expressed and their targets are difficult to find because of a lack of complete overlap between sRNAs and target mRNAs (trans-acting). While many sRNAs have been validated experimentally, a regulatory role has only been reported for very few of them. Further work is needed to elucidate sRNA-RNA binding mechanisms, the molecular determinants of sRNA-mediated regulation, whether protein components are involved, and how sRNAs integrate with complex regulatory networks.

The mitigation of NLOS (non-line-of-sight) propagation conditions is one of main challenges in wireless signals based indoor localization. When RFID localization technology is applied in applications, RSS fluctuates frequently due to the shade and multipath effect of RF signal, which could result in localization inaccuracy. In particularly, when tags carriers are walking in LOS (line-of-sight) and NLOS hybrid environment, great attenuation of RSS will happen, which would result in great location deviation. The paper proposes an IMU-assisted (Inertial Measurement Unit) RFID based indoor localization in LOS/NLOS hybrid environment. The proposed method includes three improvements over previous RSS based positioning methods: IMU aided RSS filtering, IMU aided LOS/NLOS distinguishing and IMU aided LOS/NLOS environment switching. Also, CRLB (Cramér-Rao Low Bound) is calculated to prove theoretically that indoor positioning accuracy for proposed method in LOS/NLOS mixed environment is higher than position precision of only use RSS information. Simulation and experiments are conducted to show that proposed method can reduce the mean positioning error to around 3 meters without site survey.

In light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programs will identify hundreds of novel viruses that might someday pose a threat to humans. Our capacity to identify which viruses are capable of zoonotic emergence depends on the existence of a technology—a machine learning model or other informatic system—that leverages available data on known zoonoses to identify which animal pathogens could someday pose a threat to global health. We synthesize the findings of an interdisciplinary workshop on zoonotic risk technologies to answer the following questions: What are the prerequisites, in terms of open data, equity, and interdisciplinary collaboration, to the development and application of those tools? What effect could the technology have on global health? Who would control that technology, who would have access to it, and who would benefit from it? Would it improve pandemic prevention? Could it create new challenges?

Vibration measurement serves as the basis for various engineering practices such as natural frequency or resonant frequency estimation. As image acquisition devices become cheaper and faster, vibration measurement and frequency estimation through image sequence analysis continue to receive increasing attention. In the conventional photogrammetry and optical methods of frequency measurement, vibration signals are first extracted before implementing the vibration frequency analysis algorithm. In this work, we demonstrated that frequency prediction can be achieved using a single feed-forward convolutional neural network. The proposed method is verified using a vibration signal generator and excitation system, and the result obtained was compared with that of an industrial contact vibrometer in a real application. Our experimental results demonstrate that the proposed method can achieve acceptable prediction accuracy even in unfavorable field conditions.

Acquisition of real-time hydraulic data is an essential component for flood forecasting. However, we frequently face difficulties in obtaining discharge data using classical contact methods during high magnitude floods and for systems experiencing rapid hydro-geomorphological adjustment. Therefore, we developed low-cost, non-contact sensors and platforms that are designed to overcome these difficulties. These advances enable flood flow properties to be monitored at multiple locations across a river catchment, at low-cost, and communicated in near real-time by using an image velocimetry method. This is an optics-based approach for stream flow measurement using commercially available near-infrared digital cameras to acquire video footage in full HD (30fps). Video footage is then subjected to optical flow tracking techniques based on cross-correlation, and feature-based tracking, enabling the displacement rates of detected features (for example natural foam, seeds, woody debris, and turbulent structures) to be computed. This manual provides step by step guidance to install an image-based gauging station. It contains the list of necessary components, the calibration process of a new camera and the assembly procedure of the system.

Human factors are the most relevant issues contributing to adverse events in obstetrics. Specific training of Crisis Resource Management (CRM) skills (i.e., problem solving and team management, resource allocation, awareness of environment, and dynamic decision-making) are now widespread and are often based on High Fidelity Simulation. In order to be used as a guideline in simulated scenarios, they need to be translated into specific and observable behavioral markers. To this purpose, we developed a set of observable behaviors related to the main elements of CRM in the delivery room. The observational tool was then adopted in a two-days seminar on obstetric hemorrhage where teams working in obstetric wards of six Italian hospitals took part to simulations. The tool was used as guide for the Io and as a peer-to-peer feedback. It was then rated for its usefulness in facilitating the reflection upon one’s own behavior, its ease of use, and its usefulness for the peer-to-peer feedback. The ratings were highly positive, around 4 in a 5-point scale. The CRM observational tool is therefore a useful, quick and easy solution to facilitate the debriefing, the peer-to-peer feedback and, most of all, the transfer of safe behavior from simulation to everyday practice.

The importance and near ubiquity of the Golden Ratio in disciplines like chemistry and biology is well known, but only recently has it come to light in areas pertaining to the Quantum domain. By using a modified tool-kit of hyper-complex numbers (known as Dimensional Gate Operators) and numerical analysis, we uncover a connection between hyper-dimensional objects, the Fibonacci sequence and that of quasiparticles and excitations. The results show that dimensionality increases in step with the Fibonacci sequence.

This publication delves into the intricate world of human communication, extending beyond the realm of spoken and written language to explore the profound influence of non-verbal communication. Focusing on body language—comprising gestures, facial expressions, postures, and movements—it reveals the pivotal role it plays in conveying emotions, intentions, and psychological states. The rapidly evolving fields of neuroscience and cognitive science are investigating the neural mechanisms and cognitive processes that underpin the interpretation and utilization of these non-verbal cues. Notably, the amygdala's involvement in processing emotional facial expressions has provided a neurological foundation for our emotional understanding in non-verbal communication. Concurrently, cognitive psychology sheds light on how perception, attention, and memory influence our interpretation of non-verbal cues and communication strategies.In our modern, technologically advancing society characterized by global interconnectivity and cultural diversity, the significance of non-verbal communication, especially in digital and virtual contexts, is paramount. The transformation of non-verbal expression into digital symbols like emoticons and emojis raises questions regarding its ability to maintain authenticity and emotional understanding. This publication endeavors to comprehensively explore the fundamental role of body language and non-verbal communication in contemporary society. By integrating insights from psychology, neuroscience, social sciences, and digital technologies, it aims to elucidate the underlying mechanisms guiding non-verbal communication. Additionally, it delves into the implications of non-verbal communication across diverse domains, including interpersonal communication, the workplace, politics, advertising, and the virtual world.The research presented herein strives to offer a thorough understanding of interpersonal dynamics, relationships, and social behavior, with the goal of promoting the development of more effective, conscious, and ethically guided communication strategies. Ultimately, this analysis aspires to inspire further interdisciplinary research and reflection, addressing emerging challenges and fully leveraging the potential of non-verbal communication in modern society. This, in turn, guides our path towards a communication landscape that is more inclusive, authentic, and empathetic.

Magnetic nanoparticles are met across many biological species ranging from magnetosensitive bacteria, fishes, bees, bats, rats, birds, to humans. They can be both of biogenetic origin and due to environmental contamination, being either in paramagnetic or ferromagnetic state. The energy of such naturally occurring single-domain magnetic nanoparticles can reach up to 10-20 room k_BT in the magnetic field of the Earth, which naturally led to supposition that they can serve as sensory elements in various animals. This work explores within a stochastic modeling framework a fascinating hypothesis of magnetosensitive ion channels with magnetic nanoparticles serving as sensory elements, especially, how realistic it is given a highly dissipative viscoelastic interior of living cells and typical sizes of nanoparticles possibly involved.

Biomimicry in additive manufacturing often refers to topology optimization and the use of lattice structures, due to the organic shape of the topology-optimized designs, and the lattices often looking similar to many light-weight structures found in nature such as trabecular bone, wood, sponges, coral, to name a few. Real biomimetic design however involves the use of design principles taken in some way from natural systems. In this work we use a methodology whereby high resolution 3D analysis of a natural material with desirable properties is “reverse-engineered” and the design tested for the purpose. This allows more accurate replication of the desired properties, and adaption of the design parameters to the material used for production (which usually differs from the biological material). One such example is the impact-protective natural design of the glyptodont body armour. In this paper we report on the production of body armour models in metal (Ti4Al4V) and analyze the resulting mechanical properties, assessing their potential for impact protective applications. This is the first biomimetic study using metal additive manufacturing to date.

Breast cancer is the most common malignancies in women and the second leading cause of cancer death in women. Triple negative breast cancer (TNBC) subtype is a breast cancer subset without ER, PR and HER2 expression, limiting treatment options and presenting a poorer survival rate. Thus, we investigated whether HDACi would be used as potential anti-cancer therapy on breast cancer cells. In this study, we found TNBC and HER2-enrich breast cancers are extremely sensitive to Panobinostat, Belinostat of HDACi via experiments of cell viability assay, apoptotic marker identification and flow cytometry measurement. On the other hand, we developed a bioluminescence based live cell non-invasive apoptosis detection sensor (IADS) detection system to evaluate the quantitative and kinetic analyses of apoptotic cell death by HDAC treatment on breast cancer cells. In addition, the use of HDACi may also be accompanied with chemotherapeutic agent such as doxorubicin to synergic drug sensitivity on TNBC cell (MDA-MB-231), but not in breast normal epithelia cells (MCF-10A), providing therapeutic benefits against breast tumor in clinic.

Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins, miRNAs) that allow the identification of their cell- or tissue-origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. As regards, a large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve informations about the onset of peculiar disease manifestations. In this Review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.

Increased access to highly active antiretroviral therapy (HAART) by HIV⁺ individuals has become a reality worldwide. In Brazil, ART currently reaches over half of the HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. For this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV⁺ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG) assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23). Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.

Below T_CO=157 K the quasi-one-dimensional charge-transfer salt (TMTTF)_2SbF_6 undergoes a pronounced phase transition to a charge-ordered ground state. We have explored the non-linear and photoconductive behavior as a function of applied voltage, laser pulse energy and temperature. Besides a decay of the photoconductive signal in a double exponential fashion in the millisecond range, we discover current oscillations in the kHz range induced by the application of short laser pulses. While the resonance frequencies do not depend on voltage or laser intensity and vary only slightly with temperature, the amplitude changes linearly with the laser intensity and voltage. The findings are discussed and compared to comparable phenomena in other low-dimensional electron systems.

Medical institutions, where several patients are treated and medical workers engaged, are always exposed to secondary viral and bacterial infections. It is critical to prevent infection transmission by indirect as well as direct contact through air or splash. The infections of most diseases can be transmitted through the air. HEPA filters installed in air conditioning equipment are used to prevent infection transmission through air in medical institutions, but air circulation takes a long time in a large space. Virus and bacteria smaller than 0.3 μm cannot be removed by the HEPA filter; hence, those microbes remain alive throughout the air ventilation. A plasma sterilizer has the capability to provide environmental friendly sterilization by employing reactive oxide species and reactive nitrogen species at a low cost. We developed an excellent plasma sterilizer by using a non-thermal atmospheric-pressure biocompatible plasma (NBP). Ozone concentration in plasma sources has been derived by Kuhn et al. [1]. The diffusion coefficients inside (D₀) and outside (D₁) the plasma sterilizer have been calculated to be 0.0641 m² s^-1 and 0.717 m² s^-1, respectively. To sustain high O₃ concentrations over 121 ppm inside the plasma source and low O₃ concentrations below 0.05 ppm outside the sterilizer, it is necessary to keep O₃ concentrations at the exit of plasma sterilizer below 0.28 ppm. so that diffusion coefficient D₁ has been designed to be as large as 11 times of D₀.

With the development of data science, more and more machine learning technologies have been designed to solve complicated and challenging real-world tasks containing a large volume of data. And many significant real-world datasets contain data in the form of networks or graphs. Graph Neural Networks is one of the powerful machine learning tools, which could provide a perfect solution to processing a large amount of non-Euclidean data. And because most bio information data in bioinformatics is in the non-Euclidean domain, Graph Neural Networks could then directly be applied to solve problems in bioinformatics. Much research has been done in the field of GNN, and there are also some surveys related to GNN and its applications. However, there has been little research focusing on GNN in bioinformatics, and we think in the future we could better utilize GNN in the field of biology, so we would like to write a literature review to help take a comprehensive look at GNN and their applications in the field of bioinformatics. In this paper, we would first introduce SOTA models in Graph Neural Networks, and second, introduce their applications in bio information. And then we would provide future directions of Graph Neural Networks in bioinformatics.

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. SARS-CoV-2 nucleic acid, peripheral lymphocyte count, and functionality were assessed. SARS-CoV-2-specific and neutralization antibodies were detected, followed by virus isolation and genome sequencing. The median age of the studied cohort was 59.83±12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. Interferon gamma (IFN-ƴ)-generated CD4+ and CD8+ cells were normal as 24.68±9.60% and 66.41±14.87%. However, the number of IFN-ƴ-generated NK cells diminished (58.03±11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (ID50=157.2, P=0.05). SARS-CoV-2 was not isolated, and a cytopathic effect was lacking. Only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity was observed in COVID-19 patients with long-term SARS-CoV-2 infection.

Past public health crises (e.g. tobacco, alcohol, opioids, cholera, HIV, lead, pollution, venereal disease, even COVID-19) have been met with interventions targeted both at the individual and all of society. While the healthcare community is very aware that the global pandemic of non-communicable diseases (NCD’s) has its origins in our Western ultraprocessed food diet, society has been slow to initiate any interventions other than public education, which has been ineffective, in part due to food industry interference. This article provides the rationale for such public health interventions, by compiling the evidence that added sugar, and by proxy the ultraprocessed food category, meets the four criteria set by the public health community as necessary and sufficient for regulation — addiction, toxicity, ubiquity, and externalities (how does your consumption affect me?). To its credit, some countries have recently heeded this science and have instituted sugar taxation policies to help ameliorate NCD’s within their borders. This article also supplies scientific counters to food industry talking points, in order to guide both scientists and policy makers in instituting further appropriate public health measures to quell this pandemic.

Efficiently targeted cancer therapy without causing detrimental side effects is necessary for alleviating patient care and improving survival rates. This paper presents observations of morphological changes in H1299 human lung cancer cells following W-band MMW irradiation (75 – 105 GHz) at a non-thermal power density of 0.2 mW/cm², investigated over 14 days of subsequent physiological incubation following exposure. Microscopic analyses of physical parameters measured indicate MMW irradiation induces significant morphological changes characteristic of apoptosis and senescence. The Immediate short-term responses translate into long-term effects, retained over the duration of the experiment(s); reminiscent of the phenomenon of Accelerated Cellular Senescence (ACS) achieving terminal tumorigenic cell growth. Further, results were observed to be treatment-specific in energy (dose) dependent manner and were achieved without the use of chemotherapeutic agents, ionizing radiation or thermal ablation employed in conventional methods; thereby overcoming associated side effects. Adaptation of the experimental parameters of this study for clinical oncology concomitant with current developmental trends of non-invasive medical endoscopy alleviates MMW therapy as an effective treatment procedure for human non-small cell lung cancer (NSCLC).

With the outbreak of the COVID-19 disease, the research community is producing unprecedented efforts dedicated to better understand and mitigate the affects of the pandemic. In this context, we review the data integration efforts required for accessing and searching genome sequences and metadata of SARS-CoV2, the virus responsible for the COVID-19 disease, which have been deposited into the most important repositories of viral sequences. Organizations that were already present in the virus domain are now dedicating special interest to the emergence of COVID-19 pandemics, by emphasizing specific SARS-CoV2 data and services. At the same time, novel organizations and resources were born in this critical period to serve specifically the purposes of COVID-19 mitigation, while setting the research ground for contrasting possible future pandemics. Accessibility and integration of viral sequence data, possibly in conjunction with the human host genotype and clinical data, are paramount to better understand the COVID-19 disease and mitigate its effects.

Background: Infectious disease is a major challenge in aquaculture and poses a constraint for development of farming of new species. In 2017, Siberian sturgeon (Acipenser baerii) juveniles were imported from Italy to a Swedish farm. Due to stressful conditions, 30% died during transport and in the first days after arrival. Ten days after arrival, mortalities started to occur again. Within two months, only 5% of the juveniles were still alive. Methods: Diseased fish were transported live to the National Veterinary Institute (SVA) for necropsy and further analysis. Pathological and histopathological investigation was conducted. Virology was performed on gills and internal organs by cell culture isolation and specific PCR protocols. Results: The juveniles displayed neurological signs such as lethargy, inability to maintain upright position and erratic swimming. Body condition was low. Gills were pale. One fish had petechial hemorrhage on the abdomen and the snout. The ventricles were air-filled with, but swim bladders were deflated. One specimen had intestinal hemorrhage. Viral cell cultures were negative, but PCR of gills and internal organs detected the presence of Acipenser Iridovirus European (AcIV-E). Conclusions: AcIV-E was associated with disease and high mortality in the sturgeon juveniles. Stress probably aggravated the course of the infection.

Power disaggregation aims at determining the appliance-by-appliance electricity consumption leveraging upon a single meter only, which measures the entire power demand. Data-driven procedures based on Factorial Hidden Markov Models have been proven remarkable results on energy disaggregation. Nevertheless, those procedures have various weaknesses: there is a scalability problem as the number of devices to observe raises and the algorithmic complexity of the inference step is severe. DNN architectures, such as Convolutional Neural Networks, have demonstrated to be a viable solution to deal with FHMMs shortcomings. Nonetheless, there are two significant limitations: a complicated and time-consuming training system based on back-propagation has to be employed to estimates the neural architecture parameters, and large amounts of training data covering as many operation conditions as possible need to be collected to attain top performances. In this work, we aim to overcome those limitations by leveraging upon the unique and useful characteristics of the extreme learning machine technique, which is based on a collection of randomly chosen hidden units and analytically defined output weights. Experiment evaluation has been conducted using the UK-DALE corpus. We find that the suggested approach achieves similar performances to recently proposed ANN-based methods and outperforms FHMMs. Besides, our solution generalises well to unseen houses.

Depending on human body conditions and environmental conditions, it is sometimes difficult to conduct subject experiments. In such cases, it is effective to use a thermal manikin. There are few studies that investigate the effect of the non-uniform and asymmetric outdoor thermal environment on the mean skin temperature. The purpose of this study is to clarify the influence of the non-uniform and asymmetric thermal radiation of short-wavelength solar radiation in an outdoor environment on the calculation of the mean skin temperature. The skin temperature of the front of the coronal surface, which was facing the sun and where the body received direct short-wavelength solar radiation, and the skin temperature of the rear of the coronal surface, which was in the shadow and did not receive direct short-wavelength solar radiation were respectively measured. The feet, upper arm, forearm, hand and lower leg, which are susceptible to short-wavelength solar radiation in a standing posture, had a noticeable difference in skin temperature between sites in the sun and in shade. The mean skin temperature of sites facing the sun was significantly higher than the mean skin temperature of those in the shade.

The Gilles de la Tourette syndrome (GTS) and Non-Coeliac Gluten Sensitivity (NCGS) may be associated. We analyse the efficacy of a gluten-free diet (GFD) in 29 patients with GTS (23 children; 6 adults) in a prospective pilot study. All of them followed a GFD for one year. The YGTSS, Y-BOCS/CY-BOCS and GTS-QOL questionnaires were compared before and after the GFD. 74% of children and 50% of adults were males, not significant (NS). At the beginning of the study, 69% of children and 100% of adults had associated OCD (NS). At baseline, the YGTSS scores were 55.0 ± 17.5 (children) and 55.8 ± 19.8 (adults) (NS), the Y-BOCS/CY-BOCS scores were 15.3 (SD = 12.3) (children) and 26.8 (9.2) (adults) (p = 0.043), and the GTS-QOL scores were 42.8 ± 18.5 (children) and 64 ± 7.9 (adults) (p = 0.000). NCGS was frequent in both groups, with headaches reported by 47.0% of children and 83.6% of adults (p = 0.001). After one year on a GFD there was a marked reduction in measures of tics (YGTSS) (p = 0.001), and the intensity and frequency of OCD (Y-BOCS/CY-BOCS) (p = 0.001), along with improved QOL (p = 0.001) in children and adults. In conclusion, a GFD maintained for one year in GTS patients led to a marked reduction in tics and OCD both in children and adults.

The growth of regularly generated data from many financial activities has significant implications for every corner of financial modeling. This study has investigated the utilization of these continuous growing data by a means of an automated process. The automated process can be developed by using Machine learning based techniques that analyze the data and gain experience from the underlying data. Different important domains of financial fields such as Credit card fraud detection, bankruptcy detection, loan default prediction, investment prediction, marketing and many other financial models can be modeled by implementing machine learning models. Among several machine learning based techniques, the use of parametric and non-parametric based methods are approached by this research. Two parametric models namely Logistic Regression, Gaussian Naive Bayes models and two non-parametric methods such as Random Forest, Decision Tree are implemented in this paper. All the mentioned models are developed and implemented in the field of Credit card fraud detection, bankruptcy detection, loan default prediction. In each of the aforementioned cases, the comparative study among the classification techniques is drawn and the best model is identified. The performance of each classifier on each considered domain is evaluated by various performance metrics such as accuracy, recall, precision, F1-score and mean squared error. In the credit card fraud detection model the decision tree classifier performs the best with an accuracy of 99.1% and, in the loan default prediction and bankruptcy detection model, the random forest classifier gives the best accuracy of 97% and 96.84% respectively.

Predicting the growth response of seedlings from the environmental responses of photosynthesis and metabolism may be improved by considering the dynamics of non-structural carbohydrate, NSC, over a diurnal cycle. Attenuation of growth metabolism when NSC content is low could explain why some NSC is conserved through the night. A dynamic model, incorporating diurnal variation in NSC, was developed to simulate growth of seedlings hour-by-hour. I compared predictions of this model to published growth and NSC data for seedlings that varied according to temperature, light, day length, or CO₂. Prolonged-darkness experiments showed a temperature dependent upper limit on the respiration capacity. Respiration was attenuated as NSC was depleted. Furthermore, when NSC was high at dawn, inhibition of photosynthesis could attenuate the accumulation of NSC under low temperature, or high light, or high CO₂. These concepts were used to simulate plant metabolism and growth rates and diurnal variation of NSC in tomato seedlings under two light levels and various temperatures. Comparison of other results using the same model parameters showed the dynamic model could predict results for starch and starch-less plants, and when growth was affected by CO₂ enrichment and day length.

We introduce poly-symplectic extension of Souriau Lie groups Thermodynamics based on higher-order model of statistical physics introduced by R.S. Ingarden. This extended model could be used for small data analytics and Machine Learning on Lie groups. Souriau Geometric Theory of Heat is well adapted to describe density of probability (Maximum Entropy Gibbs density) of data living on groups or on homogeneous manifolds. For Small Data Analytics (Rarified Gases , sparse statistical survey,…), density of maximum entropy should consider Higher Order Moments constraints (Gibbs density is not only defined by first moment but fluctuations request 2nd order and higher moments) as introduced by R.S. Ingarden. We use Poly-sympletic model introduced by Christian Günther, replacing the symplectic form by a vector-valued form. The poly-symplectic approach generalizes the Noether theorem, the existence of momentum mappings, the Lie algebra structure of the space of currents, the (non-)equivariant cohomology and the classification of G-homogeneous systems. The formalism is covariant, i.e. no special coordinates or coordinate systems on the parameter space are used to construct the Hamiltonian equations. We underline the contextures of these models, and the process to build these generic structures.

Mice are not natural hosts for influenza A viruses (IAVs), but they are useful models for studying antiviral immune responses and pathogenesis. Serial passage of IAV in mice invariably causes the emergence of adaptive mutations and increased virulence. Typically, mouse-adaptation studies are conducted in inbred laboratory strains BALB/c and C57BL/6, which have defects in the antiviral Mx1 gene that results in increased susceptibility to infection and disease severity. Here, we report the adaptation of IAV reference strain A/California/07/2009(H1N1) (a.k.a. CA/07) in outbred Swiss Webster mice. Serial passage led to increased virulence and lung titers, and dissemination of the virus to brains. We adapted a deep-sequencing protocol to identify and enumerate adaptive mutations across all genome segments. Among mutations that emerged during mouse-adaptation, we focused on amino acid substitutions in polymerase subunits: polymerase basic-1 (PB1) T156A and F740L, and polymerase acidic (PA) E349G. These mutations were evaluated singly and in combination in minigenome replicon assays, which revealed that PA E349G increased polymerase activity. By selectively engineering these three adaptive PB1 and PA mutations into the parental CA/07 strain, we demonstrated that adaptive mutations in polymerase subunits decreased the production of defective viral genome segments with internal deletions, and dramatically increased the release of infectious virions from mouse cells. Together, these findings increase our understanding of the contribution of polymerase subunits to successful host adaptation.

This paper considers a non-mixture cure model for right censored data. It utilizes the maximum likelihood method to estimate model parameters in the non-mixture cure model. The simulation study is based on Fréchet susceptible distribution to evaluate the performance of the method. Comparing with Weibull and exponentiated exponential distributions, the non-mixture Fréchet distribution is shown to be the best in modeling a real data on allogeneic marrow HLA-matched donors and ECOG phase III clinical trial e1684 data.

Telemedicine is the use of Information and Communication Technology (ICT) for clinical health care from a distance. The exchange of radiographic images and electronic patient health information/records (ePHI/R) for diagnostic purposes has the risk of confidentiality, ownership identity, and authenticity. In this paper, a data hiding technique for ePHI/R is proposed. The color information in the cover image is used for key generation, and stego-images are produced with ideal case. As a result, the whole stego-system is perfectly secure. This method includes the features of watermarking and steganography techniques. The method is applied to radiographic images. For the radiographic images, this method resembles watermarking, which is an ePHI/R data system. Experiments show promising results for the application of this method to radiographic images in ePHI/R for both transmission and storage purpose.

Electromagnetic eddy current sensors are commonly used to identify and quantify the surface notches of metals. However, the unintentional tilt of eddy current sensors affects results of size profiling, particularly for the depth profiling. In this paper, based on the eddy current thin-skin regime, a revised algorithm has been proposed for the analytical voltage or impedance of a tilted driver–pickup eddy current sensor scanning across a long ideal notch. Considering the resolution of the measurement, the bespoke driver–pickup, also termed as transmitter-receiver (T-R) sensor is designed with a small mean radius of 1 mm. Besides, the T-R sensor is connected to the electromagnetic instrument and controlled by a scanning stage with high spatial travel resolution , with a limit of 0.2 μm and selected as 0.25 mm. Experiments have been out on the voltage imaging of an aluminium sheet with 7 machined long notches of different depths using T-R sensor under different tilt angles. By fitting the measured voltage (both real and imaginary part) with proposed analytical algorithms, the depth profiling of notches is less affected by the tilt angle of sensors. From the results, the depth of notches can be retrieved within a deviation of 10 % for tilt angles up to 60 degrees.

Human non-conscious reasoning is one of the most successful procedures developed to solve everyday problems in an efficient way. This is why the field of artificial intelligence should analyze, formalize and emulate the multiple ways of non-conscious reasoning with the purpose of applying them in knowledge based systems, neurocomputers and similar devices for aiding people in the problem-solving process. In this paper, a framework for those non-conscious ways of reasoning is presented based on object-oriented representations, fuzzy sets and multivalued logic.

This paper introduces a novel respiratory detection system based on diaphragm wall motion tracking using an embedded ultrasound sensory system. We assess the utility and accuracy of this method in evaluating diaphragmatic function and its contribution to respiratory workload. The developed system is able to monitor the diaphragm wall activities when the sensor is placed in the zone of apposition (ZOA). This system allows the direct measurements with only one ultrasound PZT5 piezo transducer. The system both generates pulsed ultrasound waves at 2.2 MHz and amplifies reflected echoes. According to the diaphragmatic motions, the respiratory signals of the proposed system is insensitive to human motion artifacts. Promising results were obtained from six subjects on six different tests with an average sensitivity and specificity of 84% and 93% of respiration detection, respectively. Measurements are referenced to a SPR-BTA commercial spirometer. In this study, we also evaluated inertial and photoplethysmography (PPG) sensors as other conventional methods in this area.

Ultraviolet light incident on organic material can initiate its spontaneous dissipative structuring into chromophores which can catalyze their own replication. This may have been the case for one of the most ancient of all chromophores dissipating the Archean UVC photon flux, the nucleic acids. Oligos of nucleic acids with affinity to particular amino acids which foment UVC photon dissipation would have been selected through non-equilibrium thermodynamic imperatives which favor entropy production. Indeed, we show here that those amino acids with characteristics most relevant to fomenting UVC photon dissipation are precisely those with greatest chemical affinity to their codons or anticodons. Entropy production could thus provide an explanation for the accumulation of information in nucleic acids relevant to the dissipation of the externally imposed thermodynamic potentials. The accumulation of information in this manner provides a link between evolution and entropy production.

Matiyasevich's theorem states that there is no algorithm to decide whether or not a given Diophantine equation has a solution in non-negative integers. Smorynski's theorem states that the set of all Diophantine equations which have at most finitely many solutions in non-negative integers is not recursively enumerable. We prove: (1) Smorynski's theorem easily follows from Matiyasevich's theorem, (2 ) Hilbert's Tenth Problem for Q has a negative solution if and only if the set of all Diophantine equations with a finite number of rational solutions is not recursively enumerable.

Computers and artificial intelligence affect every field of life nowadays. In medical image interpretation automatic decision making using algorithms are used increasingly in every sub-field and computer aided diagnosis (CAD) is one of the main tools available to medical science today. CAD systems are used as an augmented option for both the medical practitioner and the patients, with image analysis and interpretation being of primary importance. In particular, spatial relations are used in knowledge representation, and these relations can be used for effective medical image interpretation. In this paper, we put forth an algorithm for defining non-small cells lungs cancer (NSCLC) stages in lungs images interpretation using topological spatial relations. We show an application case study in event motion predictions for lung cancer staging scoring - tumor, nodes and metastasis (TNM) - with combined topological and directional relations.

In this paper, we established the existence of PC-mild solutions for non local fractional impulsive functional integro-differential equations with finite delay. The proofs are obtained by using the techniques of fixed point theorems, semi-group theory and generalized Bellman inequality. In this paper, we have used the distributed characteristic operators to define the mild solution of the system. Results obtained here improve and extend some known results.

Low back pain (LBP) is a leading cause of disability. It significantly impacts the patient’s quality of life, limits their daily living activities, and reduces work productivity. To reduce the burden of LBP, several pharmacological and non-pharmacological treatment options are available. This review summarizes the role of heat therapy in the management of LBP. First, we outline the common causes of LBP, then discuss the general mechanisms of heat therapy on (LB)P, and finally review the published evidence regarding the impact of heat therapy in patients with acute or chronic non-specific LBP. This review demonstrates that continuous, low-level heat therapy provides pain relief, improves muscular strength, and increases flexibility. Therefore, this effective, safe, easy-to-use, and cost-effective non-pharmacological pain relief option is still relevant in modern clinical practice.

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown cause characterized by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and more recently post-COVID-19 condition (Long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. Accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and Long COVID. To address this issue, this article aimed to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.

Mitochondria are classically termed as powerhouse of a mammalian cell. Most of the cellular chemical energy in the form of adenosine tri phosphate (ATP) is generated by mitochondria and dysregulation of mitochondrial functions thus can be potentially fatal of cellular homeostasis and health. Acute respiratory distress has been earlier linked to mitochondrial dysfunction. SARS-CoV-2 infection severity leads to acute respiratory distress syndrome (ARDS) and can be fatal. We tried to investigate possible connection between SARS-CoV-2, ARDS and mitochondria. Here, we report identification of SARS-CoV-2 non-structural proteins (particularly Nsp12 and 13) that have recognition sequence with respect to mitochondrial entry. We also report that these proteins can potentially shuttle between cytoplasm and mitochondria based on the localization signals and help in downstream maintenance of the virus. Their properties to use ATP for enzymatic activities may cause ATP scavenging allowing viral RNA functions in lieu of host cell health.

Developing efficient Artificial Intelligence (AI)-enabled system to substitute human role in non-destructive testing is an emerging topic of considerable interest. In this study, we propose a novel impact-echo analysis system using online machine learning, which aims at achieving near-human performance for assessment of concrete structures. Current computerized impact-echo systems commonly employ lab-scale data to validate the models. In practice, however, the echo patterns can be far more complicated due to varying geometric shapes and materials of structures. To deal with a large variety of unseen data, we propose a sequential treatment for echo characterization. More specifically, the proposed system can adaptively update itself to approaching human performance in impact-echo data interpretation. To this end, a two-stage framework has been introduced, including echo feature extraction and the model updating scheme. Various state-of-the-art online learning algorithms have been reviewed and evaluated for the task. To conduct experimental validation, we collected 10,940 echo instances from multiple inspection sites with each sample had been annotated by human experts with healthy/defective condition labels. The results demonstrated that the proposed scheme achieved favorable echo pattern classification accuracy with high efficiency and low computation load.

Long non-coding RNAs (lncRNAs) have been found to be involved in many biological processes, including the regulation of cell differentiation, but a complete characterization of lncRNA is still lacking. Additionally, there is evidence that lncRNAs interact with ribosomes, raising questions about their functions in cells. Here, we used a developmentally staged protocol to induce cardiogenic commitment of hESCs and then investigated the differential association of lncRNAs with polysomes. Our results identified lncRNAs in both the ribosome-free and polysome-bound fractions during cardiogenesis and showed a very well-defined temporal lncRNA association with polysomes. Clustering of lncRNAs was performed according to the gene expression patterns during the five timepoints analyzed. In addition, differential lncRNA recruitment to polysomes was observed when comparing the differentially expressed lncRNAs in the ribosome-free and polysome-bound fractions or when calculating the polysome-bound vs ribosome-free ratio. The association of lncRNAs with polysomes could represent an additional cytoplasmic role of lncRNAs, e.g., in translational regulation of mRNA expression.

Covid-19 pandemic lockdown has slow down the world economic system. The pandemic has cleared the roads, close factories and grounded planes causing severe economic challenges. The damaging impact of the pandemic amid lockdown has been a blessing in guise for the environment because of significant drop in pollution level as transport and industrial sectors shutdown. Transport and industrial sectors are major contributors to environmental degradation through various emissions as a result of fossil fuel consumption. Energy consumed by transport and industrial sectors will have to shift to viable, readily available, economically and environmentally friendly with no carbon build up post Covid-19 pandemic. Hydrogen energy remains the best alternative option technologies containing green house gas emission and pollutions of several forms. Hydrogen holds the potential to provide a clean, reliable, renewable and economical source of energy for meeting the growing and unending global energy needs post pandemic. The present paper explores the economic feasibility and potential of hydrogen to serve as a competitive fuel option post pandemic. In this paper, the role of hydrogen as an energy carrier hydrogen economy structure, potential of hydrogen economy, hydrogen production methods, hydrogen application and the economic and environmental importance of hydrogen as a viable fuel option post covid-19 pandemic were discussed. There will be a surge in demand and investment for hydrogen economy post Covid-19.

Artificial Intelligence is increasingly being used by social media platforms to tackle online hate speech. The sheer quantity of content, the speed at which is it developed and the enhanced pressure companies are facing by States to remove hate speech quickly from their platforms have led to a tricky situation. This commentary argues that automated mechanisms, which may have biased datasets and be unable to pick up on the nuances of language, should not be left unattended with hate speech as this can lead to issues of violating freedom of expression and the right to non-discrimination.

Atherosclerosis (ATH) and Coronary Artery Disease (CAD) are chronic inflammatory diseases with an important genetic background which derive from the cumulative effect of multiple common risk alleles, most of them located in genomic non-coding regions. These complex diseases behave as non-linear dynamical systems that show a high dependence on their initial conditions, so that long-term predictions of disease progression are unreliable. One likely possibility is that the non-linear nature of ATH could be dependent on non-linear correlations in the structure of the human genome. In this review we show how Chaos theory analysis highlighted genomic regions that shared specific structural constraints that could have a role in ATH progression. These regions were shown to be enriched in repetitive sequences of the Alu family, genomic parasites which colonized the human genome, which show a particular secondary structure and have been involved in the regulation of gene expression. We also review the impact of Alu elements on the mechanisms that regulate gene expression, especially highlighting the molecular mechanisms by which the Alu elements could alter the inflammatory homeostasis. We devise especial attention to their relationship with the lncRNA ANRIL, the strongest risk factor for ATH, their role as miRNA sponges, and their ability to interfere with the regulatory circuitry of the NF-kB response. We aim to characterize ATH as a non-linear dynamic system in which small initial alterations in the expression of a number of repetitive elements are somehow amplified to reach phenotypic significance.

This paper seeks to explain the rapid growth of the Islamic State of Iraq & Syria (ISIS) and approach the question of “what is” the Islamic State? The paper offers several contributions. First is the proposal of a dynamic hypothesis that ISIS is an emerging-state actor and differs notably from traditional non-state actors and insurgencies. The theory consists of both a causal loop diagram and key propositions. A detailed system dynamics simulation (E-SAM) was constructed to test the theory. The propositions of emerging-state actor theory are constructed as synthetic experiments within the simulation and confirm evidence of emerging-state actor behavior. E-SAM’s novelty is its combination of combat simulation with endogenous geospatial feedback, ethnographic behavior in choosing sides in conflict, and details internal simulation of key actor mechanisms such as financing, recruiting and governance. E-SAM can be loaded with scenarios to simulate non-state actors in different geospatial domains: ISIS in Libya, Boko Haram in Nigeria, Taliban in Afghanistan and even expatriated ISIS fighters returning to pursue new conflicts such as in Indonesia.

Many systems in nature and laboratories are far from equilibrium and exhibit significant fluc- tuations, invalidating the key assumptions of small fluctuations and short memory time in or near equilibrium. A full knowledge of Probability Distribution Functions (PDFs), especially time- dependent PDFs, becomes essential in understanding far-from-equilibrium processes. We consider a stochastic logistic model with multiplicative noise, which has gamma distributions as stationary PDFs. We numerically solve the transient relaxation problem, and show that as the strength of the stochastic noise increases the time-dependent PDFs increasingly deviate from gamma distributions. For sufficiently strong noise a transition occurs whereby the PDF never reaches a stationary state, but instead forms a peak that becomes ever more narrowly concentrated at the origin. The addition of an arbitrarily small amount of additive noise regularizes these solutions, and re-establishes the existence of stationary solutions. In addition to diagnostic quantities such as mean value, standard deviation, skewness and kurtosis, the transitions between different solutions are analyzed in terms of entropy and information length, the total number of statistically distinguishable states that a system passes through in time.

The recent Zika virus (ZIKV) outbreak in Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies and Guillain-Barré syndrome. In responding to this global health outcry, unprecedented and world-wide efforts are taking place to study the ZIKV etiology. Much have been learned about this virus in the areas of epidemiology, clinical manifestation, viral sequences and protein structures, as well as effects of ZIKV infection on fetal brain development and microcephaly. However, the molecular mechanism underlying ZIKV-mediated neurologic disorders remains elusive. Some critical questions include: 1) what type of virologic changes has taken place that increased the viral virulence? 2) which ZIKV protein(s) is responsible for the enhanced viral pathogenicity? And 3) how the newly adapted and pathogenic ZIKV strains alter their interactions with host cells leading to neurologic disorders? The goal of this review is to explore the molecular insights into the ZIKV-host interactions with special focuses on host cell receptor usage for viral entry, host cellular and immune antiviral responses, ZIKV counteraction and ZIKV-induced cytopathic effects. Our hope with this literature review is to inspire additional studies focusing on molecular studies of ZIKV-host Interactions.

Sumudu transform of the Dixon elliptic function with non zero modulus a ≠ 0 for arbitrary powers sm^N(x,a) ; N ≥ 1 ; sm^N(x,a)cm(x,a) ; N ≥ 0 and sm^N(x,a)cm²(x,a) ; N ≥ 0 is given by product of Quasi C fractions. Next by assuming denominators of Quasi C fraction to 1 and hence applying Heliermann correspondance relating formal power series (Maclaurin series of Dixon elliptic functions) and regular C fraction, Hankel determinants are calculated and showed by taking a = 0 gives the Hankel determinants of regular C fraction. The derived results were back tracked to the Laplace transform of sm(x,a) ; cm(x,a) and sm(x,a)cm(x,a).

Intradermal injection of botulinum neurotoxin is a frequently performed procedure in aesthetic dermatology to improve facial skin tone, texture, fine wrinkles, and enlarged pores. In practice, botulinum neurotoxin type A is also used to reduce skin oiliness of the face. There is increasing evidence that acetylcholine plays specific roles in sebum production, suggesting that botulinum neurotoxin type A may reduce sebum production by interfering with cholinergic transmission between sebaceous glands and autonomic nerve terminals. Botulinum neurotoxins can also inhibit several pathogenetic components of acne development, suggesting that botulinum neurotoxins can be used as a safe and effective treatment modality for acne and other skin disorders related to the overactivity of sebaceous glands. This review aims to explore the current evidence behind the treatment of oily skin and acne with botulinum neurotoxin type A.

In this paper, a non-destructive test to diagnose wear of blade´s compressor of a gas turbine is reported. Gas turbine was operating in Campeche City, Mexico, in a very aggressive environment, where the entry of solid particles is unavoidable. The objective was to reduce cost of maintenance in this equipment. Analysis on a blade of gas turbine was performed, which was in operation on an offshore platform. Compressor blade was exposed to a severe damage by the impact of particles and environmental pollutants such as salts, sands and sulphurs. In first stage of this analysis, a visual inspection with a borescope was performed, which has the ability to illuminate dark internal areas, with a bright light for visual examination and/or make a photographic reproduction in semi-annual maintenance cycles. Images analysis was used to determine the typical failure modes. In a second stage, a tribological characterization was carried out. Chemical composition of the material of blades was obtained. Scanning electron microscopy (SEM) was used to measure roughness and evaluate degradation of surfaces of blades after 30,000 service hours. The points, where peak stresses were calculated, correspond to those places in witch corrosion and some irregular scratches similar to plowing action, was observed. These are the points in which failures take place. Results showed wear modes were originated by a severe stinging action. Also, large craters, similar to those observed in solid particle erosion, were developed by at normal impact. In the same way it could be found some localized areas with a witch corrosion and irregular scratches similar to plowing action, was observed. These are the points in which failures take place.

Objective: To recommend how physicians can best respond to families whose hopes for a miracle via divine intervention influence their medical decisions, like, for example, making them not want to withdraw ventilatory support in cases of poor neurologic prognosis because they are still hoping for God to intervene. Methods: Auto-ethnographic analysis of chaplaincy experience in this clinical context yields a nuanced 90-second, point-of-care spiritual intervention physicians can use to address the religious aspect of families who base medical decisions on their hopes for a miracle via divine intervention. Explanation of how spiritual intervention dovetails with existing physician communication protocol for responding to families hoping for a miracle. Results: Spiritual intervention for religious aspect of miracle-hoping families is integrated into existing physician communication protocol for responding to families hoping for a miracle with recommendations for utilization of existing communication technology when necessary. Conclusion: Properly addressing the religious dimension of families hoping for a miracle may be helpful for physicians interested in decreasing their own stress levels, improving outcomes for this clinical context, and ensuring that unintentional discrimination does not perpetuate racial disparities in end-of-life care.

This paper reviews non-intrusive load monitoring (NILM) approaches that employ deep neural networks to disaggregate appliances from low frequency data, i.e. data with sampling rates lower than the AC base frequency. We first review the many degrees of freedom of these approaches, what has already been done in literature, and compile the main characteristics of the reviewed publications in an extensive overview table. The second part of the paper discusses selected aspects of the literature and corresponding research gaps. In particular, we do a performance comparison with respect to reported MAE and F$_1$-scores and observe different recurring elements in the best performing approaches, namely data sampling intervals below 10\,s, a large field of view, the usage of GAN losses, multi-task learning, and post-processing. Subsequently, multiple input features, multi-task learning and related research gaps are discussed, the need for comparative studies is highlighted, and finally, missing elements for a successful deployment of NILM approaches based on deep neural networks are pointed out. We conclude the review with an outlook on possible future scenarios.

The development of 3D cerebral brain organoids which accurately resemble aspects of the human brain permits a more accurate characterization of physiological processes and neurological diseases. Cerebral organoids can be grown from stem cell lines with various genetic backgrounds allowing multiple neurodegenerative diseases to be modeled. While dysfunction in neurotransmission of patients with neurodegenerative diseases is expected, the impact of chronic neurodegeneration on the response to viral infection of the CNS is poorly understood. For instance, several mosquito-borne viruses like Dengue virus and West Nile Virus cause post-viral parkinsonism. How CNS infection might impact a host with inherent CNS dysfunction such as Parkinson’s Disease in poorly understood. This preliminary, observational study aimed to understand dysfunction in intrinsic and innate expression of a patient with a neurodegenerative disease and a non-affected individual in relation to potential viral infection in the CNS. Cerebral organoids were generated from human induced pluripotent stem cells with a normal genetic background or with idiopathic Parkinson’s Disease. After differentiation and maturation, organoid size, gene expression and immunofluorescence were evaluated to assess neurotransmission and innate immunity. While there was no significant difference in size of the organoids with a normal or Parkinson’s genetic background, gene expression studies identified multiple differences in innate immunity and neurotransmission. Immunofluorescence also identified differences in protein expression related to neurotransmission and innate immunity. Of note, organoids derived from a Parkinson’s patient exhibited endogenous up-regulation of dopamine and muscarinic acetylcholine receptors, GABA, glycine, and glutamate targets, and the majority of cytokines. This expression pattern suggests a chronic state of neuroexcitation and neuroinflammation in this population of organoids.

Liquid biopsies are an integral part of the diagnosis of cancer. Here, we have extended previous validation studies of a new targeted NGS panel to include the detection of copy number amplifications (CNAs), fusions, and exon skipping variants. Detection of these gene classes included specimens from clinical and healthy donors and cell lines (fusions: ROS1, EML4-ALK, NTRK1), (exon skipping: MET exon 14), and (CNAs: HER2, CDK6, EGFR, MYC and MET). The limit of detection (LOD) for fusion/skipping was 42 copies (QC threshold = 3 copies) and was verified using 3 additional fusion/skipping variants. LOD for CNAs was 1.40-fold-change (QC threshold = 1.15-fold change) and was verified with 3 additional CNAs. In precision studies, all fusion/skipping variants were detected in all runs and all days of testing (n=18/18; 100%); average CV for repeatability was 20.5% (range 8.7% - 34.8%), and for reproducibility was 20.8% (range 15.7% - 30.5%). For CNAs, 28/29 (96.6%) copy gains were detected. For CNAs, average CV of 1.85% (range 0% to 5.49%) for repeatability and 6.59% (range 1.65% to 9.22%) for reproducibility. The test panel meets the criteria for being highly sensitive and specific and extends its utility for the detection of clinically relevant variants in cancer.

T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically ‘exhausted’ in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.

This article makes a general analysis of the supply chain of photovoltaic systems in Colombia, taking as a starting point a conceptual base and the current situation of the country in this sector. This article especially will contemplate the non-interconnected areas (ZNI) to the electricity grid in the national, due to its complexity in the logistics issues. Likewise, the work performs a graphical representation of the stages and processes of the supply chain using a powerful-modeled tool such as the Petri Nets (PNs). Finally, it identifies some of the flaws in the operation and the joint of all the links of the logistic part and from there it is based the importance of the strategy of orientation to the supply chain (SCO) as a possible alternative to improve and to enhance the logistic processes of this type of systems.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral genome is an RNA virus consisting of approximately 30,000 bases. As part of testing efforts, whole genome sequencing of human isolates has resulted in over 1,600 complete genomes publicly available from GenBank. We have performed a comparative phylogenetic analysis of the sequences, in order to detect common mutations within the population. Analysis of variants occurring within the assembled genomes yields 417 variants occurring in at least 1% of the completed genomes, including 229 within the 5’ untranslated region (UTR), 152 within the 3’UTR, 2 within intergenic regions and 34 within coding sequences.

COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.

This paper builds upon a theory of emerging-state actors using ISIS as a case study. This paper seeks to apply the theory in analyzing intervention & containment policies to use against emerging-state actors, using ISIS as the case study. Two baseline scenarios are used for evaluation – one replicating the historical foreign intervention against ISIS and a counter-factual where no foreign intervention occurred. Eleven contemporary military policies were tested against these baseline in isolation, combination, at different timing windows and under hypothetical “best case” conditions as well as operationally constrained. Insights of these tests include the influence of ethnographic envelopes, timing windows. Finally, a policy based on emerging-state actor theory is tested performing substantially better across primary measures than other policies or the historical baseline. This is compared against a falsified-policy designed to disprove that emerging-state actor theory contributed to the benefits. This paper’s contributions are a practical application of system dynamics simulations and systems-thinking to current problems, generate insights into the dynamics of emerging-state actors and intervention strategies, and demonstrate utility for future application of the underlying simulation in other scenarios involving non-state actor irregular conflict including terrorism, insurgents, or emerging-state actors.

A temperate deep lake, Lake Kuttara, Hokkaido, Japan (148 m deep at maximum) was completely frozen every winter in the 20th century. However, unfrozen conditions of the lake over winter occurred four times in the 21st century, which is probably due to global warming. In order to understand how thermal regime of the lake responds to climate change, its heat storage change was calculated by estimating heat budget of the lake and monitoring water temperature at the deepest point for September 2012–June 2016. As a result, temporal change of the heat storage from the heat budget was very consistent with that from the direct temperature measurement (determination coefficient R² = 0.827). The 1978–2017 data at a meteorological station near Kuttara indicated that there are significant (less than 5% level) long-term trends for air temperature (0.024 °C/yr) and wind speed (−0.010 m/s/yr). A sensitivity analysis for the heat storage from the heat budget estimate and an estimate of return periods for mean air temperature in mid-winter allow us to conclude that the lake could be unfrozen once per about two year in a decade.

The scope of a lucrative career promoted by Google through its video distribution platform YouTube 1 has attracted a large number of users to become content creators. An important aspect of this line of work is the feedback received in the form of comments which show how well the content is being received by the audience. However, volume of comments coupled with spam and limited tools for comment classification makes it virtually impossible for a creator to go through each and every comment and gather constructive feedback. Automatic classification of comments is a challenge even for established classification models, since comments are often of variable lengths riddled with slang, symbols and abbreviations. This is a greater challenge where comments are multilingual as the messages are often rife with the respective vernacular. In this work, we have evaluated top-performing classification models and four different vectorizers, for classifying comments which are a mix of different combinations of English and Malayalam (only English, only Malayalam and Mix of English and Malayalam). The statistical analysis of results indicates that Multinomial Naïve Bayes, K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Random Forest and Decision Trees offer similar level of accuracy in comment classification. Further, we have also evaluated 3 multilingual sub-types of the novel NLP language model, BERT and compared its’ performance to the conventional machine learning classification techniques. XLM was the top-performing BERT model with an accuracy of 67.31%. Random Forest with Term Frequency Vectorizer was the best the top-performing model out of all the traditional classification models with an accuracy of 63.59%.

This work promotes new methods in Mathematical Modeling, consisting in the use of the methods of Non-standard Analysis in Topoi, having as its main purpose, the mathematical definitions of the pseudoparticles from the title, with arguments from Biology/Physiology (Mathematical Neuroscience), Physics (String Theory and Emergent Quantum Mechanics), and Cybernetics (Global Brain, including Natural and Artificial Intelligence). The connections between brain and mind will be scketched via the genetic/epigenetic interplay. The topoi model the intuitionistic logic (multi-valued) and have been used in Quantum Physics while Non-Standard Analysis in SET (= the Category of sets) has been applied in Mathematical Economics; topics from Theory of Categories were also used in the study of Consciousness; however, the combination topoi - non-standard analysis was never used until now in Applied Mathematics. Another important objective is to produce progress in this aria of Pure Mathematics also - the build of non-standard analysis in classes of topoi, already used in Physics. We propose the logic of non-standard extensions in topoi as a model of the human thinking (based on infons/receptons), these theories representing new top and very difficult results in Abstract Mathematics either.

In this study, we used the natural and anthropogenic characteristics of a coastal region to generate risk maps showing vulnerability and potential hazards, and proposed design criteria for coastal defense and land use for the various kinds of risks faced. The Yunlin coast: a first-level protection area in mid-west Taiwan, was then used as an example to illustrate the proposed design criteria. The safety of the present coastal defenses and land use of the Yunlin coastal area was assessed, and coastal protection measures for hazard prevention were proposed based on the generated risk map. The results can be informative for future coastal management and the promotion of sustainable development of coastal zones.

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

In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the province of Wuhan, China. Since then, it has spread worldwide with new mutations being reported. We performed genomic analysis to identify the changes in genetic diversity of SARS-CoV-2 between December 2019 and November 2020, and through molecular surveillance, we monitored the mutations that could be involved in viral fitness. We analyzed 2,213 complete genomes from 6 geographical regions worldwide, which were downloaded from GenBank and GISAID databases. Although SARS-CoV-2 presented low genetic diversity, there has been an increase over time, with the presence of several hotspot mutations throughout its genome. We identified 7 frequent mutations that resulted in non-synonymous substitutions (dN). Two of them, C14408T>P323L and A23403G>D614G, located in the nsp12 and Spike protein, respectively, emerged early in the pandemic and showed a considerable increase in frequency over time. Two other mutations, A1163T>I120F in nsp2 and G22992A>S477N in the Spike protein emerged recently and have spread in Oceania and Europe. Continuous molecular surveillance of SARS-CoV-2 will be necessary to detect and describe the transmission dynamics of new variants of the virus with clinical relevance. This information is important to improve programs to control the virus.

Suitable measures of grazing impacts on ground cover, that enable separation of the effects of climatic variations, are needed to inform land managers and policy makers across the arid rangelands of the Northern Territory of Australia. This work developed and tested a time-series, change-point detection method for application to time series of vegetation fractional cover derived from Landsat data to identify irregular and episodic ground-cover growth cycles. These cycles were classified to distinguish grazing impacts from that of climate variability. A measure of grazing impact was developed using a multivariate technique to quantify the rate and degree of ground cover change. The method was successful in detecting both long term (> 3 years) and short term (< 3 years) growth cycles. Growth cycle detection was assessed against rainfall surplus measures indicating a relationship with high rainfall periods. Ground cover change associated with grazing impacts was also assessed against field measurements of ground cover indicating a relationship between both field and remotely sensed ground cover. Cause and effects between grazing practices and ground cover resilience can now be explored in isolation to climatic drivers. This is important to the long term balance between ground cover utilisation and overall landscape function and resilience.

Insufficient mixing in large-scale bioreactors, provokes gradient zones of substrate, dissolved oxygen, pH and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and -methyl-norleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids, but also that pyruvate pulses produce the same effect. Therefore we combined the enzyme based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions, produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor. To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

The expanding use of devices emitting Pulsed Telecommunication Signals (PTS) has launched a serious debate over the possible effects of electromagnetic radiation (EMR) on living organisms. Our previous work has indicated that PTS exposure alters Amyloid Precursor Protein (APP) and alpha-synuclein (α-syn) metabolism in human cells of neural origin, providing a possible connection between exposure and neurodegeneration. This investigation aimed to reveal, in vitro in human non-neural cells (HEK293), the aftermath of the same exposure on the processing of APP and α-syn. Data presented here, indicate changes in APP metabolism, acquisition of different cellular topologies of the newly generated APP fragments, changes in monomeric α-syn accumulation and multimerization, indicating that APP and α-syn processing is possibly altered in the periphery by EMR. These effects are accompanied by a substantial increase in the levels of Reactive Oxygen Species (ROS). Further investigation is required in order to provide insights into the interaction of PTS with non-neural cells affecting the peripheral systemic functional stability. This is necessary because nowadays whole body human exposure from various EMR sources is a fact in normal life with the valid estimation that they may be increased in view of the forthcoming 5G telecommunications network implementation.

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, 3CLpro of the SARS-CoV-2 virus causing COVID-19. From our screening of over one million compounds including approved drugs, investigational drugs, natural products, and organic compounds, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective 3CLpro inhibitors. Importantly, some of the identified compounds had previously been reported to exhibit inhibitory activities against the 3CLpro enzyme of the closely related SARS-CoV virus. The top- ranking compounds are characterized by the presence of multiple bi- and monocyclic rings, many of them being heterocycles and aromatic, which are flexibly linked allowing the ligands to adapt to the geometry of the 3CLpro substrate site and involve a high amount of functional groups enabling hydrogen bond formation with surrounding amino acid residues, including the catalytic dyad residues H41 and C145. Among the top binding compounds we identified several tyrosine kinase inhibitors, which include a bioflavonoid, the group of natural products that binds best to 3CLpro. Another class of compounds that decently binds to the SARS-CoV-2 main protease are steroid hormones, which thus may be endogenous inhibitors and might provide an explanation for the age-dependent severity of COVID-19. Many of the compounds identified by our work show a considerably stronger binding than found for reference compounds with in vitro demonstrated 3CLpro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.

The Cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most prominent and most studied secondary metabolites— Δ9-Tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD). Both Δ9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids—of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus SARS-COV2, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.

We prove: (1) the set of all Diophantine equations which have at most finitely many solutions in non-negative integers is not recursively enumerable, (2) the set of all Diophantine equations which have at most finitely many solutions in positive integers is not recursively enumerable, (3) the set of all Diophantine equations which have at most finitely many integer solutions is not recursively enumerable, (4) analogous theorems hold for Diophantine equations D(x₁, …, x_p) = 0, where p ∈ N\{0} and for every i ∈ {1, …, p} the polynomial D(x₁, …, x_p) involves a monomial M with a non-zero coefficient such that x_i divides M, (5) the set of all Diophantine equations which have at most k variables (where k ≥ 9) and at most finitely many solutions in non-negative integers is not recursively enumerable.

The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes mellitus, hypertension and obesity.

Literature is inconsistent as to how coffee affects the features of the metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. We aimed to compare the in-vivo effects of unfiltered coffee with a selected mixture of its compounds on diet-induced MetS. 24 male Sprague-Dawley rats were fed a high-fat (35% W/W) food plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water in a dosage equal to 4 cups/day in a human. Compared to the controls, only coffee supplementation decreased total food intake, weight gain, and estimated average plasma glucose. Surrogate measures of insulin resistance (fasting insulin, HOMA-IR, and oral glucose tolerance) were improved at endpoint in the coffee group. Circulating triglyceride levels were also reduced by coffee. Histopathological and quantitative measurements indicated lower grades of liver steatosis after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped viruses with positive-stranded RNA and envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics delineating their distinct strategies for efficient spread.